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28599261

Secretory immunoglobulin purification from whey by chromatographic techniques.

Secretory immunoglobulins (SIg) are a major fraction of the mucosal immune system and represent potential drug candidates. So far, platform technologies for their purification do not exist. SIg from animal whey was used as a model to develop a simple, efficient and potentially generic chromatographic purification process. Several chromatographic stationary phases were tested. A combination of two anion-exchange steps resulted in the highest purity. The key step was the use of a small-porous anion exchanger operated in flow-through mode. Diffusion of SIg into the resin particles was significantly hindered, while the main impurities, IgG and serum albumin, were bound. In this step, initial purity was increased from 66% to 89% with a step yield of 88%. In a second anion-exchange step using giga-porous material, SIg was captured and purified by step or linear gradient elution to obtain fractions with purities >95%. For the step gradient elution step yield of highly pure SIg was 54%. Elution of SIgA and SIgM with a linear gradient resulted in a step yield of 56% and 35%, respectively. Overall yields for both anion exchange steps were 43% for the combination of flow-through and step elution mode. Combination of flow-through and linear gradient elution mode resulted in a yield of 44% for SIgA and 39% for SIgM. The proposed process allows the purification of biologically active SIg from animal whey in preparative scale. For future applications, the process can easily be adopted for purification of recombinant secretory immunoglobulin species.

['Matlschweiger|Alexander|A|', 'Engelmaier|Hannah|H|', 'Himmler|Gottfried|G|', 'Hahn|Rainer|R|']

2017

23948612

The OH-initiated atmospheric reaction mechanism and kinetics for levoglucosan emitted in biomass burning.

Levoglucosan is a typical molecular tracer of biomass-burning aerosols in the atmosphere. The mechanism for OH-initiated reaction with levoglucosan is studied at the level of MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p). The possible subsequent reactions in the presence of O2, NO and H2O are also taken into consideration. The study shows that the H atom abstraction from the C4-position by the OH radical is an energetically favorable pathway, and that the OH-initiated products contribute to the formation of SOA and atmospheric acidity. The kinetic calculation is performed and the rate constants are calculated over the temperature range of 200-1500 K, using the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The rate constant of levoglucosan reacting with the OH radical at 298 K is 2.21×10(-13) cm(3) molecule(-1) s(-1) and the atmospheric lifetime is 26 days ([OH]=2.0×10(6) molecule cm(-3)). The equilibrium constants both in gas phase and aqueous are computed. The free energy ΔG indicates that, the subsequent reactions tend to take place more spontaneously once the reaction occurs. This work provides a comprehensive investigation about OH-initiated atmospheric reactions with levoglucosan, which is helpful for experiment and risk assessment.

['Bai|Jing|J|', 'Sun|Xiaomin|X|', 'Zhang|Chenxi|C|', 'Xu|Yisheng|Y|', 'Qi|Chuansong|C|']

2013

30107959

Supporting Radiology Residents' Professional Development Through a Competitive Intramural Grant.

Research and other scholarly activities are an important and required component of diagnostic radiology training. Several strategies, both at the departmental and the larger organizational levels, have been implemented to encourage radiology trainees to participate in these activities. In this article, we review and discuss our institution's 10-year experience in supporting the development and realization of scholarly projects through a competitive intramural grant for residents.

['Mendoza|Dexter|D|', 'Holbrook|Anna|A|', 'Bertino|Frederic|F|', 'Balthazar|Patricia|P|', 'Newell|Mary|M|', 'Meltzer|Carolyn C|CC|']

2019

31694267

Air Pollution as a Cause of Obesity: Micro-Level Evidence from Chinese Cities.

Chinese air pollution is obviously increasing, and the government makes efforts to strengthen air pollution treatment. Although adverse health effects gradually emerge, research determining individual vulnerability is limited. This study estimated the relationship between air pollution and obesity. Individual information of 13,414 respondents from 125 cities is used in the analysis. This study employs ordinary least squares (OLS) and multinomial logit model (m-logit) to estimate the impact of air pollution on obesity. We choose different air pollution and Body Mass Index (BMI) indicators for estimation. Empirical results show Air Quality Index (AQI) is significantly positively associated with the BMI score. As AQI adds one unit, the BMI score increases 0.031 (SE = 0.002; p < 0.001). The influence coefficients of particle size smaller than 2.5 μm (PM2.5), particle size smaller than 10 μm (PM10), carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2) to the BMI score are 0.034 (SE = 0.002; p < 0.001), 0.023 (SE = 0.001; p < 0.001), 0.52 (SE = 0.095; p < 0.001), 0.045 (SE = 0.004; p < 0.001), 0.021 (SE = 0.002; p < 0.001), 0.008 (SE = 0.003; p = 0.015), respectively. Generally, air pollution has an adverse effect on body weight. CO is the most influential pollutant, and female, middle-aged, and low-education populations are more severely affected. The results confirm that the adverse health effects of air pollution should be considered when making the air pollution policies. Findings also provide justification for health interventions, especially for people with obesity.

['Yang|Zhiming|Z|0000-0001-8468-2077', 'Song|Qianhao|Q|', 'Li|Jing|J|', 'Zhang|Yunquan|Y|0000-0002-2618-5088']

2019

29972347

Clinical outcome and time trends of surgically treated renal cell carcinoma between 1986 and 2010: results from a single centre in Sweden.

OBJECTIVE The aims of this study were to create a cohort of retrospectively collected renal cell carcinoma (RCC) specimens to be used a basis for prognostic molecular studies, and to investigate the outcome and time trends in patients surgically treated for RCC in a single-centre cohort. MATERIALS AND METHODS Patients undergoing surgery for RCC between 1986 and 2010 were included in the study. Medical records were reviewed, and the diagnostic tissue was re-evaluated according to a modern classification. The change in patient and tumour characteristics over time was analysed. RESULTS The study included 345 patients. Smaller tumours, as indicated by primary tumour diameter, tumour (T) stage and American Joint Committee on Cancer (AJCC) stage, were found more frequently in later years compared to the early 1990s. No changes in the clinical outcome for the patients were seen among the time periods investigated. Increasing T stage, AJCC stage, primary tumour diameter and decreasing haemoglobin levels were associated with cancer-specific mortality in univariate analysis. A high calcium level was significantly associated with increased cancer-specific mortality (hazard ratio = 4.25, 95% confidence interval 1.36-13.28) in multivariate analysis. CONCLUSIONS This study on patients who underwent surgery for RCC from 1986 to 2010 at a single institution in Sweden indicates that there has been a change in tumour characteristics of patients diagnosed with RCC over time. It was also shown that calcium levels were an independent prognostic factor for cancer-specific mortality in this cohort. This cohort could provide a valuable basis for further molecular studies.

['Grabowska|Beata|B|', 'Ulvskog|Emma|E|', 'Carlsson|Jessica|J|', 'Fiorentino|Michelangelo|M|', 'Giunchi|Francesca|F|', 'Lindblad|Per|P|', 'Sundqvist|Pernilla|P|']

2018

33170391

Personality Disorders in Time of Pandemic.

PURPOSE OF REVIEW We report evidence on the negative psychological effects of pandemics in people with personality disorders (PDs) and on the role of personality pathology in compliance with mitigation-related behaviors. Considering the paucity of studies, after a description of the main features of PDs, on the basis of the current literature on pandemic and quarantine mental health impact, we trace some clinical hypotheses. RECENT FINDINGS Paranoid traits and detachment (cluster A) might lead to worse psychological outcomes. Cluster B patients may show more intense stress-related reactions and react strongly to social distancing, especially considering borderline personality disorder. Cluster C patients might be particularly prone to anxiety and stress due to fear of contagion and may be less flexible in adaptation to new routines. Evidence on compliance with mitigation measures is mixed, with lower compliance in cluster B patients and higher in cluster C ones. We suggest that PD patients might be particularly affected by pandemics. Furthermore, they might react differently, according to their main diagnosis. Similarly, compliance with mitigation measures may differ according to specific PDs. Our results should be considered as a starting point to reflect on therapeutic strategies to be adopted in the post-COVID-19 situation.

['Preti|Emanuele|E|', 'Di Pierro|Rossella|R|', 'Fanti|Erika|E|', 'Madeddu|Fabio|F|', 'Calati|Raffaella|R|']

2020

34513660

GAS6-AS1 Overexpression Increases GIMAP6 Expression and Inhibits Lung Adenocarcinoma Progression by Sponging miR-24-3p.

GAS6 antisense RNA 1 (GAS6-AS1) is a long non-coding RNA involved in hepatocellular carcinoma and gastric cancer. However, the functional role of GAS6-AS1 in lung adenocarcinoma (LUAD) remains unclear. In the present study, qRT-PCR was used to measure the levels of GAS6-AS1, GIMAP6 and miR-24-3p expression in LUAD samples and cell lines. CCK-8 and colony formation assays were used to determine cell proliferation. Cell migration and invasion were evaluated using wound healing and transwell assays, respectively. The potential interactions between molecules were assessed using RNA immunoprecipitation and luciferase reporter assays. Western blot analysis was used to quantify protein expression. The anti-tumor effect of over-expressed GAS6-AS1 on LUAD was also examined in vivo in xenograft tumor experiments. The expression of GAS6-AS1 was notably downregulated in LUAD samples and cell lines and associated with a poor prognosis. GAS6-AS1 overexpression inhibited the migration and invasion of A549 and H1650 cells. Down-expressed GAS6-AS1 acted as a sponge for miR-24-3p and down-regulated the expression of its target, GTPase IMAP Family Member 6. These findings suggested that GAS6-AS1 might represent a potential diagnostic biomarker for LUAD.

['Wang|Yuanyong|Y|', 'Ma|Minge|M|', 'Li|Chuan|C|', 'Yang|Yuling|Y|', 'Wang|Maolong|M|']

2021

23972396

Effect of dissimilatory Fe(III) reducers on bio-reduction and nickel-cobalt recovery from Sukinda chromite-overburden.

The effect of an adapted dissimilatory iron reducing bacterial consortium (DIRB) towards bio-reduction of Sukinda chromite overburden (COB) with enhanced recovery of nickel and cobalt is being reported for the first time. The remarkable ability of DIRB to utilize Fe(III) as terminal electron acceptor reducing it to Fe(II) proved beneficial for treatment of COB as compared to previous reports for nickel leaching. XRD studies showed goethite as the major iron-bearing phase in COB. Under facultative anaerobic conditions, goethite was reduced to hematite and magnetite with the exposure of nickel oxide. FESEM studies showed DIRB to be associated with COB through biofilm formation with secondary mineral precipitates of magnetite deposited as tiny globular clusters on the extra polymeric substances. The morphological and mineralogical changes in COB, post DIRB application, yielded a maximum of 68.5% nickel and 80.98% cobalt in 10 days using 8M H2SO4.

['Esther|Jacintha|J|', 'Panda|Sandeep|S|', 'Behera|Sunil K|SK|', 'Sukla|Lala B|LB|', 'Pradhan|Nilotpala|N|', 'Mishra|Barada K|BK|']

2013

25737615

Progesterone vaginal ring for luteal support.

Progesterone supplementation is universally used and has been shown to be beneficial in supplementation of the luteal phase in IVF. There are multiple options and the most commonly used include intramuscular and vaginal progesterone. A progesterone vaginal ring is a novel system for luteal support with advantages of controlled release with less frequent dosing. This review examines options for progesterone luteal support focusing on the rationale for a progesterone vaginal ring. Pub-med search of the literature. A weekly vaginal ring, although not yet FDA approved, is an effective and safe alternative for luteal supplementation in IVF. Large prospective clinical trials are needed to determine the best protocols for replacement cycles.

['Stadtmauer|Laurel|L|', 'Waud|Kay|K|']

2015

27789728

Is preoperative hypercapnia a justified exclusion criterion for lung volume reduction surgery?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether potential surgical candidates for lung volume reduction surgery (LVRS), who have preoperative hypercapnia, should be excluded on this basis. Using the reported search, 45 papers were found, of which 14 represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. Of these, seven papers showed a significant (P < 0.05) improvement in postoperative forced expiratory volume in 1 second (FEV1) at up to 6 months in hypercapnic patients. There were six papers which found significant decreases in postoperative arterial carbon dioxide partial pressures (PaCO2) levels following LVRS up to 6 months. There were three papers which showed significant (P < 0.05) improvements in the 6-min walk test in hypercapnic patients following LVRS. Only two papers showed an increased operative mortality in the hypercapnic group compared to the normocapnic group, while nine papers did not find a difference in perioperative mortality. The only randomized controlled study, the landmark NETT study, excluded patients with severe hypercapnia (PaCO2 >55 mmHg and >60 mmHg) and the mean PaCO2 in the surgical and medical group were 43.3 ± 5.9 and 43.0 ± 5.8, respectively. We conclude that the evidence is not strong enough to consider hypercapnia in isolation as high risk or unsuitable for LVRS.

['Ariyaratnam|Priyadharshanan|P|', 'Tcherveniakov|Peter|P|', 'Milton|Richard|R|', 'Chaudhuri|Nilanjan|N|']

2017

32024726

Fast, Simple, and Cheap: the Kudoh-Ogawa Swab Method as an Alternative to the Petroff-Lowenstein-Jensen Method for Culturing of Mycobacterium tuberculosis.

The objective of this study was to compare the diagnostic yield of the Kudoh-Ogawa (K-O) swab method for the culturing of Mycobacterium tuberculosis from clinical samples with the standard Petroff-Lowenstein-Jensen (P-LJ) procedure. A total of 2,287 sputum samples and 685 extrapulmonary clinical specimens were processed with both decontamination methods and compared for M. tuberculosis detection rate, recovery of M. tuberculosis colonies, and culture contamination. Overall, 23.9% and 23.5% of the samples, processed with, respectively, the K-O swab method and the P-LJ procedure, yielded M. tuberculosis after 8 weeks of incubation. The K-O swab method and the P-LJ procedure provided comparable diagnostic yields for extrapulmonary clinical specimens (P = 0.688), but the K-O method showed a slightly but statistically significantly higher diagnostic yield for pulmonary samples (P = 0.002). No significant difference for culture contamination or colony recovery was found for either method. The turnaround time for the isolation of M. tuberculosis was significantly shorter for the K-O swab method, with 77% of the M. tuberculosis cultures being positive within 3 weeks of incubation, and only 6.1% positivity for the P-LJ method. Concerning the workload, the K-O swab method needs a minimum sample manipulation and takes less than 4 min per sample, as the samples are not centrifuged in this procedure. The K-O swab method is an efficient and fast (in terms of sample processing and culture growth) alternative for culturing M. tuberculosis from either pulmonary or extrapulmonary clinical specimens. The method is particularly suitable for laboratories with a high workload and for laboratories lacking a special infrastructure.

['Franco-Sotomayor|Greta|G|', 'Rivera-Olivero|Ismar A|IA|0000-0001-8345-8217', 'Leon-Benitez|Margarita|M|', 'Uruchima-Campoverde|Sandra E|SE|', 'Cardenas-Franco|Greta|G|', 'Perdomo-Castro|Mercedes E|ME|', 'Cardenas-Franco|Camilo S|CS|', 'Ortega-Vivanco|Jackeline|J|', 'Abad-Ruiz|Ana S|AS|', 'de Waard|Jacobus H|JH|0000-0003-4118-1015', 'Garcia-Bereguiain|Miguel Angel|MA|0000-0003-0025-3609']

2020

25442962

Endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events: post-ERCP pancreatitis.

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), and not uncommonly is the reason behind ERCP-related lawsuits. Patients at high risk for PEP include young women with abdominal pain, normal liver tests, and unremarkable imaging. Procedure-related factors include traumatic and persistent cannulation attempts, multiple injections of the pancreatic duct, pancreatic sphincterotomy, and, possibly, use of precut sphincterotomy. Aggressive hydration, use of rectal indomethacin, and prophylactic pancreatic stenting can diminish the risk (and likely severity) of PEP. Though hugely beneficial, these measures do not supersede careful patient selection and technique.

['Rustagi|Tarun|T|', 'Jamidar|Priya A|PA|']

2015

32542459

Common genetic predisposition for heart failure and cancer.

Cardiovascular diseases and cancer are major causes of mortality in industrialized societies. They share common risk factors (e.g., genetics, lifestyle, age, infection, toxins, and pollution) and might also mutually promote the onset of the respective other disease. Cancer can affect cardiac function directly while antitumor therapies may have acute- and/or late-onset cardiotoxic effects. Recent studies suggest that heart failure might promote tumorigenesis and tumor progression. In both cancer and cardiovascular diseases, genetic predisposition is implicated in the disease onset and development. In this regard, genetic variants classically associated with cardiomyopathies increase the risk for toxic side effects on the cardiovascular system. Genetic variants associated with increased cancer risk are frequent in patients with peripartum cardiomyopathy complicated by cancer, pointing to a common genetic predisposition for both diseases. Common risk factors, cardiotoxic antitumor treatment, genetic variants (associated with cardiomyopathies and/or cancer), and increased cardiac stress lead us to propose the "multi-hit hypothesis" linking cancer and cardiovascular diseases. In the present review, we summarize the current knowledge on potential connecting factors between cancer and cardiovascular diseases with a major focus on the role of genetic predisposition and its implication for individual therapeutic strategies and risk assessment in the novel field of oncocardiology.

['Pfeffer|Tobias J|TJ|', 'Pietzsch|Stefan|S|', 'Hilfiker-Kleiner|Denise|D|']

2020

29325915

In vivo nonspecific immunomodulatory and antispasmodic effects of common purslane (Portulaca oleracea Linn.) leaf extracts in ICR mice.

ETHNOPHARMACOLOGICAL RELEVANCE Portulaca oleracea (common purslane) is used in traditional medicine to cure various illnesses. However, its immune-protective properties and antispasmodic effects still need more pharmacological data if the plant will be utilized in herbal and drug formulations. Therefore, the present study determined the capacity of this plant species to modulate nonspecific immune responses and to confirm its antispasmodic activity in vivo in ICR mice. MATERIALS AND METHODS Phagocytic activity of peritoneal macrophage, splenic lymphocyte proliferation and plasma lysozyme levels were measured in mice that were immunosuppressed using cyclophosphamide and treated with the ethyl acetate extract of Portulaca oleracea. In addition, the charcoal meal transit test was used to measure intestinal motility using ethanolic (EtOH), hexane (HEX), and ethyl acetate (EA) solvent extracts. Phytochemical analysis was undertaken and DPPH scavenging properties of the three solvent extracts were also determined. RESULTS The EA extract of P. oleracea exhibited immunoactivity through significant increase in phagocytosis and higher proliferative response in splenic lymphocytes. Plasma lysozyme level was also higher in EA-treated mice at high dose but this was not statistically significant. Decreased intestinal motility was also exhibited in mice treated with the three leaf solvent extracts compared to the negative control and the acetylcholine-treated group. The antispasmodic activity of the solvent extracts was comparable to that of the atropine-treated group. Phytochemical analysis showed the presence of tannins in EA extract in addition to alkaloids and steroids. The EtOH and HEX extracts contain alkaloids, steroids and terpenoids. DPPH scavenging activity was highest in the EA extract. CONCLUSIONS The present study showed that the EA extract of P. oleracea leaves ameliorated the immunosuppressive action of cyclophosphamide in mice. The results also indicated that the three solvent extracts of the plant decreased smooth muscle spasms in mice ileum. However, further experiments are warranted to further isolate the plant's immunoactive component. Also, the mechanisms involved in the immunoactivity and antispasmodic properties of P. oleracea deserve full elucidation.

