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  • 1
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Brielin C. Brown, Nicolas L. Bray, Lior Pachter Population structure in genotype data has been extensively studied, and is revealed by looking at the principal components of the genotype matrix. However, no similar analysis of population structure in gene expression data has been conducted, in part because a naïve principal components analysis of the gene expression matrix does not cluster by population. We identify a linear projection that reveals population structure in gene expression data. Our approach relies on the coupling of the principal components of genotype to the principal components of gene expression via canonical correlation analysis. Our method is able to determine the significance of the variance in the canonical correlation projection explained by each gene. We identify 3,571 significant genes, only 837 of which had been previously reported to have an associated eQTL in the GEUVADIS results. We show that our projections are not primarily driven by differences in allele frequency at known cis-eQTLs and that similar projections can be recovered using only several hundred randomly selected genes and SNPs. Finally, we present preliminary work on the consequences for eQTL analysis. We observe that using our projection co-ordinates as covariates results in the discovery of slightly fewer genes with eQTLs, but that these genes replicate in GTEx matched tissue at a slightly higher rate.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 2
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Mark A. Zezza, Marcus A. Bachhuber Background While the rise in opioid analgesic prescribing and overdose deaths was multifactorial, financial relationships between opioid drug manufacturers and physicians may be one important factor. Methods Using national data from 2013 to 2015, we conducted a retrospective cohort study linking the Open Payments database and Medicare Part D drug utilization data. We created two cohorts of physicians, those receiving opioid-related payments in 2014 and 2015, but not in 2013, and those receiving opioid-related payments in 2015 but not in 2013 and 2014. Our main outcome measures were expenditures on filled prescriptions, daily doses filled, and expenditures per daily dose. For each cohort, we created a comparison group that did not receive an opioid-related payment in any year and was matched on state, specialty, and baseline opioid expenditures. We used a difference-in-differences analysis with linear generalized estimating equations regression models. Results We identified 6,322 physicians who received opioid-related payments in 2014 and 2015, but not in 2013; they received a mean total of $251. Relative to comparison group physicians, they had a significantly larger increase in mean opioid expenditures ($6,171; 95% CI: 4,997 to 7,346), daily doses dispensed (1,574; 95%CI: 1,330 to 1,818) and mean expenditures per daily dose ($0.38; 95% CI: 0.29 to 0.47). We identified 8,669 physicians who received opioid-related payments in 2015, but not in 2013 or 2014; they received a mean total of $40. Relative to comparison physicians, they also had a larger increase in mean opioid expenditures ($1,031; 95% CI: 603 to 1,460), daily doses dispensed (557; 95% CI: 417 to 697), and expenditures per daily dose ($0.06; 95% CI: 0.002 to 0.13). Conclusions Our findings add to the growing public policy concern that payments from opioid drug manufacturers can influence physician prescribing. Interventions are needed to reduce such promotional activities or to mitigate their influence.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 3
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Tak Kyu Oh, In Sun Park, Eunjeong Ji, Hyo-Seok Na Whether preoperative spirometry in non-thoracic surgery can predict postoperative pulmonary complications (PPCs) is controversial. We investigated whether preoperative spirometry results can predict the occurrence of PPCs in patients who had undergone laparoscopic abdominal surgery. This retrospective observational study analyzed the records of patients who underwent inpatient laparoscopic gastric or colorectal cancer surgery at Seoul National University Bundang Hospital between January 2010 and June 2017. Preoperative spirometry was performed for patients at a high risk of PPCs, such as elderly patients (age 〉60 years), patients aged
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 4
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by James Tosin Akinlua, Richard Meakin, Ibrahim Bashir, Nick Freemantle Objective The main objective of the study was to elicit beliefs about hypertension among Nigerian Primary Health Care clients and workers. Background In many regions of Nigeria, the primary health care facility is usually the only source of formal health care available. Since hypertension is a chronic condition that requires lifelong life style modification and drug treatment, it is important to understand the context and background to the condition through the beliefs and perceptions among both lay persons and health care providers who manage the condition. Setting Rural and urban primary health care facilities in the Federal Capital Territory Nigeria. Participants A total of Eighty-one (81) primary health care clients and workers participated in the study. Methods and outcome measure A qualitative research using interviews, focus group discussions and reflective work as sources of data collection. The outcome measures were emerging themes from thematic framework analysis. Results There were four themes that summarize beliefs of both PHC workers and clients namely: (1) Meaning of hypertension (2) causes of hypertension, (3) Consequences of hypertension (4) Perceptions of treatment, one additional distinct theme was elicited among PHC workers “contextual explanation”. However, under each of the shared four themes, there were both similarities and differences in beliefs expressed between PHC workers and clients. Conclusions This study highlights important similarities and differences in beliefs about hypertension among primary health care clients and primary health care workers that have significant implications for management of hypertension in primary care settings in Nigeria.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 5
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by David Matesanz, Florian Holzmayer, Benno Torgler, Sascha L. Schmidt, Guillermo J. Ortega Professional football is a globalized game in which players are the most valuable assets for clubs. In this study, we explore the evolution of the football players’ transfer network among 21 European first leagues between the seasons 1996/1997 and 2015/2016. From a topological point of view, we show that this network achieved an upper limit expansion around season 2007/2008, thereafter becoming more connected and dense. Using a machine learning approach based on Self-Organizing Maps and Principal Component Analysis we confirm that European competitions, such as the UEFA Champions League or UEFA Europa League, are indeed a “money game” where the clubs with the highest transfer spending achieve better sportive performance. Some clubs’ transfer market activities also affect domestic performance. We conclude from our findings that the relationship between transfer spending and domestic or international sportive performance might lead to substantial inequality between clubs and leagues, while potentially creating a virtuous (vicious) circle in which these variables reinforce (weaken) each other.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 6
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Julia Heger-Stevic, Peter Zimmermann, Lauriane Lecoq, Bettina Böttcher, Michael Nassal Hepatitis B virus (HBV) replicates its 3 kb DNA genome through capsid-internal reverse transcription, initiated by assembly of 120 core protein (HBc) dimers around a complex of viral pregenomic (pg) RNA and polymerase. Following synthesis of relaxed circular (RC) DNA capsids can be enveloped and secreted as stable virions. Upon infection of a new cell, however, the capsid disintegrates to release the RC-DNA into the nucleus for conversion into covalently closed circular (ccc) DNA. HBc´s interactions with nucleic acids are mediated by an arginine-rich C terminal domain (CTD) with intrinsically strong non-specific RNA binding activity. Adaptation to the changing demands for nucleic acid binding during the viral life cycle is thought to involve dynamic phosphorylation / dephosphorylation events. However, neither the relevant enzymes nor their target sites in HBc are firmly established. Here we developed a bacterial coexpression system enabling access to definably phosphorylated HBc. Combining Phos-tag gel electrophoresis, mass spectrometry and mutagenesis we identified seven of the eight hydroxy amino acids in the CTD as target sites for serine-arginine rich protein kinase 1 (SRPK1); fewer sites were phosphorylated by PKA and PKC. Phosphorylation of all seven sites reduced nonspecific RNA encapsidation as drastically as deletion of the entire CTD and altered CTD surface accessibility, without major structure changes in the capsid shell. The bulk of capsids from human hepatoma cells was similarly highly, yet non-identically, phosphorylated as by SRPK1. While not proving SRPK1 as the infection-relevant HBc kinase the data suggest a mechanism whereby high-level HBc phosphorylation principally suppresses RNA binding whereas one or few strategic dephosphorylation events enable selective packaging of the pgRNA/polymerase complex. The tools developed in this study should greatly facilitate the further deciphering of the role of HBc phosphorylation in HBV infection and its evaluation as a potential new therapeutic target.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 7
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Claudia Sala, Nina T. Odermatt, Paloma Soler-Arnedo, Muhammet F. Gülen, Sofia von Schultz, Andrej Benjak, Stewart T. Cole The ESX-1, type VII, secretion system represents the major virulence determinant of Mycobacterium tuberculosis , one of the most successful intracellular pathogens. Here, by combining genetic and high-throughput approaches, we show that EspL, a protein of 115 amino acids, is essential for mediating ESX-1-dependent virulence and for stabilization of EspE, EspF and EspH protein levels. Indeed, an espL knock-out mutant was unable to replicate intracellularly, secrete ESX-1 substrates or stimulate innate cytokine production. Moreover, proteomic studies detected greatly reduced amounts of EspE, EspF and EspH in the espL mutant as compared to the wild type strain, suggesting a role for EspL as a chaperone. The latter conclusion was further supported by discovering that EspL interacts with EspD, which was previously demonstrated to stabilize the ESX-1 substrates and effector proteins, EspA and EspC. Loss of EspL also leads to downregulation in M . tuberculosis of WhiB6, a redox-sensitive transcriptional activator of ESX-1 genes. Overall, our data highlight the importance of a so-far overlooked, though conserved, component of the ESX-1 secretion system and begin to delineate the role played by EspE, EspF and EspH in virulence and host-pathogen interaction.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 8
