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34211386

A Genetic-Algorithm-Based Optimization Routing for FANETs.

In view of the characteristics of high mobility of FANETs nodes, combined with the features of Topology-based class routing protocol on-demand search, a Genetic-algorithm-based routing (GAR) protocol is proposed for FANETs which based on improved genetic algorithm for FANETs route search, and it taking into account the link stability, link bandwidth, node energy, and other factors. GAR improves the selection, crossover, and variation operators of the genetic algorithm so that GAR can finally plan an optimized route from the communication initiating node to the destination node quickly using a smaller cost. The experimental results show that GAR can largely improve the throughput, reduce the delay and improve the stability of the network, which is more suitable for FANETs.

['Wei|Xing|X|', 'Yang|Hua|H|', 'Huang|Wentao|W|']

2021

24325553

Values associated with public involvement in health and social care research: a narrative review.

BACKGROUND Much has been written about public involvement (PI) in health and social care research, but underpinning values are rarely made explicit despite the potential for these to have significant influence on the practice and assessment of PI. OBJECTIVE The narrative review reported here is part of a larger MRC-funded study which is producing a framework and related guidance on assessing the impact of PI in health and social care research. The review aimed to identify and characterize the range of values associated with PI that are central elements of the framework. METHODS We undertook a review and narrative synthesis of diverse literatures of PI in health and social care research, including twenty existing reviews and twenty-four chapters in sixteen textbooks. RESULTS Three overarching value systems were identified, each containing five value clusters. (i) A system concerned with ethical and/or political issues including value clusters associated with empowerment; change/action; accountability/transparency; rights; and ethics (normative values). (ii). A system concerned with the consequences of public involvement in research including value clusters associated with effectiveness; quality/relevance; validity/reliability; representativeness/objectivity/generalizability; and evidence (substantive values). (iii) A system concerned with the conduct of public involvement in including value clusters associated with Partnership/equality; respect/trust; openness and honesty; independence; and clarity (process values). CONCLUSION Our review identified three systems associated with PI in health and social care research focused on normative, substantive and process values. The findings suggest that research teams should consider and make explicit the values they attach to PI in research and discuss ways in which potential tensions may be managed in order to maximize the benefits of PI for researchers, lay experts and the research.

['Gradinger|Felix|F|', 'Britten|Nicky|N|', 'Wyatt|Katrina|K|', 'Froggatt|Katherine|K|', 'Gibson|Andy|A|', 'Jacoby|Ann|A|', 'Lobban|Fiona|F|', 'Mayes|Debbie|D|', 'Snape|Dee|D|', 'Rawcliffe|Tim|T|', 'Popay|Jennie|J|']

2015

31561579

Analysis of Promoter-Associated Chromatin Interactions Reveals Biologically Relevant Candidate Target Genes at Endometrial Cancer Risk Loci.

The identification of target genes at genome-wide association study (GWAS) loci is a major obstacle for GWAS follow-up. To identify candidate target genes at the 16 known endometrial cancer GWAS risk loci, we performed HiChIP chromatin looping analysis of endometrial cell lines. To enrich for enhancer-promoter interactions, a mechanism through which GWAS variation may target genes, we captured chromatin loops associated with H3K27Ac histone, characteristic of promoters and enhancers. Analysis of HiChIP loops contacting promoters revealed enrichment for endometrial cancer GWAS heritability and intersection with endometrial cancer risk variation identified 103 HiChIP target genes at 13 risk loci. Expression of four HiChIP target genes (SNX11, SRP14, HOXB2 and BCL11A) was associated with risk variation, providing further evidence for their targeting. Network analysis functionally prioritized a set of proteins that interact with those encoded by HiChIP target genes, and this set was enriched for pan-cancer and endometrial cancer drivers. Lastly, HiChIP target genes and prioritized interacting proteins were over-represented in pathways related to endometrial cancer development. In summary, we have generated the first global chromatin looping data from normal and tumoral endometrial cells, enabling analysis of all known endometrial cancer risk loci and identifying biologically relevant candidate target genes.

["O'Mara|Tracy A|TA|0000-0002-5436-3232", 'Spurdle|Amanda B|AB|0000-0003-1337-7897', 'Glubb|Dylan M|DM|0000-0002-2184-7708', '|||']

2019

32721292

Dynamic optimization of input production factors for urban industrial water supply and demand management.

To help minimize urban industrial water consumption and realize the goal of a water-saving society, this paper develops a method for the dynamic optimization of the input production factors in an urban industrial water supply model. A negative exponential curve describes the urban industrial water consumption per Yuan of urban industrial value added, the latter being described by a Gompertz curve. The product of the two describes the urban industrial water demand. The production function of urban industrial water supply is expressed by the fixed substitution proportional production function. Taking investment and labor input as control variables, the system goal is to balance of industrial water supply and demand. The time-varying model can not only solve the stable state problem for infinite time horizon, but also the transient problem for finite time horizon. Taking Jiangsu province in eastern China as an example, the applicability of the method was investigated under different parameter combinations. The simulation results show its effectiveness in these cases. In the earlier period, meeting balance requirements is easier using the straight-line capital depreciation method. In the later period, the fixed rate on declining balance method allows to meet the requirements more easily. In general, it is easier to achieve the goal by choosing a smaller and feasible weight matrix coefficient of the control variables.

['Li|Kebai|K|', 'Hajar|Samlali|S|', 'Ding|Zhilei|Z|', 'Dooling|Tom|T|', 'Wei|Guo|G|', 'Hu|Chenke|C|', 'Zhang|Yuting|Y|', 'Zhang|Kaiyi|K|']

2020

34646399

Direct C(sp3)-H allylation of 2-alkylpyridines with Morita-Baylis-Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement.

A base- and catalyst-free C(sp3)-H allylic alkylation of 2-alkylpyridines with Morita-Baylis-Hillman (MBH) carbonates is described. A plausible mechanism of the reaction might involve a tandem SN2' type nucleophilic substitution followed by an aza-Cope rearrangement. Various alkyl substituents on 2-alkylpyridines were tolerated in the reaction to give the allylation products in 26-91% yields. The developed method provides a straightforward and operational simple strategy for the allylic functionalization of 2-alkypyridine derivatives.

['Wang|Siyu|S|', 'Zheng|Lianyou|L|https://orcid.org/0000-0002-7304-6734', 'Wang|Shutao|S|https://orcid.org/0000-0003-4895-2687', 'Ning|Shulin|S|', 'Zhang|Zhuoqi|Z|', 'Xiang|Jinbao|J|']

2021

31392845

The Role of Culture and Evolution for Human Cognition.

Since the emergence of our species at least, natural selection based on genetic variation has been replaced by culture as the major driving force in human evolution. It has made us what we are today, by ratcheting up cultural innovations, promoting new cognitive skills, rewiring brain networks, and even shifting gene distributions. Adopting an evolutionary perspective can therefore be highly informative for cognitive science in several ways: It encourages us to ask grand questions about the origins and ramifications of our cognitive abilities; it equips us with the means to investigate, explain, and understand key dimensions of cognition; and it allows us to recognize the continued and ubiquitous workings of culture and evolution in everyday instances of cognitive behavior. Taking advantage of this reorientation presupposes a shift in focus, though, from human cognition as a general, homogenous phenomenon to the appreciation of cultural diversity in cognition as an invaluable source of data.

['Bender|Andrea|A|']

2020

27833444

Association of macrophage migration inhibitory factor promoter polymorphism -173G/C with susceptibility to childhood asthma.

INTRODUCTION Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in the pathogenesis of asthma. Polymorphisms associated with inflammatory diseases exist in the promoter region of MIF, which alter its expression. We aimed to study the association of MIF promoter polymorphism -173G/C with childhood asthma. MATERIAL AND METHODS In this case-control study, we recruited 60 pediatric patients with bronchial asthma and 90 age- and sex-matched healthy controls. MIF-173G/C was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS Genotype distribution between cases and healthy controls was statistically evaluated. Our results revealed that the frequency of the MIF-173C allele was significantly higher in children with asthma than in the control group (p = 0.002, odds ratio [OR] = 3.61, 95% confidence interval [CI] = 1.63-7.97). The frequency of the MIF-173CC genotype was higher in the asthmatic children than in the controls (p = 0.028, OR = 6.24, 95% CI = 1.24-31.29). Comparing carriage of the MIF-173C allele in pediatric patients with asthma with that observed in healthy controls (GC + CC vs. GG) revealed a positive association with the disease (p = 0.019, OR = 3.12, 95% CI = 1.22-7.99). CONCLUSIONS These results suggest that MIF-173G/C polymorphism confers an increased risk of susceptibility to the development of childhood asthma in an Egyptian population.

['El-Adly|Tarek Z|TZ|', 'Kamal|Sally|S|', 'Selim|Hala|H|', 'Botros|Shahira|S|']

2016

28137758

Derlin-1 promotes ubiquitylation and degradation of the epithelial Na+ channel, ENaC.

Ubiquitylation of the epithelial Na+ channel (ENaC) plays a critical role in cellular functions, including transmembrane transport of Na+, Na+ and water balance, and blood pressure stabilization. Published studies have suggested that ENaC subunits are targets of ER-related degradation (ERAD) in yeast systems. However, the molecular mechanism underlying proteasome-mediated degradation of ENaC subunits remains to be established. Derlin-1, an E3 ligase mediator, links recognized target proteins to ubiquitin-mediated proteasomal degradation in the cytosol. In the present study, we found that derlin-1 suppressed the expression of ENaC at the protein level and that the subunit α-ENaC (also known as SCNN1A) physically interacted with derlin-1 at the membrane-anchored domains or the loop regions, and that derlin-1 initiated α-ENaC retrotranslocation. In addition, HUWE1, an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase, was recruited and promoted K11-linked polyubiquitylation of α-ENaC and, hence, formation of an α-ENaC ubiquitin-mediated degradation complex. These findings suggest that derlin-1 promotes ENaC ubiquitylation and enhances ENaC ubiquitin- mediated proteasome degradation. The derlin-1 pathway therefore may represent a significant early checkpoint in the recognition and degradation of ENaC in mammalian cells.

['You|Hui|H|0000-0002-6545-7787', 'Ge|Yamei|Y|0000-0002-8739-8773', 'Zhang|Jian|J|0000-0003-4779-0786', 'Cao|Yizhi|Y|0000-0001-6469-5962', 'Xing|Jing|J|0000-0003-3397-0655', 'Su|Dongming|D|', 'Huang|Yujie|Y|0000-0002-4430-0158', 'Li|Min|M|', 'Qu|Shen|S|', 'Sun|Fei|F|', 'Liang|Xiubin|X|0000-0001-9169-0390']

2017

31034618

Sex Differences in Ethanol Reward Seeking Under Conflict in Mice.

BACKGROUND Alcohol use disorders are characterized by inflexible alcohol seeking that occurs despite adverse consequences. Males and females are differentially sensitive to ethanol (EtOH) reward, but it is unclear whether sex differences in EtOH seeking under reward-aversion conflict are present. METHODS To investigate sex differences in EtOH seeking under conflict, adult male and female C57BL/6J mice underwent chronic intermittent EtOH (CIE) exposure by vapor inhalation or served as air-exposed controls. After CIE, mice were trained in a modified EtOH conditioned place preference paradigm. During 3 conditioning sessions, 2 g/kg EtOH was administered prior to confinement in the "EtOH-paired" chamber. On alternating days, saline was injected prior to confinement in the "saline-paired" chamber. After conditioning, mice experienced a footshock in the EtOH-paired chamber. EtOH-seeking behavior was assessed before and after footshock. RESULTS Control and CIE-exposed males reduced the time spent in and increased latency to enter the reward-paired chamber following footshock. Control females did not alter EtOH-seeking behavior following footshock. CIE-exposed females spent more time in the EtOH-paired chamber at baseline. However, following a footshock, CIE-exposed females significantly reduced the time spent in and increased latency to enter the EtOH-paired chamber. CONCLUSIONS Nondependent female mice exhibited aversion-resistant alcohol seeking to a greater degree than males. Chronic EtOH exposure did not impact EtOH seeking in males. In females, CIE enhanced EtOH seeking in the absence of conflict, but reduced EtOH seeking after an aversive experience. While these sex-specific effects of CIE are not present when reward seeking is assessed in the absence of an aversive experience, multiple factors may underlie the differences in reward seeking despite adverse consequences, including reward- and aversion-related learning and decision making under conflict. These data highlight the importance of considering sex as a variable influencing EtOH seeking and provide a greater understanding of how sex interacts with EtOH exposure to alter behavior.

['Xie|Qiaowei|Q|', 'Buck|Lauren A|LA|', 'Bryant|Kathleen G|KG|', 'Barker|Jacqueline M|JM|0000-0002-1176-5397']

2019

28922096

The Effects of Ramadan Fasting on Body Composition, Blood Pressure, Glucose Metabolism, and Markers of Inflammation in NAFLD Patients: An Observational Trial.

BACKGROUND AND AIM Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and is a serious global health problem. Regarding the increasing prevalence of NAFLD, finding various strategies to prevent and manage the disease is of great importance. The aim of this study was to determine the effects of caloric restriction during Ramadan fasting on anthropometric indices, fasting glucose, plasma insulin, insulin resistance, and inflammatory cytokines (C-reactive protein and interleukin 6) in patients with NAFLD. METHODS We conducted this study with 83 patients with NAFLD, 42 of whom decided to fast and 41 controls who decided not to fast for Ramadan, between June 18 and July 17, 2015. Anthropometric parameters were measured and a sample of venous blood was obtained for biochemical assays before and after Ramadan. RESULTS There was a significant decrease in all anthropometric parameters as well as fasting glucose, plasma insulin, and insulin resistance. Relative to the nonfasting group, fasting significantly reduced circulating inflammatory, but changes in blood pressure after Ramadan were not significant. CONCLUSIONS This study shows significant effects on parameters during Ramadan fasting such as anthropometric indices, fasting glucose, plasma insulin, and inflammatory cytokines in patients with NAFLD. The results of this study suggest that Ramadan fasting may be useful to improve NAFLD, so further studies are needed in this area.

['Aliasghari|Fereshteh|F|', 'Izadi|Azimeh|A|', 'Gargari|Bahram Pourghassem|BP|', 'Ebrahimi|Sara|S|']

2017

33053471

Kinetics model adaptability analysis of CO2 sequestration process utilizing steelmaking slag and cold-rolling wastewater.

Better adaptive kinetics model for CO2 sequestration utilizing wastes in steelmaking plant has a big significance for establishing green out-circulating network system. This work investigated the effect of temperature, L/S ratio and cold-rolling wastewater concentration on carbonation degree in basic oxygen furnace slag and CRW carbonation process, then their kinetics was discussed by surface coverage model and shrinking core model, respectively, in order to evaluate their adaptability and accuracy. Furthermore, CO2 sequestration intensifying factor was originally proposed for considering the carbonation depth, through comparing diffusion coefficient of CO2 between water carbonation and wastewater carbonation. The results showed that carbonation conversion increased as temperature and CRW concentration increased except for L/S ratio, and the maximum carbonation could reach 41.499 ± 1.240%. Because higher prediction error existed in surface coverage model, the shrinking core model had a better adaptability and accuracy for analyzing carbonation process in autoclave. Meanwhile, the CO2 sequestration intensifying factor was 1.6 times as big as carbonation process in distilled water as a result of DCO2 value. CO2 sequestration reaction in our work was controlled by calcium diffused because of DCO2 (0.700-0.976 × 10-4 cm2 s-1) and DCa (0.935-1.149 × 10-5 cm2 s-1). The results above will be helpful for us to better comprehend the reaction kinetics at micro-scale, when the idea of triple wastes self-circulation system network will be established to industrial application.

['Wei|Chao|C|', 'Dong|Jianping|J|', 'Zhang|Huining|H|', 'Wang|Xu|X|']

2021

34015706

Prenatal exposure to di-n-butyl phthalate induces erectile dysfunction in male adult rats.

Di-n-butyl phthalate (DBP) is a widely used plasticizer and an environmental endocrine-disrupting compound. However, whether prenatal exposure to DBP can impair erectile function remains unknown. We conducted this study to investigate the potential effects of prenatal exposure to DBP on erectile function and the underlying mechanisms. A rat model of prenatal DBP exposure (12.5, 100 or 800 mg/kg/day by gavage during gestational days 13-21) was established. Prenatal DBP exposure significantly decreased penis/body weight ratio, myelin sheath thickness of cavernosum nerves and serum testosterone level in male rats at the age of 10 weeks. Furthermore, erectile dysfunction was detected in all DBP exposure groups, which exhibited substantial increases in transforming growth factor-β1 (TGF-β1) expression and decreases in the expression of alpha smooth muscle actin (α-SMA), neuronal and endothelial nitric oxide synthase (nNOS and eNOS). Additionally, the phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were remarkably lower, but the Bcl-2-associated X protein (Bax)/Bcl-2 ratio and caspase-3 were higher in DBP exposure groups than in the control group. Notably, prenatal exposure to DBP increase the risk of ED in male adult rats, even taking low dose of DBP (12.5 mg/kg/day). DBP exposure causing penile fibrosis, decreased testosterone level, and endothelial dysfunction may be responsible for ED by activating Akt/Bad/Bax/caspase-3 pathway and suppressing NOS/cGMP pathway in penis.

['Zhou|Xiang|X|', 'Zhang|Tongtong|T|', 'Song|Lebin|L|', 'Wang|Yichun|Y|', 'Zhang|Qijie|Q|', 'Cong|Rong|R|', 'Ji|Chengjian|C|', 'Luan|Jiaochen|J|', 'Yao|Liangyu|L|', 'Zhang|Wei|W|', 'Song|Ninghong|N|', 'Wang|Shangqian|S|']

2021

32939678

The effect of benzyl isothiocyanate on Candida albicans growth, cell size, morphogenesis, and ultrastructure.

Candida albicans is a commensal yeast that may become pathogenic and even lethal to the host. Over the last few decades, antifungal resistance has increased, promoting screening of the antifungal potential of old and new substances. This study investigates the antifungal potential of isothiocyanates (ITCs) against C. albicans oral isolates. A preliminary susceptibility disk diffusion test (DD) was performed using allyl isothiocyanate (AITC), benzyl isothiocynanate (BITC) and phenyl ethyl isothiocyanate (PEITC) at a fixed concentration range (0.001-0.1 M). Because C. albicans isolates were more susceptible to BITC and PEITC, their effect on cell size and on germ tube formation (GTF) were tested. The most promising molecule, BITC, was further tested for effects on cell viability, oxidative stress and for ultrastructure. ITCs, especially the aromatic ones, had a significant type-, dose- and isolate-dependent anti-Candida activity. Although BITC and PEITC had similar activity against the yeast cells, BITC had a more pronounced effect on cell size and GTF. Furthermore, BITC appears to induce oxidative stress and promote changes in the cell ultrastructure, interfering with cell wall structure. Our work showed that aromatic ITCs have the potential to effect C. albicans cells in multiple ways, including size, shape and GTF (BITC and PEITC), oxidative stress, and ultrastructure (BITC). Overall, our results suggest that BITC may be effectively used against C. albicans to modulate its growth, and control or suppress its invasive potential.

['Pereira|Cheila|C|', 'Calado|Ana Margarida|AM|', 'Sampaio|Ana Cristina|AC|http://orcid.org/0000-0001-7989-0779']

2020

23683498

Association between health behaviors and cardiorespiratory fitness in adolescents: results from the cross-sectional MoMo-study.

PURPOSE The aim of this study was to analyze the association between adolescent and familial health behavioral factors and cardiorespiratory fitness in German adolescent boys and girls. METHODS This study is based on a large nationwide cross-sectional study and its substudy on physical activity and fitness of children and adolescents ("Motorik-Modul"). For 1,328 adolescents between 11 and 17 years of age, data on cardiorespiratory fitness (Physical working capacity 170, PWC(170)) and familial and adolescent health behavioral factors were collected. Health behavior was assessed using psychometric questionnaires (socioeconomic status, pubertal stage, daily physical activity, sports-club time, parental physical activity habits, etc.). A hierarchical multiple regression model was used to quantify the association between relative PWC(170) values and health behavior. RESULTS The relationship between adolescents' health behavioral factors and cardiorespiratory fitness was stronger than the relationship between age, social status, familial health behavior and cardiorespiratory fitness. Familial health behavioral factors explained 4.1% and 2.1% of variance in cardiorespiratory fitness in girls and boys, respectively. Adolescents' health behavioral factors explained 15.2% of variance in girls and 25.7% of variance in boys. For both girls (β = .273) and boys (β = .400), being normal weight had the greatest effect on relative PWC(170) values. CONCLUSIONS The difference in explained variance in cardiorespiratory fitness by familial and adolescents' health behavioral factors between girls and boys indicates that different predictors for cardiorespiratory fitness are important for girls and boys. Hence, sex specific research and interventions aimed at improving familial and adolescent health behavior may be important.