['Catap|Elena S|ES|', 'Kho|Markyn Jared L|MJL|', 'Jimenez|Maria Rexie R|MRR|']

2018

29222991

Salivary immune proteins monitoring can help detection of binge and chronic alcohol drinkers: Preliminary findings.

BACKGROUND We compared effects of binge and chronic alcohol drinking on oral health and salivary immunity proteins. METHODS The study involved males: 13 healthy social-drinking (C), 10 alcohol-dependent after chronic alcohol-intoxication (A), and 8 binge-drinkers after a single binge-drinking session (B). We compared periodontal/dental state and salivary immune proteins (lactoferrin -Lf, lysozyme -Lz, oral peroxidase -OPO, immunoglobulin A -IgA) in all groups. RESULTS Group A had worse dental and periodontal states than group C and B. Group B had a lower OPO activity and Lz concentration, and a higher IgA concentration in comparison to group C. Group A had a higher OPO activity than group C. Group B had a lower Lz and a higher LF and IgA outputs than C. Group A had a lower IgA output and a strong tendency of Lf and Lz outputs to be lower than in group C. Positive correlations were found between alcohol amounts and OPO and Lf output in group A, with no such correlations in group B. Only IgA concentration in group B and OPO activity in group A have potential to be markers that help to differentiate binge from chronic alcohol drinking, and OPO activity had better accuracy than IgA. CONCLUSION Binge alcohol consumption resulted in specific disturbances in salivary innate immunity (Lz), whereas chronic drinking led to disturbances in both adaptive and innate immunity (IgA, Lz and Lf). There is potential applicability of raised salivary IgA concentration and especially OPO activity in binge and chronic drinking detection and differential-diagnosis.

['Waszkiewicz|Napoleon|N|', 'Galińska-Skok|Beata|B|', 'Zalewska|Anna|A|', 'Szajda|Sławomir Dariusz|SD|', 'Zwierz|Krzysztof|K|', 'Więdłocha|Magdalena|M|', 'Szulc|Agata|A|']

2018

23843772

Recent progress of genome study for anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) belongs to the most malignant and rapidly progressive human thyroid cancers and its prognosis is very poor. Also, it shows high resistance to cancer treatments, so that effective treatment for ATC has not been found to date, and virtually all patients terminate their life rapidly after diagnosis. Although targeted treatment of genetic alterations has emerged as an extremely promising approach to human cancers, such as BRAF in metastatic melanoma, it remains unclear that how commonly genomic alterations are influenced in ATC tumorigenesis. In recent years, genome wide approaches have been exploited to find genetic alterations associated with complex diseases, including cancer. Here, we reviewed the comprehensive genetic alterations in ATC and recent approaches in the context of identifying genomic alterations associated with ATC. Since surprisingly few reports have been published on the genome wide study of ATC, this review puts emphasis on the urgent needs of genomic research for the prevention and treatment of ATC.

['Lee|Jieun|J|', 'Hwang|Jung-Ah|JA|', 'Lee|Eun Kyung|EK|']

2013

29637349

The Brazilian Portuguese version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Brazilian Portuguese language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 231 JIA patients (14.7% systemic, 43.3% oligoarticular, 22.5% RF negative polyarthritis, 19.5% other categories) and 72 healthy children, were enrolled in three centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Brazilian Portuguese version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

['Fernandes|Taciana A Pedrosa|TAP|', 'Magalhães|Claudia Saad|CS|', 'Oliveira|Sheila Knupp|SK|', 'Sztajnbok|Flavio|F|', 'de Oliveira Sato|Juliana|J|', 'Darze|Layla Saba|LS|', 'de Almeida|Rozana Gasparello|RG|', 'Consolaro|Alessandro|A|', 'Bovis|Francesca|F|', 'Ruperto|Nicolino|N|', '|||']

2018

32844249

Long-term complications and implant survival rates after cranioplastic surgery: a single-center study of 392 patients.

Cranioplasty (CP) is a standard procedure in neurosurgical practice for patients after (decompressive) craniectomy. However, CP surgery is not standardized, is carried out in different ways, and is associated with considerable complication rates. Here, we report our experiences with the use of different CP materials and analyze long-term complications and implant survival rates. We retrospectively studied patients who underwent CP surgery at our institution between 2004 and 2014. Binary logistic regression analysis was performed in order to identify risk factors for the development of complications. Kaplan-Meier analysis was used to estimate implant survival rates. A total of 392 patients (182 females, 210 males) with a mean age of 48 years were included. These patients underwent a total of 508 CP surgeries. The overall complication rate of primary CP was 33.2%, due to bone resorption/loosening (14.6%) and graft infection (7.9%) with a mean implant survival of 120 ± 5 months. Binary logistic regression analysis showed that young age (< 30 years) (p = 0.026, OR 3.150), the presence of multidrug-resistant bacteria (p = 0.045, OR 2.273), and cerebrospinal fluid (CSF) shunt (p = 0.001, OR 3.137) were risk factors for postoperative complications. The use of titanium miniplates for CP fixation was associated with reduced complication rates and bone flap osteolysis as well as longer implant survival rates. The present study highlights the risk profile of CP surgery. Young age (< 30 years) and shunt-dependent hydrocephalus are associated with postoperative complications especially due to bone flap autolysis. Furthermore, a rigid CP fixation seems to play a crucial role in reducing complication rates.

['Giese|Henrik|H|http://orcid.org/0000-0002-9277-5406', 'Meyer|Jennifer|J|', 'Unterberg|Andreas|A|', 'Beynon|Christopher|C|']

2021

31989921

Actin assembly ruptures the nuclear envelope by prying the lamina away from nuclear pores and nuclear membranes in starfish oocytes.

The nucleus of oocytes (germinal vesicle) is unusually large and its nuclear envelope (NE) is densely packed with nuclear pore complexes (NPCs) that are stockpiled for embryonic development. We showed that breakdown of this specialized NE is mediated by an Arp2/3-nucleated F-actin 'shell' in starfish oocytes, in contrast to microtubule-driven tearing in mammalian fibroblasts. Here, we address the mechanism of F-actin-driven NE rupture by correlated live-cell, super-resolution and electron microscopy. We show that actin is nucleated within the lamina, sprouting filopodia-like spikes towards the nuclear membranes. These F-actin spikes protrude pore-free nuclear membranes, whereas the adjoining stretches of membrane accumulate NPCs that are associated with the still-intact lamina. Packed NPCs sort into a distinct membrane network, while breaks appear in ER-like, pore-free regions. We reveal a new function for actin-mediated membrane shaping in nuclear rupture that is likely to have implications in other contexts, such as nuclear rupture observed in cancer cells.

['Wesolowska|Natalia|N|', 'Avilov|Ivan|I|', 'Machado|Pedro|P|', 'Geiss|Celina|C|', 'Kondo|Hiroshi|H|', 'Mori|Masashi|M|', 'Lenart|Peter|P|0000-0002-3927-248X']

2020

21874117

Emerging trends in the treatment of triple-negative breast cancer in Canada: a survey.

Triple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes and lacks common therapeutic targets, including HER 2 and the estrogen and progesterone receptors. The clinicopathological heterogeneity of the disease and limited treatment options make clinical management particularly challenging. Here we present the results of a survey of Canadian clinical oncologists regarding treatment of TNBC, and review recent and ongoing clinical research in this area. Our survey results show that the majority of respondents use a combination of anthracyclines-taxanes as adjuvant therapy for early TNBC. For the first-line treatment of metastatic TNBC, most clinicians recommend taxanes, while single agent capecitabine and platinum-based therapies are more common for subsequent lines of therapy. Despite the ongoing development of novel targeted therapies, chemotherapy remains the mainstay of treatment for TNBC.

['Verma|S|S|', 'Provencher|L|L|', 'Dent|R|R|']

2011

30641804

Differential performance of surrogate indices of fasting insulin resistance in low-birthweight and normal-birth weight cohorts: Observations from Hyperinsulinaemic-Euglycaemic clamp studies in young, Asian Indian males.

AIM To evaluate the predictive accuracy of surrogate measures of fasting insulin resistance/sensitivity like the Homeostasis model assessment for insulin resistance (HOMA -IR), Fasting glucose/insulin ratio (FG-IR), Quantitative insulin sensitivity check index (QUICKI), and the 20/fasting C peptide x fasting plasma glucose [20/(FCP × FPG)] index in comparison to M value derived from hyperinsulinaemic-euglycaemic clamp (HEC) studies in two birth weight based cohorts of Asian Indian males. METHODS HEC studies were performed in non-diabetic Asian Indian males (n = 117), born of normal birth weight (n = 59, birth weight > 2.5 kgs) and low birth weight (n = 58, birth weight < 2.5 kgs). Anthropometry and biochemical analysis were done. Surrogate indices of fasting insulin resistance were calculated and data were analysed by Pearson's correlation and Random calibration model analysis. RESULTS Amongst surrogate indices of fasting insulin resistance/sensitivity, the mean values for HOMA-IR, QUICKI, FG-IR, 20/(FCP × FPG) index and M value were similar between the two groups. Significant positive correlation was observed for FG-IR and QUICKI with M value (the gold standard measure of insulin sensitivity derived from HEC procedure) in the low birth weight cohort in contrast to the normal birth weight cohort, wherein no significant correlation was observed for any of the indices. Random calibration model analysis showed highest predictive accuracy for QUICKI in both the study groups. CONCLUSION The QUICKI index showed highest predictive accuracy in the normal birth weight and the low birth weight cohorts of Asian Indian males.

['Dasgupta|Riddhi|R|', 'Anoop|Shajith|S|', 'Venkatesan|Padmanaban|P|', 'Inbakumari|Mercy|M|', 'Finney|Geethanjali|G|', 'Thomas|Nihal|N|']

2019

32400234

Twelve tips for teaching ophthalmology in the undergraduate curriculum.

Ophthalmology education in the undergraduate medical curriculum has declined, and graduating healthcare professionals express discomfort with basic evaluation and management of ophthalmic complaints. With the growing aging population, ophthalmic needs will continue to rise, underscoring the need for increased eye care. This article offers 12 tips for increasing undergraduate ophthalmic education, which can be implemented strategically within limited established curricular time, or in novel ways outside the traditional curriculum. Within the curriculum, existing ophthalmology sessions can be enhanced through use of simulation technology and partnership with ophthalmology faculty. Additional curricular time can be justified through needs assessments and alignment of content with other disciplines, and ophthalmology content on licensing examinations. Finally, ophthalmology can be reinforced in service-based initiatives and through use of online resources and social media.

['Chadha|Nisha|N|', 'Gooding|Holly|H|']

2021

34210087

A Pencil-Drawn Electronic Tongue for Environmental Applications.

We report on the development of a simple and cost-effective potentiometric sensor array that is based on manual "drawing" on the polymeric support with the pencils composed of graphite and different types of zeolites. The sensor array demonstrates distinct sensitivity towards a variety of inorganic ions in aqueous media. This multisensor system has been successfully applied to quantitative analysis of 100 real-life surface waters sampled in Mahananda and Hooghly rivers in the West Bengal state (India). Partial least squares regression has been utilized to relate responses of the sensors to the values of different water quality parameters. It has been found that the developed sensor array, or electronic tongue, is capable of quantifying total hardness, total alkalinity, and calcium content in the samples, with the mean relative errors below 18%.

['Kirsanov|Dmitry|D|0000-0002-5667-6910', 'Mukherjee|Subhankar|S|', 'Pal|Souvik|S|0000-0001-8189-906X', 'Ghosh|Koustuv|K|0000-0003-2180-7236', 'Bhattacharyya|Nabarun|N|0000-0002-7313-6182', 'Bandyopadhyay|Rajib|R|0000-0003-1655-9899', 'Jendrlin|Martin|M|0000-0001-5921-2241', 'Radu|Aleksandar|A|0000-0002-5141-1884', 'Zholobenko|Vladimir|V|', 'Dehabadi|Monireh|M|0000-0002-2333-5394', 'Legin|Andrey|A|']

2021

32232612

Application of improved single blastomere fixation technique in preimplantation genetic diagnosis.

To modify a fixation method improving the intensity and clarity of the single blastomeric signal detection by fluorescence in situ hybridization (FISH) in preimplantation genetic diagnosis. 333 cycles of assisted reproduction with preimplantation genetic diagnosis FISH (PGD-FISH) performed in our hospital were analyzed and a total of 3452 single blastomeres were obtained. For the conventional fixation method, the blastomeres were kept in 0.1% sodium citrate with 0.2 mg/ml bovine serum albumin (BSA) for 2-5 min. FISH was performed and the internal relationship between embryo quality and fixed rate, signal detection rate, and signal determination rate was explored. With the modified method, 91.54% of blastomeres were fixed, while 88.30% were fixed with the conventional method. The signal detection rate was significantly increased for the modified group than for the conventional group (compared 98.53% with 94.78%, P < 0.001). Especially, the signal determination rate also showed a significant difference between the two methods (compared 90.51% with 74.17%, P < 0.001). After the development of the fixation method, the fixation efficiency and the signal determination rate were greatly improved, providing more definite diagnosis for the patient. It will hopefully allow more assisted reproduction programs to offer their patients preimplantation genetic diagnosis with FISH.

['Yu|Guanling|G|', 'Ma|Shuiying|S|', 'Zhu|Yueting|Y|', 'Liu|Yujin|Y|', 'Zhang|Haozhen|H|', 'Wu|Keliang|K|', 'Hao|Aijun|A|']

2020

34435577

The invasive crayfish Cherax quadricarinatus facing chlordecone in Martinique: Bioaccumulation and depuration study.

The redclaw crayfish, Cherax quadricarinatus, was introduced to Martinique Island for aquaculture purposes at the beginning of the 21st century, in an attempt to revitalize the freshwater crustacean aquaculture sector. Mainly due to its high economical value, it was intentionally released in the wild and was caught and sold by fishermen. Martinican rivers are polluted by chlordecone, considered as one of the worst Persistant Organic Pollutants (POP). Despite its dangerousness, it was used until 1993 in the French West Indies against a banana pest and was always found in the ecosystems. This study aimed to investigate the level of contamination in the muscle of crayfish caught in the wild, as well as the potential of bioconcentration and depuration in the C. quadricarinatus muscle. This study could allow us to quantify the risk for consumers but also, to evaluate a depuration process to reduce the risk related to its consumption. Using both in-vitro and in-situ experiments, results highlighted the importance of the chlordecone concentration in the water and the time of exposure to the pollutant. The bioconcentration seems to be very quick and continuous in crayfish muscle, as chlordecone can be detectable as early as 6 h of exposure, whatever the concentration tested. Finally, it appears that, even after 20 days of depuration in chlordecone-free water, chlordecone concentrations remained higher to the residual maximum limit (i.e. 20 ng/g wet weight), concluding that the decontamination of the muscle seems not very efficient, and the risk for the Martinican people could be serious.

['Baudry|Thomas|T|', 'Gismondi|Eric|E|', 'Goût|Jean-Pierre|JP|', 'Arqué|Alexandre|A|', 'Smith-Ravin|Juliette|J|', 'Grandjean|Frédéric|F|']

2022

29677971

Monitoring Daily Physical Conditions of Older Adults Using Acoustic Features: A Preliminary Result.

Health monitoring in everyday situations has become important due to the rapid aging of many societies. Speech changes have been suggested as a means of measuring an individual's state, such as emotion and stress, and screening for neurodegenerative diseases. However, how speech features are associated with daily physical conditions remains unknown. In this study, we investigated whether acoustic features collected in everyday situations could be used for inferring the daily physical conditions of older adults. We analyzed speech data collected in two settings of monitoring the health of older adults: during phone calls with an actual service for regularly monitoring older adults and with a tablet-based monitoring system we developed. Through analyses, we suggest that acoustic features extracted from speech data in everyday situations may be used for detecting poor physical conditions.

['Yamada|Yasunori|Y|', 'Shinkawa|Kaoru|K|', 'Takase|Toshiro|T|', 'Kosugi|Akihiro|A|', 'Fukuda|Kentarou|K|', 'Kobayashi|Masatomo|M|']

2018

33176256

A rare case of caecal volvulus post gastrectomy for gastric cancer.

INTRODUCTION Surgery for gastric cancer is associated with a high morbidity and mortality rate. Postoperative complications are not uncommon in this setting and an understanding of risk factors and patient profile can impact clinical outcomes. PRESENTATION OF CASE We present a rare event where a 64 year old patient post gastrectomy for a T1 gastric carcinoma developed a caecal volvulus leading to critical instability. This demonstrates how two events can occur in time leading to critical instability. Exploratory laparotomy revealed a caecal volvulus that had obstructed the jejunostomy site. She had a right hemicolectomy and the jejunostomy was unkinked. This is the first documented case report of this type in the literature. DISCUSSION Surgical resection remains the cornerstone therapy for gastric cancer. Postoperative complications are not uncommon in this setting where risk factors impact clinical outcomes. The importance of risk factors has been demonstrated in patients who underwent gastrectomy. We present a rare event where a patient post gastrectomy develops a caecal volvulus demonstrating how two events can occur in time leading to critical instability. CONCLUSION Post operative complications are not uncommon in gastrectomies. Although common things occur commonly, one must consider rare events when a patient significantly deteriorates.

['Diab|Jason|J|', 'Bender|Kyle|K|', 'Lorenzo|Aldenb|A|', 'Merrett|Neil|N|']

2020

24780112

Neoadjuvant chemo-immunotherapy modifies CD4(+)CD25(+) regulatory T cells (Treg) in non-small cell lung cancer (NSCLC) patients.

BACKGROUND Regulatory T cells (Treg) are critical for cancer immune evasion; whereas natural killer (NK) cells are central for effective anti-tumor immunity including antibody-induced cellular cytotoxicity (ADCC). The predictive role of Treg levels for clinical response to chemo-immunotherapy in non-small cell lung cancer (NSCLC) as well as therapy-induced Treg changes remain to be defined. PATIENTS AND METHODS The impact of Treg on NK-mediated cetuximab-dependent cellular cytoxicity was tested in vitro. Frequency and functional activity of Treg was analyzed in 31 NSCLC stage IB-IIIA patients treated by neoadjuvant Cetuximab/Docetaxel/Cisplatin prior to surgery. Data were correlated with clinical outcome variables and Treg tumor infiltration. RESULTS Treg potently inhibit NK-mediated and cetuximab-induced ADCC in vitro. In addition, a significant correlation between Treg reduction and clinical response was seen. However, the grade of tumor infiltrating Treg in resected tumors did not correlate with peripheral Treg levels. Moreover, Treg levels at diagnosis did not predict clinical response to chemo-immunotherapy. CONCLUSIONS The drop of Treg levels during neoadjuvant chemo-immunotherapy in NSCLC patients significantly correlates with clinical response. However, Treg at diagnosis are not linked to inferior clinical response to chemo-immunotherapy in NSCLC in vivo even though Treg efficiently inhibit ADCC in vitro.

['Pircher|Andreas|A|', 'Gamerith|Gabriele|G|', 'Amann|Arno|A|', 'Reinold|Susanne|S|', 'Popper|Helmut|H|', 'Gächter|Anneliese|A|', 'Pall|Georg|G|', 'Wöll|Ewald|E|', 'Jamnig|Herbert|H|', 'Gastl|Günther|G|', 'Wolf|Anna Maria|AM|', 'Hilbe|Wolfgang|W|', 'Wolf|Dominik|D|']

2014

29236325

AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation.