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Chao Zhang, Meng Dai, Wei Liu, Xiaohui Bai, Jiaming Wu, Canhua Xu, Junying Xia, Feng Fu, Xuetao Shi, Xiuzhen Dong, Faguang Jin, Fusheng You Background Electrical impedance tomography is a continuous imaging method capable of measuring lung volume changes. The purpose of this study was to examine whether EIT was capable of evaluating the degree of obstructive ventilatory defect (OVD) on the global and regional level. Methods 41 healthy subjects with no lung diseases and 67 subjects suffering from obstructive lung diseases were examined using EIT and spirometry during forced vital capacity (FVC) maneuver. The subjects were divided into control group (n = 41), early airway obstruction group (n = 26), mild group (n = 17), moderate group (n = 16) and severe group (n = 8) according to the degree of obstruction. Forced expiratory volume in 1 second (FEV 1 ) and FEV 1 /FVC were determined by EIT. The mode index (MI) was proposed to evaluate the degree of global and regional obstruction; the effectiveness of MI was validated by evaluating posture related change of lung emptying capacity in sitting and supine postures; the degree of regional obstruction was determined according to the cut-off values of MI obtained from receiver operating characteristic (ROC) analysis; regional obstruction was located in the four-quadrant region of interest (ROI) and the contour-map ROI with contour lines at the cut-off values of MI. Results Significant differences were found between different groups (P
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 9
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Judith Olejnik, Adam J. Hume, Elke Mühlberger
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 10
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Luis Miguel Serrano-Bermúdez, Andrés Fernando González Barrios, Dolly Montoya Background Extensive experimentation has been conducted to increment 1,3-propanediol (PDO) production using Clostridium butyricum cultures in glycerol, but computational predictions are limited. Previously, we reconstructed the genome-scale metabolic (GSM) model i Cbu641, the first such model of a PDO-producing Clostridium strain, which was validated at steady state using flux balance analysis (FBA). However, the prediction ability of FBA is limited for batch and fed-batch cultures, which are the most often employed industrial processes. Results We used the i Cbu641 GSM model to develop a dynamic flux balance analysis (DFBA) approach to predict the PDO production of the Colombian strain Clostridium sp IBUN 158B. First, we compared the predictions of the dynamic optimization approach (DOA), static optimization approach (SOA), and direct approach (DA). We found no differences between approaches, but the DOA simulation duration was nearly 5000 times that of the SOA and DA simulations. Experimental results at glycerol limitation and glycerol excess allowed for validating dynamic predictions of growth, glycerol consumption, and PDO formation. These results indicated a 4.4% error in PDO prediction and therefore validated the previously proposed objective functions. We performed two global sensitivity analyses, finding that the kinetic input parameters of glycerol uptake flux had the most significant effect on PDO predictions. The other input parameters evaluated during global sensitivity analysis were biomass composition (precursors and macromolecules), death constants, and the kinetic parameters of acetic acid secretion flux. These last input parameters, all obtained from other Clostridium butyricum cultures, were used to develop a population balance model (PBM). Finally, we simulated fed-batch cultures, predicting a final PDO production near to 66 g/L, almost three times the PDO predicted in the best batch culture. Conclusions We developed and validated a dynamic approach to predict PDO production using the i Cbu641 GSM model and the previously proposed objective functions. This validated approach was used to propose a population model and then an increment in predictions of PDO production through fed-batch cultures. Therefore, this dynamic model could predict different scenarios, including its integration into downstream processes to predict technical-economic feasibilities and reducing the time and costs associated with experimentation.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 11
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Miei Takeda, Shinji Watanabe, Harutaka Katano, Kazuma Noguchi, Yuko Sato, Sayaka Kojima, Takuya Miura, Ryuichi Majima, Souichi Yamada, Naoki Inoue Cytomegaloviruses (CMVs) encode cellular homologs to evade host immune functions. In this study, we analyzed the roles of GP33, a guinea pig CMV (GPCMV)-encoded G protein-coupled receptor (GPCR) homolog, in cellular signaling, viral growth and pathogenesis. The cDNA structure of GP33 was determined by RACE. The effects of GP33 on some signaling pathways were analyzed in transient transfection assays. The redET two-step recombination system for a BAC containing the GPCMV genome was used to construct a mutant GPCMV containing an early stop codon in the GP33 gene (Δ33) and a rescued GPCMV (r33). We found the following: 1) GP33 activated the CRE- and NFAT-, but not the NFκB-mediated signaling pathway. 2) GP33 was dispensable for infection in tissue cultures and in normal animals. 3) In pregnant animals, viral loads of r33 in the livers, lungs, spleens, and placentas at 6 days post-infection were higher than those of Δ33, although the viruses were cleared by 3 weeks post-infection. 4) The presence of GP33 was associated with frequent lesions, including alveolar hemorrhage in the lungs, and inflammation in the lungs, livers, and spleens of the dams. Our findings suggest that GP33 has critical roles in the pathogenesis of GPCMV during pregnancy. We hypothesize that GP33-mediated signaling activates cytokine secretion from the infected cells, which results in inflammation in some of the maternal organs and the placentas. Alternatively, GP33 may facilitate transient inflammation that is induced by the chemokine network specific to the pregnancy.
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  • 12
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Sayuri Tanaka, Ippei Kanazawa, Toshitsugu Sugimoto Objective Previous studies suggest that the presence of diabetic peripheral polyneuropathy (DPN) is associated with atherosclerotic diseases; however, little is known about the relationship between diabetic nerve conduction velocity (NCV) versus arterial stiffness and atherosclerosis parameters. Methods The subjects in this study were 292 men with type 2 diabetes mellitus (T2DM). All subjects underwent NCV examination at median and tibial nerves as motor nerve (MCV) as well as median and sural nerves as sensory nerve (SCV). Brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT) were evaluated as arterial stiffness and atherosclerosis parameters. Results Pearson’s correlation coefficient showed that NCV at all sites negatively correlated with baPWV, maximal and mean IMT (IMT-Max and IMT-Mean), and plaque score (all p values p
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 13
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Joshua S. Halofsky, David R. Conklin, Daniel C. Donato, Jessica E. Halofsky, John B. Kim Future vegetation shifts under changing climate are uncertain for forests with infrequent stand-replacing disturbance regimes. These high-inertia forests may have long persistence even with climate change because disturbance-free periods can span centuries, broad-scale regeneration opportunities are fewer relative to frequent-fire systems, and mature tree species are long-lived with relatively high tolerance for sub-optimal growing conditions. Here, we used a combination of empirical and process-based modeling approaches to examine vegetation projections across high-inertia forests of Washington State, USA, under different climate and wildfire futures. We ran our models without forest management (to assess inherent system behavior/potential) and also with wildfire suppression. Projections suggested relatively stable mid-elevation forests through the end of the century despite anticipated increases in wildfire. The largest changes were projected at the lowest and uppermost forest boundaries, with upward expansion of the driest low-elevation forests and contraction of cold, high-elevation subalpine parklands. While forests were overall relatively stable in simulations, increases in early-seral conditions and decreases in late-seral conditions occurred as wildfire became more frequent. With partial fire suppression, projected changes were dampened or delayed, suggesting a potential tool to forestall change in some (but not all) high-inertia forests, especially since extending fire-free periods does little to alter overall fire regimes in these systems. Model projections also illustrated the importance of fire regime context and projection limitations; the time horizon over which disturbances will eventually allow the system to shift are so long that the prevailing climatic conditions under which many of those shifts will occur are beyond what most climate models can predict with any certainty. This will present a fundamental challenge to setting expectations and managing for long-term change in these systems.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 14
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Mohammed A. M. Farooqi, Nikita Malhotra, Som D. Mukherjee, Stephanie Sanger, Sukhbinder K. Dhesy-Thind, Peter Ellis, Darryl P. Leong Background Preclinical evidence suggests statins may have anti-tumor properties. Large observational studies are also consistent with improved survival and cancer-specific outcomes among cancer patients on statins. We sought to evaluate the randomized controlled trials of statins in addition to usual anti-cancer therapy. Methods A systematic search of MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, Papers First and Clinicaltrials.gov was performed from inception through to July 4, 2017 to identify randomized clinical trials that investigated statin therapy in cancer patients. Our primary outcome was overall survival and our secondary outcome was progression-free survival. We calculated summary hazard ratio’s (HR) and 95% confidence intervals (CI) based on random-effects models using aggregate data. PROSPERO (CRD42017065503). Results Ten studies with 1,881 individuals were included with 1,572 deaths and a median follow-up of 23 months. All trials included patients with advanced (stage 3 or higher) disease. There was minimal between-study statistical heterogeneity ( I 2 = 1.8%, for OS; I 2 = 0%, for PFS). The pooled HR for overall survival in patients randomized to statins plus standard anti-cancer therapy versus standard therapy alone was 0.94 (95% CI, 0.85 to 1.04). In the 9 studies that reported progression-free survival (1,798 participants), the pooled HR for statin plus standard therapy versus standard therapy alone was 0.97 (95% CI, 0.87 to 1.07). Conclusions In patients with advanced cancer and a prognosis