['Peterhans|Eliane|E|', 'Worth|Annette|A|', 'Woll|Alexander|A|']

2013

32730712

The Effect of Resveratrol on Radioiodine Therapy-Associated Lacrimal Gland Damage.

PURPOSE We have evaluated the potential radioprotective, antioxidant and anti-apoptotic effects of resveratrol (RSV) against high-dose radioactive iodine (RAI) therapy associated damage of the lacrimal glands by biochemical, histopathological and immunohistochemical methods. MATERIALS AND METHODS Thirty Wistar-albino rats were randomly divided into three groups; the control group received no treatment or medication, the RAI group received RAI but no medication and the RSV group received oral RAI and intraperitoneal RSV. RSV was started at day one, before RAI administration, and continued for 8 days. Bilateral intraorbital (IG), extraorbital (EG), and Harderian (HG) lacrimal glands were evaluated in all rats for histopathological, immunohistochemical, tissue cytokine and oxidant and antioxidant level assessment. RESULTS RSV group restored inflammation, fibrosis, vacuolization, change in nucleus characteristics, lipofuscin-like accumulation and cellular morphologic patterns were statistically significant in all lacrimal gland types, compared to the RAI group (p < .05 for all variables). Similarly, elevated Caspase-3 and TUNEL levels in the RAI group were significantly alleviated in the RSV group in all lacrimal gland types (p < .05 for all variables). RAI administration significantly elevated TNF-α, IL-6, NF-кb levels, and decreased IL-10 levels (p < .05 for all parameters) whereas TOS levels significantly increased and TAS levels were significantly decreased. However, RSV significantly diminished TNF-α, IL-6, IL-4, and NF-кb levels. Furthermore, RSV significantly decreased TOS and increased TAS levels (p < .05 for all variables). CONCLUSIONS We conclude that with its anti-cancer effect as well as its antioxidant effect RSV has protected the histopathological pattern of the lacrimal glands from the damage, decreased inflammation in histopathologic assessments, and decreased tissue cytokine levels, apoptosis and DNA fragmentation on the lacrimal glands after RAI.

['Koca|Gökhan|G|0000-0003-2842-9223', 'Singar|Evin|E|', 'Akbulut|Aylin|A|0000-0003-4665-7895', 'Yazihan|Nuray|N|0000-0003-1237-8468', 'Yumuşak|Nihat|N|', 'Demir|Ayten|A|', 'Korkmaz|Meliha|M|']

2021

25524813

Parents with serious mental illness: differences in internalised and externalised mental illness stigma and gender stigma between mothers and fathers.

Research demonstrates that people living with serious mental illness (SMI) contend with widespread public stigma; however, little is known about the specific experiences of stigma that mothers, and in particular fathers, with SMI encounter as parents. This study aimed to explore and compare the experiences of stigma for mothers and fathers with SMI inferred not only by living with a mental illness but also potential compounding gender effects, and the associated impact of stigma on parenting. Telephone surveys were conducted with 93 participants with SMI who previously identified as parents in the Second Australian National Survey of Psychosis. Results indicated that mothers were more likely than fathers to perceive and internalise stigma associated with their mental illness. Conversely, fathers were more inclined to perceive stigma relating to their gender and to hold stigmatising attitudes towards others. Mental illness and gender stigma predicted poorer self-reported parenting experiences for both mothers and fathers. These findings may assist in tailoring interventions for mothers and fathers with SMI.

['Lacey|Melanie|M|', 'Paolini|Stefania|S|', 'Hanlon|Mary-Claire|MC|', 'Melville|Jessica|J|', 'Galletly|Cherrie|C|', 'Campbell|Linda E|LE|']

2015

34051118

Serum lipocalin-2 and carotid artery intima-media thickness in relation to obesity in eugonadal males over forty with venogenic erectile dysfunction.

Obesity is a risk factor for erectile dysfunction and atherosclerosis. Lipocalin-2 is an adipocytokine with proinflammatory properties involved in several disorders with metabolic alterations. Our aim was to study the relation of serum lipocalin-2 and carotid artery intima-media thickness (CIMT) to obesity in erectile dysfunction. Serum lipocalin-2 and CIMT were measured in 25 obese and 25 nonobese eugonadal patients over forty with venogenic erectile dysfunction and 25 healthy controls. Their relation to different patient- and disease-related parameters was studied. Results revealed lipocalin-2 to be significantly higher in obese compared with nonobese patients and with controls, and in nonobese patients compared with controls. CIMT was lower in controls compared with both obese and nonobese patients. In obese and nonobese patients, lipocalin-2 was positively correlated with disease duration, body mass index, waist circumference and end-diastolic velocity. Lipocalin-2 was negatively correlated with the short form of the international index of erectile function scores in both groups. In conclusion, the elevated lipocalin-2 in obese and to a lesser extent in nonobese patients and its association with disease severity points to its potential value as a diagnostic marker and a possible therapeutic target that could ameliorate the metabolic derangement associated with erectile dysfunction.

['El Mulla|Khaled Fawzy|KF|', 'El Abd|Amr|A|', 'Donia|Hanaa Mahmoud|HM|', 'Hussein|Reham Magdy|RM|', 'Eid|Amira Abulfotooh|AA|https://orcid.org/0000-0002-4916-2778']

2021

27267563

Objective Assessment of Laparoscopic Force and Psychomotor Skills in a Novel Virtual Reality-Based Haptic Simulator.

BACKGROUND Most of the commercially available virtual reality-based laparoscopic simulators do not effectively evaluate combined psychomotor and force-based laparoscopic skills. Consequently, the lack of training on these critical skills leads to intraoperative errors. OBJECTIVES To assess the effectiveness of the novel virtual reality-based simulator, this study analyzed the combined psychomotor (i.e., motion or movement) and force skills of residents and expert surgeons. The study also examined the effectiveness of real-time visual force feedback and tool motion during training. DESIGN Bimanual fundamental (i.e., probing, pulling, sweeping, grasping, and twisting) and complex tasks (i.e., tissue dissection) were evaluated. In both tasks, visual feedback on applied force and tool motion were provided. The skills of the participants while performing the early tasks were assessed with and without visual feedback. Participants performed 5 repetitions of fundamental and complex tasks. Reaction force and instrument acceleration were used as metrics. SETTING Surgical Gastroenterology, Government Stanley Medical College and Hospital; Institute of Surgical Gastroenterology, Madras Medical College and Rajiv Gandhi Government General Hospital. PARTICIPANTS Residents (N = 25; postgraduates and surgeons with <2 years of laparoscopic surgery) and expert surgeons (N = 25; surgeons with >4 and ≤10 years of laparoscopic surgery). RESULTS Residents applied large forces compared with expert surgeons and performed abrupt tool movements (p < 0.001). However, visual + haptic feedback improved the performance of residents (p < 0.001). In complex tasks, visual + haptic feedback did not influence the applied force of expert surgeons, but influenced their tool motion (p < 0.001). Furthermore, in complex tissue sweeping task, expert surgeons applied more force, but were within the tissue damage limits. In both groups, exertion of large forces and abrupt tool motion were observed during grasping, probing or pulling, and tissue sweeping maneuvers (p < 0.001). CONCLUSIONS Modern day curriculum-based training should evaluate the skills of residents with robust force and psychomotor-based exercises for proficient laparoscopy. Visual feedback on force and motion during training has the potential to enhance the learning curve of residents.

['Prasad|M S Raghu|MS|', 'Manivannan|Muniyandi|M|', 'Manoharan|Govindan|G|', 'Chandramohan|S M|SM|']

2016

33937250

Membrane Interactions of the Peroxisomal Proteins PEX5 and PEX14.

Human PEX5 and PEX14 are essential components of the peroxisomal translocon, which mediates import of cargo enzymes into peroxisomes. PEX5 is a soluble receptor for cargo enzymes comprised of an N-terminal intrinsically disordered domain (NTD) and a C-terminal tetratricopeptide (TPR) domain, which recognizes peroxisomal targeting signal 1 (PTS1) peptide motif in cargo proteins. The PEX5 NTD harbors multiple WF peptide motifs (WxxxF/Y or related motifs) that are recognized by a small globular domain in the NTD of the membrane-associated protein PEX14. How the PEX5 or PEX14 NTDs bind to the peroxisomal membrane and how the interaction between the two proteins is modulated at the membrane is unknown. Here, we characterize the membrane interactions of the PEX5 NTD and PEX14 NTD in vitro by membrane mimicking bicelles and nanodiscs using NMR spectroscopy and isothermal titration calorimetry. The PEX14 NTD weakly interacts with membrane mimicking bicelles with a surface that partially overlaps with the WxxxF/Y binding site. The PEX5 NTD harbors multiple interaction sites with the membrane that involve a number of amphipathic α-helical regions, which include some of the WxxxF/Y-motifs. The partially formed α-helical conformation of these regions is stabilized in the presence of bicelles. Notably, ITC data show that the interaction between the PEX5 and PEX14 NTDs is largely unaffected by the presence of the membrane. The PEX5/PEX14 interaction exhibits similar free binding enthalpies, where reduced binding enthalpy in the presence of bicelles is compensated by a reduced entropy loss. This demonstrates that docking of PEX5 to PEX14 at the membrane does not reduce the overall binding affinity between the two proteins, providing insights into the initial phase of PEX5-PEX14 docking in the assembly of the peroxisome translocon.

['Gaussmann|Stefan|S|', 'Gopalswamy|Mohanraj|M|', 'Eberhardt|Maike|M|', 'Reuter|Maren|M|', 'Zou|Peijian|P|', 'Schliebs|Wolfgang|W|', 'Erdmann|Ralf|R|', 'Sattler|Michael|M|']

2021

30537423

Hyperactivation of Nrf2 increases stress tolerance at the cost of aging acceleration due to metabolic deregulation.

Metazoans viability depends on their ability to regulate metabolic processes and also to respond to harmful challenges by mounting anti-stress responses; these adaptations were fundamental forces during evolution. Central to anti-stress responses are a number of short-lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors. We show here that increased expression of nuclear factor erythroid 2-related factor (Nrf2) in Drosophila activated cytoprotective modules and enhanced stress tolerance. However, while mild Nrf2 activation extended lifespan, high Nrf2 expression levels resulted in developmental lethality or, after inducible activation in adult flies, in altered mitochondrial bioenergetics, the appearance of Diabetes Type 1 hallmarks and aging acceleration. Genetic or dietary suppression of Insulin/IGF-like signaling (IIS) titrated Nrf2 activity to lower levels, largely normalized metabolic pathways signaling, and extended flies' lifespan. Thus, prolonged stress signaling by otherwise cytoprotective short-lived stress sensors perturbs IIS resulting in re-allocation of resources from growth and longevity to somatic preservation and stress tolerance. These findings provide a reasonable explanation of why most (if not all) cytoprotective stress sensors are short-lived proteins, and it also explains the build-in negative feedback loops (shown here for Nrf2); the low basal levels of these proteins, and why their suppressors were favored by evolution.

['Tsakiri|Eleni N|EN|', 'Gumeni|Sentiljana|S|', 'Iliaki|Kalliopi K|KK|', 'Benaki|Dimitra|D|', 'Vougas|Konstantinos|K|', 'Sykiotis|Gerasimos P|GP|', 'Gorgoulis|Vassilis G|VG|', 'Mikros|Emmanuel|E|', 'Scorrano|Luca|L|', 'Trougakos|Ioannis P|IP|0000-0002-6179-2772']

2019

25238928

Correlates of functional outcome among stroke survivors in a developing country--a prospective community-based study from India.

Stroke survivors (SS) are rising with higher incidence of stroke in developing countries. In addition to physical impairment, other factors such as cognition, social interaction, and depression determine the functional outcome after stroke. Considering the paucity of data from developing countries, we planned to determine the change in various functional parameters among SS. This community-based prospective study was carried out in Kolkata, India among 283 SS between 2006 and 2010. Functional outcome was assessed at baseline and at 3 annual follow-up visits using validated tools. A stepwise regression analysis was performed with demographic and stroke-related covariates against various measures of functional outcome. Result showed that mean Barthel Index score at baseline was 76.4 ± 30.8. Bengali version of mental status examination and Geriatric Depression Scale scores trended down over time with a negative regression coefficient of -.2061 (standard error [SE], .0937) and -.4488 (SE, .2145). Other outcomes did not change. Female gender, depression, and cognitive dysfunction had an unfavorable impact, whereas education correlated positively. In conclusions female gender and neuropsychiatric disturbances showed poor functional outcome compared with education, which correlates with better outcome. This information will be helpful for patients in developing countries for planning stroke rehabilitation.

['Ghosal|Malay Kumar|MK|', 'Burman|Prabir|P|', 'Singh|Vineeta|V|', 'Das|Sujata|S|', 'Paul|Neelanjana|N|', 'Ray|Biman Kanti|BK|', 'Hazra|Avijit|A|', 'Banerjee|Tapas Kumar|TK|', 'Basu|Arindam|A|', 'Chaudhuri|Arijit|A|', 'Das|Shyamal Kumar|SK|']

2014

34195377

Current management of button battery injuries.

Button batteries (BB) are found in common household items and can lead to significant morbidity and mortality in the pediatric population when ingested. BBs are made of various chemistries and have a unique size and shape that yield significant injury when lodged in the pediatric esophagus. BBs create a local tissue pH environment of 10 to 13 and can induce liquefactive necrosis at the negative pole. This initial injury can progress with further tissue breakdown even after removal. Unfortunately, patients may present with vague symptoms similar to viral illnesses and there is not always a known history of ingestion. Plain film X-ray can be diagnostic. Exposure can lead to caustic injury within 2 hours. Thus, timely endoscopic removal is the mainstay of treatment. Novel mitigation and neutralization strategies have been implemented into treatment guidelines. These include the preremoval ingestion of honey or sucralfate and intraoperative irrigation with acetic acid. Depending on the severity of injury following removal, careful consideration should be given for potential delayed complications including fistulization into major vessels which often leads to death. The National Button Battery Taskforce and several industry members have implemented prevention strategies such as educational safety outreach campaigns, child-resistant packaging changes, and warning labels. Governmental regulation and industry changes are key to limit not only the amount of BB ingestions, but also the devastating consequences that can result. Anonymous reporting of BB injuries through the Global Injury Research Collaborative has been made convenient and centralized through the advent of a user-friendly smartphone iOS/App Store and Android/GooglePlay application called the "GIRC App"; all specialists who manage foreign body cases should contribute their cases to help prevent future injuries. BB ingestion must be recognized and treated promptly using a multidisciplinary approach to optimize outcomes for these patients. Ultimately, a safer BB technology is critically needed to reduce or eliminate the severe and life-threatening injuries in children. Level of Evidence 5.

['Sethia|Rishabh|R|https://orcid.org/0000-0003-0425-7682', 'Gibbs|Hannah|H|', 'Jacobs|Ian N|IN|', 'Reilly|James S|JS|https://orcid.org/0000-0003-0843-2644', 'Rhoades|Keith|K|', 'Jatana|Kris R|KR|https://orcid.org/0000-0002-8475-9780']

2021

31922885

Diverse Injury Pathways Induce Alveolar Epithelial Cell CCL2/12, Which Promotes Lung Fibrosis.

Accumulating evidence suggests that fibrosis is a multicellular process with contributions from alveolar epithelial cells (AECs), recruited monocytes/macrophages, and fibroblasts. We have previously shown that AEC injury is sufficient to induce fibrosis, but the precise mechanism remains unclear. Several cell types, including AECs, can produce CCL2 and CCL12, which can promote fibrosis through CCR2 activation. CCR2 signaling is critical for the initiation and progression of pulmonary fibrosis, in part through recruitment of profibrotic bone marrow-derived monocytes. Attempts at inhibiting CCL2 in patients with fibrosis demonstrated a marked upregulation of CCL2 production and no therapeutic response. To better understand the mechanisms involved in CCL2/CCR2 signaling, we generated mice with conditional deletion of CCL12, a murine homolog of human CCL2. Surprisingly, we found that mice with complete deletion of CCL12 had markedly increased concentrations of other CCR2 ligands and were not protected from fibrosis after bleomycin injury. In contrast, mice with lung epithelial cell-specific deletion of CCL12 were protected from bleomycin-induced fibrosis and had expression of CCL2 and CCL7 similar to that of control mice treated with bleomycin. Deletion of CCL12 within AECs led to decreased recruitment of exudate macrophages. Finally, injury to murine and human primary AECs resulted in increased production of CCL2 and CCL12, in part through activation of the mTOR pathway. In conclusion, these data suggest that targeting CCL2 may be a viable antifibrotic strategy once the pathways involved in the production and function of CCL2 and other CCR2 ligands are better defined.

['Yang|Jibing|J|', 'Agarwal|Manisha|M|', 'Ling|Song|S|', 'Teitz-Tennenbaum|Seagal|S|', 'Zemans|Rachel L|RL|', 'Osterholzer|John J|JJ|', 'Sisson|Thomas H|TH|', 'Kim|Kevin K|KK|']

2020

24813594

In vitro and in vivo activities of piperacillin-tazobactam and meropenem at different inoculum sizes of ESBL-producing Klebsiella pneumoniae.

The inoculum effect is a laboratory phenomenon in which the minimal inhibitory concentration (MIC) of an antibiotic is increased when a large number of organisms are exposed. Due to the emergence of extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-Kpn) infections, the inoculum effect of ESBL-Kpn on β-lactams was studied in vitro and in vivo using an experimental model of pneumonia. The in vitro inoculum effect of 45 clinical ESBL-Kpn isolates on β-lactams was evaluated at standard (10(5) CFU/mL) and high (10(7) CFU/mL) organism concentrations. The MIC50 of piperacillin-tazobactam, cefotaxime and cefepime was increased eight-fold or more and that of meropenem was increased two-fold. The in vivo inoculum effect was evaluated in an ESBL-Kpn pneumonia mouse model treated with bacteriostatic effect-adjusted doses of piperacillin-tazobactam (1000 mg/kg four times daily, %T>MIC; 32.60%) or meropenem (100 mg/kg twice daily, %T>MIC; 28.65%) at low/standard (10(4) CFU/mouse) and high (10(6) CFU/mouse) inocula. In mice administered a low inoculum, no mice died after treatment with piperacillin-tazobactam or meropenem, whereas all the control mice died. In contrast, in the high inoculum model, all mice in the piperacillin-tazobactam-treated group died, whereas all meropenem-treated mice survived and had a decreased bacterial load in the lungs and no invasion into the blood. In conclusion, meropenem was more resistant to the inoculum effect of ESBL-Kpn than piperacillin-tazobactam both in vitro and in vivo. In the management of severe pneumonia caused by ESBL-Kpn, carbapenems may be the drugs of choice to achieve a successful outcome.

['Harada|Y|Y|', 'Morinaga|Y|Y|', 'Kaku|N|N|', 'Nakamura|S|S|', 'Uno|N|N|', 'Hasegawa|H|H|', 'Izumikawa|K|K|', 'Kohno|S|S|', 'Yanagihara|K|K|']

2014

27610938

Covert contrast and covert errors in persistent velar fronting.

Acoustic and articulatory studies demonstrate covert contrast in perceptually neutralised phonemic contrasts in both typical children and children with speech disorders. These covert contrasts are thought to be relatively common and symptomatic of phonetic speech disorders. However, clinicians in the speech therapy clinic have had no easy way of identifying this covertness. This study uses ultrasound tongue imaging to compare tongue contours for /t/and /k/in seven children with persistent velar fronting. We present a method of overlaying tongue contours to identify covert contrast at the articulatory level. Results show that all seven children, contrary to expectations, produced both /t/and /k/with near-identical tongue shapes showing no evidence of covert contrast. However, further analysis of one of the participants showed highly variable tongue shapes for /t/and /k/, including retroflex productions of both. Although not phonologically conditioned, this covert error is evidence of speech disorder at the phonetic level.