['Tian|Ying|Y|0000-0002-2672-6382', 'Wang|Genjie|G|', 'Hu|Qingzhu|Q|', 'Xiao|Xichun|X|', 'Chen|Shuxia|S|']

2018

29961003

Association between recreational drug use and sexual practices among people who inject drugs in Southwest China: a cross-sectional study.

OBJECTIVE To describe the differences in sexual practices among individuals with various drug administration patterns. SETTING A detoxification centre in Southwest China, a part of the Chinese national sentential surveillance network for hepatitis C virus (HCV), HIV and syphilis infections, was recruited. PARTICIPANTS A total of 610 newly enrolled injection drug users (IDUs) from detoxification centre were included during 2015. PRIMARY AND SECONDARY OUTCOME MEASURES Self-reported sexual activities, drug-related practices and laboratory-confirmed HCV, HIV and syphilis infection status were collected. RESULTS Of the 610 IDU, 295 (48.4%) used heroin only, 277 (45.4%) poly-drug users reported the mixed use of synthetic drugs (SDs) with heroin and 38 (6.2%) used SDs only. The average daily drug injection frequency for poly-drug users (3.3±1.2 times) was the highest, followed by heroin-only (2.2±0.8 times) and SD-only users (1.2±0.4 time). SD-only drug users reported the highest proportion (86.8%) of engaging in sexual activities in the previous month, with more than half (54.5%) reporting any condomless sex. A higher frequency of daily injecting in heroin-only users was significantly correlated with the less likelihood of sex, condomless sex in the past month, having sex with fixed partners, condomless commercial sex in the previous 12 months (all p<0.01). In poly-drug users, who injected drugs two times per day was associated with the highest proportion of people who engaged in sex and commercial sex (p<0.05). For SD-only users, increased drug use was not associated with reducing sexual risk (p>0.05). Different patterns of HCV, HIV and syphilis infections prevalence rates were shown among the IDU depending on the roles and length of exposure. CONCLUSIONS The daily drug injecting frequency of heroin-only and poly-drug users was negatively associated with sexual activities, but SD-only users kept a high frequent engagement in sex. The interventions for relevant diseases should adapt to characteristics of IDU.

['Su|Shu|S|', 'Zhang|Lei|L|0000-0003-2343-084X', 'Cheng|Feng|F|', 'Li|Shunxiang|S|', 'Li|Shifu|S|', 'Jing|Jun|J|', 'Fairley|Christopher Kincaid|CK|', 'Chen|Liang|L|', 'Zhao|Jinxian|J|', 'Mao|Limin|L|']

2018

32533539

Improving Representation of Underrepresented Minority (URM) Students in Oncology Biomedical Research Workforce: Outcome Evaluation from the ReTOOL Program.

The Research Training Opportunities for Outstanding Leaders (ReTOOL) program was implemented in 2012 to increase the representation of racial and ethnic minorities in the biomedical workforce. Specifically, the ReTOOL program aims to foster the capacity for scientific research among underserved populations as well as address the cultural appropriateness of research projects. This paper describes the impact of the ReTOOL program in enhancing the research training of underrepresented minority (URM) students. Forty URM students who completed the ReTOOL program between 2012 and 2019 were invited to participate in the program evaluation. The response rate was 73% with 29 participants. Of the 29 participants, 26 trainees self-identified as Black or African-American. A structured survey developed for the program was employed for data collection, using a Likert Scale ranging from 1 to 5, with 5 being the best. The item ratings ranged from 4.45 to 4.80. Responses to open-ended questions show that ReTOOL has been instrumental in socializing and acculturating participants into the habits of scientific thinking. The combined use of quantitative and qualitative inquiry depicts that ReTOOL has been highly successful in fostering participant enrollment in advanced health-related or professional degree programs.

['Odedina|Folakemi T|FT|http://orcid.org/0000-0003-3796-1385', 'Behar-Horenstein|Linda S|LS|', 'Fathi|Parisa|P|', 'Kaninjing|Ernest|E|', 'Nguyen|Jennifer|J|', 'Askins|Nissa|N|', 'Reams|R Renee|RR|', 'Mochona|Bereket|B|', 'Ezeani|Adaora|A|', 'Lyon|Debra|D|', 'Jacobs|Kayanna|K|', 'Maduka|Michael|M|']

2020

23748192

Hospital workers' perceptions of waste: a qualitative study involving photo-elicitation.

OBJECTIVES To elicit sources of waste as viewed by hospital workers. DESIGN Qualitative study using photo-elicitation, an ethnographic technique for prompting in-depth discussion. SETTING U.S. academic tertiary care hospital. PARTICIPANTS Physicians, nurses, pharmacists, administrative support personnel, administrators and respiratory therapists. METHODS A purposive sample of personnel at an academic tertiary care hospital was invited to take up to 10 photos of waste. Participants discussed their selections using photos as prompts during in-depth interviews. Transcripts were analysed in an iterative process using grounded theory; open and axial coding was performed, followed by selective and thematic coding to develop major themes and subthemes. RESULTS Twenty-one participants (nine women, average number of years in field=19.3) took 159 photos. Major themes included types of waste and recommendations to reduce waste. Types of waste comprised four major categories: Time, Materials, Energy and Talent. Participants emphasised time wastage (50% of photos) over other types of waste such as excess utilisation (2.5%). Energy and Talent were novel categories of waste. Recommendations to reduce waste included interventions at the micro-level (eg, individual/ward), meso-level (eg, institution) and macro-level (eg, payor/public policy). CONCLUSIONS The waste hospital workers identified differed from previously described waste both in the types of waste described and the emphasis placed on wasted time. The findings of this study represent a possible need for education of hospital workers about known types of waste, an opportunity to assess the impact of novel types of waste described and an opportunity to intervene to reduce the waste identified.

['Goff|Sarah L|SL|', 'Kleppel|Reva|R|', 'Lindenauer|Peter K|PK|', 'Rothberg|Michael B|MB|']

2013

28104977

Fecal incontinence - Challenges and solutions.

Fecal incontinence is not a diagnosis but a frequent and debilitating common final pathway symptom resulting from numerous different causes. Incontinence not only impacts the patient's self-esteem and quality of life but may result in significant secondary morbidity, disability, and cost. Treatment is difficult without any panacea and an individualized approach should be chosen that frequently combines different modalities. Several new technologies have been developed and their specific roles will have to be defined. The scope of this review is outline the evaluation and treatment of patients with fecal incontinence.

['Saldana Ruiz|Nallely|N|', 'Kaiser|Andreas M|AM|']

2017

28685385

Exclusive Activation of Caspase-3 in Mossy Fibers and Altered Dynamics of Autophagy Markers in the Mice Hippocampus upon Status Epilepticus Induced by Kainic Acid.

Epileptic seizures are generally associated with pathological changes in the hippocampus such as astrogliosis, mossy fiber sprouting, and neuronal damage. However, more than 30% of temporal lobe epilepsy in humans shows neither neuronal damage nor mossy fiber sprouting despite chronic epileptic seizures. A similar situation exists in certain commonly used strains of mice, specifically C57BL/6 and BALB/c, which exhibit epileptic seizures, but no neuronal damage upon kainic acid administration. This suggests that intrinsic factors may influence the pathological manifestations of epilepsy. Mechanisms which are behind the resistance of hippocampal cells to KA-induced neuronal death are unknown. Autophagy seems to be involved in the pathogenesis of many brain insults and to have a dual nature in neuroprotection and cell death. This study addresses the role of autophagy upon status epilepticus (SE) that has been induced by kainic acid (KA) in the C57BL/6 strain which is classified as seizure resistant. We analyzed the dynamics in the expression of autophagic and cell death markers in the hippocampus upon SE. Immunofluorescence data show that KA did not induce neuronal death in the hippocampal CA1-CA3 subfields; however, it leads to an exclusive activation of caspase-3 in the mossy fibers. We also found alterations in the expression of core proteins of the autophagic machinery. Levels of MAP1LC3, phospho-mTOR/mTOR, and Beclin 1 were significantly increased after induction of seizures. However, levels of Atg3, Atg14, Atg5-Atg12, Atg7, BAG3, Hsp70, and LAMP1 showed no significant alterations compared to controls. Although KA did not induce neuronal death, this study provides morphological and biochemical evidence that status epilepticus induced by KA activates caspase-3 in mossy fibers and induces autophagy in the C57BL/6 hippocampus. These data indicate that autophagic factors may modulate the sensitivity of pyramidal cells to KA and that autophagy may constitute a part of an endogenous neuroprotective arsenal which might be behind the resistance of C57BL/6-hippocampal cells to KA-induced neuronal death.

['Rami|A|A|http://orcid.org/0000-0002-4989-2690', 'Benz|A|A|']

2018

32359794

Transcatheter mitral valve repair for functional mitral regurgitation: Evaluating the evidence.

OBJECTIVES Two trials (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation Trial and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation Trial) were published in 2018 evaluating the effectiveness and safety of transcatheter repair for patients with heart failure with significant functional mitral regurgitation, which yielded different results. This article reviews the strength of the evidence, differences in trial designs, ethical and implementation implications, and delineates future research needs to help guide the appropriate dissemination of transcatheter repair for functional patients with mitral regurgitation. METHODS The National Heart, Lung, and Blood Institute convened a workshop of interdisciplinary experts to address these objectives. RESULTS Transcatheter repair of functional mitral regurgitation can provide significant benefits in terms of heart failure hospitalizations, survival, and quality of life when appropriate heart failure candidates with moderate to severe or severe mitral regurgitation while on optimal guideline-directed medical therapy can be identified. Key ingredients for success are preoperative evaluation and management and postoperative care by an interdisciplinary heart team. CONCLUSIONS Given the discordance observed between trials, ongoing innovation in patient management, and potential expansion of indications for use, the evidence base must be expanded to optimize appropriate implementation of this complex therapy. This will require more complete capture of outcome data in real-world settings for all eligible candidates whether or not they receive this therapy. Inevitably, the indications for use of this therapy will expand, as will the devices and therapeutic approaches for this population, necessitating the study of comparative effectiveness through randomized trials or observational studies. Moreover, given the substantial variations in care delivery, conducting implementation research to delineate characteristics of the optimal care model would be of benefit.

['Gelijns|Annetine C|AC|', 'Moskowitz|Alan J|AJ|', "O'Gara|Patrick T|PT|", 'Giustino|Gennaro|G|', 'Mack|Michael J|MJ|', 'Mancini|Donna M|DM|', 'Bagiella|Emilia|E|', 'Hung|Judy|J|', 'Ailawadi|Gorav|G|', 'Leon|Martin B|MB|', 'Acker|Michael A|MA|', 'Alexander|John H|JH|', 'Dickert|Neal W|NW|', 'Taddei-Peters|Wendy C|WC|', 'Miller|Marissa A|MA|']

2021

26009574

Surgical care for the aged: a retrospective cross-sectional study of a national surgical mortality audit.

OBJECTIVES It is assumed that increased age signifies increased surgical care. Few surgical studies describe the differences in care provided to older patients compared with younger patients. We aimed to examine the relationships between increasing age, preoperative factors and markers of postoperative care in adults who died in-hospital after surgery in Australia. DESIGN This retrospective cross-sectional study extracted data from a national surgical mortality audit--an independent, peer-reviewed process. SETTING From January 2009 to December 2012, 111 public and 61 private Australian hospitals notified the audit of in-hospital deaths after general anaesthetic surgery or if the patient was admitted under a surgeon. PARTICIPANTS Notified deaths totalled 19,723. We excluded deaths if patients were brain dead, younger than 17 years or never had an operation (n=11,376). From this baseline population, we divided 11,201 deaths into three patient age groups: youngest (17-64 years), medium (65-79 years) and oldest (≥80 years). OUTCOME MEASURES Univariable and multivariable logistic regression analyses determined the relationships between increasing age and the measured preoperative factors and postoperative variables. RESULTS The baseline population's median age was 78 years (IQR 66-85), 43.7% (4892/11,201) were 80 years or older and 83.4% (9319/11,173) had emergency admissions. The oldest group had increased trauma and emergency admissions than the medium and youngest age groups. Seven of the eight measured markers of postoperative care demonstrate strong and significant relationships with increasing age. The oldest group compared with the medium group had decreased rates of: unplanned returns to theatre (11.2% (526/4709) vs 20.2% (726/3586)), unplanned intensive care admissions (16.3% (545/3350) vs 24.0% (601/2504)) and treatment in intensive care units (59.7% (2689/4507) vs 76.7% (2754/3590)). CONCLUSIONS The oldest patients received lower levels of care than the medium and youngest age groups.

['Allen|Jennifer|J|', 'North|John B|JB|', 'Wysocki|Arkadiusz Peter|AP|http://orcid.org/0000-0001-6880-9285', 'Ware|Robert S|RS|', 'Rey-Conde|Therese|T|http://orcid.org/0000-0002-6875-3565']

2015

27518854

Ellipsis and Coreference Resolution in a Computerized Virtual Patient Dialogue System.

This paper describes the design of an ellipsis and coreference resolution module integrated in a computerized virtual patient dialogue system. Real medical diagnosis dialogues have been collected and analyzed. Several groups of diagnosis-related concepts were defined and used to construct rules, patterns, and features to detect and resolve ellipsis and coreference. The best F-scores of ellipsis detection and resolution were 89.15 % and 83.40 %, respectively. The best F-scores of phrasal coreference detection and resolution were 93.83 % and 83.40 %, respectively. The accuracy of pronominal anaphora resolution was 92 % for the 3rd-person singular pronouns referring to specific entities, and 97.31 % for other pronouns.

['Lin|Chuan-Jie|CJ|', 'Pao|Chien-Wei|CW|', 'Chen|Yen-Heng|YH|', 'Liu|Chi-Ting|CT|', 'Hsu|Hui-Huang|HH|']

2016

33025591

Primary immunodeficiencies, autoimmune hyperthyroidism, coeliac disease and systemic lupus erythematosus in childhood immune thrombocytopenia.

AIM To evaluate the cumulative prevalence of coeliac disease, systemic lupus erythematosus, autoimmune hyperthyroidism and primary immunodeficiencies in children with either newly diagnosed/persistent or chronic immune thrombocytopenia (ITP). METHODS Monocentric retrospective analysis of the clinical and biochemical features of 330 consecutive patients with ITP referred to our Pediatric Hematology Unit between January 2009 and December 2018. RESULTS The prevalence of systemic lupus erythematosus (0.3%), coeliac disease (0.3%) and autoimmune hyperthyroidism (0.6%) was not increased compared to general paediatric population. Of note, the prevalence of underlying primary immunodeficiencies was 2.4%, remarkably higher than the general paediatric population (P = .005). All the patients diagnosed with immunodeficiency developed either bi-/trilinear cytopenia or splenomegaly. CONCLUSION Whilst autoimmune and immunological screening is already recommended at the onset of immune thrombocytopenia, we recommend that primary immunodeficiencies be regularly screened during follow-up, especially in case of additional cytopenia or lymphoproliferation.

['Saettini|Francesco|F|0000-0003-0767-3905', 'Cattoni|Alessandro|A|', 'Redaelli|Martina|M|', 'Silvestri|Daniela|D|', 'Ferrari|Giulia Maria|GM|', 'Biondi|Andrea|A|', 'Jankovic|Momcilo|M|', 'Spinelli|Marco|M|']

2021

28357068

Differential proteomics analysis of liver failure in peripheral blood mononuclear cells using isobaric tags for relative and absolute quantitation.

The aim of the present study was to examine differentially expressed proteome profiles for candidate biomarkers in peripheral blood mononuclear cells (PBMCs) of liver failure (LF) patients. Ten patients were diagnosed as LF and 10 age- and gender-matched subjects were recruited as healthy controls. Isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technology is efficiently applicable for identification and relative quantitation of the proteomes of PBMCs. Eight-plex iTRAQ coupled with strong cation exchange chromatography, and liquid chromatography coupled with tandem mass spectrometry were used to analyze total proteins in LF patients and healthy control subjects. Molecular variations were detected using the iTRAQ method, and western blotting was used to verify the results. LF is a complex type of medical emergency that evolves following a catastrophic insult to the liver, and its outcome remains the most ominous of all gastroenterologic diseases. Serious complications tend to occur during the course of the disease and further exacerbate the problems. Using the iTRAQ method, differentially expressed proteome profiles of LF patients were determined. In the present study, 627 proteins with different expression levels were identified in LF patients compared with the control subjects; with 409 proteins upregulated and 218 proteins downregulated. Among them, four proteins were significantly differentially expressed; acylaminoacyl-peptide hydrolase and WW domain binding protein 2 were upregulated, and resistin and tubulin β 2A class IIa were downregulated. These proteins demonstrated differences in their expression levels compared with other proteins with normal expression levels and the significant positive correlation with LF. The western blot results were consistent with the results from iTRAQ. Thus, investigation of the molecular mechanism of the proteins involved in LF may facilitate an improved understanding of the pathogenesis of LF and elucidation of novel biomarker candidates.

['Lin|Hua|H|', 'Tan|Qiu-Pei|QP|', 'Sui|Wei-Guo|WG|', 'Chen|Wen-Biao|WB|', 'Peng|Wu-Jian|WJ|', 'Liu|Xing-Chao|XC|', 'Dai|Yong|Y|']

2017

25506144

Investigate the correlation between clinical sign and symptoms and the presence of P. gingivalis, T. denticola, and T. forsythia individually or as a "Red complex" by a multiplex PCR method.

AIM The aim of this study was to investigate the correlation between endodontic clinical signs and symptoms and the presence of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia or their association by Multiplex polymerase chain reaction assay. MATERIALS AND METHODS Microbial samples were taken from 30 cases with necrotic pulp tissues in primary infections. DNA was extracted from the samples, which were analyzed for the presence of three endodontic pathogens by using species-specific primers. RESULTS P. gingivalis, T. denticola, T. forsythia, and Red Complex were present in 11, 17, 4, and 2 canals, respectively. Clinical and statistically significant relationships were found between T. forsythia and mobility and between T. denticola and swelling. (P < 0.05). Presence of other Red complex bacteria shows clinical association with presence of signs and symptoms but no statistically significant relationship. CONCLUSION The high prevalence of P. gingivalis, T. denticola, and T. forsythia in the examined samples suggests that these bacteria are related to the etiology of symptomatic periradicular diseases.

['Sanghavi|Tulsi Hasmukhrai|TH|', 'Shah|Nimisha|N|', 'Shah|Ruchi Rani|RR|', 'Sanghavi|Akta|A|']

2014

32951323

Characterization of the novel HLA-B*51:296 allele by next-generation sequencing.

B*51:296 differs from B*51:01:01:01 by one nucleotide substitution at position 1030 in exon 6.

['Genebrier|Steve|S|0000-0002-6353-5497', 'Elsermans|Vincent|V|0000-0002-0881-0695', 'Texeraud|Emeric|E|', 'Bertrand|Gerald|G|', 'Renac|Virginie|V|0000-0002-4429-4421']

2021

27419229

Active micromachines: Microfluidics powered by mesoscale turbulence.

Dense active matter, from bacterial suspensions and microtubule bundles driven by motor proteins to cellular monolayers and synthetic Janus particles, is characterized by mesoscale turbulence, which is the emergence of chaotic flow structures. By immersing an ordered array of symmetric rotors in an active fluid, we introduce a microfluidic system that exploits spontaneous symmetry breaking in mesoscale turbulence to generate work. The lattice of rotors self-organizes into a spin state where neighboring discs continuously rotate in permanent alternating directions due to combined hydrodynamic and elastic effects. Our virtual prototype demonstrates a new research direction for the design of micromachines powered by the nematohydrodynamic properties of active turbulence.