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 15
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Olujuwon Ibiloye, Tom Decroo, Nathaniel Eyona, Peter Eze, Peter Agada Background Despite a call for differentiated care, there are limited data from sub-Saharan Africa on comprehensive community-based HIV care for key populations (KP), including commercial sex workers (CSW), men who have sex with men (MSM), and people who inject drugs (PWID). In Nigeria, a programme was implemented that liaised with community-based organizations and offered HIV testing, same-day ART initiation, and ART follow-up to KP. Here we characterize KP and their partners enrolled on ART. Our objective is to assess the early treatment outcomes and to estimate predictors of attrition among KP. Method This is a retrospective cohort study of routinely collected data in a community-based HIV program for KP in Nasarawa state, Nigeria from August 2016 to November 2017. Variables of interest were socio-demographic, KP types, treatment outcomes, ART adherence, WHO stage, TB status and viral load. Summary statistics, logistic and Cox proportional hazard regression were used to describe the characteristics of KP and estimate predictors of attrition (patients either lost to follow-up (LTFU) or dead). Result Seven hundred and ten (710) KP and their partners were enrolled into this study, 77.3% (549) of study participants were female and the median age was 30 years (IQR: 24–35). Respectively, 74.2%, 4.5%, 1.1% and 20% were FSW, MSM, PWID and their partners. Of 710 KP who started ART, 13.9% (99/710) discontinued after the first visit. After a median follow-up time of 7 months on ART 73.2% of patients were retained, 23.4% were LTFU, and 3.4% were dead. Lack of formal education (aHR 1.8; 95% CI 1.3–2.6) and unemployment (aHR 1.8; 95% CI 1.2–2.6) were significantly associated with attrition. Conclusion Comprehensive community-based HIV care, including HIV testing and same-day ART is feasible. However, ART initiation on the same day of confirmatory HIV testing resulted in a high uptake of ART, but possibly inflated early attrition on ART. To mitigate early attrition among KP after same-day ART initiation, the psychosocial readiness of clients should be assessed better. We strongly recommend further studies to understand factors contributing to high attrition among the KP.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 16
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Teminioluwa A. Ajayi, Sarah Cantrell, Ashley Spann, Katherine S. Garman
    Print ISSN: 1553-7366
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  • 17
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Kun Zhu, Yi Tang, Xuan Xu, Hien Dang, Liu-Ya Tang, Xiang Wang, Xin Wei Wang, Ying E. Zhang Nonalcoholic fatty liver disease (NAFLD) is characterized by abnormal accumulation of triglycerides (TG) in the liver and other metabolic syndrome symptoms, but its molecular genetic causes are not completely understood. Here, we show that mice deficient for ubiquitin ligase (E3) Smad ubiquitin regulatory factor 1 (Smurf1) spontaneously develop hepatic steatosis as they age and exhibit the exacerbated phenotype under a high-fat diet (HFD). Our data indicate that loss of Smurf1 up-regulates the expression of peroxisome proliferator-activated receptor γ (PPARγ) and its target genes involved in lipid synthesis and fatty acid uptake. We further show that PPARγ is a direct substrate of Smurf1-mediated non-proteolytic lysine 63 (K63)-linked ubiquitin modification that suppresses its transcriptional activity, and treatment of Smurf1-deficient mice with a PPARγ antagonist, GW9662, completely reversed the lipid accumulation in the liver. Finally, we demonstrate an inverse correlation of low SMURF1 expression to high body mass index (BMI) values in human patients, thus revealing a new role of SMURF1 in NAFLD pathogenesis.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 18
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Dan Xu, Minghui Yao, Yaqing Wang, Ling Yuan, Joerg D. Hoeck, Jingwen Yu, Liang Liu, Yvonne Y. C. Yeap, Weiya Zhang, Feng Zhang, Yinghang Feng, Tiantian Ma, Yujie Wang, Dominic C. H. Ng, Xiaoyin Niu, Bing Su, Axel Behrens, Zhiheng Xu Mutations of WD repeat domain 62 ( WDR62 ) lead to autosomal recessive primary microcephaly (MCPH), and down-regulation of WDR62 expression causes the loss of neural progenitor cells (NPCs). However, how WDR62 is regulated and hence controls neurogenesis and brain size remains elusive. Here, we demonstrate that mitogen-activated protein kinase kinase kinase 3 (MEKK3) forms a complex with WDR62 to promote c-Jun N-terminal kinase (JNK) signaling synergistically in the control of neurogenesis. The deletion of Mekk3 , Wdr62 , or Jnk1 resulted in phenocopied defects, including premature NPC differentiation. We further showed that WDR62 protein is positively regulated by MEKK3 and JNK1 in the developing brain and that the defects of wdr62 deficiency can be rescued by the transgenic expression of JNK1 . Meanwhile, WDR62 is also negatively regulated by T1053 phosphorylation, leading to the recruitment of F-box and WD repeat domain-containing protein 7 (FBW7) and proteasomal degradation. Our findings demonstrate that the coordinated reciprocal and bidirectional regulation among MEKK3, FBW7, WDR62, and JNK1, is required for fine-tuned JNK signaling for the control of balanced NPC self-renewal and differentiation during cortical development.
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  • 19
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Stanislav Nagy, Gianna W. Maurer, Julie L. Hentze, Morten Rose, Thomas M. Werge, Kim Rewitz The human 1q21.1 deletion of ten genes is associated with increased risk of schizophrenia. This deletion involves the β-subunit of the AMP-activated protein kinase (AMPK) complex, a key energy sensor in the cell. Although neurons have a high demand for energy and low capacity to store nutrients, the role of AMPK in neuronal physiology is poorly defined. Here we show that AMPK is important in the nervous system for maintaining neuronal integrity and for stress survival and longevity in Drosophila . To understand the impact of this signaling system on behavior and its potential contribution to the 1q21.1 deletion syndrome, we focused on sleep, an important role of which is proposed to be the reestablishment of neuronal energy levels that are diminished during energy-demanding wakefulness. Sleep disturbances are one of the most common problems affecting individuals with psychiatric disorders. We show that AMPK is required for maintenance of proper sleep architecture and for sleep recovery following sleep deprivation. Neuronal AMPKβ loss specifically leads to sleep fragmentation and causes dysregulation of genes believed to play a role in sleep homeostasis. Our data also suggest that AMPKβ loss may contribute to the increased risk of developing mental disorders and sleep disturbances associated with the human 1q21.1 deletion.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 20
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser, Irina Kowalska, Jenny A. Visser, Marianne Andersen, Ken Ong, Elisabet Stener-Victorin, David Ehrmann, Richard S. Legro, Andres Salumets, Mark I. McCarthy, Laure Morin-Papunen, Unnur Thorsteinsdottir, Kari Stefansson, the 23andMe Research Team , Unnur Styrkarsdottir, John R. B. Perry, Andrea Dunaif, Joop Laven, Steve Franks, Cecilia M. Lindgren, Corrine K. Welt Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT , ZBTB16 and MAPRE1 ), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Laura A. Steenhuis, Maaike H. Nauta, Claudi L. H. Bockting, Gerdina H. M. Pijnenborg
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 22
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
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  • 23
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Melissa J. Bell, Luigi Sedda, Mikel A. Gonzalez, Cristian F. de Souza, Erin Dilger, Reginaldo P. Brazil, Orin Courtenay, James G. C. Hamilton In South America, the Protist parasite that causes visceral leishmaniasis, a potentially fatal human disease, is transmitted by blood-feeding female Lutzomyia longipalpis sand flies. A synthetic copy of the male produced sex-aggregation pheromone offers new opportunities for vector control applications. We have previously shown that the pheromone placed in plastic sachets (lures) can attract both females and males to insecticide treated sites for up to 3 months. To use the pheromone lure in a control program we need to understand how the application of lures in the field can be optimised. In this study we investigated the effect of increasing the number of lures and their proximity to each other on their ability to attract Lu . longipalpis . Also for the first time we applied a Bayesian log-linear model rather than a classic simple (deterministic) log-linear model to fully exploit the field-collected data. We found that sand fly response to pheromone is significantly related to the quantity of pheromone and is not influenced by the proximity of other pheromone sources. Thus sand flies are attracted to the pheromone source at a non-linear rate determined by the amount of pheromone being released. This rate is independent of the proximity of other pheromone releasing traps and indicates the role of the pheromone in aggregation formation. These results have important implications for optimisation of the pheromone as a vector control tool and indicate that multiple lures placed in relatively close proximity to each other (5 m apart) are unlikely to interfere with one another.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
    Topics: Medicine
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  • 24
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Kaori Hanabusa, Manabu Oi, Naotake Tsukidate, Yuko Yoshimura The aim of the present study was to test the hypothesis that individuals with higher Autism Spectrum Quotient (AQ) scores would be more permissive of pragmatic impairments than those with lower AQ scores. We investigated the presence of a correlation between the AQ scores of mothers with children in grades 1 to 6 and their evaluation of assumed pragmatic impairments in children using the Maternal Evaluation of Pragmatic Impairments in Children (MEPC) measure. Mothers were asked to rate how they would feel if their child showed the communication behaviors listed in scales D (coherence), E (inappropriate initiation), F (stereotyped language), G (use of context), and H (nonverbal communication) of the Children’s Communication Checklist-2, which measures pragmatic impairments. All responses were given on a five-point Likert scale. The results indicated that the higher the maternal AQ score, the less the mother tended to evaluate pragmatic impairments as a problem. We also examined whether the age and gender of assumed children influenced the correlation between AQ and MEPC scores, but found no significant correlation. The partial correlation coefficients were calculated for each subscale, none of which was significant. A negative correlation was found between AQ and MEPC scores as a whole.