['Cleland|Joanne|J|', 'Scobbie|James M|JM|', 'Heyde|Cornelia|C|', 'Roxburgh|Zoe|Z|', 'Wrench|Alan A|AA|']

2017

25155979

What's in a name: putting the skills of librarianship back into circulation.

Anne Brice, recipient of the 2014 Cyril Barnard Memorial Prize, reflects on the themes of names and skills of the health library and information professions. She questions whether service users share the same concerns of librarians that this nomenclature is too narrow and too closely associated with the buildings that provide its name. She proposes that in mediation between the users and their required knowledge sits a unique opportunity to place the profession in the centre of knowledge translation.

['Brice|Anne|A|', 'Grant|Maria J|MJ|']

2014

31151532

Absolute quantification of twelve oligosaccharides in human milk using a targeted mass spectrometry-based approach.

Human milk oligosaccharides (HMOs) are beneficial to infants' growth. Currently, the challenges were the complex operation and weak separation which limited the accurate quantification of HMOs. Liquid chromatography-mass spectrometry (LC-MS/MS) under multi-reaction monitoring (MRM) mode was developed here to separate and quantitatively determine 12 oligosaccharides in human milk. The degree of polymerization of 12 oligosaccharides ranged from 3 to 6. Among 12 HMOS, four pairs of isomeric oligosaccharides (LNFPⅠand LNFPⅢ; LSTa、LSTb and LSTc; 2FL and 3FL; 3SL and 6SL) were successfully separated. Variations of HMOs among 61 individuals from Beijing, China were observed using the present method. Pairwise correlations analysis showed high correlation in abundance between LNDFH Ⅱand 6SL, LSTc and 6SL, LNDFH Ⅱ and LSTa, LSTa and LSTc, LSTa and 6SL. This method allows accurate and reliable quantitative determination of 12 oligosaccharides in human milk, and could be adopted in determining variations in HMOs among samples.

['Zhang|Wenyuan|W|', 'Wang|Tong|T|', 'Chen|Xinxin|X|', 'Pang|Xiaoyang|X|', 'Zhang|Shuwen|S|', 'Obaroakpo|Joy Ujiroghene|JU|', 'Shilong|Jiang|J|', 'Lu|Jing|J|', 'Lv|Jiaping|J|']

2019

33510515

Comparison of Perinatal Outcomes between Borderline and Normal Amniotic Fluid Index in Term Singleton Pregnancies.

BACKGROUND Amniotic fluid provides necessary fluid and growth factors for normal development of fetal lungs, cushions the umbilical cord from compression and protects the fetus. This study aims to compare the perinatal outcome between pregnancy with borderline and normal Amniotic Fluid Index that provide greatest chance for appropriate safe delivery with least maternal fetal and neonatal risk. METHODS A total of 94 singleton full term pregnant women were included in the study-at Kathmandu Model Hospital from February to August 2020. Forty Seven women each with Amniotic Fluid Index 5-8 cm was taken as borderline oligohydramnios group and Amniotic Fluid Index 8.1-24 cm was taken as normal group. Ultrasonography was taken as the medium for measuring Amniotic Fluid Index. RESULTS The rate of intra-partum fetal distress, meconium-stained amniotic fluid, low birth weight and neonatal intensive care unit admission were not statistically significant between the two groups while rate of cesarean section was noted to be 76.6% in exposed groups as compared to 44.7% among women with non-exposed normal group [RR=1.71; 95%CI: 1.2-2.44 p=0.006]. CONCLUSIONS We concluded that in cases of borderline oligohydramnios there was higher risk of operative delivery.

['Bajracharya|Nishma|N|', 'Dangal|Ganesh|G|', 'Poudel|Rekha|R|', 'Tiwari|Kenusha Devi|KD|', 'Bharati|Sonu|S|', 'Maharjan|Ostha|O|', 'Maharjan|Sunita|S|', 'Karki|Aruna|A|', 'Pradhan|Hema Kumari|HK|', 'Shrestha|Ranjana|R|', 'Bhattachan|Kabin|K|']

2021

29360150

Correcting TG 119 confidence limits.

PURPOSE Task Group 119 (TG-119) has been adopted for evaluating the adequacy of intensity-modulated radiation therapy (IMRT) commissioning and for establishing patient-specific IMRT quality assurance (QA) passing criteria in clinical practice. TG-119 establishes 95% confidence limits (CLs), which help clinics identify systematic IMRT QA errors and identify outliers. In TG-119, the 95% CLs are established by fitting the Gamma Γ analysis passing rate results to an assumed distribution, then calculating the limit in which 95% of the data fall. CLs for a given dataset will depend greatly on the type of distribution used, and those determined by following the TG-119 guidelines are only valid if the underlying data follows a Gaussian distribution. Gaussian distributions assume symmetry about the mean, which would imply the possibility of negative Γ analysis failing rates. This study demonstrates that the gamma distribution is a more reasonable assumption for establishing CLs than the Gaussian distribution used in TG-119. Thus, the gamma distribution is suggested as a replacement to the conventional Gaussian statistical model used in TG-119. MATERIALS AND METHODS The moments estimator (ME) for the gamma family is used to obtain the CLs of the failing rates for all Γ analysis criteria. To demonstrate the congruence of the gamma distribution, the root mean squared error and the CL values for the MEs of the gamma and the Gaussian families were compared. RESULTS In this study, the empirical 95% CLs generated using 302 plans represent the ground truth, which resulted in a 91.83% passing rate using 3%/3 mm error local criteria. The gamma distribution underestimates the 95% CL by 0.09%, while the Gaussian distribution overestimates the 95% CL by 4.12%. CONCLUSIONS Although IMRT QA equipment may vary between clinics, the mathematical formalism presented in this study applies to any combination of planning and delivery systems. This study has demonstrated that a gamma distribution should be favored over a Gaussian distribution when establishing CLs for IMRT QA.

['Kearney|Vasant|V|', 'Solberg|Timothy|T|', 'Jensen|Shane|S|', 'Cheung|Joey|J|', 'Chuang|Cynthia|C|', 'Valdes|Gilmer|G|']

2018

27909483

From Incidental, Mechanically-Induced Arrhythmias to Reflex-Defined Arrhythmogenicity: On The Track of The Ternary Reflex System Resemblance to The "Infancy" of New Era or Rediscovery.

The underlying pathophysiology of supraventricular and ventricular arrhythmias remains a matter of intense investigation. Though evolving, the contemporary explanations do not encompass all aspects of arrhythmogenicity. An improved understanding of arrhythmia substrate is needed to augment therapeutic capabilities. Our observation and literature sources demonstrate relatively high incidence of transitory arrhythmias which are non-intentionally generated by the endocardial lead/catheter manipulation. These findings are interesting and potentially may crystallize the reflex-dependent proarrhythmic cardiac activity. Herein we suggest the "reflexogenic arrhythmogenicity" concept extending an overall spectrum of known hypotheses. Cardiovascular reflex action can be categorized into three-tiered levels - intra-cellular, inter-cellular and inter-organic. The first two levels of the triplicate system reside within the cardiac anatomical landmarks (in fact intramurally, intra-organically), however the third one implicates central (cerebral) activity which boomerangs back via centripetal and centrifugal connections. These levels likely compose synoptic ternary reflex set system which may be validated in future studies. To hypothesize, coordinated mutual reciprocity of reflex activity results in stabilization of heart rhythm in robust heart. Any stressful cardiac event may lead to the shift of the rhythm toward unfavorable clinical entity probably via the loss of the influence of dominant reflex. Overall, an interaction and likely intrinsic inter-tiered competition along with possible interplay between physiological and pathological reflexes may be treated as contributing factors for the inception and maintaining of arrhythmias and cardiac performance as well. These assumptions await further documentation. If such a tenet were recognized, the changes in the clinical approach to arrhythmia management might be anticipated, preferably by selective reflex suppression or activation strategy.

['Stirbys|Petras|P|']

2016

33271868

A Novel Micro-Displacement Sensor Based on Double Optical Fiber Probes Made through Photopolymer Materials.

In this paper, a novel micro-displacement sensor with double optical fiber probes is proposed and designed, which can realize the highly sensitive sensing of longitudinal or lateral micro-displacements. The optical fiber probes are made through photopolymer formulation, and the effects of reaction time and optical power on the growth length of the probe are illustrated. The relationship between light intensity and longitudinal micro-displacement is a power function in the range of 0-100 μm at room temperature with a correlation coefficient of 98.92%. For lateral micro-displacement, the sensitivity is -2.9697 dBm/μm in the range of 0-6 μm with a linear fit of 99.61%. In addition, the linear correlation coefficient decreases as the initial longitudinal distance increases, and the function of these correlation coefficients is also linear with a linearity of 96.14%. This sensor has a simple manufacturing process, low cost, high sensitivity, and fast response speed. It is suitable for harsh environments such as strong electromagnetic interference and corrosivity, and has a broad application prospect in the field of micro-displacement sensing.

['Zhang|Fuzheng|F|0000-0002-4815-6560', 'Lin|Qijing|Q|', 'Zhu|Liangquan|L|', 'Zhao|Na|N|', 'Han|Feng|F|', 'Zhao|Libo|L|', 'Jiang|Zhuangde|Z|']

2020

34355116

Does high COVID-19 spread impact neighbouring countries? Quasi-experimental evidence from the first year of the pandemic in Ireland.

Background Coronavirus disease 2019 (COVID-19) has necessitated public health responses on an unprecedented scale. Controlling infectious diseases requires understanding of the conditions that increase spread. Prior studies have identified sociodemographic, epidemiological and geographic associations. Ireland offers an unusual opportunity to quantify how high infection rates in one country impacted cases in a neighbouring country. Methods We analysed official statistics on confirmed COVID-19 cases on the island of Ireland for 52 weeks from March 2020. Our main research question was: Did higher cases in Northern Ireland (NI) impact the number of cases in the Republic of Ireland (ROI)? We used least squares regression to compare confirmed cases in ROI counties that border NI with the rest of the state. We included in our model sociodemographic, epidemiological and geographic factors. We employed the latitude of each county town as an instrumental variable to isolate a quasi-experimental estimate of the cross-border spread. Results In the quasi-experimental framework, and controlling for population density, age distribution and circulatory disease prevalence, border counties had an extra 21.0 (95%CI: 8.4-33.6) confirmed COVID-19 cases per 1000 people. This equates to an estimated 9,611 additional cases in ROI, or 4% of the national total in the first year of the pandemic. Our results were substantively similar in non-experimental frameworks, with alternative additional predictors, and in sensitivity analyses. Additionally, population density in ROI counties was positively associated with confirmed cases and higher proportions of residents in the professional classes was negatively associated. Conclusion On the island of Ireland during the first year of the COVID-19 pandemic, high infection rates in NI increased cases in the neighbouring ROI. Maximising co-ordination of pandemic responses among neighbouring countries is essential to minimising disease spread, and its associated disruptions to society and the economy. Socioeconomic disadvantage appeared to confer significant additional risk of spread.

['Ahmed|Rakesh|R|https://orcid.org/0000-0002-7813-4207', 'May|Peter|P|https://orcid.org/0000-0001-8501-6500']

2021

28832120

Single Continuous Near-Infrared Laser-Triggered Photodynamic and Photothermal Ablation of Antibiotic-Resistant Bacteria Using Effective Targeted Copper Sulfide Nanoclusters.

The emergence of antibiotic-resistant bacterial strains has made conventional antibiotic therapies less efficient. The development of a novel nanoantibiotic approach for efficiently ablating such bacterial infections is becoming crucial. Herein, a collection of poly(5-(2-ethyl acrylate)-4-methylthiazole-g-butyl)/copper sulfide nanoclusters (PATA-C4@CuS) was synthesized for efficient capture and effective ablation of levofloxacin-resistant Gram-negative and Gram-positive bacteria upon tissue-penetrable near-infrared (NIR) laser irradiation. In this work, we took advantage of the excellent photothermal and photodynamic properties of copper sulfide nanoparticles (CuSNPs) upon NIR laser irradiation and thiazole derivative as a membrane-targeting cationic ligand toward bacteria. The conjugated nanoclusters could anchor the bacteria to trigger the bacterial aggregation quickly and efficiently kill them. These conjugated nanoclusters could significantly inhibit levofloxacin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus amyloliquefaciens at 5.5 μg/mL under NIR laser irradiation (980 nm, 1.5 W cm-2, 5 min), which suggested that the heat and reactive oxygen species (ROS) generated from the irradiated CuSNPs attached to bacteria were effective in eliminating and preventing the regrowth of the bacteria. Importantly, the conjugated nanoclusters could promote healing in bacteria-infected rat wounds without nonspecific damage to normal tissue. These findings highlight the promise of the highly versatile multifunctional nanoantibiotics in bacterial infection.

['Dai|Xiaomei|X|', 'Zhao|Yu|Y|', 'Yu|Yunjian|Y|', 'Chen|Xuelei|X|', 'Wei|Xiaosong|X|', 'Zhang|Xinge|X|http://orcid.org/0000-0003-3399-1659', 'Li|Chaoxing|C|']

2017

27131449

Amitriptyline removal using palygorskite clay.

With the increased detections of commonly used pharmaceuticals in surface water and wastewater, extensive attentions were paid recently to the fate and transport of these pharmaceuticals in the environment. Amitriptyline (AMI) is a tricyclic antidepressant widely applied to treat patients with anxiety and depression. In this study, the removal of AMI with palygorskite clay (PFl-1) was investigated under different physico-chemical conditions and supplemented by instrumental analyses. The uptake of AMI on PFl-1 was well fitted by the Langmuir isotherm with an adsorption capacity of 0.168 mmol g(-1) at pH 6-7. The AMI uptake was fast and reached equilibrium in 15 min. The X-ray diffraction patterns showed no shift of the (110) peak position of palygorskite after AMI uptake. However, the (001) peak position of the minor component smectite (about 10%) shifted to lower angle as the amounts of AMI input increased. These results suggested surface uptake of AMI on palygorskite and interlayer uptake of AMI in smectite. As smectite is a common component of palygorskite clays, its role in assessing the properties and performances of palygorskite clays for the uptake and removal of contaminants should not be neglected. Overall, the high affinity of AMI for PFl-1 and strong retention of AMI on PFl-1 suggested that it could be a good adsorbent to remove AMI from wastewater. Palygorskite clays can also be a sink for many cationic pharmaceuticals in the environmental of the arid regions.

['Tsai|Yo-Lin|YL|', 'Chang|Po-Hsiang|PH|', 'Gao|Zong-You|ZY|', 'Xu|Xiao-Yuan|XY|', 'Chen|Yan-Hsin|YH|', 'Wang|Zheng-Hong|ZH|', 'Chen|Xin-Yu|XY|', 'Yang|Zheng-Ying|ZY|', 'Wang|Tzu-Hao|TH|', 'Jean|Jiin-Shuh|JS|', 'Li|Zhaohui|Z|', 'Jiang|Wei-Teh|WT|']

2016

25468844

Perioperative beta-blockade: might the baby go out with the bath water?

Perioperative β-blocker therapy has been advocated to reduce cardiac mortality and morbidity in high-risk cardiac patients undergoing non-cardiac surgery. Core data that supported this intervention and informed international societal guidelines has recently been withdrawn. A subsequent meta-analysis of the remaining data reporting excess mortality has re-opened the debate about the utility of β-blocker therapy in the perioperative period. Criticism of remaining trial designs and new insights into the protective mechanisms of β-blocker therapy in critical illness raise important questions that should now be addressed by a further robust, high-quality randomised control trial.

['Mistry|Ravin|R|', 'Walker|David|D|']

2014

34564146

Marine Algae-Derived Bioactive Compounds: A New Wave of Nanodrugs?

Marine algae are rich in bioactive nutraceuticals (e.g., carbohydrates, proteins, minerals, fatty acids, antioxidants, and pigments). Biotic (e.g., plants, microorganisms) and abiotic factors (e.g., temperature, pH, salinity, light intensity) contribute to the production of primary and secondary metabolites by algae. Easy, profitable, and sustainable recovery methods include novel solid-liquid and liquid-liquid extraction techniques (e.g., supercritical, high pressure, microwave, ultrasound, enzymatic). The spectacular findings of algal-mediated synthesis of nanotheranostics has attracted further interest because of the availability of microalgae-based natural bioactive therapeutic compounds and the cost-effective commercialization of stable microalgal drugs. Algal extracts can serve as stabilizing/capping and reducing agents for the synthesis of thermodynamically stable nanoparticles (NPs). Different types of nanotherapeutics have been synthesized using physical, chemical, and biological methods. Marine algae are a fascinating source of lead theranostics compounds, and the development of nanotheranostics has been linked to enhanced drug efficacy and safety. Indeed, algae are remarkable nanobiofactories, and their pragmatic properties reside in their (i) ease of handling; (ii) capacity to absorb/accumulate inorganic metallic ions; (iii) cost-effectiveness; and (iv) capacity of eco-friendly, rapid, and healthier synthesis of NPs. Preclinical and clinical trials shall enable to really define effective algal-based nanotherapies. This review aims to provide an overview of the main algal compounds that are nutraceuticals and that can be extracted and purified for nanotheranostic purposes.

['Menaa|Farid|F|0000-0002-0258-7322', 'Wijesinghe|Udari|U|0000-0001-5422-7321', 'Thiripuranathar|Gobika|G|0000-0002-0904-9519', 'Althobaiti|Norah A|NA|0000-0001-6893-5521', 'Albalawi|Aishah E|AE|0000-0002-7695-8691', 'Khan|Barkat Ali|BA|0000-0003-4920-1770', 'Menaa|Bouzid|B|']

2021

33412456

Sleep problems in Australian children with Down syndrome: the need for greater awareness.

BACKGROUND Children with Down Syndrome (DS) have a high prevalence of obstructive sleep apnoea (OSA). Non-respiratory sleep disorders also occur commonly but are less well recognised. This cross-sectional study evaluates the prevalence of sleep difficulties in a community sample of Australian children with DS (DScomm), using the Children's Sleep Habits Questionnaire (CSHQ), and compares them to children referred to the sleep clinic (DSref). To our knowledge this is the first study to have reported prevalence of sleep problems in Australian children with DS and to compare a community and referred group of children with DS directly. METHODS The CSHQ was completed by parents of children with DS recruited from the community (DScomm) via survey distributed by Down syndrome Queensland and Australia. A second group was recruited through the tertiary sleep clinic at our institution (DSref) and completed the same questionnaire on enrolment. Data from these groups was compared. RESULTS There were 76 participants in the DScomm group (57% male; median age 9.7yrs) and 42 participants in the DSref group (50% male; median age 6.97yrs). The overall prevalence of sleep disturbances was 90.9% in the DScomm group, and 85.7% in the DSref group (p = 0.54). There was a statistically significant difference in the mean total CSHQ score, with the DScomm having the higher score (p = 0.023). CONCLUSIONS This study reports a high prevalence of sleep problems in both a community and referred group of Australian children with DS and suggests that there are many children with DS with sleep problems, particularly non-respiratory difficulties, who are potentially not receiving adequate treatment.

['Chawla|Jasneek K|JK|', 'Howard|Aidan|A|', 'Burgess|Scott|S|', 'Heussler|Helen|H|']

2021

28955339

Deregulated MicroRNA-21 Expression in Monocytes from HIV-Infected Patients Contributes to Elevated IP-10 Secretion in HIV Infection.

Persistent activation and inflammation impair immune response and trigger disease progression in HIV infection. Emerging evidence supports the supposition that excessive production of interferon-inducible protein 10 (IP-10), a critical inflammatory cytokine, leads to immune dysfunction and disease progression in HIV infection. In this study, we sought to elucidate the cause of the upregulated production of IP-10 in HIV infection and explore the underlying mechanisms. Bolstering miR-21 levels using mimics resulted in the obvious suppression of lipopolysaccharide (LPS)-induced IP-10 in monocyte leukemia cells THP-1 and vice versa. The analysis of the primary monocytes of HIV patients revealed significantly less miR-21 than in healthy controls; this was opposite to the tendency of IP-10 levels in plasma. The secretion of IP-10 due to LPS stimulation was not affected by miR-21 modulation in the differentiated THP-1 macrophages (THP-1-MA). We found a novel switch, IFN-stimulated gene 15 (ISG15), which triggers the expression of IP-10 and is significantly upregulated during the differentiation of THP-1 into THP-1-MA. The inhibition of ISG15 can restore the regulation of IP-10 by miR-21. In summary, IP-10 expression in monocytes is regulated by miR-21, whereas in macrophages, this fine-tuning is attenuated by the enhanced expression of ISG15. This study paves the way to a comprehensive understanding of the molecular regulatory mechanism of IP-10, a key point in immune intervention strategy.