['Thampi|Sumesh P|SP|0000-0002-8486-8653', 'Doostmohammadi|Amin|A|0000-0002-1116-4268', 'Shendruk|Tyler N|TN|0000-0001-7671-2184', 'Golestanian|Ramin|R|', 'Yeomans|Julia M|JM|']

2016

29974542

Reactive Polymorphic Nanoparticles: Preparation via Polymerization-Induced Self-Assembly and Postsynthesis Thiol-para-Fluoro Core Modification.

The use of 2,3,4,5,6-pentafluorobenzyl methacrylate (PFBMA) as a core-forming monomer in ethanolic reversible addition-fragmentation chain transfer dispersion polymerization formulations is presented. Poly[poly(ethylene glycol) methyl ether methacrylate] (pPEGMA) macromolecular chain transfer agents were chain-extended with PFBMA leading to nanoparticle formation via polymerization-induced self-assembly (PISA). pPEGMA-pPFBMA particles exhibited the full range of morphologies (spheres, worms, and vesicles), including pure and mixed phases. Worm phases formed gels that underwent a thermo-reversible degelation and morphological transition to spheres (or spheres and vesicles) upon heating. Postsynthesis, the pPFBMA cores were modified through thiol-para-fluoro substitution reactions in ethanol using 1,8-diazabicyclo[5.4.0]undec-7-ene as the base. For monothiols, conversions were 64% (1-octanethiol) and 94% (benzyl mercaptan). Spherical and worm-shaped nano-objects were core cross-linked using 1,8-octanedithiol, which prevented their dissociation in nonselective solvents. For a temperature-responsive worm sample, cross-linking additionally resulted in the loss of the temperature-triggered morphological transition. The use of the reactive monomer PFBMA in PISA formulations presents a simple method to prepare well-defined nano-objects similar to those produced with nonreactive monomers (e.g., benzyl methacrylate) and to retain morphologies independent of solvent and temperature.

['Busatto|Nicolas|N|', 'Stolojan|Vlad|V|', 'Shaw|Michael|M|', 'Keddie|Joseph L|JL|', 'Roth|Peter J|PJ|']

2019

26104900

Exogenous NO depletes Cd-induced toxicity by eliminating oxidative damage, re-establishing ATPase activity, and maintaining stress-related hormone equilibrium in white clover plants.

Various nitric oxide (NO) regulators [including the NO donor sodium nitroprusside (SNP), the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), the NO-synthase inhibitor N (G)-nitro-L-Arg-methyl ester (L-NAME), and the SNP analogues sodium nitrite/nitrate and sodium ferrocyanide] were investigated to elucidate the role of NO in white clover (Trifolium repens L.) plants after long-term (5 days) exposure to cadmium (Cd). A dose of 100 μM Cd stress significantly restrained plant growth and decreased the concentrations of chlorophyll and NO in vivo, whereas it disrupted the balance of stress-related hormones and enhanced the accumulation of Cd, thereby inducing reactive oxygen species (ROS) burst. However, the inhibition of plant growth was relieved by 50 μM SNP through its stimulation of ROS-scavenging compounds (ascorbic acid, ascorbate peroxidase, catalase, glutathione reductase, non-protein thiol, superoxide dismutase, and total glutathione), regulation of H(+)-ATPase activity of proton pumps, and increasing jasmonic acid and proline but decreasing ethylene in plant tissues. Even so, the alleviating effect of SNP on plant growth was counteracted by cPTIO and L-NAME and was not observed with SNP analogues, suggesting that the protective roles of SNP are related to the induction of NO. These results suggest that NO may improve the Cd tolerance of white clover plants by eliminating oxidative damage, re-establishing ATPase activity, and maintaining hormone equilibrium. Improving our understanding of the role of NO in white clover plants is key to expanding the plantations to various regions and the recovery of pasture species in the future.

['Liu|S L|SL|', 'Yang|R J|RJ|', 'Pan|Y Z|YZ|', 'Wang|M H|MH|', 'Zhao|Y|Y|', 'Wu|M X|MX|', 'Hu|J|J|', 'Zhang|L L|LL|', 'Ma|M D|MD|']

2015

31319749

Participation in daily life for adults with profound intellectual (and multiple) disabilities: How high do they climb on Shier's ladder of participation?

Participation is the goal of Swedish disability policy, but it is difficult to achieve for adults with profound intellectual (and multiple) disabilities (PI(M)D). Since these adults are dependent on others in every aspect of their lives, others control their ability to participate in everyday life decisions. This study used observations, analyzed with Shier's ladder of participation, to elucidate and describe participation in daily life for adults with PI(M)D living in a group home. The results showed that the adults often reached the first three levels of Shier's ladder, one adult reached the fourth level once, and no one reached the fifth level. Participation on a higher level, therefore, seems hard to reach for adults. Staff members' attitudes toward the adults' capability can also be a barrier to participation. Applying Shier's ladder of participation can provide valuable information that might lead to increased participation in daily life for adults with PI(M)D.

['Talman|Lena|L|https://orcid.org/0000-0003-0305-7929', 'Stier|Jonas|J|', 'Wilder|Jenny|J|', 'Gustafsson|Christine|C|']

2021

32293478

Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): a framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group.

BACKGROUND Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA. METHODS The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria. Consensus required 80% agreement. RESULTS The PFAPA working group developed CTPs resulting in 4 different treatment arms: 1. Antipyretic, 2. Abortive (corticosteroids), 3. Prophylaxis (colchicine or cimetidine) and 4. Surgical (tonsillectomy). Consensus was obtained among CARRA members for those defining patient characteristics who qualify for participation in the CTP PFAPA study. CONCLUSION The goal is for the CTPs developed by our group to lead to future comparative effectiveness studies that will generate evidence-driven therapeutic guidelines for this periodic inflammatory disease.

['Amarilyo|Gil|G|', 'Rothman|Deborah|D|', 'Manthiram|Kalpana|K|', 'Edwards|Kathryn M|KM|', 'Li|Suzanne C|SC|', 'Marshall|Gary S|GS|', 'Yildirim-Toruner|Cagri|C|', 'Haines|Kathleen|K|', 'Ferguson|Polly J|PJ|', 'Lionetti|Geraldina|G|', 'Cherian|Julie|J|', 'Zhao|Yongdong|Y|', 'DeLaMora|Patricia|P|', 'Syverson|Grant|G|', 'Nativ|Simona|S|', 'Twilt|Marinka|M|', 'Michelow|Ian C|IC|', 'Stepanovskiy|Yuriy|Y|', 'Thatayatikom|Akaluck|A|', 'Harel|Liora|L|', 'Akoghlanian|Shoghik|S|', 'Tucker|Lori|L|', 'Marques|Mariana Correia|MC|', 'Srinivasalu|Hemalatha|H|', 'Propst|Evan J|EJ|', 'Licameli|Greg R|GR|', 'Dedeoglu|Fatma|F|', 'Lapidus|Sivia|S|', '|||']

2020

28964664

Comparison of Emla cream and lidocaine injection for local anaesthetic before radiofrequency reduction of the inferior turbinates.

We compared the effectiveness of local anaesthetic with Emla cream with that of an injection of lidocaine for radiofrequency reduction of the inferior turbinates. We studied 98 consecutive patients with hypertrophied inferior turbinates, 46 of whom were given Emla cream and 52 lidocaine injection. The procedure began five minutes after the injection of lidocaine and 10minutes after the Emla cream had been applied. Patients were asked to indicate on a visual analogue scale (VAS) the degree of perioperative pain, anxiety, sensation of choking, and discomfort on swallowing that they felt after the procedure. Patients treated with Emla had significantly lower VAS scores for discomfort on swallowing than those treated with lidocaine (p=0.001), but there were no other significant differences between the two groups. We conclude that Emla cream is an efficacious alternative to infiltration of lidocaine for radiofrequency reduction of the inferior turbinates.

['Ata|N|N|', 'Bülbül|T|T|', 'Demirkan|A|A|']

2017

32684182

Impact of protein-losing enteropathy in children who underwent the Fontan operation.

Previous reports have identified risk factors associated with development of post-Fontan protein-losing enteropathy. Less is known about the economic impact and resource utilisation required for post-Fontan protein-losing enteropathy in the current era. We conducted a single-centre retrospective study to assess the impact of post-Fontan protein-losing enteropathy on transplant-free survival. We also described resource utilisation and treatment variations among post-Fontan protein-losing enteropathy patients. Children who received care at our centre between 2009 and 2017 after the Fontan surgery were eligible. Initial admissions for the Fontan operative procedure were excluded. Demographics, hospital admissions, resource utilisation, medications and charges were reviewed. Patients were divided into two groups based on the presence of post-Fontan protein-losing enteropathy. Of the 343 patients screened, 147 met the eligibility criteria. Of these, 28 (19%) developed protein-losing enteropathy. After adjusting for follow-up duration, the protein-losing enteropathy group had higher number of encounters (2.15 ± 2.16 versus 1.47 ± 2.56, p 0.002), hospital length of stay (days) (25 ± 51.3 versus 11.4 ± 41.7, p < 0.0001) and total charges (2018US$) (388,489 ± 759,859 versus 202,725 ± 1,076,625, p < 0.0001). Encounters for patients with protein-losing enteropathy utilised more therapies. Among those with protein-losing enteropathy, use of digoxin was associated with slightly decreased odds for mortality and/or transplant (0.95, confidence interval 0.90-0.99, p 0.021). The 10-year transplant-free survival for patients with/without protein-losing enteropathy was 65.7/97.3% (p 0.002), respectively. Post-Fontan protein-losing enteropathy is associated with reduced 10-year transplant-free survival, higher resource utilisation, charges and medication use compared with the non-protein-losing enteropathy group. Practice variation among post-Fontan protein-losing-enteropathy patients is common. Further larger studies are needed to assess the impact of standardisation on the well-being of children with post-Fontan protein-losing enteropathy.

['Alkofair|Baneen|B|', 'Alruwaili|Abdulmajeed|A|', 'Gai|Jiaxiang|J|', 'Harahsheh|Ashraf S|AS|https://orcid.org/0000-0002-2622-573X']

2020

24825885

Genetic degeneration of old and young Y chromosomes in the flowering plant Rumex hastatulus.

Heteromorphic sex chromosomes have originated independently in many species, and a common feature of their evolution is the degeneration of the Y chromosome, characterized by a loss of gene content and function. Despite being of broad significance to our understanding of sex chromosome evolution, the genetic changes that occur during the early stages of Y-chromosome degeneration are poorly understood, especially in plants. Here, we investigate sex chromosome evolution in the dioecious plant Rumex hastatulus, in which X and Y chromosomes have evolved relatively recently and occur in two distinct systems: an ancestral XX/XY system and a derived XX/XY1Y2 system. This polymorphism provides a unique opportunity to investigate the effect of sex chromosome age on patterns of divergence and gene degeneration within a species. Despite recent suppression of recombination and low X-Y divergence in both systems, we find evidence that Y-linked genes have started to undergo gene loss, causing ∼ 28% and ∼ 8% hemizygosity of the ancestral and derived X chromosomes, respectively. Furthermore, genes remaining on Y chromosomes have accumulated more amino acid replacements, contain more unpreferred changes in codon use, and exhibit significantly reduced gene expression compared with their X-linked alleles, with the magnitude of these effects being greatest for older sex-linked genes. Our results provide evidence for reduced selection efficiency and ongoing Y-chromosome degeneration in a flowering plant, and indicate that Y degeneration can occur soon after recombination suppression between sex chromosomes.

['Hough|Josh|J|', 'Hollister|Jesse D|JD|', 'Wang|Wei|W|', 'Barrett|Spencer C H|SC|', 'Wright|Stephen I|SI|']

2014

33208462

Identification of a druggable protein-protein interaction site between mutant p53 and its stabilizing chaperone DNAJA1.

The TP53 gene is the most frequently mutated gene in human cancers, and the majority of TP53 mutations are missense mutations. As a result, these mutant p53 (mutp53) either directly lose wildtype p53 (wtp53) tumor suppressor function or exhibit a dominant negative effect over wtp53. In addition, some mutp53 have acquired new oncogenic function (gain of function). Therefore, targeting mutp53 for its degradation may serve as a promising strategy for cancer prevention and therapy. Based on our previous finding that farnesylated DNAJA1 is a crucial chaperone in maintaining mutp53 stabilization, and by using an in silico approach, we built 3D homology models of human DNAJA1 and mutp53R175H proteins, identified the interacting pocket in the DNAJA1-mutp53R175H complex, and found one critical druggable small molecule binding site in the DNAJA1 glycine/phenylalanine-rich region. We confirmed that the interacting pocket in the DNAJA1-mutp53R175H complex was crucial for stabilizing mutp53R175H using a site-directed mutagenesis approach. We further screened a drug-like library to identify a promising small molecule hit (GY1-22) against the interacting pocket in the DNAJA1-mutp53R175H complex. The GY1-22 compound displayed an effective activity against the DNAJA1-mutp53R175H complex. Treatment with GY1-22 significantly reduced mutp53 protein levels, enhanced Waf1p21 expression, suppressed cyclin D1 expression, and inhibited mutp53-driven pancreatic cancer growth both in vitro and in vivo. Together, our results indicate that the interacting pocket in the DNAJA1-mutp53R175H complex is critical for mutp53's stability and oncogenic function, and DNAJA1 is a robust therapeutic target for developing the efficient small molecule inhibitors against oncogenic mutp53.

['Tong|Xin|X|', 'Xu|Dandan|D|', 'Mishra|Rama K|RK|', 'Jones|Ryan D|RD|', 'Sun|Leyu|L|', 'Schiltz|Gary E|GE|', 'Liao|Jie|J|', 'Yang|Guang-Yu|GY|']

2021

33397443

Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism.

BACKGROUND Pioglitazone is a promising therapeutic method for nonalcoholic fatty liver disease (NAFLD) patients with or without type 2 diabetes. However, there is remarkable variability in treatment response. We analyzed our previous randomized controlled trial to examine the effects of gender and other factors on the efficacy of pioglitazone in treating Chinese nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism. METHODS This is a post hoc analysis of a previous randomized, parallel controlled, open-label clinical trial (RCT) with an original purpose of evaluating the efficacy of berberine and pioglitazone on NAFLD. The total population (n = 185) was randomly divided into three groups: lifestyle intervention (LSI), LSI + pioglitazone (PGZ) 15 mg qd, and LSI + berberine (BBR) 0.5 g tid, respectively, for 16 weeks. The study used proton magnetic resonance spectroscopy (1H-MRS) to assess liver fat content. RESULTS As compared with LSI, PGZ + LSI treatment further decreased liver fat content in women (- 15.24% ± 14.54% vs. - 8.76% ± 13.49%, p = 0.025), but less decreased liver fat content in men (- 9.95% ± 15.18% vs. - 12.64% ± 17.78%, p = 0.046). There was a significant interaction between gender and efficacy of pioglitazone before and after adjustment for age, smoking, drinking, baseline BMI, BMI change, treatment adherence, baseline liver fat content, and glucose metabolism. CONCLUSION The study recommends pioglitazone plus lifestyle intervention for Chinese NAFLD female patients with abnormal glucose metabolism. TRIAL REGISTRATION Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease, NCT00633282 . Registered on 3 March 2008, https://register.clinicaltrials.gov .

['Yan|Hongmei|H|', 'Wu|Weiyun|W|', 'Chang|Xinxia|X|', 'Xia|Mingfeng|M|', 'Ma|Sicheng|S|', 'Wang|Liu|L|', 'Gao|Jian|J|']

2021

26013305

National survey of fibrinogen concentrate usage for post-partum hemorrhage in Japan: investigated by the Perinatology Committee, Japan Society of Obstetrics and Gynecology.

AIM The aim of this study was to provide basic documents applicable to studying the usefulness of administering fibrinogen concentrate to patients with massive post-partum hemorrhage. We investigated the usage of fibrinogen concentrate at training institutions for specialist physicians of the Japan Society of Obstetrics and Gynecology. MATERIAL AND METHODS The subjects were women who required fibrinogen concentrate for hemostasis of post-partum hemorrhage during the period between April 2008 and March 2013. The underlying diseases, obstetric disseminated intravascular coagulation scores, blood loss, amount of blood transfusion, dose of fibrinogen concentrate administered, and plasma fibrinogen levels before and after the administration of fibrinogen concentrate were retrospectively investigated. RESULTS Ninety-nine (98.0%) patients survived and two died after taking fibrinogen concentrate. Of the surviving 99 cases, the average amount of blood loss at the time of initial fibrinogen administration and total blood loss was 3559 ± 2103 mL and 4562 ± 3198 mL, respectively. The dose per administration was 3 g, and the plasma fibrinogen level before the initial administration of fibrinogen concentrate was 70.5 mg/dL, thereafter increasing to 187.0 mg/dL. The increase in the fibrinogen level was 32.9 mg/dL/g of fibrinogen concentrate. It was less than 150 mg/dL after the first administration of fibrinogen concentrate only in patients with amniotic fluid embolism and patients with atonic bleeding showed the smallest increase in fibrinogen per gram of fibrinogen concentrate. No adverse events, including thromboembolism, were reported. CONCLUSION The results indicated the increase in blood fibrinogen levels to, on occasion, be insufficient even with fibrinogen concentrate use; however, this survey may support the safety and usefulness of fibrinogen concentrate for PPH.

['Makino|Shintaro|S|', 'Takeda|Satoru|S|', 'Kobayashi|Takao|T|', 'Murakami|Maki|M|', 'Kubo|Takahiko|T|', 'Hata|Toshiyuki|T|', 'Masuzaki|Hideaki|H|']

2015

25943247

Cutaneous manifestations in trisomy 13 mosaicism: A rare case and review of the literature.

Trisomy 13 mosaicism is a rare genetic disorder affecting a small minority of all trisomy 13 cases. It occurs when two cell populations that are karyotypically different are present in the same individual and are derived from a single zygote. As a rule, the phenotype is mitigated to a less dysmorphic appearance and longer survival, making genetic counseling a difficult task. Capillary hemangiomas are a common feature of full trisomy 13, seen in 27-56% of all cases. We report on an 18-months-old girl with extensive cutaneous anomalies, mild dysmorphic features, and slight psychomotor delay, without structural defects and provide an up-to-date review of all cases of trisomy 13 mosaicism with skin involvement. To our knowledge, this is the second clinical report of a patient with trisomy 13 mosaicism with hemangiomas and port wine stains, but no structural defects. © 2015 Wiley Periodicals, Inc.

['Wieser|Iris|I|', 'Wohlmuth|Christoph|C|', 'Rittinger|Olaf|O|', 'Fischer|Thorsten|T|', 'Wertaschnigg|Dagmar|D|']

2015

32292271

Two new species of Desmopachria Babington, 1841 in the D. convexa species group (Coleoptera, Adephaga, Dytiscidae, Hydroporinae, Hyphydrini).

Two new species are described in the Desmopachria convexa species group in the Neotropical genus Desmopachria Babington: D. manco sp. nov. (Guyana), and D. mortimer sp. nov. (Costa Rica). Two subgroups, the D. convexa-convexa and the D. convexa-signata groups are defined. Desmopachria convexa-convexa species are from North and Central America and have a subapical articulable lobe on the male lateral lobe that is large and elongate and extends well beyond the slender, oblique apex of the lateral lobe. Desmopachria convexa-signata species are from South America and have a subapical articulable lobe on the male lateral lobe that is small and discrete and does not extend beyond the truncate apex of the lateral lobe. The male genitalia of all recognized species in the D. convexa group are redrawn from the literature. New species are illustrated from specimens and described species have morphological features redrawn from published illustrations.