    Electronic ISSN: 1932-6203
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  • 25
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Valentine U. Chukwuma, Nurgun Kose, D. Noah Sather, Gopal Sapparapu, Rachel Falk, Hannah King, Vidisha Singh, Rebecca Lampley, Delphine C. Malherbe, Noah T. Ditto, Jonathan T. Sullivan, Trevor Barnes, Benjamin J. Doranz, Celia C. Labranche, David C. Montefiori, Spyros A. Kalams, Nancy L. Haigwood, James E. Crowe Jr. Broadly neutralizing antibodies (bNAbs) are rarely elicited by current human immunodeficiency virus type 1 (HIV-1) vaccine designs, but the presence of bNAbs in naturally infected individuals may be associated with high plasma viral loads, suggesting that the magnitude, duration, and diversity of viral exposure may contribute to the development of bNAbs. Here, we report the isolation and characterization of a panel of human monoclonal antibodies (mAbs) from two subjects who developed broadly neutralizing autologous antibody responses during HIV-1 infection. In both subjects, we identified collections of mAbs that exhibited specificity only to a few autologous envelopes (Envs), with some mAbs exhibiting specificity only to a subset of Envs within the quasispecies of a particular sample at one time point. Neutralizing antibodies (NAbs) isolated from these subjects mapped mostly to epitopes in the Env V3 loop region and the CD4 binding site. None of the individual neutralizing mAbs recovered exhibited the cumulative breadth of neutralization present in the serum of the subjects. Surprisingly, however, the activity of polyclonal mixtures comprising individual mAbs that each possessed limited neutralizing activity, could achieve increased breadth of neutralizing activity against autologous isolates. While a single broadly neutralizing antibody targeting one epitope can mediate neutralization breadth, the findings presented here suggest that a cooperative polyclonal process mediated by diverse antibodies with more limited breadth targeting multiple epitopes also can achieve neutralization breadth against HIV-1.
    Electronic ISSN: 1932-6203
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  • 26
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Marieke de Visser, Cornelia Fluit, Janke Cohen-Schotanus, Roland Laan Background Medical schools aim to contribute to a pool of doctors who are ready for a future practice that will be ever-changing requiring collaboration skills and lifelong learning. They adapt their curricula and selection procedures to fulfil this responsibility. This study aims to determine whether two different selection procedures in one medical school, both matching the key characteristics of the subsequent curricula (one traditional, knowledge-based, and one recently designed for self directed learning and focusing on practice), select students with different personality traits as a side-effect. This perspective was chosen as personality has been related to the CanMeds competencies, innovation capacities, medical school performance and medical professional success. Methods A total of 621 students admitted through the new or the traditional selection procedure were invited to complete a Big Five Inventory questionnaire at the start of their Bachelor’s programme. Using ANCOVA, we compared Big Five traits of students admitted through the new selection procedure (n = 196) and the traditional selection procedure (n = 425). Results The group of students admitted through the procedure matching the newly designed curriculum had a lower mean score on neuroticism (p 〈 .01) and higher mean scores on conscientiousness, extraversion, agreeableness and openness (p 〈 .001) than the other group. Conclusions The findings of the current study indicate that the medical school population is influenced in terms of personality traits as a side-effect of a changing selection procedure. We recommend studying this mechanism and its implications further and using it more consciously in selection procedure design.
    Electronic ISSN: 1932-6203
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  • 27
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Christian Thue Bjørndal, Live S. Luteberget, Kevin Till, Simen Holm Many elite sport organisations have introduced structured talent identification and development (TID) initiatives in youth sports to better facilitate elite sport performance. However, selection mechanisms for TID programmes (e.g., junior international team) are biased towards relatively older athletes and limited studies exist with Scandinavian contexts. Therefore, the aim of this study was to explore the relative age effect (RAE) in youth, junior and senior male and female international team selections among Norwegian handball players (n = 657). A Chi-square goodness-of-fit test assessed whether a skewed birthdate distribution occurred at the youth, junior and senior international team levels and odds-ratios were calculated for RAE distribution. Moreover, a Kruskal-Wallis test was used to assess differences between the number of international youth, junior and senior level appearances by birth quartiles. Significant uneven birth date distributions were shown for youth (χ 2 (7) = female 40.383 and male 105.716, p
    Electronic ISSN: 1932-6203
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  • 28
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Saul Justin Newman This study highlights how the mortality plateau in Barbi and colleagues can be generated by low-frequency, randomly distributed age-misreporting errors. Furthermore, sensitivity of the late-life mortality plateau in Barbi and colleagues to the particular age range selected for regression is illustrated. Collectively, the simulation of age-misreporting errors in late-life human mortality data and a less-specific model choice than that of Barbi and colleagues highlight a clear alternative hypothesis to explanations based on evolution, the cessation of ageing, and population heterogeneity.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Saul Justin Newman Several organisms, including humans, display a deceleration in mortality rates at advanced ages. This mortality deceleration is sufficiently rapid to allow late-life mortality to plateau in old age in several species, causing the apparent cessation of biological ageing. Here, it is shown that late-life mortality deceleration (LLMD) and late-life plateaus are caused by common demographic errors. Age estimation and cohort blending errors introduced at rates below 1 in 10,000 are sufficient to cause LLMD and plateaus. In humans, observed error rates of birth and death registration predict the magnitude of LLMD. Correction for these sources of demographic error using a mixed linear model eliminates LLMD and late-life mortality plateaus (LLMPs) without recourse to biological or evolutionary models. These results suggest models developed to explain LLMD have been fitted to an error distribution, that ageing does not slow or stop during old age in humans, and that there is a finite limit to human longevity.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
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  • 30
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Jochen Hammes, Melanie Hohberg, Philipp Täger, Markus Wild, Boris Zlatopolskiy, Philipp Krapf, Bernd Neumaier, Klaus Schomäcker, Carsten Kobe, Matthias Schmidt, Markus Dietlein, Alexander Drzezga Introduction [ 68 Ga]PSMA-HBED-CC and [ 18 F]DCFPyL show a high potential for the detection of recurrent prostate cancer. While 18 F-based tracers have several advantages in availability and image resolution, their sensitivity in the skeleton might be impaired by released [ 18 F]fluoride due to its high bone affinity. In turn, chemically unbound trivalent 68 Ga might also accumulate in osseous tissue, in cases of occupied binding sites of plasma proteins and thereby influence bone signal. Methods A comparison of average bone SUV was performed in 17 bone-negative and 4 bone-positive patients. All patients underwent PET/CT 125 minutes after application of [ 18 F]DCFPyL and 73 minutes after application of [ 68 Ga]PSMA-HBED-CC at another date. Results Native SUVs in unaffected bone tissue and SUVs relative to liver uptake were lower in [ 18 F]DCFPyL (0.49) than in [ 68 Ga]PSMA-HBED-CC scans (0.52). SUVs relative to gluteal muscles did not differ between the two tracers. Average lesional SUVs did not differ between tracers. Conclusion No difference of average bone signal intensity was observed for [ 18 F]DCFPyL-PET/CT in comparison to [ 68 Ga]PSMA-HBED-CC scans indicating that diagnostic assessment of the skeleton is not affected by non-specific accumulation of free [ 18 F]fluoride or 68 Ga.
    Electronic ISSN: 1932-6203
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by André B. B. Wilke, Chalmers Vasquez, William Petrie, Alberto J. Caban-Martinez, John C. Beier Urbanization is increasing globally, and construction sites are an integral part of the urbanization process. It is unknown to what extent construction sites create favorable breeding conditions for mosquitoes. The main objectives of the present study were to identify what species of mosquitoes are present at construction sites and the respective physical features associated with their production. Eleven construction sites were cross-sectionally surveyed for the presence of mosquitoes in Miami-Dade County, Florida including in areas previously affected by the Zika virus outbreak in 2016. A total of 3.351 mosquitoes were collected; 2.680 adults and 671 immatures. Aedes aegypti and Culex quinquefasciatus comprised 95% of all collected mosquitoes and were the only species found in their immature forms breeding inside construction sites. Results for the Shannon and Simpson indices, considering both immature and adult specimens, yielded the highest values for Cx . quinquefasciatus and Ae . aegypti . The individual rarefaction curves indicated that sampling sufficiency was highly asymptotic for Cx . quinquefasciatus and Ae . aegypti , and the plots of cumulative species abundance (ln S), Shannon index (H) and log evenness (ln E) (SHE) revealed the lack of heterogeneity of species composition, diversity and evenness for the mosquitoes found breeding in construction sites. The most productive construction site breeding features were elevator shafts, Jersey plastic barriers, flooded floors and stair shafts. The findings of this study indicate that vector mosquitoes breed in high numbers at construction sites and display reduced biodiversity comprising almost exclusively Ae . aegypti and Cx . quinquefasciatus . Such findings suggest that early phase construction sites have suitable conditions for the proliferation of vector mosquitoes. More studies are needed to identify modifiable worker- and organizational-level factors to improve mosquito control practices and guide future mosquito control strategies in urban environments.