['Wu|Xian|X|', 'Zhang|Le-Le|LL|', 'Yin|Lin-Bo|LB|', 'Fu|Ya-Jing|YJ|', 'Jiang|Yong-Jun|YJ|', 'Ding|Hai-Bo|HB|', 'Chu|Zhen-Xing|ZX|', 'Shang|Hong|H|', 'Zhang|Zi-Ning|ZN|']

2017

22298969

Pathophysiology, evaluation, and treatment of bloating: hope, hype, or hot air?

Abdominal bloating is commonly reported by men and women of all ages. Bloating occurs in nearly all patients with irritable bowel syndrome, and it also occurs in patients with other functional and organic disorders. Bloating is frequently disturbing to patients and frustrating to clinicians, as effective treatments are limited and are not universally successful. Although the terms bloating and abdominal distention are often used interchangeably, these symptoms likely involve different pathophysiologic processes, both of which are still not completely understood. The goal of this paper is to review the pathophysiology, evaluation, and treatment of bloating and abdominal distention.

['Lacy|Brian E|BE|', 'Gabbard|Scott L|SL|', 'Crowell|Michael D|MD|']

2011

33013297

Telmisartan, an Antagonist of Angiotensin II Receptors, Accentuates Voltage-Gated Na+ Currents and Hippocampal Neuronal Excitability.

Telmisartan (TEL), a non-peptide blocker of the angiotensin II type 1 receptor, is a widely used antihypertensive agent. Nevertheless, its neuronal ionic effects and how they potentially affect neuronal network excitability remain largely unclear. With the aid of patch-clamp technology, the effects of TEL on membrane ion currents present in hippocampal neurons (mHippoE-14 cells) were investigated. For additional characterization of the effects of TEL on hippocampal neuronal excitability, we undertook in vivo studies on Sprague Dawley (SD) rats using pilocarpine-induced seizure modeling, a hippocampal histopathological analysis, and inhibitory avoidance testing. In these hippocampal neurons, TEL increased the peak amplitude of I , with a concomitant decline in the current inactivation rate. The TEL concentration dependently enhanced the peak amplitude of depolarization-elicited I and lessened the inactivation rate of I . By comparison, TEL was more efficacious in stimulating the peak I and in prolonging the inactivation time course of this current than tefluthrin or (-)-epicatechin-3-gallate. In the continued presence of pioglitazone, the TEL-perturbed stimulation of I remained effective. In addition, cell exposure to TEL shifted the steady-state inactivation I curve to fewer negative potentials with no perturbations of the slope factor. Unlike chlorotoxin, either ranolazine, eugenol, or KMUP-1 reversed TEL-mediated increases in the strength of non-inactivating I . In the cell-attached voltage-clamp recordings, TEL shortened the latency in the generation of action currents. Meanwhile, TEL increased the peak I , with a concurrent decrease in current inactivation in HEKT293T cells expressing SCN5A. Furthermore, although TEL did not aggravate pilocarpine-induced chronic seizures and tended to preserve cognitive performance, it significantly accentuated hippocampal mossy fiber sprouting. Collectively, TEL stimulation of peak I in combination with an apparent retardation in current inactivation could be an important mechanism through which hippocampal neuronal excitability is increased, and hippocampal network excitability is accentuated following status epilepticus, suggesting further attention to this finding.

['Lai|Ming-Chi|MC|', 'Wu|Sheng-Nan|SN|', 'Huang|Chin-Wei|CW|']

2020

29779660

In Vitro Analysis of Cyanobacterial Nonheme Iron-Dependent Aliphatic Halogenases WelO5 and AmbO5.

Aliphatic carbon-halogen (C-X) bonds are prevalent in modern pharmaceuticals and bioactive natural products. Three distinct chemical strategies are known in Nature to generate these structural motifs. The first is via the nucleophilic substitution at a prefunctionalized electrophilic carbon center with a halide anion (X-), known for the S-adenosyl-l-methionine-dependent halogenases. The second is via the electrophilic activation of an alkene or its equivalent by a halenium ion (X+) donor, known for the haloperoxidases and flavin-dependent halogenases. The third is via the direct functionalization of an unactivated aliphatic C-H bond with a halogen radical (X) equivalent, known for the 2-oxo-glutarate and nonheme iron-dependent halogenases. Due to the ubiquitous nature of aliphatic C-H groups in organic molecules, transformations that permit chemo-, regio-, and stereo-selective modification(s) at an unactivated sp3-carbon center have been a long sought-after goal in chemical science. Two nonheme iron-dependent halogenases, WelO5 and AmbO5 involved in the biogenesis of cyanobacterial hapalindole-type alkaloids, have been recently shown able to perform this type of challenging transformation. In this chapter, experimental details for the in vitro reconstitution of WelO5 and AmbO5 enzymatic activities are presented.

['Liu|Xinyu|X|']

2018

24913195

Should myeloid and lymphoid neoplasms with PCM1-JAK2 and other rearrangements of JAK2 be recognized as specific entities?

Since the publication of the 2001 and 2008 World Health Organization classifications of tumours of haematopoietic and lymphoid tissues, there has been an increasing move towards classification of haematological neoplasms on the basis of the underlying molecular genetic disorder. In recent decades there have been a significant number of reports of haematological neoplasms with rearrangement of JAK2. Published data on such cases have therefore been analysed to determine if any specific entities could be identified. On the basis of this analysis, it is suggested that lymphoid and myeloid neoplasms associated with t(8;9)(p22;p24); PCM1-JAK2 fusion should be recognized as an entity. Furthermore, lymphoid and myeloid neoplasms associated respectively with t(9;12)(p24;p13); ETV6-JAK2 and with t(9;22)(p24;q11·2); BCR-JAK2 should be documented carefully in order to define their features more clearly and assess whether they can be recognized as entities. Identification of all these conditions is important because of the possibility of response to JAK2 inhibitors.

['Bain|Barbara J|BJ|', 'Ahmad|Shahzaib|S|']

2014

21769217

Revisiting hemophilia management in acute medicine.

The World Federation of Hemophilia estimates that more than 350,000 people globally have a form of the disease. Hemophilia A is a bleeding disorder that has a spectrum of manifestations ranging from persistent bleeding after minor trauma to spontaneous hemorrhage. We report a case of a male patient with hemophilia A who received general anesthesia for removal of foreign body from the nose. There was no excessive blood loss during surgery. Perioperatively, the patient received recombinant factor VIII coverage. Rest of the postoperative course was uneventful. Literature on the clinical management of patient with hemophilia A are reviewed and considerations for perioperative preparation and management of hemophilic patient are presented.

['Sahu|Sandeep|S|', 'Lata|Indu|I|', 'Singh|Surendra|S|', 'Kumar|Mukesh|M|']

2011

31304988

Acute Changes in NADPH Oxidase 4 in Early Post-Traumatic Osteoarthritis.

Knee injuries cause structural damage and acute inflammation that initiates the development of post-traumatic osteoarthritis (PTOA). NADPH oxidase 4 (Nox4), a member of a family of enzymes that generates reactive oxygen species (ROS), plays a pivotal role in normal development of the musculoskeletal system, but may increase ROS production to harmful levels after joint injury. The role of ROS in both normal joint homeostasis and injury is poorly understood, but inhibition of excessive ROS production by Nox4 after joint injury could be protective to the joint, decreasing oxidative stress, and initiation of PTOA. Knee injuries were simulated using inflammatory cytokines in cultured primary human chondrocytes and a non-invasive mouse model of PTOA in C57BL/6N and Nox4 knockout mice. There is an acute decrease in Nox4 activity within 24 h after injury in both systems, followed by a subsequent sustained low-level increase, a novel finding not seen in any other system. Inhibition of Nox4 activity by GKT137831 was protective against early structural changes after non-invasive knee injury in a mouse model. Nox4 knockout mice had significant differences in structural and mechanical properties of bone, providing further evidence for the role of Nox4 in development of joint tissues and biochemical response after joint injury. Nox4 plays a significant role in the acute phase after joint injury, and targeted inhibition of inflammation caused by Nox4 may be protective against early joint changes in the pathogenesis of PTOA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2429-2436, 2019.

['Wegner|Adam M|AM|0000-0001-5862-800X', 'Campos|Nestor R|NR|', 'Robbins|Michael A|MA|', 'Haddad|Andrew F|AF|', 'Cunningham|Hailey C|HC|', 'Yik|Jasper H N|JHN|', 'Christiansen|Blaine A|BA|0000-0002-0105-6458', 'Haudenschild|Dominik R|DR|0000-0001-9947-9864']

2019

31910734

Evolutionary rates are correlated between cockroach symbionts and mitochondrial genomes.

Bacterial endosymbionts evolve under strong host-driven selection. Factors influencing host evolution might affect symbionts in similar ways, potentially leading to correlations between the molecular evolutionary rates of hosts and symbionts. Although there is evidence of rate correlations between mitochondrial and nuclear genes, similar investigations of hosts and symbionts are lacking. Here, we demonstrate a correlation in molecular rates between the genomes of an endosymbiont (Blattabacterium cuenoti) and the mitochondrial genomes of their hosts (cockroaches). We used partial genome data for multiple strains of B. cuenoti to compare phylogenetic relationships and evolutionary rates for 55 cockroach/symbiont pairs. The phylogenies inferred for B. cuenoti and the mitochondrial genomes of their hosts were largely congruent, as expected from their identical maternal and cytoplasmic mode of inheritance. We found a correlation between evolutionary rates of the two genomes, based on comparisons of root-to-tip distances and on comparisons of the branch lengths of phylogenetically independent species pairs. Our results underscore the profound effects that long-term symbiosis can have on the biology of each symbiotic partner.

['Arab|Daej A|DA|', 'Bourguignon|Thomas|T|', 'Wang|Zongqing|Z|', 'Ho|Simon Y W|SYW|', 'Lo|Nathan|N|']

2020

33346135

Catheter ablation of ventricular arrhythmias in left ventricular noncompaction cardiomyopathy.

BACKGROUND There are limited data on ventricular arrhythmias (VAs) associated with left ventricular noncompaction (LVNC) cardiomyopathy. OBJECTIVES This study aims to analyze the clinical and electrocardiographic characteristics of VAs in a group of patients with LVNC. METHODS Forty-two nonrelated patients with LVNC and VAs were included that were evaluated at the Inherited Cardiac Disease Unit of the University Hospital Virgen Arrixaca (Murcia-Spain) (ERN Guard-Heart Centre, European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart). RESULTS Thirteen patients (30.9%) had isolated LVNC, 27 (64.3%) had LVNC associated with dilated cardiomyopathy, and 2 (4.8%) had LVNC associated with hypertrophic cardiomyopathy. Among isolated LVNC individuals, 9 (69.2%) had premature ventricular complexes (PVCs)/nonsustained ventricular tachycardias (VTs), and 4 (30.8%) VTs (1 VT degenerating in ventricular fibrillation). In the dilated cardiomyopathy group, 11 (40.7%) patients had PVCs, 14 (51.9%) VTs, and 2 (7.4%) ventricular fibrillation. In the hypertrophic cardiomyopathy group, one patient had PVCs and the other VTs. Endocardial mapping and ablation were performed in 19 patients (45.2%): 7 ventricular outflow tracts (4 right ventricular outflow tract, 1 left coronary cusp, and 2 right coronary cusp), 2 in the left ventricular summit, 5 related to Purkinje potentials at the mid inferoseptal area, and 5 associated with endocardial scar localized in the basal anterolateral and inferolateral segments. Epicardial ablation was performed in 3 cases. CONCLUSION The substrate of VAs in LVNC cardiomyopathy is heterogeneous, with origin in ventricular outflow tracts, Purkinje system related, and resembling scar patterns in nonischemic cardiomyopathy.

['Sánchez Muñoz|Juan José|JJ|', 'Muñoz-Esparza|Carmen|C|', 'Verdú|Pablo Peñafiel|PP|', 'Sánchez|Juan Martínez|JM|', 'Almagro|Francisco García|FG|', 'Ruiz|Ginés Elvira|GE|', 'Gimeno Blanes|Juan Ramón|JR|', 'Alberola|Arcadio García|AG|']

2021

30612641

A novel two-dimensional liquid chromatography - Mass spectrometry method for direct drug impurity identification from HPLC eluent containing ion-pairing reagent in mobile phases.

In this study, a novel two dimensional liquid chromatography - mass spectrometry (2D-LC-MS) method with use of a weak anion exchange column between the 1st DLC RP column and the 2nd DLC RP column (RP1-WAX-RP2) was developed and applied to identify drug impurities from MS incompatible mobile phases containing sodium 1-octanesulfonate and non-volatile buffer. The 1st DLC conditions follow exactly the original standard HPLC method recorded in Chinese Pharmacopeia (ChP), European Pharmacopeia (EP) or US Pharmacopeia (USP). An impurity fraction was collected with a built-in sample loop (100 μL) and transferred to the WAX column where 1-octanesulfonate and phosphate were trapped and removed. While, the impurity and other cations were eluted to the 2nd D column (RP2) for separation and identification by connected IT-TOF MS. Methods were programmed and applied to identify impurities in two generic drugs, sulpiride (hydrophilic drug with logP 0.57) and dobutamine (hydrophobic drug with logP 3.6). The results indicate that the methods based on RP1-WAX-RP2 column configuration offer a feasible solution for direct impurity identification in generic drug product or API without needs of off-line desalting from the MS incompatible mobile phases containing ion-pairing reagent and non-volatile buffer.

['Long|Zhen|Z|', 'Zhan|Zhaoqi|Z|', 'Guo|Zhimou|Z|', 'Li|Yueqi|Y|', 'Yao|Jinting|J|', 'Ji|Feng|F|', 'Li|Changkun|C|', 'Zheng|Xin|X|', 'Ren|Biao|B|', 'Huang|Taohong|T|']

2019

25167168

Amphiphilic polymer-mediated formation of laponite-based nanohybrids with robust stability and pH sensitivity for anticancer drug delivery.

The development of pH-sensitive drug delivery nanosystems that present a low drug release at the physiological pH and are able to increase the extent of the release at a lower pH value (like those existent in the interstitial space of solid tumors (pH 6.5) and in the intracellular endolysosomal compartments (pH 5.0)) is very important for an efficient and safe cancer therapy. Laponite (LP) is a synthetic silicate nanoparticle with a nanodisk structure (25 nm in diameter and 0.92 nm in thickness) and negative-charged surface, which can be used for the encapsulation of doxorubicin (DOX, a cationic drug) through electrostatic interactions and exhibit good pH sensitivity in drug delivery. However, the colloidal instability of LP still limits its potential clinical applications. In this study, we demonstrate an elegant strategy to develop stable Laponite-based nanohybrids through the functionalization of its surface with an amphiphile PEG-PLA copolymer by a self-assembly process. The hydrophobic block of PEG-PLA acts as an anchor that binds to the surface of drug-loaded LP nanodisks, maintaining the core structure, whereas the hydrophilic PEG part serves as a protective stealth shell that improves the whole stability of the nanohybrids under physiological conditions. The resulting nanocarriers can effectively load the DOX drug (the encapsulation efficiency is 85%), and display a pH-enhanced drug release behavior in a sustained way. In vitro biological evaluation indicated that the DOX-loaded nanocarriers can be effectively internalized by CAL-72 cells (an osteosarcoma cell line), and exhibit a remarkable higher anticancer cytotoxicity than free DOX. The merits of Laponite/PEG-PLA nanohybrids, such as good cytocompatibility, excellent physiological stability, sustained pH-responsive release properties, and improved anticancer activity, make them a promising platform for the delivery of other therapeutic agents beyond DOX.

['Wang|Guoying|G|', 'Maciel|Dina|D|', 'Wu|Yilun|Y|', 'Rodrigues|João|J|', 'Shi|Xiangyang|X|', 'Yuan|Yuan|Y|', 'Liu|Changsheng|C|', 'Tomás|Helena|H|', 'Li|Yulin|Y|']

2014

26117347

Glucose supplementation has minimal effects on blood neutrophil function and gene expression in vitro.

During early lactation, glucose availability is low and the effect of glucose supply on bovine polymorphonuclear leukocyte (PMNL) function is poorly understood. The objective of this study was to determine the effect of glucose supplementation on the function and transcriptomic inflammatory response of PMNL from cows in early and mid-lactation in vitro. Twenty Holstein cows in early (n=10; days in milk=17±3.1) and mid-lactation (n=10; days in milk=168±14.8) were used for this study. Jugular blood was analyzed for serum concentrations of nonesterified fatty acids, β-hydroxybutyrate, and glucose. Polymorphonuclear leukocytes were isolated and diluted using RPMI (basal glucose concentration was 7.2 mM) to different concentrations of PMNL/mL for phagocytosis, chemotaxis, gene expression, and medium analyses. Working solutions of glucose (0 or 4 mM of d-glucose) and lipopolysaccharide (0 or 50μg/mL) were added and tubes were incubated for 120 min at 37°C. Media were analyzed for concentrations of glucose and tumor necrosis factor-α (TNF-α). Data were analyzed in a randomized block (stage of lactation) design. Challenge with lipopolysaccharide increased the expression of the genes encoding for nuclear factor kappa B (NFKB1), IL-10 (IL10), IL1B, IL6, IL8, TNF-α (TNFA), glucose transporter 3 (SLC2A3), and the concentration of TNF-α in medium (147.3 vs. 72.5 pg/mL for lipopolysaccharide and control, respectively). Main effect of stage of lactation was minimal where the expression of IL10 increased for cows in early compared with cows in mid-lactation. After lipopolysaccharide challenge, cows in early lactation experienced more marked increases in the expression of IL6, TNFA, and IL8 when compared with cows in mid-lactation. Glucose supplementation had minimal effects on gene expression where glucose supplementation increased the expression of lysozyme (LYZ). Glucose supplementation increased PMNL phagocytosis but did not alter chemotaxis, morphology, or concentration of TNF-α in the medium. Under the conditions of the experiment, stage of lactation had minimal effects on PMNL response to glucose supply where only the expression of NFKB1 and the production of TNF-α were greater for cows in mid-lactation when compared with early lactation. Metabolic profiles for cows in early lactation did not parallel those for cows during the early postpartum period and may partly explain results for this study. Future studies investigating the effect of glucose supply on bovine PMNL function in vivo and how this may be altered by stage of lactation are warranted.

['Garcia|M|M|', 'Elsasser|T H|TH|', 'Qu|Y|Y|', 'Zhu|X|X|', 'Moyes|K M|KM|']

2015

30276930

Abnormal esophageal motility during a solid test meal in systemic sclerosis-detection even in very early disease and association with disease progression.

OBJECTIVE This study assessed whether high-resolution manometry (HRM) with a test meal can detect clinically relevant, abnormal motility already in very early systemic sclerosis (SSc) and whether this finding is associated with subsequent disease progression. METHODS This prospective, longitudinal cohort study recruited 68 consecutive SSc patients (group #1: 32 established disease (ACR, American College of Rheumatology /EULAR, The European League against Rheumatism 2013 and ACR 1980 criteria fulfilled); group #2: 24 early disease (only ACR/EULAR 2013 fulfilled); group #3: 12 very early disease (clinical expert diagnosis of SSc) and 72 healthy controls. HRM evaluated esophageal motility for water swallows and a solid test meal. RESULTS Systemic sclerosis patients had less frequent effective esophageal contractions during the test meal compared to healthy controls even in very early disease (0.15, 1.0, 2.1 per minute for groups #1, #2, and #3, vs 2.5 per minute in health; P < 0.001, P < 0.001, and P < 0.0085, respectively). Ineffective motility at HRM was associated with a higher modified Rodnan skin score at baseline. Moreover, at mean 18 (10-31) months of follow-up, the presence of ineffective motility at baseline was associated with progression of skin disease (P = 0.01). Cox proportional hazard regression analysis identified hypotensive peristalsis in the test meal (<15% effective solid swallows) and low distal contractile integral (DCI; <400 mm Hg·cm·s) as predictors for skin aggravation, but not for new organ involvement. CONCLUSION Ineffective motility during a test meal is present already in patients with very early SSc. Findings on HRM studies are associated with disease severity at baseline, and low percentage of effective swallows in test meal and low mean DCI are both predictors of skin progression during follow-up.