['Miller|Kelly B|KB|']

2020

31472349

A colorimetric chemosensor for quantification of exchangeable Cu2+ in soil.

Chemosensors have already demonstrated potential for the detection and imaging of metal ions in solutions and biological systems, however, their applications to soil analysis are limited. This study explores the potential of utilizing a chemosensor for the detection of exchangeable Cu2+ in soils via qualitative (solution visual color change) and quantitative (UV-Vis spectrophotometry) approaches. Montmorillonite and kaolin clays were doped with Cu(NO3)2 solutions from 2.5 to 50 mM, and contaminated soil samples were collected from a historic copper mine. The exchangeable Cu2+ was extracted using a standard CaCl2 cation exchange approach, and the Cu2+ concentration in the resulting solutions determined by UV-Vis spectrophotometry, using a chemosensor, and compared to traditional ICP-MS analysis. Analytical results showed that the chemosensor provided a visual response in contaminated soils at concentrations of 25 μM and quantitative detection to concentrations of 1 μM using UV-Vis spectrophotometry. This work demonstrates the first reported chemosensor for exchangeable Cu2+ with application to soil systems.

['Fanna|Daniel J|DJ|', 'Lima|Luís M P|LMP|', 'Wei|Gang|G|', 'Li|Feng|F|', 'Reynolds|Jason K|JK|']

2020

28415709

A peptide derived from apoptin inhibits glioma growth.

Glioblastoma (GBM) is associated with poor prognosis due to its resistance to surgery, irradiation, and conventional chemotherapy. Thus, efficient therapeutic approaches for the treatment of GBM are urgently needed. HSP70 is an antiapoptotic protein that participates in the inhibition of both mitochondrial and membrane receptor apoptosis pathways and is highly expressed in glioma tissues. Here, we investigated a derivative of apoptin; specifically, a chicken anemia viral protein with selective toxicity toward cancer cells that can inhibit hyperactive molecules, including HSP70. Our earlier studies demonstrated that apoptin directly binds to the promoter of HSP70 and inhibits HSP70 transcription, which contributes to HSP70 downregulation. This study provides the first demonstration of the therapeutic potential of an apoptin-derived peptide for the treatment of GBM by identifying the minimal region of the apoptin domain required for interaction with the heat-shock element (HSE). This apoptin-derived peptide (ADP) inhibits glioma cell proliferation and tumor growth as well as exhibits an increased ability to promote apoptosis in GBM cells compared with rapamycin and temozolomide. ADP treatment inhibited xenograft tumor growth and increased the overall health and survival of nude mice implanted with GBM cells. These effects were measured in tumors obtained from cell lines and were observed in both intracranial and subcutaneous xenografts. In conclusion, we provide the first demonstration that ADP has therapeutic potential for the treatment of human GBM. Specifically, this study suggests that ADP is a potent candidate for drug development based on its favorable toxicity and pharmacokinetic profiles as well as its time- and cost-saving benefits.

['Zhang|Liqiu|L|', 'Zhao|Hengyu|H|', 'Cui|Zhongqi|Z|', 'Lv|Yueshan|Y|', 'Zhang|Wenjia|W|', 'Ma|Xiaoyu|X|', 'Zhang|Jianan|J|', 'Sun|Banghao|B|', 'Zhou|Danyang|D|', 'Yuan|Lijie|L|']

2017

34341670

Use of post-mortem computed tomography during the COVID-19 pandemic.

Post mortem computed tomography (PMCT) is widely used in England and Wales to supplement or replace traditional invasive Coroner's autopsy. Using PMCT and coronary angiography, the cause of death can be determined without invasive examination in approximately 70% of cases, assuming a typical Coroner's autopsy case mix. Coroner's autopsy services continued during the COVID-19 pandemic and have identified deaths resulting from COVID-19 undiagnosed in life. In some areas of England, PMCT was used to replace traditional autopsy due to concerns over infection risk to mortuary staff associated with invasive autopsy. Health and safety concerns also resulted in changes to post mortem scanning protocols. PMCT has been used to identify potential COVID-19 deaths and assist in the selection of cases for viral studies. There is typically bilateral ground-glass opacities and consolidation within the lungs on CT; although these changes are not specific for COVID-19, the diagnosis can be confirmed with post mortem nose and throat swabs.

['Roberts|Ian Sd|IS|', 'Traill|Zoe C|ZC|']

2021

24341757

Overweight dynamics in Chinese children and adults.

China has experienced a transition from a history of undernutrition to a rapid increase in obesity. The China Health and Nutrition Survey, an ongoing longitudinal, household-based survey of urban and rural residents of nine provinces, documents these changes using measured height and weight across 53,298 observations from 18,059 participants collected from 1991 to 2011. Adult overweight (body mass index [BMI] ≥ 25 kg/m(2)) prevalence nearly tripled from 1991 (11.7%) to 2009 (29.2%), with significant cohort and age-related effects (stronger in males). Among youth, quantile regression reveals changes across the BMI distribution. By 2009, approximately 12% of children and adolescents were overweight, and 3% of 7-11-year-olds and 1% of 12-17-year-olds were obese (International Obesity Taskforce BMI 25 and 30 kg/m(2) equivalents, respectively). In 1991-2000, urbanicity was strongly and positively associated with BMI, but in 2000-2011, trends were similar across rural and urban areas. Among women, the burden has shifted to lower educated women (the reverse is true for males, as overweight was higher in men of higher education). Our findings highlight the importance of preventive measures early in the life cycle to reduce weight gain.

['Gordon-Larsen|P|P|', 'Wang|H|H|', 'Popkin|B M|BM|']

2014

34715003

COVID-19 vaccine hesitancy among youth.

The purpose of this evaluation is to describe COVID-19 vaccine hesitancy among a sample of youth aged 12-15 and inform efforts to increase vaccination uptake among youth populations. We used data collected in May 2021 through a health education program for 9th graders (N = 345). We used Spearman correlations and chi-square tests to assess the statistical significance of bivariate relationships. Less than half of students (42%) reported they are not hesitant at all about getting a COVID-19 vaccine. The remainder reported they were "a little hesitant" (22%), "somewhat hesitant" (21%), or "very hesitant" (15%). There were no statistically significant differences across age, gender, race/ethnicity, parental education, self-reported grades, or hours playing video games during school days. There was a statistically significant relationship between COVID-19 vaccine hesitancy and hours of TV watched during school days. The prevalence of COVID-19 vaccine hesitancy in this sample is high, but more research is needed to estimate its prevalence for youth at the state or national level. Correlates of COVID-19 vaccine hesitancy among adult populations may not match those found in youth populations. Research which recognizes youth as agentic rather than passive participants in decision-making opens opportunities for developing age-appropriate health communication and interventions for vaccination.

['Willis|Don E|DE|', 'Presley|Jessica|J|', 'Williams|Mark|M|', 'Zaller|Nickolas|N|', 'McElfish|Pearl A|PA|0000-0002-4033-6241']

2021

32904174

Emulating Odontolegal Practice: A Paradigm Shift in the Dental Practice Laying More Emphasis on Dental Records-A Perspective and Contemporary Study with a Reality Check.

Aim This study was conducted to evaluate the knowledge and the awareness on odontolegal practice with more emphasis on significance of maintaining dental records by the oral health professionals. Materials and methods A cross-sectional study was carried out among 120 dental practitioners of Jammu and Kashmir, Himachal Pradesh, Delhi, Punjab, Gujarat, and Odisha. A questionnaire was designed to assess their practice and knowledge regarding the importance of maintenance of dental records and the knowledge about dental jurisprudence. Total 120 questionnaire samples were distributed among dental health professionals, and the data obtained were studied and formulated for significance of dental records. Results Feedback obtained was then analyzed. Seventy percentage of the dentists are not maintaining clinical records of their patients and 20% of the dentists acknowledged that they are not keeping or maintaining dental records like X-rays and cast models of their patients. Eighty percentage of dentists were not known to the ethical importance of dental record, i.e., for how long they have to maintain records of their patients and other details. Conclusion This study concludes that the oral health professionals lacked the knowledge and awareness about odontolegal aspects and the significance of maintaining dental records. It was observed that there was insufficient knowledge about medicolegal systems and there is a need to bring awareness and knowledge of the same in the dental fraternity. Clinical significance With the increasing use of medical insurance and subsequently mediclaims, negligence suits, scientific evaluation, and research purposes, and health planning, etc., the "dental records itself have evolved as a separate science and therefore needs to be considered in the curriculum for dental students as this would introduce the concept for application in their future practice, thus avoiding legal complications in the future." How to cite this article Kaul B, Gupta S, Vaid V, et al. Emulating Odontolegal Practice: A Paradigm Shift in the Dental Practice Laying More Emphasis on Dental Records-A Perspective and Contemporary Study with a Reality Check. Int J Clin Pediatr Dent 2020;13(3):217-220.

['Kaul|Bhavna|B|', 'Gupta|Shivam|S|', 'Vaid|Vasu|V|', 'Kaul|Sambhav|S|']

2020

31981691

Basal teleosts provide new insights into the evolutionary history of teleost-duplicated aromatase.

Duplicated cyp19a1 genes (cyp19a1a encoding aromatase a and cyp19a1b encoding aromatase b) have been identified in an increasing number of teleost species. Cyp19a1a is mainly expressed in the gonads, while cyp19a1b is mainly expressed in the brain, specifically in radial glial cells, as largely investigated by Kah and collaborators. The third round of whole-genome duplication that specifically occurred in the teleost lineage (TWGD or 3R) is likely at the origin of the duplicated cyp19a1 paralogs. In contrast to the situation in other teleosts, our previous studies identified a single cyp19a1 in eels (Anguilla), which are representative species of a basal group of teleosts, Elopomorpha. In the present study, using genome data mining and phylogenetic and synteny analyses, we confirmed that the whole aromatase genomic region was duplicated in eels, with most aromatase-neighboring genes being conserved in duplicate in eels, as in other teleosts. These findings suggest that specific gene loss of one of the 3R-duplicated cyp19a1 paralogs occurred in Elopomorpha after TWGD. Similarly, a single cyp19a1 gene was found in the arowana, which is a representative species of another basal group of teleosts, Osteoglossomorpha. In eels, the single cyp19a1 is expressed in both the brain and the gonads, as observed for the single CYP19A1 gene present in other vertebrates. The results of phylogenetic, synteny, closest neighboring gene, and promoter structure analyses showed that the single cyp19a1 of the basal teleosts shared conserved properties with both teleost cyp19a1a and cyp19a1b paralogs, which did not allow us to conclude which of the 3R-duplicated paralogs (cyp19a1a or cyp19a1b) was lost in Elopomorpha. Elopomorpha and Osteoglossomorpha cyp19a1 genes exhibited preserved ancestral functions, including expression in both the gonad and brain. We propose that the subfunctionalization of the 3R-duplicated cyp19a1 paralogs expressed specifically in the gonad or brain occurred in Clupeocephala, after the split of Clupeocephala from Elopomorpha and Osteoglossomorpha, which represented a driving force for the conservation of both 3R-duplicated paralogs in all extant Clupeocephala. In contrast, the functional redundancy of the undifferentiated 3R-duplicated cyp19a1 paralogs in elopomorphs and osteoglossomorphs would have favored the loss of one 3R paralog in basal teleosts.

['Lin|Chien-Ju|CJ|', 'Maugars|Gersende|G|', 'Lafont|Anne-Gaëlle|AG|', 'Jeng|Shan-Ru|SR|', 'Wu|Guan-Chung|GC|', 'Dufour|Sylvie|S|', 'Chang|Ching-Fong|CF|']

2020

30570751

Ionotropic and metabotropic kainate receptor signalling regulates Cl- homeostasis and GABAergic inhibition.

KEY POINTS Potassium-chloride co-transporter 2 (KCC2) plays a critical role in regulating chloride homeostasis, which is essential for hyperpolarizing inhibition in the mature nervous system. KCC2 interacts with many proteins involved in excitatory neurotransmission, including the GluK2 subunit of the kainate receptor (KAR). We show that activation of KARs hyperpolarizes the reversal potential for GABA (EGABA ) via both ionotropic and metabotropic signalling mechanisms. KCC2 is required for the metabotropic KAR-mediated regulation of EGABA , although ionotropic KAR signalling can hyperpolarize EGABA independent of KCC2 transporter function. The KAR-mediated hyperpolarization of EGABA is absent in the GluK1/2-/- mouse and is independent of zinc release from mossy fibre terminals. The ability of KARs to regulate KCC2 function may have implications in diseases with disrupted excitation: inhibition balance, such as epilepsy, neuropathic pain, autism spectrum disorders and Down's syndrome. ABSTRACT Potassium-chloride co-transporter 2 (KCC2) plays a critical role in the regulation of chloride (Cl- ) homeostasis within mature neurons. KCC2 is a secondarily active transporter that extrudes Cl- from the neuron, which maintains a low intracellular Cl- concentration [Cl- ]. This results in a hyperpolarized reversal potential of GABA (EGABA ), which is required for fast synaptic inhibition in the mature central nervous system. KCC2 also plays a structural role in dendritic spines and at excitatory synapses, and interacts with 'excitatory' proteins, including the GluK2 subunit of kainate receptors (KARs). KARs are glutamate receptors that display both ionotropic and metabotropic signalling. We show that activating KARs in the hippocampus hyperpolarizes EGABA , thus strengthening inhibition. This hyperpolarization occurs via both ionotropic and metabotropic KAR signalling in the CA3 region, whereas it is absent in the GluK1/2-/- mouse, and is independent of zinc release from mossy fibre terminals. The metabotropic signalling mechanism is dependent on KCC2, although the ionotropic signalling mechanism produces a hyperpolarization of EGABA even in the absence of KCC2 transporter function. These results demonstrate a novel functional interaction between a glutamate receptor and KCC2, a transporter critical for maintaining inhibition, suggesting that the KAR:KCC2 complex may play an important role in excitatory:inhibitory balance in the hippocampus. Additionally, the ability of KARs to regulate chloride homeostasis independently of KCC2 suggests that KAR signalling can regulate inhibition via multiple mechanisms. Activation of kainate-type glutamate receptors could serve as an important mechanism for increasing the strength of inhibition during periods of strong glutamatergic activity.

['Garand|Danielle|D|', 'Mahadevan|Vivek|V|0000-0002-0805-827X', 'Woodin|Melanie A|MA|0000-0003-2984-8630']

2019

28082452

Sphingosine-1-phosphate signalling-a key player in the pathogenesis of Angiotensin II-induced hypertension.

AIMS Hypertension is a complex condition involving functional and structural alterations of the microvasculature and an activation of the immune system. T-lymphocytes play a crucial role during the development of hypertension in experimental models, yet the underlying mechanisms remain elusive. Lymphocyte egress from lymph nodes is controlled by sphingosine-1-phosphate (S1P), a natural lipid mediator regulating immune cell and vascular function in health and disease. We therefore investigated the involvement of S1P signalling in the pathogenesis of hypertension. METHODS AND RESULTS Angiotensin-II (AngII) treatment resulted in high blood pressure (BP) associated to increased plasma S1P and circulating T-cell counts. T-cell egress from lymph nodes was found to be a critical initial step for the onset of hypertension as fingolimod, a S1P-receptor agonist sequestering lymphocytes in the lymph nodes and inducing lymphopenia, blunted BP responses to AngII. Furthermore, activity of S1P-generating enzyme type 2 (SphK2) in haematopoietic cells critically contributed to AngII-induced lymphocyte mobilization from the lymph nodes as SphK2-/- mice and mice where SphK2 was ablated only in the haematopoietic system presented an accumulation of T-cells in mesenteric lymph nodes and a blunted BP response. In addition, deregulation of vascular SphK2 expression associated to a thrombo-inflammatory phenotype of the microvasculature, and to functional alterations of small resistance arteries. CONCLUSION The presented results point to a critical involvement of S1P and its signalling axis in the pathogenesis of hypertension. Specifically, SphK2 evolves as key player in immune cell trafficking and vascular dysfunction contributing to the development of overt hypertension.

['Meissner|Anja|A|', 'Miro|Francesc|F|', 'Jiménez-Altayó|Francesc|F|', 'Jurado|Andrés|A|', 'Vila|Elisabet|E|', 'Planas|Anna M|AM|']

2017

34273859

RT-PCR based SARS-CoV-2 variant screening assays require careful quality control.

BACKGROUND Distinctive genotypes of SARS-CoV-2 have emerged that are or may be associated with increased transmission, pathogenicity, and/or antibody escape. In many countries, clinical and diagnostic laboratories are under mandate to identify and report these so-called variants of concern (VOC). OBJECTIVES We used an external quality assessment scheme to determine the scope, accuracy, and reliability of laboratories using various molecular diagnostic assays to identify current VOC (03 March 2021). STUDY DESIGN Participant laboratories were sent the same five patient-derived samples and were asked to provide their variant detection methods, variant detection results and interpretation of results. RESULTS Twenty-five laboratories reported a range of RT-qPCR-based assays to identify specific variations in the SARS-CoV-2 spike protein that are characteristic of three VOC lineages. Laboratories that detected VOC-associated nucleotide mutations at four specific sites had the highest ratio of correct classification. Low template copy number and additional variation in target regions resulted in loss of confidence and accuracy in sample classification. CONCLUSIONS Melting-curve-based assays to identify genomic variants are less time-consuming and require less bioinformatic analysis compared to partial or whole genome sequencing. However, our results suggest that correct classification of a given genotype/lineage (e.g., a VOC) relies on the ability to detect more than one variant site, adequate template in the sample (i.e., relatively high viral load/copy number) and results may be unclear in certain samples with additional genetic variations. These initial results suggest that some diagnostic laboratories may require additional training to interpret and report complex genetic information about a dynamic emerging virus.

['Camp|Jeremy V|JV|', 'Buchta|Christoph|C|', 'Jovanovic|Jovana|J|', 'Puchhammer-Stöckl|Elisabeth|E|', 'Benka|Bernhard|B|', 'Griesmacher|Andrea|A|', 'Aberle|Stephan W|SW|', 'Goerzer|Irene|I|']

2021

30060629

Environmentally Friendly Approach to Knoevenagel Condensation of Rhodanine in Choline Chloride: Urea Deep Eutectic Solvent and QSAR Studies on Their Antioxidant Activity.

A series of rhodanine derivatives was synthesized in the Knoevenagel condensation of rhodanine and different aldehydes using choline chloride:urea (1:2) deep eutectic solvent. This environmentally friendly and catalyst free approach was very effective in the condensation of rhodanine with commercially available aldehydes, as well as the ones synthesized in our laboratory. All rhodanine derivatives were subjected to 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity investigation and quantitative structure-activity relationship (QSAR) studies were performed to elucidate their structure-activity relationship. The best multiple linear QSAR model demonstrate a stability in the internal validation and Y-randomization (R² = 0.81; F = 24.225; Q²loo = 0.72; R²Yscr = 0.148). Sphericity of the molecule, ratio of symmetric atoms enhanced atomic mass along the principle axes in regard to total number of atoms in molecule, and 3D distribution of the atoms higher electronegativity (O, N, and S) in molecules are important characteristic for antioxidant ability of rhodanine derivatives. Molecular docking studies were carried out in order to explain in silico antioxidant studies, a specific protein tyrosine kinase (2HCK). The binding interactions of the most active compound have shown strong hydrogen bonding and van der Waals interactions with the target protein.