    Electronic ISSN: 1932-6203
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  • 32
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    Publication Date: 2018-12-21
    Description: by Hayato Miyake, Junichi Sakagami, Hiroaki Yasuda, Yoshio Sogame, Ryusuke Kato, Kanetoshi Suwa, Katsuyuki Dainaka, Tomoki Takata, Isao Yokota, Yoshito Itoh Aim The purpose of this study was to clarify whether fatty pancreas might lead to impaired pancreatic endocrine or exocrine function. Material and methods The study involved 109 participants who had undergone the glucagon stimulation test and N-benzoyl-L-tyros-p-amino benzoic acid (BT-PABA) test to assess pancreatic function as well as unenhanced abdominal computed tomography (CT). Pancreatic endocrine impairment was defined as ΔC peptide immunoreactivity less than 2 [mmol/L] in the glucagon stimulation test, and pancreatic exocrine impairment was defined as a urinary PABA excretion rate less than 70% on the BT-PABA test. We defined as the mean CT value of pancreas / CT value of spleen (P/S ratio) as a marker to assess fatty pancreas. We analyzed the association between fatty pancreas and pancreatic impairment using the logistic regression model. The odds ratio (OR) is shown per 0.1 unit. Results Pancreatic endocrine function was impaired in 33.0% of the participants, and 56.9% of those were regarded as having pancreatic exocrine impairment. The P/S ratio was significantly correlated with pancreatic endocrine impairment in univariate analysis (OR = 0.61, 95% confidence interval (CI) = 0.43–0.83, P = 0.0013) and multivariate analysis (OR = 0.38, 95% CI = 0.22–0.61, P 〈 .0001) for all participants. Similar significant relationships were observed in both univariate (OR = 0.70, 95% CI = 0.49–0.99, P = 0.04) and multivariate (OR = 0.39, 95% CI = 0.21–0.66, P = 0.0002) analyses for the participants without diabetes (n = 93). The amount of pancreatic fat was not associated with exocrine impairment in univariate analysis (OR = 0.80, 95% CI = 0.59–1.06, P = 0.12). Conclusion Fatty pancreas was associated with pancreatic endocrine impairment but did not have a clear relationship with pancreatic exocrine impairment.
    Electronic ISSN: 1932-6203
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-19
    Description: by Igor Cunha Lima Acosta, Rodrigo Martins Soares, Luis Felipe Silva Pereira Mayorga, Bruna Farias Alves, Herbert Sousa Soares, Solange Maria Gennari The main motivation for this study was to determine the occurrence of Toxoplasma gondii , a cosmopolitan widespread zoonotic parasite distribution that can infect a wide variety of mammals and birds, in Magellanic penguins ( Spheniscus magellanicus ) in Brazil. In recent decades there has been a significant increase in the number of penguins originating from Argentinian and Chilean Patagonia, where these birds are born, that arrive on the Brazilian coast, where many of them are stranded and rescued. Tissue samples were collected from 330 individuals surveyed from 2012–2015 at the Institute for Marine Animal Research and Rehabilitation (IPRAM) located in Cariacica, state of Espirito Santo, Brazil. Serum were collected from 145 animals surveyed in 2015 for the detection of anti- T . gondii antibodies using the Modified Agglutination Test (MAT ≥20) and 18 birds were positive, with titers of 20 (7 birds), 40 (9 birds) and 80 (2 birds). Mouse bioassay for the isolation of T . gondii was performed using tissues from 54 penguins that were also surveyed in 2015, but no isolates were obtained. DNA from tissue samples of 330 individuals was PCR amplified and sequenced to detect tissue cyst forming coccidians by using pan sarcocystids-directed primers (based on 18S rDNA). These samples were from animals surveyed in 2015 and from frozen stocked tissues from animals surveyed in the years 2012 and 2013. The positives were PCR amplified and sequenced with genus Sarcocystis-specific primers (based on internal transcribed spacer 1, RNA polymerase beta subunit coding gene, and cytochrome B coding gene) and with Sarcocystis falcatula / Sarcocystis neurona - specific primers (based on surface antigens SAG2, SAG3 and SAG4). Sixteen (3.0%) of pectoral muscle samples were positive by all the seven molecular markers and all the samples were identical to each other. Organisms close related to Sarcocystis falcatula were confirmed in all cases. This is the first report on molecular detection of infection by S . falcatula -related organisms and the first report of seropositivity for T . gondii in free-living Magellanic penguins in Brazil. Felids and didephid opossums are definitive hosts of T . gondii and S . falcatula , respectively. Where the penguins acquire the infective forms of the parasites shed by the terrestrial mammals remains to be elucidated.
    Electronic ISSN: 1932-6203
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  • 34
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    Publication Date: 2018-12-19
    Description: by Bruno de Cássio Veloso de Barros, Elaine Nunes Chagas, Luna Wanessa Bezerra, Laila Graziela Ribeiro, Jose Wandilson Barboza Duarte Júnior, Diego Pereira, Edvaldo Tavares da Penha Junior, Julia Rezende Silva, Delana Andreza Melo Bezerra, Renato Silva Bandeira, Helder Henrique Costa Pinheiro, Sylvia de Fátima dos Santos Guerra, Ricardo José de Paula Souza e Guimarães, Joana D'Arc Pereira Mascarenhas Acute gastroenteritis is one of the main causes of mortality in humans and young animals. Domestic and mainly wild animals such as bats, small rodents and birds are highly diversified animals in relation to their habitats and ecological niches and are widely distributed geographically in environments of forest fragmentation in some areas of the Amazon, being considered important sources for viruses that affect humans and other animals. Due to the anthropical activities, these animals changed their natural habitat and adapted to urbanized environments, thus representing risks to human and animal health. Although the knowledge of the global diversity of enteric viruses is scarce, there are reports demonstrating the detection of rotavirus in domestic animals and animals of productive systems, such as bovines and pigs. The present study investigated the prevalence of Rotavirus A in 648 fecal samples of different animal species from the northeastern mesoregion of the state of Pará, Brazil, which is characterized as an urbanized area with forest fragments. The fecal specimens were collected from October 2014 to April 2016 and subjected to a Qualitative Real-Time Polymerase Chain Reaction (RT-qPCR), using the NSP3 gene as a target. It was observed that 27.5% (178/648) of the samples presented positive results for RVA, with 178 samples distributed in birds (23.6%), canines (21.35%), chiropterans (17.98%), bovines (14.6%), horses (8.43%), small rodents (6.74%), pigs (3.93%) and felines (3.37%), demonstrating the circulation of RVA in domestic animals and suggesting that such proximity could cause transmissions between different species and the occurrence of rearrangements in the genome of RVA as already described in the literature, associated to the traces of environmental degradation in the studied areas.
    Electronic ISSN: 1932-6203
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    Publication Date: 2018-12-20
    Description: by Osei Owusu-Afriyie, W. K. B. A. Owiredu, Kwabena Owusu-Danquah, Christine Komarck, Susan K. Foltin, Rita Larsen-Reindorf, Emmanuel Acheampong, Solomon E. Quayson, Mark E. Prince, Jonathan B. McHugh, Peter Donkor, Sofia D. Merajver, J. Chad Brenner
    Electronic ISSN: 1932-6203
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  • 36
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    Publication Date: 2018-12-20
    Description: by Haesuk Park, Donghak Jeong, Pauline Nguyen, Linda Henry, Joseph Hoang, Yoona Kim, Edward Sheen, Mindie H. Nguyen
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  • 37
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    Publication Date: 2018-12-20
    Description: by Tony Bohman, Matthias Tegern, Alexandra Halvarsson, Lisbet Broman, Helena Larsson This study was performed to evaluate the reliability and agreement of the IsoKai isokinetic lift test as it is currently administered in admission to the Swedish Armed Forces. The study included an intrarater (n = 534) and interrater reliability sample (n = 137), of Swedish male conscripts who performed the test on two test occasions about two hours apart. Two-to-four lifts were performed at each occasion, and the highest mean (IsoKai MF ) and peak force (IsoKai PF ) produced (N) were used for evaluation. All intraclass coefficients showed excellent reliability. The interrater analyses resulted in intraclass coefficients of 0.942 (95% CI; 0.920–0.959) and 0.858 (95% CI; 0.806–0.896) for the IsoKai MF and IsoKai PF , respectively, while the corresponding coefficients for the intrarater analyses were 0.935 (95% CI; 0.923–0.946) and 0.865 (95% CI; 0.842–0.886). Agreement, the capability of a test to detect changes, was assessed by the standard error of measurement (SEM/SEM%) and the smallest real difference (SRD/SRD%). These estimate indicated that it is possible to achieve measurements relevant to use in real practice with the IsoKai isokinetic lift test. Bland and Altman analyses revealed no systematic errors in either sample. Based on these findings, the IsoKai isokinetic lift test is suggested to be a highly reliable test for maximal dynamic muscular strength. The test could be of use in selection procedures in order to accurately evaluate maximal dynamic muscular strength, and for evaluating longitudinal changes in strength.