['Bütikofer|Simon|S|0000-0001-9759-122X', 'Jordan|Suzana|S|', 'Sauter|Matthias|M|', 'Hollenstein|Michael|M|', 'Heinrich|Henriette|H|0000-0001-6355-0921', 'Freitas-Queiroz|Natália|N|', 'Kuntzen|Thomas|T|', 'Ang|Daphne|D|', 'Oberacher|Marcos|M|', 'Maurer|Britta|B|', 'Schwizer|Werner|W|', 'Fox|Mark|M|0000-0003-4394-5584', 'Distler|Oliver|O|', 'Misselwitz|Benjamin|B|0000-0002-8719-5175']

2019

30307819

Experimental myofascial trigger point creation in rodents.

Myofascial pain syndrome is one of the most common forms of muscle pain. In this syndrome, pain is originated by the so-called trigger points, which consists of a set of palpable contraction knots in the muscle. It has been proposed that a high, spontaneous neurotransmission may be involved in the generation of these contraction knots. To confirm this hypothesis, we exposed mouse muscles to an anticholinesterasic agent to increase the neurotransmision in the synaptic cleft in two different conditions, in vivo and ex vivo experiments. Using intracellular recordings, a sharp increase in the spontaneous neurotransmission in the levator auris longus muscle and a lower increase in the diaphragm muscle could be seen. Likewise, electromyography recordings reveal an elevated endplate noise in gastrocnemius muscle of treated animals. These changes are associated with structural changes such as abundant neuromuscular contracted zones observed by rhodaminated α-bungarotoxin and the presence of abundant glycosaminoglycans around the contraction knots, as shown by Alcian PAS staining. In a second set of experiments, we aimed at demonstrating that the increases in the neurotransmission reproduced most of the clinical signs associated to a trigger point. We exposed rats to the anticholinesterase agent neostigmine, and 30 min afterward we observed the presence of palpable taut bands, the echocardiographic presence of contraction knots, and local twitch responses upon needle stimulation. In summary, we demonstrated that increased neurotransmission induced trigger points in both rats and mice, as evidenced by glycosaminoglycans around the contraction zones as a novel hallmark of this pathology. NEW & NOTEWORTHY In rodents, when neostigmine was injected subcutaneously, the neuromuscular neurotransmission increased, and several changes can be observed: an elevated endplate noise compared with normal endplate noise, as evidenced by electromyographyc recording; many muscular fibers with contraction knots (narrower sarcomeres and locally thickened muscle fiber) surrounded by infiltration of connective tissue like glycosaminoglycans molecules; and palpable taut bands and local twitch responses upon needle stimulation. Several of these signs are also observed in humans with muscle pain.

['Margalef|Ramon|R|', 'Sisquella|Marc|M|', 'Bosque|Marc|M|', 'Romeu|Clara|C|', 'Mayoral|Orlando|O|', 'Monterde|Sonia|S|', 'Priego|Mercedes|M|', 'Guerra-Perez|Rafael|R|', 'Ortiz|Nicolau|N|', 'Tomàs|Josep|J|', 'Santafe|Manel M|MM|0000-0002-5462-5108']

2019

32076449

Sixth Nerve Palsy Secondary to Traumatic Carotid-Jugular Fistula.

Carotid-jugular fistulae are rare complications of penetrating head and neck trauma. We report an unusual case of an external carotid-internal jugular fistula presenting with diplopia due to sixth nerve paresis. A 38-year-old Caucasian female presented in the setting of acute neurovascular neck trauma and weeks later developed symptomatic diplopia. An acquired carotid-internal jugular fistula affecting the abducens nerve secondarily via compression from a distended inferior petrosal sinus was diagnosed and treated using endovascular coil embolisation, resolving the patient's symptoms. A posteriorly draining external carotid artery-internal jugular venous fistula can be an uncommon cause of a compressive sixth cranial nerve palsy.

['Halenda|Kevin M|KM|0000-0003-3966-9660', 'Rahimi|Scott Y|SY|', 'Patton|Jordan J|JJ|', 'Thomas|Dilip A|DA|']

2020

30165836

Health behaviours of Australian men and the likelihood of attending a dedicated men's health service.

BACKGROUND Redesigning primary health services may enhance timely and effective uptake by men. The primary aim of this study was to assess the likelihood of Australian men attending a dedicated men's health service (DMHS). The further aims were to better understand the reasons for their preferences and determine how health behaviours influence likelihood. METHODS A survey on health service use and preferences, health help-seeking behaviours, and the likelihood of attending a DMHS was administered by telephone to 1506 randomly selected men (median age 56 years, range 19-95). Likelihood of attending a DMHS was rated using a single item Likert scale where 0 was not at all likely and 10 highly likely. Respondents were classified by age (< or > = 65 years) and health status. Principal component analyses were used to define health behaviours, specifically help-seeking and delay/avoidance regarding visiting a doctor. Multivariable linear and logistic regression analyses were used to examine predictors of likelihood of attending a DMHS. RESULTS The mean likelihood of attending a DMHS was 5.8 (SD 3.3, median 6, moderate likelihood) and 21%, 26% and 23% of men rated likelihood as moderate, high and very high respectively. Being happy with their existing doctor was the most common reason (52%) for being less likely to attend a DMHS. In unadjusted analyses, younger men reported being more likely to attend a DMHS (p < 0.001) with older-sick men reporting being least likely (p < 0.001). Younger men were more likely than older men to score higher on delay/avoidance and were more likely to self-monitor. In the full model, men with current health concerns (p ≤ 0.01), who scored higher on delay/avoidance (p ≤ 0.0006), who were more likely to be information-seekers (p < 0.0001) and/or were motivated to change their health (p ≤ 0.0001) reported a higher likelihood of attending a DMHS irrespective of age and health status. CONCLUSIONS Seventy percent of men reported a moderate or higher likelihood of attending a DMHS. As young healthy men are more likely than older men to display health behaviours that are associated with a higher likelihood of attending a DHMS, such as delay/avoidance, marketing a DMHS to such men may be of value.

['Vincent|Andrew D|AD|', 'Drioli-Phillips|Phoebe G|PG|', 'Le|Jana|J|', 'Cusack|Lynette|L|', 'Schultz|Timothy J|TJ|', 'McGee|Margaret A|MA|http://orcid.org/0000-0002-0816-518X', 'Turnbull|Deborah A|DA|', 'Wittert|Gary A|GA|']

2018

25600154

Baseline working memory activation deficits in dimensional anxious depression as detected by magnetoencephalography.

OBJECTIVE Anxiety often co-occurs with major depressive disorder (MDD). This preliminary study sought to ascertain the extent to which anxious depression drives group neurobiological differences between patients with MDD and healthy volunteers (HVs). METHODS Magnetoencephalography beta-band frequency was used to compare differences in brain response during the N-back working memory task between 30 medication-free patients with treatment-resistant MDD (anxious depression=18; nonanxious depression=12) and 28 HVs. RESULTS Compared to HVs, patients with anxious depression had significantly reduced desynchronisation (less activation) in the left precuneus, right cuneus, and left insula extending into the inferior and middle frontal cortex during the 2-back condition compared with the 1-back condition of the N-back working memory task--indicating less activation of these neural networks in patients with anxious depression during the condition with the highest level of task demands. No other significant group differences were found during the working memory conditions. CONCLUSION This preliminary study suggests that a subset of patients--those with anxious depression--may be driving observed group differences between patients with MDD and HVs. Further neurobiological studies and replication experiments are necessary to determine the extent to which this subgroup has preferentially influenced our understanding of the underlying neurobiology of depression.

['Ionescu|Dawn F|DF|', 'Nugent|Allison C|AC|', 'Luckenbaugh|David A|DA|', 'Niciu|Mark J|MJ|', 'Richards|Erica M|EM|', 'Zarate|Carlos A|CA|', 'Furey|Maura L|ML|']

2015

28043614

Multidrug-resistant tuberculosis: The problem and some priorities in controlling it.

Multidrug-resistant tuberculosis (MDR-TB), and even more severe forms of drug resistance, cause significant problems and costs for national TB control programs and constitutes an increasing public health concern globally. In parts of the former Soviet Union, the prevalence of MDR-TB is as high as 50% and one third of all newly detected TB patients are infected with MDR strains. Such strains transmit and certain MDR-TB clones constitute an important part of the problem, especially in high MDR-TB burden areas. There are several actions that should be given priority to control this situation. A first important step is timely detection of all patients infected with resistant strains, which makes possible prompt change of standard TB chemotherapy to more effective combinations of drugs. This is important both from the public health and clinical perspectives, since it renders the individual patient noninfectious and subsequently cured. Early detection of MDR-TB also allows infection control to be focused where it is most needed. Strengthened infection control measures are crucial for limiting the ongoing spread of resistant TB in hospitals and elsewhere. In addition, a sustainable drug supply must be ensured to guarantee that all patients are initiated on effective treatment and can avoid interruptions due to drug shortages. An extra focus should be put on vulnerable cases, such as immunosuppressed individuals, prisoners, drug addicts, and migrants, in whom TB is generally more frequent and difficult to control than in the normal population. Finally, political support is needed to ensure necessary infrastructures, human and financial resources to effectively control drug resistant TB.

['Hoffner|Sven|S|']

2016

28077883

Performance Pressure Enhances Speech Learning.

Real-world speech learning often occurs in high pressure situations such as trying to communicate in a foreign country. However, the impact of pressure on speech learning success is largely unexplored. In this study, adult, native speakers of English learned non-native speech categories under pressure or no-pressure conditions. In the pressure conditions, participants were informed that they were paired with a (fictitious) partner, and that each had to independently exceed a performance criterion for both to receive a monetary bonus. They were then informed that their partner had exceeded the bonus and the fate of both bonuses depended upon the participant's performance. Our results demonstrate that pressure significantly enhanced speech learning success. In addition, neurobiologically-inspired computational modeling revealed that the performance advantage was due to faster and more frequent use of procedural learning strategies. These results integrate two well-studied research domains and suggest a facilitatory role of motivational factors in speech learning performance that may not be captured in traditional training paradigms.

['Maddox|W Todd|WT|', 'Koslov|Seth|S|', 'Yi|Han-Gyol|HG|', 'Chandrasekaran|Bharath|B|']

2016

29759631

Idiopathic Lead Migration: Concept and Variants of an Uncommon Cause of Cardiac Implantable Electronic Device Dysfunction.

OBJECTIVES This cumulative case study was performed to properly address the possible mechanisms, forms, and consequences of "twiddler's," "reel," and "ratchet" syndromes. BACKGROUND Twiddler's, reel, and ratchet syndromes are rare entities responsible for lead displacement of cardiac implantable electronic devices (CIED). METHODS From 2007 to 2012, 1,472 CIED were implanted at our center. Eighty-nine cases were reviewed for failure of pacing circuit integrity. Only 9 met the inclusion criteria for idiopathic lead migration (ILM) and were grouped as ILM (twiddler) or ILM (reel). For a pooled analysis of cases, a review of the literature from 1990 to 2012 was performed, and the authors identified 78 cases from 64 publications. RESULTS The study population consisted of 87 cases (45 women; median age, 66 years; 46 with ILM [twiddler] and 41 with ILM [reel]). Migration affected only 1 lead in 65% of 46 devices with more than 1 lead. None of the previously reported risk factors-manual manipulation of the device, elderly age, obesity, oversized pocket, and psychiatric history-correlated with the risk of ILM. CONCLUSIONS Neither manual manipulation of the device nor the other traditional risk factors reported in the literature for ILM syndrome correlated with the risk of ILM.

['Morales|José L|JL|', 'Nava|Santiago|S|', 'Márquez|Manlio F|MF|', 'González|Jorge|J|', 'Gómez-Flores|Jorge|J|', 'Colín|Luis|L|', 'Martínez-Ríos|Marco A|MA|', 'Iturralde|Pedro|P|']

2017

28257087

Risk Factors for Chronic Diseases and Multimorbidity in a Primary Care Context of Central Argentina: A Web-Based Interactive and Cross-Sectional Study.

Global health agencies estimate an increase of chronic diseases in South America. Nevertheless, few studies have investigated chronic diseases and their risk factors in the perspective of multimorbidity. This research aimed to identify these aspects in a primary health care setting of central Argentina. The Pan America version of the STEP wise approach surveillance (STEPS) instrument of the World Health Organization was applied to 1044 participants, 365 men and 679 women, with a mean age of 43 years. High prevalence of overweight (33.5%), obesity (35.2%), central obesity (54%), dyslipidemia (43.5%), metabolic syndrome (21.1%), low intake of fruit and vegetables (91.8%), low levels of physical activity (71.5%), risky alcohol consumption (28%), and smoking (22.5%) were detected. Hypertension and diabetes were the most prevalent chronic conditions and the total prevalence of multimorbidity was 33.1%, with 2, 3, 4, 5 and 6 chronic conditions found in 19.9%, 9.1%, 2.6%, 1.1% and 0.4% of the population, respectively. Multimorbidity affected 6.4% of the young, 31.7% of the adults, and 60.6% of the elderly, and was more prevalent among women, and in participants with lower levels of education. Having multimorbidity was significantly associated with obesity, central obesity, and higher concentrations of total blood cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose. A website was made available to the participants in order to share the experimental results and health-promoting information.

['Olivares|David E V|DE|', 'Chambi|Frank R V|FR|', 'Chañi|Evelyn M M|EM|', 'Craig|Winston J|WJ|', 'Pacheco|Sandaly O S|SO|', 'Pacheco|Fabio J|FJ|']

2017

31200593

A Glove-Based Form Factor for Collecting Joint Acoustic Emissions: Design and Validation.

Sounds produced by the articulation of joints have been shown to contain information characteristic of underlying joint health, morphology, and loading. In this work, we explore the use of a novel form factor for non-invasively acquiring acoustic/vibrational signals from the knee joint: an instrumented glove with a fingertip-mounted accelerometer. We validated the glove-based approach by comparing it to conventional mounting techniques (tape and foam microphone pads) in an experimental framework previously shown to reliably alter healthy knee joint sounds (vertical leg press). Measurements from healthy subjects (N = 11) in this proof-of-concept study demonstrated a highly consistent, monotonic, and significant (p < 0.01) increase in low-frequency signal root-mean-squared (RMS) amplitude-a straightforward metric relating to joint grinding loudness-with increasing vertical load across all three techniques. This finding suggests that a glove-based approach is a suitable alternative for collecting joint sounds that eliminates the need for consumables like tape and the interface noise associated with them.

['Bolus|Nicholas B|NB|', 'Jeong|Hyeon Ki|HK|', 'Whittingslow|Daniel C|DC|', 'Inan|Omer T|OT|']

2019

28479056

Utility of Synovial White Blood Cell Count and Differential Before Reimplantation Surgery.

BACKGROUND Determining optimal timing of reimplantation during 2-stage exchange for periprosthetic joint infection (PJI) remains elusive. Joint aspiration for synovial white blood cell (WBC) count and neutrophil percentage (PMN%) before reimplantation is widely performed; yet, the implications are rarely understood. Therefore, this study investigates (1) the diagnostic yield of synovial WBC count and differential analysis and (2) the calculated thresholds for persistent infection. METHODS Institutional PJI databases identified 129 patients undergoing 2-stage exchange arthroplasty who had joint aspiration before reimplantation between February 2005 and May 2014. Persistent infection was defined as a positive aspirate culture, positive intraoperative cultures, or persistent symptoms of PJI-including subsequent PJI-related surgery. Receiver-operating characteristic curve was used to calculate thresholds maximizing sensitivity and specificity. RESULTS Thirty-three cases (33 of 129; 25.6%) were classified with persistent PJI. Compared with infection-free patients, these patients had significantly elevated PMN% (62.2% vs 48.9%; P = .03) and WBC count (1804 vs 954 cells/μL; P = .04). The receiver-operating characteristic curve provided thresholds of 62% and 640 cells/μL for synovial PMN% and WBC count, respectively. These thresholds provided sensitivity of 63% and 54.5% and specificity of 62% and 60.0%, respectively. The risk of persistent PJI for patients with PMN% >90% was 46.7% (7 of 15). CONCLUSION Synovial fluid analysis before reimplantation has unclear utility. Although statistically significant elevations in synovial WBC count and PMN% are observed for patients with persistent PJI, this did not translate into useful thresholds with clinical importance. However, with little other guidance regarding the timing of reimplantation, severely elevated WBC count and differential analysis may be of use.

['Zmistowski|Benjamin M|BM|', 'Clyde|Corey T|CT|', 'Ghanem|Elie S|ES|', 'Gotoff|James R|JR|', 'Deirmengian|Carl A|CA|', 'Parvizi|Javad|J|']

2017

29643214

Anemone bleaching increases the metabolic demands of symbiont anemonefish.

Increased ocean temperatures are causing mass bleaching of anemones and corals in the tropics worldwide. While such heat-induced loss of algal symbionts (zooxanthellae) directly affects anemones and corals physiologically, this damage may also cascade on to other animal symbionts. Metabolic rate is an integrative physiological trait shown to relate to various aspects of organismal performance, behaviour and locomotor capacity, and also shows plasticity during exposure to acute and chronic stressors. As climate warming is expected to affect the physiology, behaviour and life history of animals, including ectotherms such as fish, we measured if residing in bleached versus unbleached sea anemones (Heteractis magnifica) affected the standard (i.e. baseline) metabolic rate and behaviour (activity) of juvenile orange-fin anemonefish (Amphiprion chrysopterus). Metabolic rate was estimated from rates of oxygen uptake [Formula: see text], and the standard metabolic rate [Formula: see text] of anemonefish from bleached anemones was significantly higher by 8.2% compared with that of fish residing in unbleached anemones, possibly due to increased stress levels. Activity levels did not differ between fish from bleached and unbleached anemones. As [Formula: see text] reflects the minimum cost of living, the increased metabolic demands may contribute to the negative impacts of bleaching on important anemonefish life history and fitness traits observed previously (e.g. reduced spawning frequency and lower fecundity).

['Norin|Tommy|T|0000-0003-4323-7254', 'Mills|Suzanne C|SC|0000-0001-8948-3384', 'Crespel|Amélie|A|', 'Cortese|Daphne|D|', 'Killen|Shaun S|SS|0000-0003-4949-3988', 'Beldade|Ricardo|R|']

2018

32988583

Dual specificity phosphatase 9: A novel binding partner cum substrate of proapoptotic serine protease HtrA2.

Human high temperature requirement protease A2 (HtrA2) is a trimeric PDZ bearing proapoptotic serine protease, which is involved in various cellular processes and pathologies. Research in the last decade strongly advocates its role as a potential therapeutic target and therefore warrants the need to minutely investigate its mechanism of action, regulation, interactions with other proteins and its binding specificities. In this particular study, we adopted an in silico approach to predict novel interacting partners and/or substrates of HtrA2 by building a peptide library using a binding pattern search. This library was used to look for novel ligand proteins in the human proteome. Thereafter, the putative interaction was validated using biochemical and cell-based studies. In a first, here we report that HtrA2 shows robust interactions with DUSP9 (Dual specificity phosphatase 9) in GST-pulldown and Co-Immunoprecipitation (Co-IP) experiments and cleaves it in vitro. Besides, we also provided a detailed characterization of the interaction interface. Moreover, this study in general provides an efficient, fast and practical method of candidate ligand library screening for exploring the binding properties of HtrA2.

['Acharya|Saujanya|S|', 'Dutta|Shubhankar|S|', 'Mudrale|Snehal Pandav|SP|', 'Bose|Kakoli|K|']

2020

33078975

Responses to iron oxide and zinc oxide nanoparticles in echinoderm embryos and microalgae: uptake, growth, morphology, and transcriptomic analysis.