['Molnar|Maja|M|', 'Brahmbhatt|Harshad|H|', 'Rastija|Vesna|V|', 'Pavić|Valentina|V|0000-0001-5369-1755', 'Komar|Mario|M|', 'Karnaš|Maja|M|', 'Babić|Jurislav|J|']

2018

32415407

Editing of Endogenous Genes in Cellular Immunotherapies.

PURPOSE OF REVIEW T cell-based cellular and antibody immunotherapies have dramatically altered the landscape of cancer treatment over the past decade. Over the same time span, gene editing technologies have enabled unprecedented degrees of genetic control. RECENT FINDINGS Knock-outs of endogenous genes, especially based on electroporation of targetable nucleases such as CRISPR/Cas9, have rapidly proliferated. Simultaneous introduction of large DNA sequences can integrate new synthetic genetic instructions with specific endogenous loci to alter T cell function and specificity. Recently developed discovery technologies to perform genome-wide knock-out and large-scale knock-in screens in T cells can rapidly identify endogenous gene targets and therapeutic knock-in programs. Endogenous gene knock-outs and targeted knock-ins may offer the chance to expand beyond the current limitations of randomly integrating viral vector-based T cell therapies, and extend immunotherapies' therapeutic advances to wider hematologic and solid tumor indications.

['Roth|Theodore L|TL|']

2020

25218871

Peripheral DISC1 protein levels as a trait marker for schizophrenia and modulating effects of nicotine.

The Disrupted-in-Schizophrenia 1 (DISC1) protein plays a key role in behavioral control and vulnerability for mental illnesses, including schizophrenia. In this study we asked whether peripheral DISC1 protein levels in lymphocytes of patients diagnosed with schizophrenia can serve as a trait marker for the disease. Since a prominent comorbidity of schizophrenia patients is nicotine abuse or addiction, we also examined modulation of lymphocyte DISC1 protein levels in smokers, as well as the relationship between nicotine and DISC1 solubility status. We show decreased DISC1 levels in patients diagnosed with schizophrenia independent of smoking, indicating its potential use as a trait marker of this disease. In addition, lymphocytic DISC1 protein levels were decreased in smoking, mentally healthy individuals but not to the degree of overriding the trait level. Since DISC1 protein has been reported to exist in different solubility states in the brain, we also investigated DISC1 protein solubility in brains of rats treated with nicotine. Sub-chronic treatment with progressively increasing doses of nicotine from 0.25mg/kg to 1mg/kg for 15 days led to a decrease of insoluble DISC1 in the medial prefrontal cortex. Our results demonstrate that DISC1 protein levels in human lymphocytes are correlated with the diagnosis of schizophrenia independent of smoking and thus present a potential biomarker. Reduced DISC1 protein levels in lymphocytes of healthy individuals exposed to nicotine suggest that peripheral DISC1 could have potential for monitoring the effects of psychoactive substances.

['Trossbach|Svenja V|SV|', 'Fehsel|Karin|K|', 'Henning|Uwe|U|', 'Winterer|Georg|G|', 'Luckhaus|Christian|C|', 'Schäble|Sandra|S|', 'Silva|M Angelica de Souza|MA|', 'Korth|Carsten|C|']

2014

25411403

Long-term surgical outcomes of infantile-onset esotropia in preterm patients compared with full-term patients.

BACKGROUND/AIMS To compare surgical outcomes between preterm and full-term patients with infantile-onset esotropia. METHODS This study included 56 preterm and 162 full-term patients with infantile-onset esotropia who underwent strabismus surgery. The extent of surgery was reduced by 0.5 mm per muscle in preterm patients who were born at <30 weeks of gestation. Surgical outcomes over time, including surgical success, overcorrection rate, undercorrection rate and surgical dose-response were compared between preterm and full-term patients. RESULTS The Cox proportional hazards regression model and competing risk analysis showed no statistically significant differences in the rate of surgical success or undercorrection over time between preterm and full-term patients. However, the final overcorrection rate was greater in preterm children than in full-term children (p=0.019). The average surgical dose-response was 3.99 prism dioptres (PD)/mm in full-term children and 4.40 PD/mm in preterm children. CONCLUSIONS The results of this study showed a favourable outcome using a mildly reduced amount of surgery in preterm patients with infantile-onset esotropia. Surgical dose-response was significantly greater in preterm patients than in full-term patients.

['Park|Kyung-Ah|KA|', 'Oh|Sei Yeul|SY|']

2015

31037763

Cancer drug resistance: A fleet to conquer.

Cancer is a disease that claims millions of lives each year across the world. Despite advancement in technologies and therapeutics for treating the disease, these modes are often found to turn ineffective during the course of treatment. The resistance against drugs in cancer patients stems from multiple factors, which constitute genetic heterogeneity like gene mutations, tumor microenvironment, exosomes, miRNAs, high rate of drug efflux from cells, and so on. This review attempts to collate all such known and reported factors that influence cancer drug resistance and may help researchers with information that might be useful in developing better therapeutics in near future to enable better management of several cancers across the world.

['Hussain|Showket|S|0000-0003-1456-9217', 'Singh|Ankita|A|', 'Nazir|Sheeraz Un|SU|', 'Tulsyan|Sonam|S|', 'Khan|Asiya|A|', 'Kumar|Ramesh|R|', 'Bashir|Nasreena|N|', 'Tanwar|Pranay|P|', 'Mehrotra|Ravi|R|']

2019

32075928

Silent Infection of B and CD8+ T Lymphocytes by Influenza A Virus in Children with Tonsillar Hypertrophy.

Influenza A viruses (IAVs) cause more than 2 million annual episodes of seasonal acute respiratory infections (ARI) and approximately 500,000 deaths worldwide. Depending on virus strain and host immune status, acute infections by IAV may reach sites other than the respiratory tract. In the present study, IAV RNA and antigens were searched for in tissues of palatine tonsils and adenoids removed from patients without ARI symptoms. A real-time reverse transcriptase PCR (RT-PCR) screening revealed that 8 tissue samples from 7 patients out of 103 were positive for IAV. Positive samples were subjected to next-generation sequencing (NGS) and 3 of 8 tissues yielded complete IAV pH1N1 genomes, whereas in 5 samples, the PB1 gene was not fully assembled. Phylogenetic analysis placed tonsil-derived IAV in clusters clearly segregated from contemporaneous Brazilian viruses. Flow cytometry of dispersed tissue fragments and serial immunohistochemistry of paraffin-embedded sections of naturally infected biopsies indicated that CD20+ B lymphocytes, CD8+ T lymphocytes, and CD11c+ cells are susceptible to IAV infection. We sought to investigate whether these lymphoid tissues could be sites of viral replication and sources of viable virus particles. MDCK cells were inoculated with tissue lysates, enabling recovery of one IAV isolate confirmed by immunofluorescence, reverse transcriptase quantitative PCR (RT-qPCR), and NGS. The data indicate that lymphoid tissues not only harbor expression of IAV proteins but also contain infectious virus. Asymptomatic long-term infection raises the possibility of IAV shedding from tonsils, which may have an impact on host-to-host transmission.IMPORTANCE Influenza A virus (IAV) infections are important threats to human health worldwide. Although extensively studied, some aspects of virus pathogenesis and tissue tropism remain unclear. Here, by different strategies, we describe the asymptomatic infection of human lymphoid organs by IAV in children. Our results indicate that IAV was not only detected and isolated from human tonsils but displayed unique genetic features in comparison with those of contemporaneous IAVs circulating in Brazil and detected in swabs and nasal washes. Inside the tissue microenvironment, immune cells were shown to be carrying IAV antigens, especially B and T CD8+ lymphocytes. Taken together, these results suggest that human lymphoid tissues can be sites of silent IAV infections with possible impact on virus shedding to the population.

['Castro|Italo A|IA|0000-0001-7885-7547', 'Jorge|Daniel M M|DMM|', 'Ferreri|Lucas M|LM|', 'Martins|Ronaldo B|RB|0000-0002-8902-5962', 'Pontelli|Marjorie C|MC|0000-0003-3173-5977', 'Jesus|Bruna L S|BLS|', 'Cardoso|Ricardo S|RS|0000-0003-2858-2076', 'Criado|Miria F|MF|', 'Carenzi|Lucas|L|', 'Valera|Fabiana C P|FCP|', 'Tamashiro|Edwin|E|', 'Anselmo-Lima|Wilma T|WT|', 'Perez|Daniel R|DR|', 'Arruda|Eurico|E|0000-0002-0978-410X']

2020

27351195

Remediation of Cr(VI)-Contaminated Soil Using the Acidified Hydrazine Hydrate.

Acidified hydrazine hydrate was used to remediate Cr(VI)-contaminated soil. The content of water-soluble Cr(VI) in contaminated soil was 4977.53 mg/kg. The optimal initial pH of hydrazine hydrate solution, soil to solution ratio and molar ratio of Cr(VI) to hydrazine hydrate for remediation of Cr(VI)-contaminated soil were 5.0, 3:1 and 1:3, respectively. Over 99.50 % of water-soluble Cr(VI) in the contaminated soil was reduced at the optimal condition within 30 min. The remediated soil can keep stable within 4 months. Meanwhile the total phosphorus increased from 0.47 to 4.29 g/kg, indicating that using of acidified hydrazine hydrate is an effective method to remediate Cr(VI)-contaminated soil.

['Ma|Yameng|Y|', 'Li|Fangfang|F|', 'Jiang|Yuling|Y|', 'Yang|Weihua|W|', 'Lv|Lv|L|', 'Xue|Haotian|H|', 'Wang|Yangyang|Y|']

2016

29370572

Use of Gevokizumab in Patients with Behçet's Disease Uveitis: An International, Randomized, Double-Masked, Placebo-Controlled Study and Open-Label Extension Study.

PURPOSE The purpose of this article is to demonstrate the superiority of gevokizumab as compared to placebo, on top of current standard of care, in reducing the risk of Behçet's disease uveitis (BDU) exacerbations. METHODS Randomized, double-masked, placebo-controlled, parallel group, event-driven trial in BDU patients having recently experienced an ocular exacerbation, subsequently undergoing a tapering procedure from high-dose corticosteroids and receiving 60 mg gevokizumab or placebo every 4 weeks subcutaneously (EYEGUARD B-ClinicalTrials.gov NCT 01965145). RESULTS A total of 83 patients (40 gevokizumab, 43 placebo) were included. Gevokizumab did not significantly affect the risk of occurrence of ocular exacerbations. However, data suggested that gevokizumab could preserve visual acuity, reduce the uveitis severity, decrease the emergence of macular edema, and have a corticosteroid sparing effect. Gevokizumab was well tolerated. CONCLUSIONS While the primary efficacy endpoint was not met with gevokizumab, the control of IL-1β pathway in patients with BDU may still be a relevant target.

['Tugal-Tutkun|Ilknur|I|', 'Pavesio|Carlos|C|', 'De Cordoue|Agnès|A|', 'Bernard-Poenaru|Oana|O|', 'Gül|Ahmet|A|']

2018

29662622

Quantitative parameters in dynamic contrast-enhanced magnetic resonance imaging for the detection and characterization of prostate cancer.

Objectives to assess the diagnostic accuracy of quantitative parameters of DCE-MRI in multi-parametric MRI (mpMRI) in comparison to the histopathology (including Gleason grade) of prostate cancer. Patients and methods 150 men with suspected prostate cancer (abnormal digital rectum examination and or elevated prostate-specific antigen) received pre-biopsy 3T mpMRI and were recruited into peer-reviewed, protocol-based prospective study. The DCE-MRI quantitative parameters (K (influx transfer constant) and k (efflux rate constant)) of the cancerous and normal areas were recorded using four different kinetic models employing Olea Sphere (Olea Medical, La Ciotat, France). The correlation between these parameters and the histopathology of the lesions (biopsy and in a sub-cohort 41 radical prostatectomy specimen) was assessed. Results The quantitative parameters showed a significant difference between non-cancerous (benign) and cancerous lesions (Gleason score≥3+3) in the prostate gland. The cut-off values for prostate cancer differentiation were: K (0.205 min-1) and k (0.665 min-1) in the extended Tofts model (ET) and K (0.205 min-1 and k (0.63 min-1) in the Lawrence and Lee delay (LD) models respectively. The mean K value also showed a difference between low-grade cancer (Gleason score=3+3) and high-grade cancer (Gleason score ≥ 3+4). With the addition of DCE-MRI quantitative parameters, the sensitivity of the PIRAD scoring system was increased from 56.6% to 92.1% (K _ET), 93.1% (k _ET), 91.0%, (K _LD) and 89.4% (k _LD). Conclusion Quantitative DCE-MRI parameters improved the diagnostic performance of conventional MRI in distinguishing normal and prostate cancers, including characterization of grade of cancers. The ET and LD models in post-image processing analysis provided better cut-off values for prostate cancer differentiation than the other quantitative DCE-MRI parameters.

['Wei|Cheng|C|', 'Jin|Bowen|B|', 'Szewczyk-Bieda|Magdalena|M|', 'Gandy|Stephen|S|', 'Lang|Stephen|S|', 'Zhang|Yilong|Y|', 'Huang|Zhihong|Z|', 'Nabi|Ghulam|G|']

2018

23345976

Preparation and characterization of an anti-inflammatory agent based on a zinc-layered hydroxide-salicylate nanohybrid and its effect on viability of Vero-3 cells.

A new organic-inorganic nanohybrid based on zinc-layered hydroxide intercalated with an anti-inflammatory agent was synthesized through direct reaction of salicylic acid at various concentrations with commercially available zinc oxide. The basal spacing of the pure phase nanohybrid was 15.73 Å, with the salicylate anions arranged in a monolayer form and an angle of 57 degrees between the zinc-layered hydroxide interlayers. Fourier transform infrared study further confirmed intercalation of salicylate into the interlayers of zinc-layered hydroxide. The loading of salicylate in the nanohybrid was estimated to be around 29.66%, and the nanohybrid exhibited the properties of a mesoporous-type material, with greatly enhanced thermal stability of the salicylate compared with its free counterpart. In vitro cytotoxicity assay revealed that free salicylic acid, pure zinc oxide, and the nanohybrid have a mild effect on viability of African green monkey kidney (Vero-3) cells.

['Ramli|Munirah|M|', 'Hussein|Mohd Zobir|MZ|', 'Yusoff|Khatijah|K|']

2013

26011652

Application of systems thinking: 12-month postintervention evaluation of a complex health system intervention in Zambia: the case of the BHOMA.

RATIONALE, AIMS AND OBJECTIVES Strong health systems are said to be paramount to achieving effective and equitable health care. The World Health Organization has been advocating for using system-wide approaches such as 'systems thinking' to guide intervention design and evaluation. In this paper we report the system-wide effects of a complex health system intervention in Zambia known as Better Health Outcome through Mentorship and Assessment (BHOMA) that aimed to improve service quality. METHODS We conducted a qualitative study in three target districts. We used a systems thinking conceptual framework to guide the analysis focusing on intended and unintended consequences of the intervention. NVivo version 10 was used for data analysis. RESULTS The addressed community responded positively to the BHOMA intervention. The indications were that in the short term there was increased demand for services but the health worker capacity was not severely affected. This means that the prediction that service demand would increase with implementation of BHOMA was correct and the workload also increased, but the help of clinic lay supporters meant that some of the work of clinicians was transferred to these lay workers. However, from a systems perspective, unintended consequences also occurred during the implementation of the BHOMA. CONCLUSIONS We applied an innovative approach to evaluate a complex intervention in low-income settings, exploring empirically how systems thinking can be applied in the context of health system strengthening. Although the intervention had some positive outcomes by employing system-wide approaches, we also noted unintended consequences.

['Mutale|Wilbroad|W|', 'Ayles|Helen|H|', 'Bond|Virginia|V|', 'Chintu|Namwinga|N|', 'Chilengi|Roma|R|', 'Mwanamwenge|Margaret Tembo|MT|', 'Taylor|Angela|A|', 'Spicer|Neil|N|', 'Balabanova|Dina|D|']

2017

34264779

Mixed logit approach to analyzing pedestrian injury severity in pedestrian-vehicle crashes in North Carolina: Considering time-of-day and day-of-week.

OBJECTIVE The objective of this research is to identify and compare contributing factors to pedestrian injury severities in pedestrian-vehicle crashes considering both time-of-day and day-of-week. METHODS The pedestrian-vehicle crash data are collected from 2007 to 2018 in North Carolina with categorical factors of pedestrian, driver, vehicle type, crash group, geography, environment, and traffic control characteristics. The final dataset includes 17,904 observations with 69 categorized variables. Four mixed logit models are developed to analyze the crash dataset with segmentations of weekday daytime, weekday nighttime, weekend daytime, and weekend nighttime. RESULTS A total number of 31 fixed significant factors and 6 random parameter factors to the pedestrian injury severity are detected in four mixed logit models. According to marginal effects, large vehicle involved, pedestrians with age over 65, hit and run, drunk pedestrian, down/dusk light, dark without roadside light, and industrial land use are identified as the contributing factors that result in more than a 0.08 increase in the probability of fatal injury. Compared to the daytime, most factors are found to have more impact on severe injuries in the nighttime. Also, most factors are found to result in more severe injuries on weekends than on weekdays. CONCLUSIONS This study identifies and compares the factors to pedestrian injury severity in pedestrian-vehicle crashes considering the temporal variance in time-of-day (i.e., daytime vs. nighttime) and day-of-week (i.e., weekdays vs. weekends). Random effects are explored in mixed logit models. Differences and possible reasons for the significant factors' impact within and across time-of-day and day-of-week are also investigated. Corresponding countermeasures and suggestions to mitigate the impacts of major factors are also discussed, which give practical guidance to planners and engineers, and provide a solid reference to further explore the temporal variance of the crash data.

['Song|Li|L|', 'Li|Yang|Y|', 'Fan|Wei David|WD|0000-0001-9815-710X', 'Liu|Pengfei|P|']

2021

22792033

Three new species of Lathrobium Gravenhorst (Coleoptera, Staphylinidae, Paederinae) from Sichuan, Southwest China.

Three new species of the genus Lathrobium Gravenhorst, 1802 from Sichuan Province, Southwest China are described and illustrated: Lathrobium acutissimumsp. n., Lathrobium hailuogouensesp. n. and Lathrobium labahensesp. n. A checklist of Chinese Lathrobium is provided.

['Peng|Zhong|Z|', 'Li|Li-Zhen|LZ|', 'Zhao|Mei-Jun|MJ|']

2012

31390574

Development of a Mouse Pain Scale Using Sub-second Behavioral Mapping and Statistical Modeling.

Rodents are the main model systems for pain research, but determining their pain state is challenging. To develop an objective method to assess pain sensation in mice, we adopt high-speed videography to capture sub-second behavioral features following hind paw stimulation with both noxious and innocuous stimuli and identify several differentiating parameters indicating the affective and reflexive aspects of nociception. Using statistical modeling and machine learning, we integrate these parameters into a single index and create a "mouse pain scale," which allows us to assess pain sensation in a graded manner for each withdrawal. We demonstrate the utility of this method by determining sensations triggered by three different von Frey hairs and optogenetic activation of two different nociceptor populations. Our behavior-based "pain scale" approach will help improve the rigor and reproducibility of using withdrawal reflex assays to assess pain sensation in mice.