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  • 38
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    Publication Date: 2018-12-20
    Description: by Jéssica da Silva Ferreira, Diego Augusto Souza, João Pedro Santos, Carla Carolina Dias Uzedo Ribeiro, Bruna A. Baêta, Rafaella Câmara Teixeira, Arthur da Silva Neumann, Patricia Sammarco Rosa, Maria Cristina Vidal Pessolani, Milton Ozório Moraes, Gervásio Henrique Bechara, Pedro L. de Oliveira, Marcos Henrique Ferreira Sorgine, Philip Noel Suffys, Amanda Nogueira Brum Fontes, Lesley Bell-Sakyi, Adivaldo H. Fonseca, Flavio Alves Lara Leprosy is an infectious disease caused by Mycobacterium leprae and frequently resulting in irreversible deformities and disabilities. Ticks play an important role in infectious disease transmission due to their low host specificity, worldwide distribution, and the biological ability to support transovarial transmission of a wide spectrum of pathogens, including viruses, bacteria and protozoa. To investigate a possible role for ticks as vectors of leprosy, we assessed transovarial transmission of M . leprae in artificially-fed adult female Amblyomma sculptum ticks, and infection and growth of M . leprae in tick cell lines. Our results revealed M . leprae RNA and antigens persisting in the midgut and present in the ovaries of adult female A . sculptum at least 2 days after oral infection, and present in their progeny (eggs and larvae), which demonstrates the occurrence of transovarial transmission of this pathogen. Infected tick larvae were able to inoculate viable bacilli during blood-feeding on a rabbit. Moreover, following inoculation with M . leprae , the Ixodes scapularis embryo-derived tick cell line IDE8 supported a detectable increase in the number of bacilli for at least 20 days, presenting a doubling time of approximately 12 days. As far as we know, this is the first in vitro cellular system able to promote growth of M . leprae . Finally, we successfully transformed a clinical M . leprae isolate by inserting the reporter plasmid pCHERRY3; transformed bacteria infected and grew in IDE8 cells over a 2-month period. Taken together, our data not only support the hypothesis that ticks may have the potential to act as a reservoir and/or vector of leprosy, but also suggest the feasibility of technological development of tick cell lines as a tool for large-scale production of M . leprae bacteria, as well as describing for the first time a method for their transformation.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
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  • 39
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    Publication Date: 2018-12-20
    Description: by Francisco J. Santiago-Avila, Ari M. Cornman, Adrian Treves
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    Publication Date: 2018-12-20
    Description: by Aurora Sabrià, Rosa M. Pintó, Albert Bosch, Josep Quer, Damir Garcia-Cehic, Josep Gregori, Angela Dominguez, Mónica Carol, Maria-Rosa Sala-Farré, Susana Guix, the Working Group for the Study of Outbreaks of Acute Gastroenteritis in Catalonia
    Electronic ISSN: 1932-6203
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Yuwei Qin, Sangwon Suh In life cycle assessment (LCA), performing Monte Carlo simulation (MCS) using fully dependent sampling typically involves repeated inversion of a technology matrix for a sufficiently large number of times. As the dimension of technology matrices for life cycle inventory (LCI) databases grows, MCS using fully dependent sampling is becoming a computational challenge. In our previous work, we pre-calculated the distribution functions of the entire LCI flows in the ecoinvent ver. 3.1 database to help reduce the computation time of running fully dependent sampling by individual LCA practitioners. However, it remains as a question whether the additional errors due to the use of pre-calculated uncertainty values are large enough to alter the conclusion of a comparative study, and, if so, what is the odds of such cases. In this study, we empirically tested the probability of altering the conclusion of a comparative LCA due to the use of pre-calculated uncertainty values. We sampled 10,000 random pairs of elementary flows of ecoinvent LCIs ( a i and b i ) and ran MCSs (1) using pre-calculated uncertainty values and (2) using fully dependent sampling. We analyzed the distribution of the differences between a i and b i (i.e., a i − b i ) of each run, and quantified the probability of reversing (e.g., a i 〉 b i became a i 〈 b i ) or moderating the conclusion (e.g., a i 〉 b i became a i ≈ b i ). In order to better replicate the situation under a comparative LCA setting, we also sampled 10,000 random pairs of elementary flows from the processes that produce electricity, and repeated the same procedure. The results show that no LCIs derived using pre-calculated uncertainty values constitute large enough differences from those using fully dependent sampling to reverse the conclusion. However, in 5.3% of the cases, the conclusion from one approach is moderated under the other approach or vice versa . When elementary flow pairs are sampled only from the electricity-producing processes, the probability of moderating the conclusions increases to 10.5%, while that of reversing the conclusions remains nil. As the number of unit processes in LCI databases increases, running full MCSs in a PC-environment will continue to be a challenge, which may lead some LCA practitioners to avoid uncertainty analysis altogether. Our results indicate that pre-calculated distributions for LCIs can be used as a proxy for comparative LCA studies in the absence of adequate computational resources for full MCS. Depending on the goal and scope of the study, LCA practitioners should consider using pre-calculated distributions if the benefits of doing so outweighs the associated risks of altering the conclusion.
    Electronic ISSN: 1932-6203
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  • 42
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    Publication Date: 2018-12-21
    Description: by Farah H. Bardai, Dalila G. Ordonez, Rachel M. Bailey, Matthew Hamm, Jada Lewis, Mel B. Feany Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson disease. Genetics and neuropathology link Parkinson disease with the microtubule-binding protein tau, but the mechanism of action of LRRK2 mutations and the molecular connection between tau and Parkinson disease are unclear. Here, we investigate the interaction of LRRK and tau in Drosophila and mouse models of tauopathy. We find that either increasing or decreasing the level of fly Lrrk enhances tau neurotoxicity, which is further exacerbated by expressing Lrrk with dominantly acting Parkinson disease—associated mutations. At the cellular level, altering Lrrk expression promotes tau neurotoxicity via excess stabilization of filamentous actin (F-actin) and subsequent mislocalization of the critical mitochondrial fission protein dynamin-1-like protein (Drp1). Biochemically, monomeric LRRK2 exhibits actin-severing activity, which is reduced as increasing concentrations of wild-type LRRK2, or expression of mutant forms of LRRK2 promote oligomerization of the protein. Overall, our findings provide a potential mechanistic basis for a dominant negative mechanism in LRRK2-mediated Parkinson disease, suggest a common molecular pathway with other familial forms of Parkinson disease linked to abnormalities of mitochondrial dynamics and quality control, and raise the possibility of new therapeutic approaches to Parkinson disease and related disorders.
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  • 43
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    Publication Date: 2018-12-21
    Description: by Marius Somveille, Josh A. Firth, Lucy M. Aplin, Damien R. Farine, Ben C. Sheldon, Robin N. Thompson The social transmission of information is critical to the emergence of animal culture. Two processes are predicted to play key roles in how socially-transmitted information spreads in animal populations: the movement of individuals across the landscape and conformist social learning. We develop a model that, for the first time, explicitly integrates these processes to investigate their impacts on the spread of behavioural preferences. Our results reveal a strong interplay between movement and conformity in determining whether locally-variable traditions establish across a landscape or whether a single preference dominates the whole population. The model is able to replicate a real-world cultural diffusion experiment in great tits Parus major , but also allows for a range of predictions for the emergence of animal culture under various initial conditions, habitat structure and strength of conformist bias to be made. Integrating social behaviour with ecological variation will be important for understanding the stability and diversity of culture in animals.
    Print ISSN: 1553-734X
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  • 44
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    Publication Date: 2018-12-21
    Description: by Benjamin D. Lee
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  • 45
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    Publication Date: 2018-12-21
    Description: by Nele Vandersickel, Masaya Watanabe, Qian Tao, Jan Fostier, Katja Zeppenfeld, Alexander V. Panfilov Rotors are functional reentry sources identified in clinically relevant cardiac arrhythmias, such as ventricular and atrial fibrillation. Ablation targeting rotor sites has resulted in arrhythmia termination. Recent clinical, experimental and modelling studies demonstrate that rotors are often anchored around fibrotic scars or regions with increased fibrosis. However the mechanisms leading to abundance of rotors at these locations are not clear. The current study explores the hypothesis whether fibrotic scars just serve as anchoring sites for the rotors or whether there are other active processes which drive the rotors to these fibrotic regions. Rotors were induced at different distances from fibrotic scars of various sizes and degree of fibrosis. Simulations were performed in a 2D model of human ventricular tissue and in a patient-specific model of the left ventricle of a patient with remote myocardial infarction. In both the 2D and the patient-specific model we found that without fibrotic scars, the rotors were stable at the site of their initiation. However, in the presence of a scar, rotors were eventually dynamically anchored from large distances by the fibrotic scar via a process of dynamical reorganization of the excitation pattern. This process coalesces with a change from polymorphic to monomorphic ventricular tachycardia.
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  • 46
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    Publication Date: 2018-12-21
    Description: by Vlad Elgart, Jia-Ren Lin, Joseph Loscalzo The physiochemical determinants of drug-target interactions in the microenvironment of the cell are complex and generally not defined by simple diffusion and intrinsic chemical reactivity. Non-specific interactions of drugs and macromolecules in cells are rarely considered formally in assessing pharmacodynamics. Here, we demonstrate that non-specific interactions lead to very slow incorporation kinetics of DNA binding drugs. We observe a rate of drug incorporation in cell nuclei three orders of magnitude slower than in vitro due to anomalous drug diffusion within cells. This slow diffusion, however, has an advantageous consequence: it leads to virtually irreversible binding of the drug to specific DNA targets in cells. We show that non-specific interactions drive slow drug diffusion manifesting as slow reaction front propagation. We study the effect of non-specific interactions in different cellular compartments by permeabilization of plasma and nuclear membranes in order to pinpoint differential compartment effects on variability in intracellular drug kinetics. These results provide the basis for a comprehensive model of the determinants of intracellular diffusion of small-molecule drugs, their target-seeking trajectories, and the consequences of these processes on the apparent kinetics of drug-target interactions.