We investigated the toxicity of Iron oxide and Zinc oxide engineered nanoparticles (ENPs) on Paracentrotus lividus sea urchin embryos and three species of microalgae. Morphological responses, internalization, and potential impacts of Fe2O3 and ZnO ENPs on physiology and metabolism were assessed. Both types of ENPs affected P. lividus larval development, but ZnO ENPs had a much stronger effect. While growth of the alga Micromonas commoda was severely impaired by both ENPs, Ostreococcus tauri or Nannochloris sp. were unaffected. Transmission electron microscopy showed the internalization of ENPs in sea urchin embryonic cells while only nanoparticle interaction with external membranes was evidenced in microalgae, suggesting that marine organisms react in diverse ways to ENPs. Transcriptome-wide analysis in P. lividus and M. commoda showed that many different physiological pathways were affected, some of which were common to both species, giving insights about the mechanisms underpinning toxic responses.

['Genevière|Anne-Marie|AM|0000-0003-4721-4076', 'Derelle|Evelyne|E|', 'Escande|Marie-Line|ML|', 'Grimsley|Nigel|N|', 'Klopp|Christophe|C|', 'Ménager|Christine|C|', 'Michel|Aude|A|', 'Moreau|Hervé|H|']

2020

27245870

Rod-cone based color vision in seals under photopic conditions.

Marine mammals have lost the ability to express S-cone opsin, and possess only one type of M/L-cone in addition to numerous rods. As they are cone monochromats they should be color blind. However, early behavioral experiments with fur seals and sea lions indicated discrimination ability between many shades of grey and blue or green. On the other hand, most recent training experiments with harbor seals under "mesopic" conditions demonstrated rod based color blindness (Scholtyssek et al., 2015). In our experiments we trained two harbor seals (Phoca vitulina) and two South African fur seals (Arctocephalus pusillus) with surface colors under photopic conditions. The seals had to detect a triangle on grey background shown on one of three test fields while the other two test fields were homogeneously grey. In a first series of experiments we determined brightness detection. We found a luminance contrast of >3% sufficient for correctly choosing the triangle. In the tests for color vision the triangle was blue, green or yellow in grey surround. The results show that the animals could see the colored triangle despite minimal or zero brightness contrast. Thus, seals have color vision based on the contribution of cones and rods even in bright daylight.

['Oppermann|Daniela|D|', 'Schramme|Jürgen|J|', 'Neumeyer|Christa|C|']

2016

24573644

Adaptation of an Acculturation Scale for African Refugee Women.

Newly-arrived African refugees are a vulnerable group of immigrants for whom no validated acculturation measures exist. A valid measurement tool is essential to understand how acculturative processes impact health and health disparities. We adapted the Bicultural Involvement Questionnaire (BIQ) to characterize its reliability among ethnic Somali women residing in Minnesota, and Somali, Somali Bantu, and Burundian women in Arizona. Surveys were administered to 164 adult women. Analyses were conducted along socio-demographic variables of ethnicity, geographic residence, age, and length of time in the United States through t tests and one-way analysis of variance. Exploratory factor analysis was conducted on the modified BIQ. Exploratory factor analyses yielded five subscales: "Speak Native Language", "Speak English Language", "Enjoy Native Activities", "Enjoy American Activities", and "Desired Ideal Culture". The subscales of the modified BIQ possessed Cronbach's α ranging from 0.68 to 0.92, suggestive that all subscales had acceptable to excellent internal consistency. The modified BIQ maintained its psychometric properties across geographic regions of resettled Central and East African refugees.

['Johnson-Agbakwu|Crista E|CE|', 'Flynn|Priscilla|P|', 'Asiedu|Gladys B|GB|', 'Hedberg|Eric|E|', 'Breitkopf|Carmen Radecki|CR|']

2016

32075457

Inhibitors of the protein-protein interaction between phosphorylated p62 and Keap1 attenuate chemoresistance in a human hepatocellular carcinoma cell line.

Resistance to anticancer agents has been an obstacle to developing therapeutics and reducing medical costs. Whereas sorafenib is used for the treatment of human hepatocellular carcinoma (HCC), resistance limits its efficacy. p62, a multifunctional protein, is overexpressed in several HCC cell lines, such as Huh-1 cells. Phosphorylated p62 (p-p62) inhibits the protein-protein interaction (PPI) between Keap1 and Nrf2, resulting in the Nrf2 overactivation that causes drug resistance. We have found a unique Nrf2 inactivator, named K67, that inhibited the PPI between Keap1 and p-p62 and attenuated sorafenib resistance in Huh-1 cells. Herein, we designed and synthesised novel K67 derivatives by modification of the substituent at the 4-position of the two benzenesulfonyl groups of K67. Although these new derivatives inhibited the Keap1-p-p62 PPI to a level comparable to or weaker than that of K67, the isopropoxy derivative enhanced the sensitivity of Huh-1 cells to sorafenib to a greater extent than K67 without any influence on the viability of Huh-7 cells, which is a non-resistant HCC cell line. The isopropoxy derivative also increased the sensitivity of Huh-1 cells to regorafenib, which suggests that this derivative has the potential to be used as an agent to overcome chemoresistance based on Nrf2 inactivation.

['Yasuda|Daisuke|D|', 'Ohe|Tomoyuki|T|https://orcid.org/0000-0002-0931-1708', 'Takahashi|Kyoko|K|', 'Imamura|Riyo|R|', 'Kojima|Hirotatsu|H|', 'Okabe|Takayoshi|T|', 'Ichimura|Yoshinobu|Y|', 'Komatsu|Masaaki|M|https://orcid.org/0000-0001-7672-7722', 'Yamamoto|Masayuki|M|', 'Nagano|Tetsuo|T|', 'Mashino|Tadahiko|T|']

2020

27449523

Prevalence and Associated Factors of Cancer-Related Fatigue Among Cancer Patients in Eastern China.

BACKGROUND Cancer-related fatigue (CRF) is a subjective and distressing symptom, and its associated factors in developing countries remain ambiguous. The goal of this study was to determine the prevalence of and factors associated with CRF among cancer patients in China. METHODS This study was designed as a cross-sectional study to determine the prevalence of and factors associated with CRF among cancer patients in eastern China, regardless of their diagnoses. Data were collected by using a questionnaire survey (including demographic information and brief fatigue inventory) after informed written consent was obtained. A chi-square test was used to analyze the correlations between single categorical factors and CRF, and multiple logistic regression analysis was used to evaluate the associations of potential risk factors with the presence of CRF. RESULTS Out of a total population of 1,938 cancer patients, 1,749 had completed the study questionnaire; 52.07% (n = 904) reported clinically significant fatigue (score ≥4 on Brief Fatigue Inventory). Four hundred twenty-seven (48.47%) patients younger than age 58 years (the median age) and 475 (55.69%) patients age 58 years or older reported clinically significant fatigue. In multivariate analysis, higher sleep quality (p < .01) was negatively associated with CRF, whereas never engaging in physical exercise (p < .01) and higher clinical stage of cancer (p < .01) were positively associated factors that could increase the odds of CRF. CONCLUSION The results of this study suggest that effective management of the two changeable contributing factors of CRF may reduce CRF and thus could be used as references for CRF management. IMPLICATIONS FOR PRACTICE The two modifiable factors of cancer-related fatigue (CRF)-sleep disturbance and physical exercise-should be specifically assessed and managed to mitigate CRF.

['Tian|Li|L|', 'Lin|Lu|L|', 'Li|Hui L|HL|', 'Chen|Ke J|KJ|', 'Zhang|Xiao J|XJ|', 'Qian|Shu J|SJ|', 'Hu|Yan|Y|']

2016

32736950

DIGEST: Developing innovative gastroenterology specialty training.

Individuals with cystic fibrosis (CF) now have an increased life expectancy, due to advances in care provided by a multidisciplinary team. The care model has expanded over time to include multiple subspecialties. The Cystic Fibrosis Foundation conducted a survey of Care Center Directors and identified a need for pediatric and adult gastroenterologists with expertise in the diagnosis and treatment of intestinal, pancreatic and hepatic complications of CF. To address this need, the Developing Innovative GastroEnterology Specialty Training (DIGEST) program was created. The development, implementation, and early results of this training program are reported herein.

['Lusman|Sarah Shrager|SS|', 'Borowitz|Drucy|D|', 'Marshall|Bruce C|BC|', 'Narkewicz|Michael R|MR|', 'Gonska|Tanja|T|', 'Grand|Richard J|RJ|', 'Simon|Richard H|RH|', 'Mascarenhas|Maria R|MR|', 'Schwarzenberg|Sarah Jane|SJ|', 'Freedman|Steven D|SD|']

2021

32045663

AED and text message responders density in residential areas for rapid response in out-of-hospital cardiac arrest.

BACKGROUND For out-of-hospital cardiac arrest (OHCA) in residential areas, a dispatcher driven alert-system using text messages (TM-system) directing local rescuers (TM-responders) to OHCA patients was implemented and the desired density of automated external defibrillators (AEDs) or TM-responders investigated. METHODS We included OHCA cases with the TM-system activated in residential areas between 2010-2017. For each case, densities/km2 of activated AEDs and TM-responders within a 1000 m circle were calculated. Time intervals between 112-call and first defibrillation were calculated. RESULTS In total, 813 patients (45%) had a shockable initial rhythm. In 17% a TM-system AED delivered the first shock. With increasing AED density, the median time to shock decreased from 10:59 to 08:17 min. (p < 0.001) and shocks <6 min increased from 6% to 12% (p = 0.024). Increasing density of TM-responders was associated with a decrease in median time to shock from 10:59 to 08:20 min. (p < 0.001) and increase of shocks <6 min from 6% to 13% (p = 0.005). Increasing density of AEDs and TM-responders resulted in a decline of ambulance first defibrillation by 19% (p = 0.016) and 22% (p = 0.001), respectively. First responder AED defibrillation did not change significantly. Densities of >2 AEDs/km2 did not result in further decrease of time to first shock but >10 TM-responders/km2 resulted in more defibrillations <6 min. CONCLUSION With increasing AED and TM-responder density within a TM-system, time to defibrillation in residential areas decreased. AED and TM-responders only competed with ambulances, not with first responders. The recommended density of AEDs and TM-responders for earliest defibrillation is 2 AEDs/km2 and >10 TM-responders/km2.

['Stieglis|Remy|R|', 'Zijlstra|Jolande A|JA|', 'Riedijk|Frank|F|', 'Smeekes|Martin|M|', 'van der Worp|Wim E|WE|', 'Koster|Rudolph W|RW|']

2020

28554975

Mechanical and electrostatic experiments with dust particles collected in the inner coma of comet 67P by COSIMA onboard Rosetta.

The in situ cometary dust particle instrument COSIMA (COmetary Secondary Ion Mass Analyser) onboard ESA's Rosetta mission has collected about 31 000 dust particles in the inner coma of comet 67P/Churyumov-Gerasimenko since August 2014. The particles are identified by optical microscope imaging and analysed by time-of-flight secondary ion mass spectrometry. After dust particle collection by low speed impact on metal targets, the collected particle morphology points towards four families of cometary dust particles. COSIMA is an in situ laboratory that operates remotely controlled next to the comet nucleus. The particles can be further manipulated within the instrument by mechanical and electrostatic means after their collection by impact. The particles are stored above 0°C in the instrument and the experiments are carried out on the refractory, ice-free matter of the captured cometary dust particles. An interesting particle morphology class, the compact particles, is not fragmented on impact. One of these particles was mechanically pressed and thereby crushed into large fragments. The particles are good electrical insulators and transform into rubble pile agglomerates by the application of an energetic indium ion beam during the secondary ion mass spectrometry analysis.This article is part of the themed issue 'Cometary science after Rosetta'.

['Hilchenbach|Martin|M|0000-0003-1703-7777', 'Fischer|Henning|H|', 'Langevin|Yves|Y|', 'Merouane|Sihane|S|', 'Paquette|John|J|', 'Rynö|Jouni|J|', 'Stenzel|Oliver|O|', 'Briois|Christelle|C|', 'Kissel|Jochen|J|', 'Koch|Andreas|A|', 'Schulz|Rita|R|', 'Silen|Johan|J|', 'Altobelli|Nicolas|N|', 'Baklouti|Donia|D|', 'Bardyn|Anais|A|', 'Cottin|Herve|H|', 'Engrand|Cecile|C|', 'Fray|Nicolas|N|', 'Haerendel|Gerhard|G|', 'Henkel|Hartmut|H|', 'Höfner|Herwig|H|', 'Hornung|Klaus|K|', 'Lehto|Harry|H|', 'Mellado|Eva Maria|EM|', 'Modica|Paola|P|', 'Le Roy|Lena|L|', 'Siljeström|Sandra|S|', 'Steiger|Wolfgang|W|', 'Thirkell|Laurent|L|', 'Thomas|Roger|R|', 'Torkar|Klaus|K|', 'Varmuza|Kurt|K|', 'Zaprudin|Boris|B|', '|||']

2017

28689868

Evaluation of haemodialysis as a protective technique for preventing high daily dose amikacin nephrotoxicity: an experimental study in an ovine model.

Changes in pharmacokinetic parameters of critically ill patients make the treatment of infections challenging, particularly when multidrug-resistant bacteria are involved. The aim of this study was to evaluate the ability of haemodialysis to reduce the exposure to high dose amikacin and prevent nephrotoxicity. Amikacin 50 mg/kg was administered intravenously to six adult sheep once-daily for four days. The sheep were divided into two groups according to the implementation (group 1) or not (group 2) of haemodialysis. In group 1, haemodialysis was performed for 4 h, initiated 2 h after starting amikacin infusion. Amikacin area under the curve (AUC) and trough concentrations (Cmin) were used as markers of amikacin-induced nephrotoxicity. The median haemodialysis amikacin clearance was 2.14 L/h (35.6 mL/min), 14% of the mean total body clearance for 24 h. Haemodialysis reduced Cmin (group 1: 0.3 µg/mL [0.3-1.1]; group 2: 1.4 µg/mL [1.1-3.9]; P = 0.0003). A trend towards reduced AUC with haemodialysis was observed (group 1: 1450 µg/mL⋅h [1311-1716]; group 2: 3126 µg/mL⋅h [2581-3171]; P = 0.10). In conclusion, haemodialysis seems interesting in reducing AUC and Cmin after the injection of high-dose of amikacin, parameters known to be involved in its induced nephrotoxicity, in an experimental ovine model.

['Pouzot-Nevoret|Céline|C|', 'Magnin|Mathieu|M|', 'Ayoub|Jean-Yves|JY|', 'Bourguignon|Laurent|L|', 'Maire|Pascal|P|', 'Wertz|Damien|D|', 'Goy-Thollot|Isabelle|I|', 'Barthélemy|Anthony|A|', 'Boselli|Emmanuel|E|', 'Allaouchiche|Bernard|B|', 'Bonnet-Garin|Jeanne Marie|JM|']

2017

29873281

Differentiating Intrarenal Ectopic Adrenal Tissue From Renal Cell Carcinoma in the Kidney.

BACKGROUND Adrenal rest (AR) is the presence of ectopic adrenal cortical tissue, often identified incidentally during autopsy (20% of postmortem examination). In the kidney, AR can be found in 6% of the general population. Ectopic adrenal tissue is of no functional significance but may in some cases, pose a diagnostic challenge for the pathologist, especially in the context of renal clear cell renal cell carcinoma (RCC) and small needle biopsies. AIM To investigate the utility of immunohistochemical stains in distinguishing AR from RCC. METHODS Archival cases of AR, in our institution, were reviewed and compared with a cohort of RCC cases using a panel of immunohistochemical stains, including PAX2, PAX8, calretinin, and inhibin. RESULTS Nine of 10 (90%) cases of AR showed positive staining for inhibin and negative staining for calretinin, PAX2 and PAX8. One AR case was positive for PAX2 and PAX8 in addition to inhibin. All (100%) RCC cases were positive for PAX2 and PAX8, but negative for inhibin and calretinin. CONCLUSIONS A panel of PAX2, PAX8 and inhibin may be useful markers for distinguishing AR from RCC. Calretinin was noncontributory in our study.

['Yousif|Mustafa Q|MQ|https://orcid.org/0000-0002-4785-8579', 'Salih|Ziyan T|ZT|', 'DeYoung|Barry R|BR|', 'Qasem|Shadi A|SA|']

2018

31858267

Disruption of gamma-delta relationship related to working memory deficits in first-episode psychosis.

Working memory (WM) deficits constitute a core symptom of schizophrenia. Inadequacy of WM maintenance in schizophrenia has been reported to reflect abnormalities in the excitation/inhibition (E/I) balance between pyramidal neurons and parvalbumin basket cells, which may explain alterations of the dynamics of gamma and delta oscillations. To address this issue, we assessed event-related gamma (35-45 Hz) and delta (0.5-4 Hz) oscillatory responses in a visual n-back WM task in patients with first-episode psychosis (FEP) and healthy controls (HC). Periodicity analyses of oscillations were computed to explore the relationship between the psychiatric status and the WM load-related processes reflected by each frequency range. The correspondence between nested delta-gamma oscillations was estimated to assess the strength of the frontal E/I balance. In HC, gamma oscillations were synchronized by the stimulus in a 50-150 ms time range for all tasks, and periodicity of the delta cycle was comparable between the tasks. In addition, synchronization of gamma oscillations in HC occurred at the maximal descending phase of the delta cycle half-period, supporting the coexistence of delta-nested gamma oscillations. Compared with controls, FEP patients showed a lack of gamma synchronization independently of the nature of the task, and the period of delta oscillation increased significantly with the difficulty of the WM task. We thus demonstrated in FEP an inability to encode multiple items in short-term memory associated with abnormalities in the relationship between oscillations related to the difficulty of the WM task. These results argue in favor of a dysfunction of the E/I balance in psychosis.

['Missonnier|Pascal|P|', 'Prévot|Anne|A|', 'Herrmann|François R|FR|', 'Ventura|Joseph|J|', 'Padée|Anna|A|', 'Merlo|Marco C G|MCG|']

2020

30279876

A case of acute and late coronary events after blunt chest trauma: Attention to the late onset angina.

Mechanisms of acute myocardial infarction caused by traumatic coronary artery injury have been reported. However, late-onset coronary artery stenosis associated with trauma is less well known. We experienced a case in which acute myocardial infarction of the right coronary artery occurred at the time of blunt chest trauma (BCT) caused by a traffic accident and an increase in coronary artery stenosis in the left anterior descending artery (LAD) branch about 1 year later. A comparison of a volume-rendering image created from enhanced-contrast computed tomography at the time of trauma and coronary angiography revealed that the trauma site and the stenotic lesion in the LAD were in very close proximity, suggesting to us that traumatic coronary artery injury without flow limitation may have developed into high-grade stenosis in the LAD 1 year later. In this case we were able to demonstrate a causal relationship between BCT and delayed coronary artery stenosis. After BCT, it is necessary to be aware of the possibility of delayed coronary artery stenosis even if coronary injury is absent in the acute phase. <Learning objective: Careful follow up for the onset of angina pectoris is necessary to prevent coronary events after blunt chest trauma.>.

['Watari|Yuichiro|Y|', 'Ueda|Hironori|H|', 'Miyamoto|Shogo|S|', 'Hashimoto|Yu|Y|', 'Tomimoto|Hideko|H|', 'Watanabe|Yoshikazu|Y|', 'Urabe|Yoji|Y|', 'Yamazato|Ryo|R|', 'Mitsuba|Naoya|N|', 'Miura|Fumiharu|F|', 'Takahashi|Masashi|M|', 'Okamoto|Mitsunori|M|']

2018

26498607

Celiac Disease: Background and Historical Context.

Medical descriptions of celiac disease date to the first century BC, and the first modern description was published in 1888. Further insights were gained throughout the 1900s, culminating in the identification of the dietary component, the major genetic determinant, and the autoantigen by the turn of the century. Understanding of the age of onset, population prevalence, and the extent of subclinical celiac disease developed in tandem. Thanks to advances in genomics, currently established loci account for over 50 % of the genetic risk. Nonetheless, much remains to be discovered. Advances in high-throughput genomic, biochemical, and cell analyses, as well as the bioinformatics needed to process the data, promise to deepen our understanding further. Here we present a primer of celiac disease, viewing the condition in turn from the historical, epidemiological, immunological, molecular, and genetic points of view. Research into any ailment has specific requirements: study subjects must be identified and relevant tissue samples collected and stored with the appropriate timing and conditions. These requirements are summarized. To conclude, a short discussion of future prospects is presented.