['Abdus-Saboor|Ishmail|I|', 'Fried|Nathan T|NT|', 'Lay|Mark|M|', 'Burdge|Justin|J|', 'Swanson|Kathryn|K|', 'Fischer|Roman|R|', 'Jones|Jessica|J|', 'Dong|Peter|P|', 'Cai|Weihua|W|', 'Guo|Xinying|X|', 'Tao|Yuan-Xiang|YX|', 'Bethea|John|J|', 'Ma|Minghong|M|', 'Dong|Xinzhong|X|', 'Ding|Long|L|', 'Luo|Wenqin|W|']

2019

27788683

Analysis of the independent risk factors of neurologic deficit after thoracolumbar burst fracture.

BACKGROUND The objective of this study is to identify the independent risk factors of neurologic deficit after thoracolumbar burst fracture. Traumatic fractures of the thoracolumbar spine are the most common type of spinal column fractures. Many studies have attempted to determine whether neurologic deficit in such fractures is related to spinal canal stenosis or other parameters observed on axial computed tomography. However, this relationship remains controversial. METHODS A review of the clinical data and axial computed tomography (CT) for 105 patients was performed. Neurologic deficit was classified according to the American Spinal Injury Association (ASIA) classification. Various preoperative CT parameters, including vertebral body compression, canal stenosis, sagittal alignment, and fragment reverse, were analyzed using ordinal logistic regression analysis. RESULTS Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification, canal volume, transverse canal diameter, median sagittal diameter, Cobb angle, compression ratio of the sagittal diameter, compression ratio of the cross-sectional area, and compression ratios of the anterior vertebral height (AVH), middle vertebral height (MVH), and posterior vertebral height (PVH) were significantly associated with severity of nerve injury (P < 0.05). However, flip angle and rotation angle of bony fragments were unrelated to severity of nerve damage. Multivariate logistic regression identified AO classification, compression ratio of median sagittal diameter, anterior vertebral compression ratio, and distance from the posterior margin to the vertebral body above to be independent variables associated with neurologic deficit. CONCLUSIONS The four CT parameters most strongly associated with neurologic deficit in thoracolumbar burst fractures are AO classification, compression ratio of median sagittal diameter, anterior vertebral compression ratio, and distance from the posterior margin to the vertebral body above.

['Tang|Peifu|P|', 'Long|Anhua|A|', 'Shi|Tao|T|', 'Zhang|Licheng|L|', 'Zhang|Lihai|L|']

2016

34679856

Effects of the Cooling Temperature at the Farm on Milk Maturation and Cheesemaking Process in the Manufacture of Parmigiano Reggiano PDO Cheese.

Parmigiano Reggiano is a hard PDO cheese made from bovine raw milk, whose microbiological characteristics have important repercussions on cheese quality. According to the EU official production protocol, milk temperature at the farm must not drop below 18 °C. The present research aimed to study the effect of cooling milk at the farm at 9 °C on the characteristics of milk and on the cheesemaking process and losses during manufacture. Six cheesemaking trials were performed in two different dairies. In each of them, two cheesemakings were made in parallel: one with milk kept at 9 °C (TM9) and the other with milk kept at 20 °C (TM20). TM9 milk, in comparison with TM20, showed after the creaming process a significant reduction not only of total bacterial count but also of psychrotrophic and lipolytic bacteria. At the same time, TM9 milk showed a higher creaming capacity and, consequently, a lower fat content than TM20. TM9 vat milk had worst coagulation properties than TM20, which caused slightly higher loss of fat and curd fines into the whey. Nevertheless, these changes were too small to influence the efficiency of the cheesemaking process; conversely, maintaining milk at the farm at 9 °C led to a reduction of the number of spoilage bacteria.

['Franceschi|Piero|P|0000-0002-4756-8280', 'Brasca|Milena|M|0000-0002-8821-0787', 'Malacarne|Massimo|M|0000-0003-3329-698X', 'Formaggioni|Paolo|P|', 'Faccia|Michele|M|0000-0001-9496-9151', 'Natrella|Giuseppe|G|0000-0001-7203-2608', 'Summer|Andrea|A|0000-0002-4833-657X']

2021

33102679

What explains the concentration of off-premise alcohol outlets in Black neighborhoods?

Introduction Greater availability of commercial alcohol is associated with increased alcohol use and related public health problems. Greater alcohol outlet density, a marker of alcohol availability, is associated with poorer and predominantly minority neighborhoods. However, poorer populations, African Americans, and Latinxs report using less alcohol compared to Whites and wealthier groups. We consider the role of structural racism in the social ecology of alcohol availability. Specifically we examine racist urban land use practices in the USA which became codified in the 1930s through Federal Home Owner Lending Corporation (HOLC) designations for assigning parcel values, known as "redlining." Redlining demarcated low-density residential zones for wealthy Whites which excluded poor and non-White people as well as certain businesses, including alcohol retailers. We assessed the impacts of historic redlining on present day risks for exposure to retail alcohol availability in urban Northern California. Methods For six contiguous and demographically diverse Northern California cities we obtained digital renderings of HOLC maps (1937) which demarcated exclusions of people and businesses for 119 neighborhood areas across four land valuation zones. We then identified the most prevalent HOLC rating for each of 520 current Census block groups in the six cities, including a residual category for areas not rated by HOLC. We geolocated all current (2016) off-premise alcohol sales outlets operating in the six cities (N = 401). We used Bayesian spatial Poisson models to relate current alcohol outlet densities and Census-based estimates of neighborhood characteristics to historic HOLC classifications. Results Spatial Poisson analyses found far greater contemporary off-premise outlet densities in the lowest-valued HOLC zones than in the highest (median relative rate [RR] 9.6, 95% CI 4.8-22.1). The lowest-valued HOLC zones were also characterized by far higher current percentages of both Black residents (RR 30.4, 95% CI 17.0-54.6) and Hispanic residents (RR 9.7, 95% CI 7.2-12.9). Conclusions Present day risks for exposure to retail alcohol availability were delimited by historic exclusionary land use practices. Current inequitable health risks may be founded on racist spatial projects of past decades.

['Lee|Juliet P|JP|', 'Ponicki|William|W|', 'Mair|Christina|C|', 'Gruenewald|Paul|P|', 'Ghanem|Lina|L|']

2020

27002474

A short-stem hip implant with metaphyseal anchorage in patients with developmental dysplasia of the hip.

BACKGROUND Short-stem implants are routinely used for total hip arthroplasty in younger patients that are more likely to have secondary osteoarthritis than older patients. OBJECTIVE To investigate the applicability of short-stem hip implants for secondary osteoarthritis due to developmental dysplasia of the hip. METHODS This study analyzed the clinical and radiological results of patients with developmental dysplasia of the hip (DDH, 58 hips) and compared them to those of patients with primary osteoarthritis (POA, 59 hips) treated with the metaphyseal total hip arthroplasty (Metha®) short stem with metaphyseal fixation. RESULTS The mean clinical and radiological follow-up periods were 2.9 ± 1.1 years and 3.8 ± 1.9 years, respectively. The mean Harris Hip Score (HHS) significantly increased in both groups over this period (p< 0.0001). The caput-collum-diaphysis (CCD) angle was significantly lower in the POA group prior to surgery and significantly increased in the POA and and decreased in DDH groups, respectively. The preoperative femoral offset was lower in the DDH group and increased significantly after surgery. CONCLUSIONS The Metha® short stem in patients with DDH allows good reconstruction of joint biomechanics with a good clinical outcome.

['Budde|Stefan|S|', 'Floerkemeier|Thilo|T|', 'Thorey|Fritz|F|', 'Ezechieli|Marco|M|', 'Claassen|Leif|L|', 'Ettinger|Max|M|', 'Bredow|Jan|J|', 'Windhagen|Henning|H|', 'Lewinski|Gabriela von|GV|']

2016

33882899

Birth prevalence of neural tube defects and associated risk factors in Africa: a systematic review and meta-analysis.

BACKGROUND Neural tube defects are common congenital anomalies that result from early malformation in the development of the spinal cord and brain. It is related to substantial mortality, morbidity, disability, and psychological and economic costs. The aim of this review is to determine the pooled birth prevalence of neural tube defects and associated risk factors in Africa. METHODS The first outcome of this review was the pooled birth prevalence of the neural tube defects and the second outcome was the pooled measure of association between neural tube defects and associated risk factors in Africa. We systematically searched PubMed, PubMed Central, Joanna Briggs Institute, Google Scopus, Cochrane Library, African Journals Online, Web of Science, Science Direct, Google Scholar, and Medline databases. The heterogeneity of studies was assessed using the Cochrane Q test statistic, I2 test statistic, and, visually, using Forest and Galbraith's plots. A random-effect model was applied to get the pooled birth prevalence of neural tube defects. Subgroup, sensitivity, meta-regression, time-trend, and meta-cumulative analyses were undertaken. The fixed-effect model was used to analyze the association between neural tube defects and associated risk factors. RESULTS Forty-three studies with a total of 6086,384 participants were included in this systematic review and meta-analysis. The pooled birth prevalence of the neural tube defects was 21.42 (95% CI (Confidence Interval): 19.29, 23.56) per 10,000 births. A high pooled birth prevalence of neural tube defects was detected in Algeria 75 (95% CI: 64.98, 85.02), Ethiopia 61.43 (95% CI: 46.70, 76.16), Eritrea 39 (95% CI: 32.88, 45.12), and Nigeria 32.77 (95% CI: 21.94, 43.59) per 10,000 births. The prevalence of neural tube defects has increased over time. Taking folic acid during early pregnancy, consanguineous marriage, male sex, and substance abuse during pregnancy were assessed and none of them was significant. CONCLUSIONS The pooled birth prevalence of neural tube defects in Africa was found to be high. The risk factors evaluated were not found significant.

['Oumer|Mohammed|M|0000-0003-4289-8712', 'Tazebew|Ashenafi|A|', 'Silamsaw|Mezgebu|M|']

2021

28970779

Thiol-reducing agents prevent sulforaphane-induced growth inhibition in ovarian cancer cells.

The inhibitory potential of sulforaphane against cancer has been suggested for different types of cancer, including ovarian cancer. We examined whether this effect is mediated by mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS), important signaling molecules related to cell survival and proliferation, in ovarian cancer cells. Sulforaphane at a concentration of 10 μM effectively inhibited the growth of cancer cells. Use of specific inhibitors revealed that activation of MAPK pathways by sulforaphane is unlikely to mediate sulforaphane-induced growth inhibition. Sulforaphane did not generate significant levels of intracellular ROS. Pretreatment with thiol reducers, but not ROS scavengers, prevented sulforaphane-induced growth inhibition. Furthermore, diamide, a thiol-oxidizing agent, enhanced both growth inhibition and cell death induced by sulforaphane, suggesting that the effect of sulforaphane on cell growth may be related to oxidation of protein thiols or change in cellular redox status. Our data indicate that supplementation with thiol-reducing agents should be avoided when sulforaphane is used to treat cancer.

['Kim|Seung Cheol|SC|', 'Choi|Boyun|B|', 'Kwon|Youngjoo|Y|0000-0003-3582-4192']

2017

31530187

Model Selection of Nested and Non-Nested Item Response Models Using Vuong Tests.

In this paper, we apply Vuong's general approach of model selection to the comparison of nested and non-nested unidimensional and multidimensional item response theory (IRT) models. Vuong's approach of model selection is useful because it allows for formal statistical tests of both nested and non-nested models. However, only the test of non-nested models has been applied in the context of IRT models to date. After summarizing the statistical theory underlying the tests, we investigate the performance of all three distinct Vuong tests in the context of IRT models using simulation studies and real data. In the non-nested case we observed that the tests can reliably distinguish between the graded response model and the generalized partial credit model. In the nested case, we observed that the tests typically perform as well as or sometimes better than the traditional likelihood ratio test. Based on these results, we argue that Vuong's approach provides a useful set of tools for researchers and practitioners to effectively compare competing nested and non-nested IRT models.

['Schneider|Lennart|L|http://orcid.org/0000-0003-4152-5308', 'Chalmers|R Philip|RP|', 'Debelak|Rudolf|R|http://orcid.org/0000-0001-8900-2106', 'Merkle|Edgar C|EC|http://orcid.org/0000-0001-7158-0653']

2020

27790506

Does 24bp Duplication of Human CHIT1 Gene (Chitotriosidase1) Predispose to Filarial Chyluria? A Case-Control Study.

INTRODUCTION Chyluria which is endemic in many parts of the world is mainly caused by Wuchereria bancrofti. CHIT1 (chitotriosidase) is produced by macrophages and plays an important role in the defense against chitin containing pathogen such as filarial parasite. Variation in the coding region with 24 bp duplication allele results in reduced CHIT1 activity that enhance the survival of parasite which may play a role in the occurrence of disease. AIM To examine the role of 24bp duplication of CHIT1 gene in patients of filarial chyluria (FC). MATERIALS AND METHODS A case-control study was carried out where 155 confirmed FC patients and equal number of age-, sex- and residence-matched controls without any symptoms or signs of lymphatic filariasis, confirmed by negative immunochromatographic card test (ICT) and IgG/IgM combo rapid antibody test, from a hospital-based population were enrolled. Filarial aetiology was confirmed on the basis of DEC-provocative test (Giemsa staining), ICT and IgG/IgM- antifiarial antibody test. The patients positive by either of these tests were enrolled as FC cases. 24bp duplication in CHIT1 gene in FC was detected by the product size 99bp of amplified gene using polymerase chain reaction. RESULTS The mean ages of patients and controls were 38.25±12.09 and 35.45±12.53 years, respectively while male: female ratio was 2.4:1. The mean duration of illness in chyluria patients was 62.81±60.83 months and mean number of episodes was 2.54±1.11. Homozygous wild type, heterozygous and homozygous mutant frequencies were 10.3%, 81.3% and 8.4% in FC patients and 18.7%, 75.5%, and 5.8% in controls, respectively. The 24bp duplication in CHIT1 gene showed a significant association in Heterozygous (HT) genotype with Odd Ratio (OR) of 1.95, 95% Confidence Interval (CI) (1.01-3.77); p=0.04. However, the homozygous mutant genotype (TT) was found to be non-significant with OR of 2.61, 95% CI (0.91-7.45); p=0.07. The combination of both HT+TT was also found to be significant with OR of 2.00, 95% CI (1.03-3.85); p=0.03. CONCLUSION In this study from Northern India, CHIT1 gene polymorphism showed an influence as a possible risk factor for susceptibility to FC. Further studies need to be done on a larger number of FC patients in different regions of the country.

['Pant|Shriya|S|', 'Agarwal|Jyotsna|J|', 'Goel|Apul|A|', 'Gangwar|Pravin K|PK|', 'Waseem|Mohammad|M|', 'Gupta|Prashant|P|', 'Sankhwar|Satya N|SN|', 'Purkait|Bimalesh|B|']

2016

25164158

In vitro evaluation of the biological performance of macro/micro-porous silk fibroin and silk-nano calcium phosphate scaffolds.

This study evaluates the biological performance of salt-leached macro/microporous silk scaffolds (S16) and silk-nano calcium phosphate scaffolds (SC16), both deriving from a 16 wt % aqueous SF solution. Enzymatic degradation results showed that the silk-based scaffolds presented desirable biostability, and the incorporation of calcium phosphate further improved the scaffolds' biostability. Human adipose tissue derived stromal cells (hASCs) were cultured onto the scaffolds in vitro. The Alamar blue assay and DNA content revealed that both scaffolds were non-cytotoxic and can support the viability and proliferation of the hASCs. Scanning electron microscopy observation demonstrated that the microporous structure was beneficial for the cell adhesion while the macroporous structure favored the cell migration and proliferation. The histological analysis displayed abundant extracellular matrix formed inside the scaffolds, leading to the significant increase of scaffolds' modulus. These results revealed that S16 and SC16 could be promising alternatives for cartilage and bone tissue engineering scaffolding applications, respectively.

['Yan|L-P|LP|', 'Oliveira|J M|JM|', 'Oliveira|A L|AL|', 'Reis|R L|RL|']

2015

28799280

Amide proton transfer-weighted imaging to differentiate malignant from benign pulmonary lesions: Comparison with diffusion-weighted imaging and FDG-PET/CT.

PURPOSE To compare the capability of amide proton transfer-weighted (APTw) imaging, diffusion-weighted imaging (DWI), and FDG-PET/CT for the differentiation of malignant from benign pulmonary nodules. MATERIALS AND METHODS In all, 82 consecutive patients with pulmonary nodules underwent APTw imaging and DWI with a 3T system, and FDG-PET/CT. All nodules were divided as either malignant (n = 49) or benign (n = 39) groups based on pathological and follow-up examinations. To evaluate the capability for differentiation of malignant from benign nodules, magnetization transfer ratio asymmetry (MTRasym )(3.5ppm) on APTw imaging, apparent diffusion coefficient (ADC), and maximum value of standard uptake value (SUVmax ) were assessed. Receiver operating characteristic (ROC) analyses were performed to computationally determine each feasible threshold value. Next, McNemar's test was used for comparing diagnostic performance with each other as well as with a combination of the significant factors determined by multivariate logistic regression analysis. RESULTS Although sensitivity of ADC was significantly higher than that of MTRasym (3.5 ppm) (P = 0.002) and SUVmax (P = 0.004), specificity of MTRasym (3.5 ppm) and SUVmax was significantly higher than that of ADC (P < 0.05). Sensitivity of combined MTRasym (3.5ppm) with SUVmax was significantly higher than that of MTRasym (3.5ppm) (P = 0.001) and SUVmax (P = 0.002) alone. Moreover, specificity and accuracy of combined MTRasym (3.5ppm) with SUVmax were significantly higher than that of ADC (specificity: P = 0.002, accuracy: P = 0.008). CONCLUSION APTw imaging appears to be as useful as DWI and FDG-PET/CT for differentiation of malignant from benign nodules. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1013-1021.

['Ohno|Yoshiharu|Y|', 'Kishida|Yuji|Y|', 'Seki|Shinichiro|S|', 'Yui|Masao|M|', 'Miyazaki|Mitsue|M|', 'Koyama|Hisanobu|H|', 'Yoshikawa|Takeshi|T|']

2018

32121455

Laboratory-Scale Preparation and Characterization of Dried Extract of Muirapuama (Ptychopetalumolacoides Benth) by Green Analytical Techniques.

This work reports on the preparation of a drying process from the ethanolic extract of Muirapuama and its characterization through green analytical techniques. The spray-drying processes were performed by using ethanolic extract in a ratio of 1:1 extract/excipient and 32 factorial design. The properties of dried powder were investigated in terms of total flavonoid content, moisture content, powder yield, and particle size distribution. An analytical eco-scale was applied to assess the greenness of the developed protocol. Ultra-high performance liquid chromatography (UHPLC)with reduced solvent consumption in the analysis was compared to the conventional HPLC method. A Fourier transform near-infrared (FT-NIR) spectroscopic method was applied based on the principal component scores for the prediction of extract/excipient mixtures and partial least squares regression model for quantitative analysis. NIR spectroscopy is an economic, powerful, and fast methodology for the detection of excipient in muirapuama dried extracts, generating no residue in the analysis. Scanning electron microscopy (SEM) images showed samples with a higher concentration of excipient, presenting better morphological characteristics and a lower moisture absorption rate. An eco-scale score value of 85 was achieved for UHPLC and 100 was achieved for NIR (excellent green analysis). Above all, these methods are rapid and green for the routine analysis of herbal medicines based on dried extracts.

['Trindade|Ester Paulitsch|EP|', 'Regis|Franklin Teixeira|FT|', 'Silva|Gabriel Araújo da|GAD|', 'Aguillar|Breno Nunes|BN|', 'Amorim|Marcelo Vítor de Paiva|MVP|', 'Ferreira|George Leandro Ramos|GLR|', 'Aragão|Cícero Flávio Soares|CFS|', 'Solon|Lílian Grace da Silva|LGDS|']

2020

25966656

Four-vessel occlusion model using aged male Wistar rats: a reliable model to resolve the discrepancy related to age in cerebral ischemia research.