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  • 47
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    Publication Date: 2018-12-21
    Description: by Kenneth W. Wachter Newman questions recent claims about a plateau in mortality rates for Italians beyond age 105 on the basis of a hypothetical model. His model implies implausibly high error rates for extreme ages. For individuals over 110, for whom birth certificates have been collected, the form in which Italian births were registered precludes the kinds of clerical errors in year of birth that Newman assumes.
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  • 48
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    Publication Date: 2018-12-21
    Description: by Andrés Camacho-Alpízar, Eric J. Fuchs, Gilbert Barrantes Populations may become isolated by distance, geographic barriers or both. Isolated populations often diverge in behavioral, morphological and genetic traits as a result of reduced inter-population gene flow. Highland species commonly present naturally fragmented distributions that confine populations to the highest mountain peaks, isolated by mountain passes and distance. The endemic Timberline Wren ( Thryorchilus browni ) inhabits the highlands of the Talamanca mountain range, including western Panama, and the highest peak in the Central Volcanic mountain range of Costa Rica. Using microsatellites and song recordings we studied the effect of a geographic barrier and distance on song, genetic and morphological divergence among four populations in Costa Rica. A lowland mountain pass resulted in the largest genetic, vocal, and morphological (bill length) differences among populations, likely due to reduce the gene flow. Cultural drift and assortative mating by females selecting songs from their own population likely accentuates the effect of isolation and limited gene flow between populations. This pattern of population divergence has been found in other Neotropical highland birds, but over larger geographical scales. We conclude that mountain passes and distance both reduce gene flow between populations in recently-isolated highland species with restricted distributions.
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  • 49
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    Publication Date: 2018-12-21
    Description: by Nils Cordes, Michael Ney, Thomas Beleites, Daniela Aust, Gustavo Baretton, Howard Thames, Michael Baumann, Mechthild Krause, Steffen Löck, Steffen Appold This retrospective study evaluated the expression of β1 integrins and associated proteins as prognostic markers for primary radio(chemo)therapy outcome of patients with locally advanced head and neck squamous cell carcinomas (HNSCC). Tissue microarrays were prepared from 224 HNSCC patients undergoing curative primary radio(chemo)therapy from 1996 to 2005. Staining intensities of β1 integrin and its downstream-proteins FAK, phosphorylated FAK as well as the β1 integrin ECM ligands fibronectin and collagen type-I were determined. Their association to the primary endpoint loco-regional control and the secondary endpoints overall survival and freedom from distant metastasis was analyzed by Cox regression. None of the considered molecular parameters showed a significant association with loco-regional control and freedom from distant metastasis. Patients with p16 positive tumors or tumors with a low intensity of fibronectin showed significantly higher overall survival in univariable regression. In multivariable regression including additional clinical parameters, however, these parameters were not significantly associated with overall survival. Our study in a HNSCC patient cohort treated with primary radio(chemo)therapy does not reveal a prognostic value of β1 integrin expression.
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  • 50
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    Publication Date: 2018-12-21
    Description: by Arkaitz Zubiaga, Rob Procter, Carsten Maple The Internet of Things (or IoT), which enables the networked interconnection of everyday objects, is becoming increasingly popular in many aspects of our lives ranging from entertainment to health care. While the IoT brings a set of invaluable advantages and opportunities with it, there is also evidence of numerous challenges that are yet to be resolved. This is certainly the case with regard to ensuring the cyber security of the IoT, and there are various examples of devices being hacked. Despite this evidence, little is known about the public perceptions of the opportunities and challenges presented by the IoT. To advance research in this direction, we mined the social media platform Twitter to learn about public opinion about the IoT. Analysing a longitudinal dataset of more than 6.7 million tweets, we reveal insights into public perceptions of the IoT, identifying big data analytics as the most positive aspect, whereas security issues are the main public concern on the negative side. Our study serves to highlight the importance of keeping IoT devices secure, and remind manufacturers that it is a concern that remains unresolved, at least insofar as the public believes.
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  • 51
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    Publication Date: 2018-12-21
    Description: by Sarah Anne J. Guagliardo, Mary G. Reynolds, Joelle Kabamba, Beata Nguete, Robert Shongo Lushima, Okito E. Wemakoy, Andrea M. McCollum Endemic to the Democratic Republic of the Congo (DRC), monkeypox is a zoonotic disease that causes smallpox-like illness in humans. Observed fluctuations in reported cases over time raises questions about when it is appropriate to mount a public health response, and what specific actions should be taken. We evaluated three different thresholds to differentiate between baseline and heightened disease incidence, and propose a novel, tiered algorithm for public health action. Monkeypox surveillance data from Tshuapa Province, 2011–2013, were used to calculate three different statistical thresholds: Cullen, c-sum, and a World Health Organization (WHO) method based on monthly incidence. When the observed cases exceeded the threshold for a given month, that month was considered to be ‘aberrant’. For each approach, the number of aberrant months detected was summed by year—each method produced vastly different results. The Cullen approach generated a number of aberrant signals over the period of consideration (9/36 months). The c-sum method was the most sensitive (30/36 months), followed by the WHO method (12/24 months). We conclude that triggering public health action based on signals detected by a single method may be inefficient and overly simplistic for monkeypox. We propose instead a response algorithm that integrates an objective threshold (WHO method) with contextual information about epidemiological and spatiotemporal links between suspected cases to determine whether a response should be operating under i) routine surveillance ii) alert status, or iii) outbreak status. This framework could be modified and adopted by national and zone level health workers in monkeypox-endemic countries. Lastly, we discuss considerations for selecting thresholds for monkeypox outbreaks across gradients of endemicity and public health resources.
    Print ISSN: 1935-2727
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  • 52
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    Publication Date: 2018-12-21
    Description: by Naraporn Somboonna, Ilada Choopara, Narong Arunrut, Kanchapan Sukhonpan, Jarun Sayasathid, Deborah Dean, Wansika Kiatpathomchai
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  • 53
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    Publication Date: 2018-12-21
    Description: by Ibtissam Khoudri, Zainab Elyoussfi, Yassine Mourchid, Mohammed Youbi, Nada Bennani Mechita, Redouane Abouqal, Abderrahmane Maaroufi Background Morocco has achieved the goal of leprosy elimination as a public health problem several years ago (less than 1 case/ 10 000 habitant). The aim of this study was to analyze trends of leprosy detection during the last 17 years taking into consideration the implementation of single dose rifampicin chemoprophylaxis (SDRC) started in 2012. Methodology Time series of leprosy cases detected at national level between 2000 and 2017. Variable collected for each year were leprosy per 100000 H, age category, gender, origin, regions, grade of disabilities and clinical forms. The detection time series was assessed by Joinpoint Regression Analysis. Annual percentage changes (APCs) were estimated to identify the years (joinpoint) when significant changes occurred in the trend. We therefore examined trends in leprosy detection according to epidemiological variables. Findings Joinpoint regression showed a reduction in the detection rate between 2000 and 2017. The APC for the period 2012–2017 (-16.83, 95% CI: -29.2 to -2.3, p
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  • 54
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    Publication Date: 2018-12-21
    Description: by Gregory P. Copenhaver, Bruce Weir, Mark Rothstein, Hua Tang, Scott M. Williams, Gregory S. Barsh
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
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  • 55
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    Publication Date: 2018-12-21
    Description: by Priscilla Medina-Sotomayor, Agustín Pascual-Moscardó, Isabel Camps
    Electronic ISSN: 1932-6203
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  • 56
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    Publication Date: 2018-12-21
    Description: by Theru A. Sivakumaran, Robert P. Igo Jr, Jeffrey M. Kidd, Andy Itsara, Laura J. Kopplin, Wei Chen, Stephanie A. Hagstrom, Neal S. Peachey, Peter J. Francis, Michael L. Klein, Emily Y. Chew, Vedam L. Ramprasad, Wan-Ting Tay, Paul Mitchell, Mark Seielstad, Dwight E. Stambolian, Albert O. Edwards, Kristine E. Lee, Dmitry V. Leontiev, Gyungah Jun, Yang Wang, Liping Tian, Feiyou Qiu, Alice K. Henning, Thomas LaFramboise, Parveen Sen, Manoharan Aarthi, Ronnie George, Rajiv Raman, Manmath Kumar Das, Lingam Vijaya, Govindasamy Kumaramanickavel, Tien Y. Wong, Anand Swaroop, Goncalo R. Abecasis, Ronald Klein, Barbara E. K. Klein, Deborah A. Nickerson, Evan E. Eichler, Sudha K. Iyengar
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  • 57
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    Publication Date: 2018-12-21
    Description: by Lucas Buyon, Randall Slaven, Paul M. Emerson, Jonathan King, Oscar Debrah, Agatha Aboe, Ernesto Ruiz-Tiben, E. Kelly Callahan Trachoma and Guinea Worm Disease (GWD) are neglected tropical diseases (NTD) slated for elimination as a public health problem and eradication respectively by the World Health Organization. As these programs wind down, uncovering the last cases becomes an urgent priority. In 2010, Ghana Health Services, along with The Carter Center, Sightsavers, and other partners, conducted integrated case searches for both GWD and the last stage of trachoma disease, trachomatous trichiasis (TT), as well as providing surgical treatment for TT to meet elimination (and eradication targets). House to house case searches for both diseases were conducted and two case management strategies were explored: a centralized referral to services method and a Point of Care (POC) delivery method. 835 suspected TT cases were discovered in the centralized method, of which 554 accepted surgery. 482 suspected TT cases were discovered in the POC method and all TT cases accepted surgery. The cost per TT case examined was lower in the POC searches compared to the centralized searches ($19.97 in the POC searches and $20.85 in the centralized searches). Both strategies resulted in high surgical uptake for TT surgery, with average uptakes of 72.4% and 83.9% for the centralized and POC searches respectively. We present here that house to house case searches offering services at POC are feasible and a potential tool for elimination and eradication programs nearing their end.