['Turner|Graham D|GD|', 'Dunne|Margaret R|MR|', 'Ryan|Anthony W|AW|']

2015

31303700

Exploring the transversus abdominis plane block in cesarean sections and the subsequent toxicity risk to neonates via breast milk.

The transversus abdominis plane (TAP) block with its wide application has shown to be an analgesic effective for use in abdominal surgeries, including for cesarean section. However, the bupivacaine delivered in the TAP block comes with the risk of toxicity, both central nerve system (CNS) and cardiovascular system, and has been shown in some instances to reach maximum serum concentrations in excess of the 2 μg/mL associated with the lower end of CNS toxicity. There is a specific concern with cesarean section TAP blocks of the anesthetic passage to the neonate via maternal breast milk and whether this poses a toxicity risk. Bupivacaine has been shown to pass into maternal milk at concentrations 0.34 times the maternal serum concentration. Preliminary statistical analyses suggest that the bupivacaine delivered in breast milk is not in concentrations high enough to cause neonatal toxicity, but further studies would be useful in identifying what the toxicity risk is, if any, to the neonates' breastfeeding after the delivery and TAP block.

['Junge|Joshua|J|', 'Inchiosa|Mario A|MA|', 'Xu|Jeff L|JL|']

2019

27867930

A Case of Primary Central Nervous System Lymphoma Located at Brain Stem in a Child.

Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis.

['Kim|Jinho|J|', 'Kim|Young Zoon|YZ|']

2016

29619670

Output factor determination based on Monte Carlo simulation for small cone field in 10-MV photon beam.

The difficulty of measuring output factor (OPF) in a small field has been frequently discussed in recent publications. This study is aimed to determine the OPF in a small field using 10-MV photon beam and stereotactic conical collimator (cone). The OPF was measured by two diode detectors (SFD, EDGE detector) and one micro-ion chamber (PinPoint 3D chamber) in a water phantom. A Monte Carlo simulation using simplified detector model was performed to obtain the correction factor for the detector measurements. About 12% OPF difference was observed in the measurement at the smallest field (7.5 mm diameter) for EDGE detector and PinPoint 3D chamber. By applying the Monte Carlo-based correction factor to the measurement, the maximum discrepancy among the three detectors was reduced to within 3%. The results indicate that determination of OPF in a small field should be carefully performed. Especially, detector choice and appropriate correction factor application are very important in this regard.

['Fukata|Kyohei|K|http://orcid.org/0000-0003-4015-6969', 'Sugimoto|Satoru|S|', 'Kurokawa|Chie|C|', 'Saito|Akito|A|', 'Inoue|Tatsuya|T|', 'Sasai|Keisuke|K|']

2018

34325760

Hyperemesis gravidarum and vitamin K deficiency: a systematic review.

Hyperemesis gravidarum (HG), severe nausea and vomiting in pregnancy, can lead to vitamin deficiencies. Little is known about HG-related vitamin K deficiency. We aimed to summarise available evidence on the occurrence of HG-related vitamin K deficiency and corresponding maternal and neonatal complications. A systematic review was conducted, searching Medline and EMBASE from inception to 12 November 2020. We identified 1564 articles, of which we included fifteen in this study: fourteen case reports (n 21 women) and one retrospective cohort study (n 109 women). Nine out of twenty-one women reported in case reports had a prolonged prothrombin time (PT). The cohort study measured PT in 39/109 women with HG, of whom 10/39 women (26 %) had prolonged PT. In total, 30-50 % women received vitamin K supplementation after vitamin K deficiency had been diagnosed. Four case reports (n 4 women) reported corresponding maternal complications, all consisting of coagulopathy-related haemorrhage. Nine case reports (n 16 neonates) reported corresponding neonatal complications including intracranial haemorrhage (n 2 neonates) and embryopathy (n 14 neonates), which consisted of Binder phenotype (n 14 neonates), chondrodysplasia punctata (n 9 neonates) and grey matter heterotopia (n 3 neonates). In conclusion, vitamin K deficiency and related complications occur among women with HG. In our systematic review, we were unable to assess the incidence rate.

['Nijsten|Kelly|K|https://orcid.org/0000-0002-5308-5293', 'van der Minnen|Loïs|L|', 'Wiegers|Hanke M G|HMG|', 'Koot|Marjette H|MH|', 'Middeldorp|Saskia|S|', 'Roseboom|Tessa J|TJ|', 'Grooten|Iris J|IJ|', 'Painter|Rebecca C|RC|']

2021

26846795

Is dextrose prolotherapy superior to placebo for the treatment of temporomandibular joint hypermobility? A randomized clinical trial.

A randomized clinical trial involving adult patients with bilateral temporomandibular joint (TMJ) hypermobility referred for treatment was implemented. The sample comprised 30 consecutive patients, who were divided randomly into two groups. The TMJ hypermobility was treated with either saline (placebo group) or dextrose injections (study group). The solution was injected into five different TMJ areas in three sessions at monthly intervals. The predictor variable was the treatment technique. The outcome variables were visual analogue scale (VAS) evaluations and maximum inter-incisal opening (MIO). Outcome variables were recorded preoperatively and at 12 months postoperatively. Descriptive and bivariate statistics were computed, and significance was set at a P-value of <0.05. The follow-up sample comprised 26 subjects: 12 in the placebo group and 14 in the study group. Masticatory efficiency increased and general pain complaints and joint sounds decreased significantly in both groups. MIO decreased significantly only in the study group. Insignificant changes in the other parameters were found for both groups. After estimating differences between follow-up and baseline outcomes, the mean change in primary outcome variables showed no statistically significant difference between the two groups. These findings suggest that dextrose prolotherapy is no more effective than placebo treatment for any of the outcome variables of TMJ hypermobility assessed.

['Cömert Kiliç|S|S|', 'Güngörmüş|M|M|']

2016

27166438

Biochemistry and Function of RNA Exosomes.

Discovery of the evolutionary conserved RNA exosome was a milestone in RNA biology. First identified as an activity essential for the processing of ribosomal RNA, the exosome has since proved to be central for RNA processing and degradation in both the nucleus and the cytoplasm of eukaryotic cells. This multisubunit protein complex consists of a catalytically inert 9-subunit core endowed with associated ribonucleolytic activities and further assisted by compartment-specific cofactors required for its activation and substrate targeting. Although many features of exosome biology are known, fundamental aspects are still under investigation. In this chapter, we review current biochemical and functional knowledge of eukaryotic exosomes. After introducing some of their nuclear and cytoplasmic functions, we discuss the structural organization and evolutionary aspects of exosome complexes. Finally, we describe catalytic properties of the complex and its regulation by cofactors.

['Lubas|Michal|M|', 'Chlebowski|Aleksander|A|', 'Dziembowski|Andrzej|A|', 'Jensen|Torben Heick|TH|']

2012

29769137

Laboratory studies on the oviposition stimuli of Culicoides stellifer (Diptera: Ceratopogonidae), a suspected vector of Orbiviruses in the United States.

BACKGROUND Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) exert a significant impact on animal agriculture worldwide because they transmit bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) to ruminants. Without effective vaccines, BTV/EHDV vector management strategies are needed, particularly in commercial white-tailed deer (WTD) facilities. However, detailed information on the ecology of midge immatures in/around cervid operations is currently lacking. Towards filling this knowledge gap, we conducted two-choice oviposition experiments with field-collected Culicoides stellifer Coquillett (a suspected vector of BTV/EHDV in the USA) under laboratory conditions to examine which natural source from the larval habitat is relatively more attractive for midge oviposition. METHODS Field-collected C. stellifer females (CDC-UV light traps) were given a blood meal from live chicken and examined for their oviposition preferences for individual (or mixed) potential larval habitat oviposition stimuli in two-choice bioassays. Substrates included mud from C. stellifer habitat, mud from allopatric site, vegetation (Sphagnum spp. mosses), field water, WTD manure and de-ionized water (control). RESULTS The majority of midges (91%) oviposited in only one dish, with few females (9%) ovipositing in both the dishes. Gravid females demonstrated an overall oviposition preference for substrates with mud and vegetation from the larval habitat, depositing a significantly higher proportion of eggs on mud (52.3%) and vegetation (81.8%) than on controls (≤ 18.2%) (P ≤ 0.0320). Moreover, greater number of eggs per female were deposited on mud (29.5-40.7 depending on trial) and vegetation (38.2) than on controls (≤ 5.8). WTD manure, field water and mud from allopatric site were not found to be more attractive than controls for oviposition. Combining individual substrates (mud + WTD manure; mud + moss + WTD manure + field water) did not elicit greater oviposition responses than mud or moss alone. CONCLUSIONS Management strategies to discourage C. stellifer oviposition in/around commercial cervid facilities should likely focus on mud and/or vegetation, rather than WTD manure. However, further studies are needed to examine whether the spatial distributions of C. stellifer and Sphagnum spp. moss are correlated, and to determine whether targeting vegetation in/around cervid facilities can contribute to reductions in local midge densities.

['Erram|Dinesh|D|', 'Burkett-Cadena|Nathan|N|']

2018

33323099

DRACP: a novel method for identification of anticancer peptides.

BACKGROUND Millions of people are suffering from cancers, but accurate early diagnosis and effective treatment are still tough for all doctors. Common ways against cancer include surgical operation, radiotherapy and chemotherapy. However, they are all very harmful for patients. Recently, the anticancer peptides (ACPs) have been discovered to be a potential way to treat cancer. Since ACPs are natural biologics, they are safer than other methods. However, the experimental technology is an expensive way to find ACPs so we purpose a new machine learning method to identify the ACPs. RESULTS Firstly, we extracted the feature of ACPs in two aspects: sequence and chemical characteristics of amino acids. For sequence, average 20 amino acids composition was extracted. For chemical characteristics, we classified amino acids into six groups based on the patterns of hydrophobic and hydrophilic residues. Then, deep belief network has been used to encode the features of ACPs. Finally, we purposed Random Relevance Vector Machines to identify the true ACPs. We call this method 'DRACP' and tested the performance of it on two independent datasets. Its AUC and AUPR are higher than 0.9 in both datasets. CONCLUSION We developed a novel method named 'DRACP' and compared it with some traditional methods. The cross-validation results showed its effectiveness in identifying ACPs.

['Zhao|Tianyi|T|', 'Hu|Yang|Y|', 'Zang|Tianyi|T|http://orcid.org/0000-0003-0195-8731']

2020

29316212

Renal artery stenting for atherosclerotic renal artery stenosis identified in patients with coronary artery disease: Does captopril renal scintigraphy predict outcomes?

The authors evaluated the effectiveness of percutaneous renal revascularization (PRR) with stenting for the treatment of atherosclerotic renal artery stenosis (ARAS) in patients with coronary artery disease and the usefulness of captopril renal scintigraphy for predicting clinical outcomes after PRR. Sixty-four consecutive patients, referred for evaluation of suspected ARAS, after coronary angiography, underwent baseline captopril renal scintigraphy followed by renal angiography. Forty-four patients (68.7%) were diagnosed with a significant ARAS≥ 60% and were treated with PRR plus medical therapy. Twenty-four months after PRR, 86.4% and 73.3% of patients showed a hypertension and renal benefit, respectively. Captopril renal scintigraphy positivity had moderate sensitivity and high specificity in predicting a hypertension and renal benefit. In patients with ARAS≥ 70%, the sensitivity and specificity were 100% for both a hypertension and renal benefit.PRR for ARAS conferred a substantial benefit in patients with a high coronary artery disease burden. Captopril renal scintigraphy was highly accurate in predicting clinical outcomes.

['Stratigis|Spyros|S|', 'Stylianou|Kostas|K|0000-0003-3678-9421', 'Kyriazis|Periklis P|PP|', 'Dermitzaki|Eleftheria-Kleio|EK|', 'Lygerou|Dimitra|D|', 'Syngelaki|Paraskevi|P|', 'Stratakis|Stavros|S|', 'Koukouraki|Sophia|S|', 'Parthenakis|Fragiskos|F|', 'Tsetis|Dimitrios|D|', 'Daphnis|Eugene|E|']

2018

32055233

Proteome Dynamics from Heavy Water Metabolic Labeling and Peptide Tandem Mass Spectrometry.

Protein homeostasis (proteostasis) is a result of a dynamic equilibrium between protein synthesis and degradation. It is important for healthy cell/organ functioning and is often associated with diseases such as neurodegenerative diseases and non-Alcoholic Fatty Liver disease. Heavy water metabolic labeling, combined with liquid-chromatography and mass spectrometry (LC-MS), is a powerful approach to study proteostasis in vivo in high throughput. Traditionally, intact peptide signals are used to estimate stable isotope incorporation in time-course experiments. The time-course of label incorporation is used to extract protein decay rate constant (DRC). Intact peptide signals, computed from integration in chromatographic time and mass-to-charge ratio (m/z) domains, usually, provide an accurate estimate of label incorporation. However, sample complexity (co-elution), limited dynamic range, and low signal-to-noise ratio (S/N) may adversely interfere with the peptide signals. These artifacts complicate the DRC estimations by distorting peak shape in chromatographic time and m/z domains. Fragment ions, on the other hand, are less prone to these artifacts and are potentially well suited in aiding DRC estimations. Here, we show that the label incorporation encoded into the isotope distributions of fragment ions reflect the isotope enrichment during the metabolic labeling with heavy water. We explore the label incorporation statistics for devising practical approaches for DRC estimations.

['Borzou|Ahmad|A|', 'Sadygov|Vugar R|VR|', 'Zhang|William|W|', 'Sadygov|Rovshan G|RG|']

2019

23576957

Regulation of zebrafish sleep and arousal states: current and prospective approaches.

Every day, we shift among various states of sleep and arousal to meet the many demands of our bodies and environment. A central puzzle in neurobiology is how the brain controls these behavioral states, which are essential to an animal's well-being and survival. Mammalian models have predominated sleep and arousal research, although in the past decade, invertebrate models have made significant contributions to our understanding of the genetic underpinnings of behavioral states. More recently, the zebrafish has emerged as a promising model system for sleep and arousal research. Here we review experimental evidence that the zebrafish, a diurnal vertebrate, exhibits fundamental behavioral and neurochemical characteristics of mammalian sleep and arousal. We also propose how specific advantages of the zebrafish can be harnessed to advance the field. These include tractable genetics to identify and manipulate molecular and cellular regulators of behavioral states, optical transparency to facilitate in vivo observation of neural structure and function, and amenability to high-throughput drug screens to discover novel therapies for neurological disorders.

['Chiu|Cindy N|CN|', 'Prober|David A|DA|']

2013

26297073

Guidelines of the French Society of Otorhinolaryngology (SFORL), short version. Diagnosis of local recurrence and metachronous locations in head and neck oncology.

Surveillance is fundamental to the management of head and neck cancer. The present guidelines of the French ENT society (SFORL) were drawn up by a group of experts in the field, and are intended to specify the modalities of management, based on a review of the literature and, where data are lacking, to provide expert opinion. The present paper deals with guidelines for the diagnosis of local and regional recurrence and metachronous head and neck locations. Locoregional recurrence usually occurs within 3 years of primary treatment and is mainly related to the characteristics of the primary tumor and the treatment measures taken. Laryngeal location, safe primary resection margins, low level of lymph node invasion, unimodal primary treatment and early diagnosis of recurrence are factors of good prognosis. Systematic imaging surveillance may be considered for patients for whom a curative technique exists and when surveillance is difficult. The role of PET-scanning remains to be determined. Metachronous locations are frequent, even in the late course; prolonged surveillance is appropriate. The best preventive measure is cessation of alcohol abuse and smoking. Patient education is primordial.

['Halimi|C|C|', 'Barry|B|B|', 'De Raucourt|D|D|', 'Choussy|O|O|', 'Dessard-Diana|B|B|', 'Hans|S|S|', 'Lafarge|D|D|', '|||']

2015

25804855

Muscle and bone, two interconnected tissues.

As bones are levers for skeletal muscle to exert forces, both are complementary and essential for locomotion and individual autonomy. In the past decades, the idea of a bone-muscle unit has emerged. Numerous studies have confirmed this hypothesis from in utero to aging works. Space flight, bed rest as well as osteoporosis and sarcopenia experimentations have allowed to accumulate considerable evidence. Mechanical loading is a key mechanism linking both tissues with a central promoting role of physical activity. Moreover, the skeletal muscle secretome accounts various molecules that affect bone including insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (FGF-2), interleukin-6 (IL-6), IL-15, myostatin, osteoglycin (OGN), FAM5C, Tmem119 and osteoactivin. Even though studies on the potential effects of bone on muscle metabolism are sparse, few osteokines have been identified. Prostaglandin E2 (PGE2) and Wnt3a, which are secreted by osteocytes, osteocalcin (OCN) and IGF-1, which are produced by osteoblasts and sclerostin which is secreted by both cell types, might impact skeletal muscle cells. Cartilage and adipose tissue are also likely to participate to this control loop and should not be set aside. Indeed, chondrocytes are known to secrete Dickkopf-1 (DKK-1) and Indian hedgehog (Ihh) and adipocytes produce leptin, adiponectin and IL-6, which potentially modulate bone and muscle metabolisms. The understanding of this system will enable to define new levers to prevent/treat sarcopenia and osteoporosis at the same time. These strategies might include nutritional interventions and physical exercise.

['Tagliaferri|Camille|C|', 'Wittrant|Yohann|Y|', 'Davicco|Marie-Jeanne|MJ|', 'Walrand|Stéphane|S|', 'Coxam|Véronique|V|']

2015

32066409

Changes in overweight/obesity and central obesity status from preadolescence to adolescence: a longitudinal study among schoolchildren in Japan.

BACKGROUND Little is known about changes in overweight/obesity and central obesity status among schoolchildren from preadolescence to adolescence in Japan, where waist circumference (WC) is generally not measured in annual health examinations at elementary and junior high schools. This study examined changes of overweight/obesity and central obesity status among schoolboys and schoolgirls from preadolescence to adolescence in Japan. METHODS Study subjects were fourth-grade school children (9 or 10 years of age) from all four of Ina town's elementary schools in Japan. Measurement of each participant's height, weight, and WC were made at baseline and 3 years later. Childhood overweight/obesity was determined according to the age- and sex-specific body mass index cut-off points proposed by the International Obesity Task Force. Central obesity was defined as waist-to-height ratio ≥ 0.5. Kappa (κ) statistic was calculated to examine the tracking of overweight/obesity and central obesity. RESULTS Data from 1436 participants (boys: n = 720, girls: n = 716) were analyzed. Overweight/obesity status tracked substantially from fourth grade to seventh grade in both boys (κ = 0.614, P value < 0.001) and girls (κ = 0.619, P value < 0.001). Among participants who were overweight/obese in fourth grade, 55.2% of boys and 63.2% of girls were still overweight/obese in seventh grade. Tracking of central obesity from fourth graders to seventh graders was substantial in boys (κ = 0.651, P value < 0.001) and moderate in girls (κ = 0.544, P value < 0.001). Among participants who had central obesity in fourth grade, 54.1% of boys and 52.6% of girls still had central obesity in seventh grade. CONCLUSIONS The present study showed that the tracking of overweight/obesity from preadolescence to adolescence was substantial in boys and girls. Moreover, more than half of those who had central obesity in preadolescence had central obesity in adolescence. This study suggests that it is important to implement a primary prevention program for overweight/obesity and central obesity in elementary schools before fourth grade.

['Ochiai|Hirotaka|H|http://orcid.org/0000-0003-0450-0718', 'Shirasawa|Takako|T|', 'Nishimura|Rimei|R|', 'Yoshimoto|Takahiko|T|', 'Minoura|Akira|A|', 'Oikawa|Kosuke|K|', 'Miki|Ayako|A|', 'Hoshino|Hiromi|H|', 'Kokaze|Akatsuki|A|']

2020

32245171

Antibody-Drug Conjugate Using Ionized Cys-Linker-MMAE as the Potent Payload Shows Optimal Therapeutic Safety.