Animal models of cerebral ischemia have typically been established and performed using young animals, even though cerebral ischemia (CI) affects primarily elderly patients. This situation represents a discrepancy that complicates the translation of novel therapeutic strategies for CI. Models of transient global CI using aged animals have demonstrated an apparent neuroprotective effect on CA1 hippocampal neurons; however, this effect is not completely understood. Our study used a model in which young (3-6 months) and aged (18-21 months) male Wistar rats were subjected to 15 min of transient global CI using the four-vessel occlusion (4 VO) model. We determined that the 4 VO model can be performed on aged rats with a slight increase in mortality rate. In aged rats, the morphological damage was completely established by the 4th day after reperfusion, displaying no difference from their younger counterparts. These results demonstrated the lack of a neuroprotective effect of aging on CA1 hippocampal neurons in aged male Wistar rats. This study determined and characterized the morphological damage to the CA1 area after 15 min of 4 VO in aged male Wistar rats, validating the use of this model in CI and aging research.

['Ancer-Rodríguez|Jesús|J|', 'Villarreal-Silva|Eliud Enrique|EE|', 'Salazar-Ybarra|Rodolfo Amador|RA|', 'Quiroga-García|Oscar|O|', 'Rodríguez-Rocha|Humberto|H|', 'García-García|Aracely|A|', 'Morales-Avalos|Rodolfo|R|', 'Morales-Gómez|Jesús Alberto|JA|', 'Quiroga-Garza|Alejandro|A|', 'Saucedo-Cárdenas|Odila|O|', 'Xu|Zao Cheng|ZC|', 'Elizondo-Omaña|Rodrigo Enrique|RE|', 'Martínez-Ponce-de-León|Angel Raymundo|AR|', 'Guzmán-López|Santos|S|']

2016

28730856

In vitro drug-drug interactions of budesonide: inhibition and induction of transporters and cytochrome P450 enzymes.

1. Budesonide is a glucocorticoid used in the treatment of several respiratory and gastrointestinal inflammatory diseases. Glucocorticoids have been demonstrated to induce cytochrome P450 (CYP) 3A and the efflux transporter P-glycoprotein (P-gp). This study aimed to evaluate the potential of budesonide to act as a perpetrator or a victim of transporter- or CYP-mediated drug-drug interactions (DDIs). 2. In vitro studies were conducted for P-gp, breast cancer resistance protein and organic anion and cation transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT2) in transporter-transfected cells. Changes in mRNA expression in human hepatocytes and enzyme activity in human liver microsomes by budesonide were determined for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A. 3. The data indicated that budesonide is a substrate of P-gp but is not a substrate or an inhibitor of the other transporters investigated. Budesonide is neither an inducer nor an inhibitor of major CYP enzymes. The effect of P-gp on budesonide disposition is anticipated to be low owing to CYP3A-mediated clearance. 4. Collectively, our data indicate there is a low risk of budesonide perpetrating clinical DDIs mediated by the transporters or CYPs studied.

['Chen|Nancy|N|', 'Cui|Donghui|D|', 'Wang|Qing|Q|', 'Wen|Zhiming|Z|', 'Finkelman|Richard D|RD|', 'Welty|Devin|D|']

2018

28455099

Membrane localization and dynamics of geranylgeranylated Rab5 hypervariable region.

The small GTPase Rab5 is a key regulator of endosomal trafficking processes and a marker for the early endosome. The C-terminal hypervariable region (HVR) of Rab5 is post-translationally modified at residues Cys212 and Cys213 to accommodate two geranylgeranyl anchors (C20 carbon chain length) in order to associate Rab5 with the membrane. The structural role of the HVR regarding protein-early endosome membrane recruitment is not resolved due to its high degree of flexibility and lack of crystallographic information. Here, full-atomistic and coarse-grained molecular dynamics simulations of the truncated Rab5 HVR206-215 in three model membranes of increasing complexity (pure phospholipid bilayer, ternary membrane with cholesterol, six-component early endosome) were performed. Specific electrostatic interactions between the HVR206-215 Arg209 residue and the phosphate group of the inositol ring of PI(3)P were detected. This shows that PI(3)P acts as a first contact site of protein recruitment to the early endosome. The free energy change of HVR206-215 extraction from the bilayer was largest for the physiological negatively charged membrane. 5μs coarse-grained simulations revealed an active recruitment of PI(3)P to the HVR206-215 supporting the formation of Rab5- and PI(3)P enriched signaling platforms.

['Edler|Eileen|E|', 'Schulze|Eric|E|', 'Stein|Matthias|M|']

2017

30771629

Ecotoxicological effects of traffic-related pollutants in roadside soils of Moscow.

The objective of this research is to find correlations between traffic-related contaminants in the roadside soils and their ecotoxicity. The study was conducted in Moscow in the vicinity of a highway of 125 000 vehicles per day. The topsoils (0-3 cm depth) were sampled perpendicular to the road at 1-, 6-, 10-, 18- and 50-m distances from the roadbed. Total petroleum hydrocarbons (TPH), polycyclic aromatic hydrocarbons (PAH), heavy metals (HM) in total and phyto-available forms, and deicing salts (DS) were determined. A battery of soil-contacting organisms was tested: phytotoxicity of rye (H. vulgare L.) and garden cress (L. sativum L.); E. foetida earthworm growth rate and mortality; basal and substrate-induced respiration activity, nitrogen fixation and the denitrification activity of the soil microbial complex. To determine the possible risk to aquatic ecosystems, the algal toxicity test (S. quadricauda) was provided. Correlations between "chemical" data and intensity of "biological" effects were analyzed. Concentrations of most contaminants declined to the background values with distance from the road increase. However, the toxicity of roadside soils was obtained for all examined organisms within the whole 50 m zone. Live organisms exhibited different sensitivities to roadside soils pollution. The intensity of inhibition effects decreased in order: higher plants > earthworms and microorganisms > algae. The risk for aquatic ecosystems was assessed as low. Higher plants toxicity correlated with TPH, PAH, some HM, and DS; earthworm toxicity correlated with TPH, some PAH, HM, and DS; microorganism toxicity correlated with TPH and DS; algae had no observed correlations with contaminants. TPH and DS were general ecotoxicants affecting all organisms. Higher plants may be considered the PAH indicators and earthworms as HM indicators. A set of higher plants and earthworms may be recommended as the reduced test-battery of relevant organisms for cost-effective assessment of the toxicity of roadside soils.

['Nikolaeva|Olga|O|', 'Tikhonov|Vladimir|V|', 'Vecherskii|Maxim|M|', 'Kostina|Natalia|N|', 'Fedoseeva|Elena|E|', 'Astaikina|Angelika|A|']

2019

31221045

Ameliorative potential of flavonoids of Aegle marmelos in vincristine-induced neuropathic pain and associated excitotoxicity.

Introduction: The objective of the study is to elucidate the effect of Aegle marmelos bark hydroalcoholic extract (AMHE) and the role of its constituents marmelosin, umbelliferone, and Para-coumaric acid in attenuating neuropathic pain.Methodology: Peripheral neuropathy was induced by vincristine 100 μg/ml. AMHE was administered in three dose levels (100, 200 and 300 mg/kg) for 21 days. Mechanical hyperalgesia and allodynia were assessed by Randall Sellitto and electronic Von-Frey test, respectively. Functional loss and recovery of the nerve were assessed by sciatic functional index test. The nerve conduction velocity and formalin test were done to assess the peripheral and central response of the extract. Inflammatory mediators in both sciatic nerve and brain and neurotransmitters glutamate and aspartate were measured to support the data.Results and discussion: The inflammatory mediators in both sciatic nerve and brain (TNF-α, IL-1β, and IL-6) were found to be attenuated with AMHE-treated group in comparison to the group treated only with vincristine, which indicates the extract has anti-inflammatory property. AMHE treated rats were found to be active in all the behavioural tests, suggesting its activity could be mediated through a central and peripheral mechanism to attenuate the pain response. The levels of excitatory neurotransmitters were found to be reduced with AMHE treatment.Conclusion: It could be concluded that AMHE is active in attenuating the neuropathic pain caused by vincristine. The peripheral action would have mediated through lowering the inflammatory mediators as well as the excitotoxicity caused due to peripheral neuropathy and neuroinflammation.

['Gautam|Mrinmoy|M|', 'Ramanathan|Muthiah|M|']

2021

31793005

Regulatory T cells and co-evolution of allele-specific MHC recognition by the TCR.

What is the evolutionary mechanism for the TCR-MHC-conserved interaction? We extend Dembic's model (Dembic Z. In, Scand J Immunol e12806, 2019) of thymus positive selection for high-avidity anti-self-MHC Tregs among double (CD4 + CD8+)-positive (DP) developing thymocytes. This model is based on competition for self-MHC (+ Pep) complexes presented on cortical epithelium. Such T cells exit as CD4 + CD25+FoxP3 + thymic-derived Tregs (tTregs). The other positively selected DP T cells are then negatively selected on medulla epithelium removing high-avidity anti-self-MHC + Pep as T cells commit to CD4 + or CD8 + lineages. The process is likened to the competitive selection and affinity maturation in Germinal Centre for the somatic hypermutation (SHM) of rearranged immunoglobulin (Ig) variable region (V[D]Js) of centrocytes bearing antigen-specific B cell receptors (BCR). We now argue that the same direct SHM processes for TCRs occur in post-antigenic Germinal Centres, but now occurring in peripheral pTregs. This model provides a potential solution to a long-standing problem previously recognized by Cohn and others (Cohn M, Anderson CC, Dembic Z. In, Scand J Immunol e12790, 2019) of how co-evolution occurs of species-specific MHC alleles with the repertoire of their germline TCR V counterparts. We suggest this is not by 'blind', slow, and random Darwinian natural selection events, but a rapid structured somatic selection vertical transmission process. The pTregs bearing somatic TCR V mutant genes then, on arrival in reproductive tissues, can donate their TCR V sequences via soma-to-germline feedback as discussed in this journal earlier. (Steele EJ, Lindley RA. In, Scand J Immunol e12670, 2018) The high-avidity tTregs also participate in the same process to maintain a biased, high-avidity anti-self-MHC germline V repertoire.

['Steele|Edward J|EJ|https://orcid.org/0000-0003-4700-3156', 'Lindley|Robyn A|RA|https://orcid.org/0000-0002-8952-1536']

2020

29215196

Comparison between sodium-glucose cotransporter 2 inhibitors and pioglitazone as additions to insulin therapy in type 2 diabetes patients: A systematic review with an indirect comparison meta-analysis.

AIMS/INTRODUCTION We aimed to evaluate the efficacy and safety of pioglitazone (PIO) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) as additions to insulin therapy for the management of type 2 diabetes mellitus. MATERIALS AND METHODS We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov through December 2016. Randomized controlled trials published in English that compared SGLT2i plus insulin (SGLT2i/INS) or PIO plus insulin (PIO/INS) with placebo plus insulin (PCB/INS) in type 2 diabetes mellitus patients were included. We compared the efficacy and safety between SGLT2i/INS and PIO/INS indirectly. RESULTS A total of 14 randomized controlled trials comparing 7,226 participants were included (8 SGLT2i and 6 PIO studies). SGLT2i/INS achieved similar reductions in hemoglobin A1c (weighted mean difference [WMD] -0.01% [-0.1 mmol/mol], 95% confidence interval [CI] -0.25 to 0.22% [-2.7 to -2.4 mmol/mol]; P = 0.896) and fasting plasma glucose (WMD -0.90 mg/dL, 95% CI: -15.50 to 13.71 mg/dL; P = 0.904), and a similar proportion of participants achieved hemoglobin A1c <7.0% (<53.0 mmol/mol; relative risk 0.98, 95% CI: 0.73 to 1.33; P = 0.917) as compared with the PIO/INS group, with greater weight reduction (WMD -4.54 kg, 95% CI: -5.67 to -3.41 kg; P < 0.001). PIO/INS showed non-significant trends toward a higher risk of hypoglycemia (relative risk 1.15, 95% CI: 0.97 to 1.35; P = 0.102) and higher reduction of total daily insulin doses (WMD -2.45 IU/day, 95% CI: -7.30 to 2.40 IU/day; P = 0.438). CONCLUSIONS Both PIO and SGLT2i are feasible adjunctive oral agents to pre-existing insulin therapy in individuals with inadequately controlled type 2 diabetes mellitus.

['Cho|Yun Kyung|YK|', 'Kim|Ye-Jee|YJ|', 'Kang|Yu Mi|YM|', 'Lee|Seung Eun|SE|', 'Park|Joong-Yeol|JY|', 'Lee|Woo Je|WJ|', 'Jung|Chang Hee|CH|http://orcid.org/0000-0003-4043-2396']

2018

22144964

Application for proteomic techniques in studying osteoarthritis: a review.

After the genomic era, proteomic corresponds to a wide variety of techniques that study the protein content of cells, tissue, or organism and that allow the isolation of protein of interest. It offers the choice between gel-based and gel-free methods or shotgun proteomics. Applications of proteomic technology may concern three principal objectives in several biomedical or clinical domains of research as in osteoarthritis: (i) to understand the physiopathology or underlying mechanisms leading to a disease or associated with a particular model, (ii), to find disease-specific biomarker, and (iii) to identify new therapeutic targets. This review aimed at gathering most of the data regarding the proteomic techniques and their applications to osteoarthritis research. It also reported technical limitations and solutions, as for example for sample preparation. Proteomics open wide perspectives in biochemical research but many technical matters still remain to be solved.

['Gharbi|Myriam|M|', 'Deberg|Michelle|M|', 'Henrotin|Yves|Y|']

2011

26287180

Identification of Proteins Modulated in the Date Palm Stem Infested with Red Palm Weevil (Rhynchophorus ferrugineus Oliv.) Using Two Dimensional Differential Gel Electrophoresis and Mass Spectrometry.

A state of the art proteomic methodology using Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI TOF) has been employed to characterize peptides modulated in the date palm stem subsequent to infestation with red palm weevil (RPW). Our analyses revealed 32 differentially expressed peptides associated with RPW infestation in date palm stem. To identify RPW infestation associated peptides (I), artificially wounded plants (W) were used as additional control beside uninfested plants, a conventional control (C). A constant unique pattern of differential expression in infested (I), wounded (W) stem samples compared to control (C) was observed. The upregulated proteins showed relative fold intensity in order of I > W and downregulated spots trend as W > I, a quite interesting pattern. This study also reveals that artificially wounding of date palm stem affects almost the same proteins as infestation; however, relative intensity is quite lower than in infested samples both in up and downregulated spots. All 32 differentially expressed spots were subjected to MALDI-TOF analysis for their identification and we were able to match 21 proteins in the already existing databases. Relatively significant modulated expression pattern of a number of peptides in infested plants predicts the possibility of developing a quick and reliable molecular methodology for detecting plants infested with date palm.

['Rasool|Khawaja Ghulam|KG|', 'Khan|Muhammad Altaf|MA|', 'Aldawood|Abdulrahman Saad|AS|', 'Tufail|Muhammad|M|', 'Mukhtar|Muhammad|M|', 'Takeda|Makio|M|']

2015

31475120

Production of Membrane Vesicles by Enterococcus faecium Cultured With or Without Subinhibitory Concentrations of Antibiotics and Their Pathological Effects on Epithelial Cells.

Enterococcus faecium is a clinically important pathogen associated with opportunistic infection and multi-drug resistance. E. faecium has been shown to produce membrane vesicles (MVs), but MV production by E. faecium under antibiotic stress conditions and the pathogenic traits thereof have yet to be determined. This study investigated the production of MVs in E. faecium ATCC 700221 cultured with sub-minimum inhibitory concentrations (MICs) of vancomycin or linezolid and determined their pathologic effects on colon epithelial Caco-2 cells. E. faecium ATCC 700221 cultured with 1/2 MIC of vancomycin or linezolid produced 3.0 and 1.5 times more MV proteins than bacteria cultured without antibiotics, respectively. Totals of 438, 461, and 513 proteins were identified in MVs from E. faecium cultured in brain heart infusion broth (MVs/BHI), BHI broth with 1/2 MIC of vancomycin (MVs/VAN), or BHI broth with 1/2 MIC of linezolid (MVs/LIN), respectively. Intact MVs/BHI induced cytotoxicity and the expression of pro-inflammatory cytokine and chemokine genes in Caco-2 cells in a dose-dependent manner, but proteinase K-treated MVs significantly suppressed these pro-inflammatory responses. MVs/LIN were more cytotoxic toward Caco-2 cells than MVs/BHI and MVs/VAN, whereas MVs/VAN stimulated more pro-inflammatory cytokine gene expression in Caco-2 cells than MVs/BHI and MVs/LIN. Overall results indicated that antibiotics modulate the biogenesis and proteomes of MVs in E. faecium at subinhibitory concentrations. MVs produced by E. faecium cultured under antibiotic stress conditions induce strong host cell responses that may contribute to the pathogenesis E. faecium.

['Kim|Mi Hyun|MH|', 'Kim|Se Yeon|SY|', 'Son|Joo Hee|JH|', 'Kim|Seung Il|SI|', 'Lee|Hayoung|H|', 'Kim|Shukho|S|', 'Shin|Minsang|M|', 'Lee|Je Chul|JC|']

2019

24177599

Stimulation of ANP by angiotensin-(1-9) via the angiotensin type 2 receptor.

AIMS Angiotensin-(1-9) [Ang-(1-9)] and Ang-(1-7) are cleaved by Ang converting enzyme 2 forming Ang I and Ang II, respectively, and the truncated Angs play a role in regulating atrial natriuretic peptide (ANP) secretion. Previously, we found that Ang-(1-7) stimulates ANP secretion via the Mas receptor. However, the effect of Ang-(1-9) on ANP secretion is still unknown. The aim of the present study is to determine whether Ang-(1-9) stimulates ANP secretion and to characterize the signaling pathway involved in stimulating secretion. MAIN METHODS We examined the effects of Ang-(1-9) on ANP secretion and atrial contractility with and without inhibitors in isolated perfused atria. KEY FINDINGS Ang-(1-9) stimulated ANP secretion and concentration without change in atrial contractility. Ang-(1-9)-induced-ANP secretion was increased from 5% to 60% by 3 μM Ang-(1-9) during the low-stretch state of the atrium. This stimulatory effect of Ang-(1-9) on ANP secretion was attenuated by pretreatment with an Ang II type 2 receptor (AT2R) antagonist but not by AT1R or Mas receptor antagonist. In addition, pretreatment with inhibitors of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), nitric oxide synthase (NOS) and soluble guanylyl cyclase (sGC) blocked Ang-(1-9)-induced ANP secretion. In the high-stretch atrial state, Ang-(1-9)-induced ANP secretion was increased more than in the low-stretch state following addition of 1 μM Ang-(1-9) (from 108% to 170%). In an in vivo experiment, acute infusion of Ang-(1-9) increased plasma ANP level without altering arterial blood pressure. This effect was attenuated by pretreatment with AT2R antagonist but not by Mas receptor antagonist. SIGNIFICANCE These results suggest that Ang-(1-9) stimulates ANP secretion via the AT2R-PI3K-Akt-NO-cGMP pathway.

['Cha|Seung Ah|SA|', 'Park|Byung Mun|BM|', 'Gao|Shan|S|', 'Kim|Suhn Hee|SH|']

2013