Monomethyl auristatin E (MMAE) is the most popular and widely used cytotoxin in the development of antibody-drug conjugates (ADCs). However, current MMAE-based ADCs are all constructed using cleavable linkers, and this design concept still has insurmountable drawbacks. Their potential instabilities and lipophilic MMAE-induced "bystander effect" inevitably increase the toxicity to normal tissues. Herein, we overturn previous negative views of MMAE-based ADCs with non-cleavable linkers and propose using ionized L-Cysteine (Cys)-linker-MMAE as a novel payload, which can ingeniously enrich and enter tumor cells through receptor-mediated endocytosis of antibodies while its lower permeability helps to avoid further off-target toxicity. We demonstrate that Cys-linker-MMAE maintains high potency similar to free MMAE at the tubulin molecular level and can also be efficiently released in target cells. As a result, the preferred ADC (mil40-15) not only exhibits ideal plasma stability and maintains potent cytotoxicity as MMAE (IC50: 10-11 M), but also shows improved safety with lower bystander toxicity (IC50: 10-9 M), its maximum tolerated dose approaching the level of the naked antibody (160 mg/kg). This study indicated that Cys-linker-MMAE has the potential as a potent payload for ADCs, which is expected to provide novel strategies for the development of MMAE-based ADCs.

['Wang|Yanming|Y|0000-0002-8022-5335', 'Liu|Lianqi|L|', 'Fan|Shiyong|S|0000-0003-4216-8226', 'Xiao|Dian|D|', 'Xie|Fei|F|', 'Li|Wei|W|', 'Zhong|Wu|W|0000-0002-0536-620X', 'Zhou|Xinbo|X|']

2020

27659554

Dopamine D1 signaling involvement in the effects of the phosphodiesterase 10A inhibitor, PDM-042 on cognitive function and extrapyramidal side effect in rats.

Inhibition of phosphodiesterase 10A (PDE10A) results in activation of a dopamine D1 receptor-mediated direct pathway in addition to a dopamine D2 receptor-mediated indirect pathway in the striatum. Therefore, PDE10A inhibitors could be novel therapeutics for schizophrenia, which differ from the currently available antipsychotics that directly block the dopamine D2 receptor. Previously, we found that a novel PDE10A inhibitor, PDM-042, had antipsychotic-like activity similar to currently available antipsychotics and minimal cataleptic effects in rats. The purpose of the present study was to examine the pharmacological effects of PDM-042 on cognitive function and extrapyramidal side effect. In addition, we aimed to examine whether these effects were mediated by activation of dopamine D1 signaling in rats. PDM-042 (1-3mg/kg) resulted in better discrimination of a novel object from a familiar one 48h after the acquisition trial, suggesting that PDM-042 increased object recognition memory. A dopamine D1 receptor antagonist, SCH23390 (0.1mg/kg), significantly blocked the enhancement of the object recognition memory induced by PDM-042 (3mg/kg) without affecting the recognition index by itself. We also found that the cataleptic effect of PDM-042 (1mg/kg) was significantly enhanced by SCH23390 (0.01-0.03mg/kg). These results indicate that PDM-042 has the potential to increase object recognition memory and that the cognitive enhancing and cataleptic effects of PDM-042 are mediated at least by activation of dopamine D1 signaling.

['Arakawa|Keita|K|', 'Nakao|Kazunari|K|', 'Maehara|Shunsuke|S|']

2017

26412381

Development and Evaluation of a Novel Real-Time PCR for Pan-Dermatophyte Detection in Nail Specimens.

An accurate diagnosis of tinea unguium is necessary for the selection of antimycotics and successful treatment. To rapidly and accurately identify the aetiological agents causing tinea unguium, we improved upon the conventional boiling method for DNA extraction and developed a novel real-time PCR detection system that includes two assays. The two assays, based on the amplification of ribosomal internal transcribed spacer regions and 28S rDNA, were designed to detect pan-dermatophyte and Trichophyton rubrum, respectively. The analytical sensitivities of both assays permitted the detection of ten copies of plasmid DNA template. The analytical specificity of the detection system was confirmed using 11 dermatophyte strains and 25 non-dermatophyte strains. In total, 165 nail specimens were examined by microscopy, culture, conventional PCR, and the novel real-time PCR method. Real-time PCR gave positive results in 47.3 % of the specimens (78), a rate exceeding those obtained using microscopy (72, 43.6 %), conventional PCR (69, 41.8 %), and culture (49, 29.7 %). All conventional PCR-positive specimens were detected by real-time PCR, and real-time PCR detected nine specimens that were missed by conventional PCR. The results from latent class analysis, and further calculations, showed that real-time PCR was the most sensitive method, but the diagnostic specificity of the four approaches was equivalent. In particular, molecular approaches may be more effective than microscopy and culture when the clinical symptoms of tinea unguium are not evident.

['Gong|Jie|J|', 'Ran|Menglong|M|', 'Wang|Xiaowen|X|', 'Wan|Zhe|Z|', 'Li|Ruoyu|R|']

2016

26597324

Effect of repeated mass drug administration with praziquantel and track and treat of taeniosis cases on the prevalence of taeniosis in Taenia solium endemic rural communities of Tanzania.

This study evaluated the effect of mass drug administration (MDA) with praziquantel administered to school-aged children (SAC) combined with 'track and treat' of taeniosis cases in the general population on the copro-antigen (Ag) prevalence of taeniosis. The study was conducted in 14 villages in Mbozi and Mbeya district, Tanzania. SAC made up 34% of the population and received MDA with praziquantel (40mg/kg) in 2012 (both districts) and in 2013 (Mbozi only). Three cross-sectional population-based surveys were performed in 2012 (R0), 2013 (R1), and 2014 (R2). In each survey approximately 3000 study subjects of all ages were tested for taeniosis using copro-Ag-ELISA. In total 9064 people were tested and copro-Ag-ELISA positive cases were offered treatment 6-8 months after sampling. The copro-Ag prevalence of taeniosis was significantly higher (Χ2-test, p=0.007) in Mbozi (3.0%) at R0 compared to Mbeya (1.5%). Twelve months after MDA in both districts (R1), the copro-Ag prevalence had dropped significantly in both Mbozi (2.0%, p=0.024) and in Mbeya (0.3%, p=0.004), but the significant difference between the districts persisted (Χ2-test, p<0.001). Ten months after the second round of MDA in Mbozi and 22 month after the first MDA (R2), the copro-Ag prevalence had dropped significantly again in Mbozi (0.8%, p<0.001), but had slightly increased in Mbeya (0.5%, p=0.051), with no difference between the two districts (Χ2-test, p=0.51). The taeniosis cases tracked and treated between round R0 and R2 represented 9% of the projected total number of taeniosis cases within the study area, based on the copro-Ag prevalence and village population data. Among SAC in Mbozi, infection significantly decreased at R1 (p=0.004, OR 0.12, CI: 0.02-0.41) and R2 (p=0.001, OR 0.24, CI: 0.09-0.53) when comparing to R0. In Mbeya infection significant decreased at R1 (p=0.013, OR 0.14, CI: 0.02-0.55), but no difference was found for R2 (p=0. 089), when comparing to R0 among SAC. This study showed that school-based MDA with praziquantel in combination with 'track and treat' of taeniosis cases significantly reduced the copro-Ag prevalence of taeniosis, and that annual MDA was significantly better than single MDA. The persistence of taeniosis cases illustrates that a One Health approach must be emphasized for effective control.

['Braae|Uffe Christian|UC|', 'Magnussen|Pascal|P|', 'Ndawi|Benedict|B|', 'Harrison|Wendy|W|', 'Lekule|Faustin|F|', 'Johansen|Maria Vang|MV|']

2017

33280206

Lower esophageal sphincter muscle of patients with achalasia exhibits profound mast cell degranulation.

BACKGROUND Eosinophils and mast cells are key effectors of allergy. When they accumulate in the esophagus, their myoactive, pro-inflammatory, and cytotoxic products potentially could cause achalasia-like motility abnormalities and neuronal degeneration. We hypothesized that there is an allergy-mediated form of achalasia. METHODS LES muscle samples obtained during Heller myotomy from patients with achalasia or EGJ outflow obstruction (EGJOO) and from organ donor controls were immunostained for tryptase. Eosinophil and mast cell density, and mast cell degranulation were assessed. LES muscle was evaluated by qPCR for genes mediating smooth muscle Ca2+ handling and contraction. KEY RESULTS There were 13 patients (7 men, median age 59; 10 achalasia, 3 EGJOO) and 7 controls (4 men, median age 42). Eosinophils were infrequent in LES muscle, but mast cells were plentiful. Patients and controls did not differ significantly in LES mast cell density. However, 12 of 13 patients exhibited profound LES mast cell degranulation involving perimysium and myenteric plexus nerves, while only mild degranulation was seen in 2 of 7 controls. Hierarchical clustering analysis of qPCR data revealed two "mototype" LES gene expression patterns, with all type II patients in one mototype, and type I and III patients in the other. CONCLUSIONS & INFERENCES LES muscle of patients with achalasia or EGJOO exhibits striking mast cell degranulation, and patients with different achalasia manometric phenotypes exhibit different LES patterns of expression for genes mediating Ca2+ handling and muscle contraction. Although these findings are not definitive, they support our hypothesis that achalasia can be allergy-driven.

['Nelson|Melissa|M|', 'Zhang|Xi|X|', 'Genta|Robert M|RM|', 'Turner|Kevin|K|', 'Podgaetz|Eitan|E|', 'Paris|Shere|S|', 'Cardenas|Jacob|J|', 'Gu|Jinghua|J|', 'Leeds|Steven|S|', 'Ward|Marc|M|', 'Nguyen|Anh|A|', 'Konda|Vani|V|', 'Furuta|Glenn T|GT|', 'Pan|Zui|Z|', 'Souza|Rhonda F|RF|0000-0003-3484-2807', 'Spechler|Stuart Jon|SJ|']

2021

34760791

Correlations Between Mandibular Asymmetries and Temporomandibular Disorders: A Systematic Review.

Objective This systematic review aimed to investigate the correlation between mandibular asymmetry and temporomandibular disorders (TMDs). Materials and Methods A systematic search of the published literature was performed in electronic databases such as PubMed (MEDLINE), Scopus, Web of Science, Cochrane, Google Scholar, Clinicaltrials.gov, and Saudi Digital Library. Gray literature was searched through System for Information on Grey Literature through OpenGrey. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed in the investigation. The focussed question according to PICO format was: "does the mandibular asymmetry contribute to temporomandibular disorders"? Eligibility criteria included clinical trials (CTs), observation studies, cross-sectional and cohort studies in English that investigated mandibular asymmetries and TMD among patients. Blind and duplicate study selection, data extraction, and risk of bias assessment were carried out. Results The initial search resulted in 1906 articles, of which 11 (8 CTs, 1 cross-sectional, 1 retrospective, and 1 observational) studies were selected for qualitative synthesis after fulfilling the eligibility criteria. Conclusion Most of the studies included in this review showed either very high risk or high risk of bias. Despite the low certainty of evidence, the current study indicated a likely relationship between mandibular asymmetries and TMDs.

['Alqhtani|Nasser|N|', 'Alshammery|Deema|D|', 'AlOtaibi|Nawaf|N|', 'AlZamil|Faisal|F|', 'Allaboon|Aljowhara|A|', 'AlTuwaijri|Dana|D|', 'Baseer|Mohammad Abdul|MA|']

2021

32020458

Emerging trends in municipal solid waste incineration ashes research: a bibliometric analysis from 1994 to 2018.

The rapidly increasing generation of municipal solid waste (MSW) threatens the environmental integrity and well-being of humans at a global level. Incineration is regarded as a technically sound technology for the management of MSW. However, the effective management of the municipal solid waste incineration (MSWI) ashes remains a challenge. This article presents the global dynamics of MSWI ashes research from 1994 to 2018 based on a bibliometric analysis of 1810 publications (research articles and conference proceedings) extracted from the Web of Science database, followed by a comprehensive summary on the research developments in the field. The results indicate the rapid growth of annual publications on MSWI ashes research, with China observed as the most productive country within the study period. Waste Management, Journal of Hazardous Materials, Chemosphere and Waste Management & Research, which accounted for 35.42% of documents on MSWI research, are the most prominent journals in the field. The most critical thematic areas on this topic are MSWI ashes characterisation, dioxin emissions from fly ash, valorisation of bottom ash and heavy metal removal. The evolution of MSWI ashes treatment technologies is also discussed, together with the challenges and future research directions. This is the first bibliometric analysis on global MSWI ashes research based on a sufficiently large dataset, which could provide new insights for researchers to initiate further research with leading institutions/authors and ultimately advance this research field.

['Wong|Syieluing|S|', 'Mah|Angel Xin Yee|AXY|', 'Nordin|Abu Hassan|AH|', 'Nyakuma|Bemgba Bevan|BB|', 'Ngadi|Norzita|N|http://orcid.org/0000-0003-1827-4096', 'Mat|Ramli|R|', 'Amin|Nor Aishah Saidina|NAS|', 'Ho|Wai Shin|WS|', 'Lee|Ting Hun|TH|']

2020

33120092

A comparison of the growth status, rainfall retention and purification effects of four green roof plant species.

Vegetation is a key component of green roofs and one of the most important factors affecting the rainfall quantity and quality of green roofs. Four plant species (Sedum lineare Thunb., Sedum spurium 'Coccineum', Sedum aizoon L. and Sedum spectabile) and two planting methods (single-plant and mixed-plant) were tested on extensive green roofs (EGRs) in 2019. Plant growth status (plant height and vegetation coverage), rainfall volume control, nutrient concentration and load reduction were used to analyse the impact of the situation and the different plant growth conditions. The results showed that the growth status of Sedum lineare Thunb., Sedum aizoon L. and Sedum spectabile was great, and the vegetation coverage was more than 95% in summer. Each EGR with different sedum species had strong rainfall retention effects. The average retention rates of Sedum spectabile, Sedum lineare Thunb, mixed plants, Sedum aizoon L. and Sedum spurium 'Coccineum' were 90.98% and 91.38%, 88.51%, 83.42% and 84.17%, respectively. The average total nitrogen (TN) and nitrate nitrogen (NO3--N) concentrations of Sedum lineare Thunb. were 13.77 mg/L and 7.64 mg/L, which were higher than those of other sedum species, and the average concentrations of ammonia nitrogen (NH4+-N) and total phosphorus (TP) of mixed plants were 4.01 mg/L and 0.48 mg/L, which were higher than those of single plants. Different plant species had different effects on nutrient loads. The EGRs of single plants and mixed plants indicated sinks of TN and NH4-N and sources of TP, but the performance of NO3--N was inconsistent. Comprehensively, Sedum lineare Thunb., Sedum aizoon L. and Sedum spectabile were suitable for the green roofs. This study provides scientific support for the green roofs' application of actual projects and has a strong reference value for the development of green infrastructure.

['Gong|Yongwei|Y|', 'Zhang|Xianwei|X|', 'Li|Haiyan|H|', 'Zhang|Xiaoran|X|', 'He|Song|S|', 'Miao|Yuhong|Y|']

2021

24120406

Comorbidity of personality disorders in mood disorders: a meta-analytic review of 122 studies from 1988 to 2010.

BACKGROUND A meta-analysis was conducted to identify the proportions of comorbid personality disorders (PD) in mood disorders. METHODS We found 122 empirical papers published in the period 1980-2010 on participants having mood disorders in addition to a comorbid PD. Mood disorders were classified as bipolar disorders (BD), major depressive disorders (MDD) and dysthymic disorders (DYS). Several moderators were coded as well. RESULTS The risk of having at least one comorbid PD (any PD) was high across all three mood disorders (BD=.42, MDD=.45), but highest in DYS (.60). Cluster B and C PDs were most frequent in BD, while cluster C PDs dominated in MDD and DYS. Among the specific PDs, the paranoid (.11 versus .07/.05), borderline (.16 versus .14/.13), histrionic (.10 versus .06/.06) and obsessive-compulsive (.18 versus .09/.12) PDs occurred more frequently in BD versus MDD/DYS, whereas the avoidant PD (.22 versus .12/.16) was most frequent in DYS versus BD/MDD. Moderator analyses showed higher comorbidity when diagnoses were based on questionnaires versus clinical interviews, DSM-III-R versus DSM-IV, more women were included or the duration of the disorder was longer. Age of onset yielded mixed results. LIMITATIONS Blind rating of diagnoses was recorded, but was employed in too few studies to be usable as an indication of diagnostic validity. CONCLUSIONS Personality disorders are common in mood disorders. Implications of the identified moderators as well as the new DSM-5 diagnostic system are considered.

['Friborg|Oddgeir|O|', 'Martinsen|Egil W|EW|', 'Martinussen|Monica|M|', 'Kaiser|Sabine|S|', 'Overgård|Karl Tore|KT|', 'Rosenvinge|Jan H|JH|']

2014

34528662

MYC Expression Is Associated With p53 Expression and TP53 Aberration and Predicts Poor Overall Survival in Acute Lymphoblastic Leukemia/Lymphoma.

OBJECTIVES We evaluated MYC and p53 expression, TP53 aberration, their relationship, and their impact on overall survival (OS) in acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). METHODS We identified 173 patients with ALL and LBL, including 12 cases of mixed-phenotype acute leukemia, 8 cases of therapy-related B-cell ALL (B-ALL), 119 cases of B-ALL, and 34 cases of T-cell ALL/LBL diagnosed from 2003 to 2019. We retrospectively assessed p53 and MYC expression by immunohistochemistry of bone marrow and correlated MYC expression with p53 expression and TP53 aberration. RESULTS Expression of p53 and MYC was present in 11.5% and 27.7% of ALL/LBL cases (n = 20 and n = 48), respectively. MYC expression was significantly correlated with p53 expression and TP53 aberration (P = .002 and P = .03), and p53 expression and MYC expression had an adverse impact on OS in patients with ALL/LBL (P < .05). MYC and p53 dual expression as well as combined MYC expression and TP53 aberration had a negative impact on OS in patients with ALL/LBL. CONCLUSIONS MYC expression is correlated with p53 overexpression, TP53 aberration, and poor OS in patients with ALL/LBL.

['Gao|Linlin|L|', 'Harbaugh|Brent|B|', 'Parr|Kevin|K|', 'Patel|Payal|P|', 'Golem|Shivani|S|', 'Zhang|Da|D|', 'Woodroof|Janet|J|', 'Cui|Wei|W|0000-0002-8177-0538']

2021

32543044

Antiplatelet strategy in primary and secondary prevention of cardiovascular disease in patients with type 2 diabetes mellitus: A perspective from the guideline appraisal.

AIMS/INTRODUCTION To appraise guidelines on the antiplatelet strategy of prevention of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus, and highlight the consensuses and controversies to aid clinician decision-making. MATERIALS AND METHODS A systematic search was carried out for guidelines regarding CVD prevention or focusing on type 2 diabetes patients. Appraisal of Guidelines for Research and Evaluation II instrument was utilized to appraise the quality of included guidelines. RESULTS Of the 15 guidelines with discrepant Appraisal of Guidelines for Research and Evaluation II scores (66%; interquartile range 51-71%), 10 were defined as "strongly recommended" guidelines. For secondary prevention, >60% of guidelines advocated that the dual antiplatelet therapy was used within 12 months when the type 2 diabetes patients experienced acute coronary syndrome and/or post-percutaneous coronary intervention or coronary artery bypass grafting, with subsequent long-term aspirin use. For primary prevention, 80% of guidelines supported that aspirin should not be routinely used by patients with type 2 diabetes. No consensus on whether to prolong dual antiplatelet therapy in secondary prevention, and whether to use aspirin in type 2 diabetes patients with high CVD risk exists in current guidelines. CONCLUSIONS Physicians should use the recommendations from "strongly recommended" guidelines to make informed decisions and know the consensuses of current guidelines. Dual antiplatelet therapy should be used within 12 months when type 2 diabetes patients experience acute coronary syndrome and/or percutaneous coronary intervention/coronary artery bypass grafting, with subsequent long-term aspirin use. In primary prevention, aspirin should not be routinely used by individuals with type 2 diabetes, but might be considered for those with high CVD risk.

['Liu|Menghui|M|https://orcid.org/0000-0001-6021-4447', 'Zhuang|Xiaodong|X|', 'Chen|Xiaohong|X|', 'Zhang|Shaozhao|S|', 'Yang|Daya|D|', 'Zhong|Xiangbin|X|https://orcid.org/0000-0002-1483-9427', 'Xiong|Zhenyu|Z|', 'Lin|Yifen|Y|', 'Zhou|Huimin|H|', 'Fan|Yongqiang|Y|', 'Xie|Peihan|P|', 'Huang|Yiquan|Y|', 'Wang|Lichun|L|', 'Liao|Xinxue|X|']

2021