    Print ISSN: 1935-2727
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  • 58
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    Publication Date: 2018-12-21
    Description: by Shiro Hayashi, Tsutomu Nishida, Tokuhiro Matsubara, Naoto Osugi, Aya Sugimoto, Kei Takahashi, Kaori Mukai, Dai Nakamatsu, Masashi Yamamoto, Koji Fukui, Masami Inada
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  • 59
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    Publication Date: 2018-12-21
    Description: by Cannan Yi, Kai Way Li, Fan Tang, Huali Zuo, Liang Ma, Hong Hu
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  • 60
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    Publication Date: 2018-12-21
    Description: by Anne-Sofie Helvik, Geir Selbæk, Jūratė Šaltytė Benth, Irene Røen, Sverre Bergh
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  • 61
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    Publication Date: 2018-12-21
    Description: by Dong Hui Lim, Jisang Han, Tae-Young Chung, Sewoong Kang, Hyeon Woo Yim, on behalf of The Epidemiologic Survey Committee of the Korean Ophthalmologic Society
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  • 62
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    Publication Date: 2018-12-21
    Description: by Xiaojian Ye, Guoqiang Zhang, Haibin Chen, Yong Li
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  • 63
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    Publication Date: 2018-12-21
    Description: by Fariborz Mahmoudi, Kost Elisevich, Hassan Bagher-Ebadian, Mohammad-Reza Nazem-Zadeh, Esmaeil Davoodi-Bojd, Jason M. Schwalb, Manpreet Kaur, Hamid Soltanian-Zadeh
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  • 64
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    Publication Date: 2018-12-21
    Description: by Nathalia Carolina Fernandes Fagundes, Leonardo Oliveira Bittencourt, Marcela Baraúna Magno, Márcia Martins Marques, Lucianne Cople Maia, Rafael Rodrigues Lima
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  • 65
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    Publication Date: 2018-12-21
    Description: by Mikkel Wallentin Background Studies have suggested that aphasia rates are different in men and women following stroke. One hypothesis says that men have more lateralized language function than women. Given unilateral stroke, this would lead to a prediction of men having higher aphasia rates than women. Another line of observations suggest that women are more severely affected by stroke, which could lead to a higher aphasia rate among women. An additional potential confounding variable could be age, given that women are typically older at the time of stroke. Methods & procedures This study consists of two parts. First, a meta-analysis of the available reports of aphasia rates in the two sexes was conducted. A comprehensive literature search yielded 25 studies with sufficient information about both aphasia and gender. These studies included a total of 48,362 stroke patients for which aphasia rates were calculated. Second, data were extracted from an American health database (with 1,967,038 stroke patients), in order to include age and stroke severity into a regression analysis of sex differences in aphasia rates. Outcomes & results Both analyses revealed significantly larger aphasia rates in women than in men (1.1–1.14 ratio). This speaks against the idea that men should be more lateralized in their language function. When age and stroke severity were included as covariates, sex failed to explain any aphasia rate sex difference above and beyond that which is explained by age differences at time of stroke.
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  • 66
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    Publication Date: 2018-12-21
    Description: by Jorge Y. P. Palencia, Alysson Saraiva, Márvio Lobão Teixeira Abreu, Marcio G. Zangeronimo, Allan P. Schinckel, Cesar Augusto Pospissil Garbossa The use of functional nutrients has been proposed to reduce the occurrence of intrauterine growth retardation in animals at birth in several mammalian species. The objective of this study was to verify the effectiveness of citrulline and N-carbamylglutamate (NCG) dietary supplementation as arginine precursors for mammalian species, and the effects on fetal development through a systematic review. The search for studies was performed during August 2018 in the PubMed, ISI Web of Science, Science Direct, and Scopus databases. The literature search was conducted using “arginine precursor”, “citrulline”, or “N-carbamylglutamate” as keywords, combined with “gestation”, “pregnancy”, “fetus”, “newborn”, or “reproduction”. Studies in which arginine precursors were evaluated in gestating mammals and their effects on parameters related to the intrauterine development of the conceptus were selected. Of 1,379 articles, 18 were selected, primarily based on the title and the abstract. Supplementation with NCG (0.5 g to 2 g/kg of feed) increased maternal plasma arginine concentrations in all studies that evaluated this variable. Fetal number increased in 55.56% of the studies that evaluated it, and fetal weight increased in the majority (62.5%) of the studies evaluating this variable. By supplementing citrulline, only fetal weight was improved, with an increase in maternal plasma arginine in 40% of the studies. In conclusion, N-carbamoyl glutamate seems to be an arginine precursor more effective than L-citrulline during gestation; however, both precursors, beside L-Arginine, should be evaluated in similar conditions to confirm the existence of specific particularities such as periods and levels of supplementation, which need to be considered for different species of animals. The supplementation of NCG increases arginine concentrations in maternal plasma, thus improving mammalian reproductive efficiency and fetal development, mainly by promoting higher birth weight.
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    Publication Date: 2018-04-05
    Description: by Binbin Wu, Lingling Ma, Enyan Zhang, Juan Du, Suning Liu, Jeffrey Price, Sheng Li, Zhangwu Zhao Sexually dimorphic phenotypes are a universal phenomenon in animals. In the model animal fruit fly Drosophila , males and females exhibit long- and short-sleep phenotypes, respectively. However, the mechanism is still a mystery. In this study, we showed that juvenile hormone (JH) is involved in regulation of sexually dimorphic sleep in Drosophila , in which gain of JH function enlarges differences of the dimorphic sleep phenotype with higher sleep in males and lower sleep in females, while loss of JH function blurs these differences and results in feminization of male sleep and masculinization of female sleep. Further studies indicate that germ cell-expressed (GCE), one of the JH receptors, mediates the response in the JH pathway because the sexually dimorphic sleep phenotypes cannot be rescued by JH hormone in a gce deletion mutant. The JH-GCE regulated sleep dimorphism is generated through the sex differentiation-related genes - fruitless ( fru ) and doublesex ( dsx ) in males and sex-lethal ( sxl ), transformer ( tra ) and doublesex ( dsx ) in females. These are the “switch” genes that separately control the sleep pattern in males and females. Moreover, analysis of sleep deprivation and circadian behaviors showed that the sexually dimorphic sleep induced by JH signals is a change of sleep drive and independent of the circadian clock. Furthermore, we found that JH seems to also play an unanticipated role in antagonism of an aging-induced sleep decrease in male flies. Taken together, these results indicate that the JH signal pathway is critical for maintenance of sexually dimorphic sleep by regulating sex-relevant genes.
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-05
    Description: by Maria Stefania Latrofa, Giada Annoscia, Vito Colella, Maria Alfonsa Cavalera, Carla Maia, Coralie Martin, Jan Šlapeta, Domenico Otranto The ocular onchocercosis is caused is by the zoonotic parasite Onchocerca lupi (Spirurida: Onchocercidae). A major hindrance to scientific progress is the absence of a reliable diagnostic test in affected individuals. Microscopic examination of skin snip sediments and the identification of adults embedded in ocular nodules are seldom performed and labour-intensive. A quantitative real-time PCR (qPCR) assay was herein standardized for the detection of O . lupi DNA and the results compared with microscopic examination and conventional PCR (cPCR). The specificity of qPCR and cPCR was assessed by processing the most common filarial nematodes infecting dogs, skin samples from O . lupi infected (n = 35 dogs) or uninfected animals (n = 21 dogs; n = 152 cats) and specimens of potential insect vector (n = 93 blackflies; n = 59 mosquitoes/midges). The analytical sensitivity of both assays was assessed using 10-fold serial dilutions of DNA from adult specimen and from a pool of microfilariae. The qPCR on skin samples revealed an analytical specificity of 100% and a sensitivity up to 8 x 10 −1 fg/2μl O . lupi adult-DNA and up to 3.6 x 10 −1 pg/2μl of mfs-DNA (corresponding to 1 x 10 −2 mfs/2μl). Only 9.5% O . lupi -infected skin samples were positive for cPCR with a sensitivity of 8 x 10 −1 pg/2μl of DNA. Out of 152 blackflies and mosquitoes/midges, eight specimens experimentally infected (n = 1 S . erythrocephalum ; n = 1 S . ornatum ; n = 6 Simulium sp.) were positive by qPCR. The qPCR assay herein standardized represents an important step forward in the diagnosis of zoonotic onchocercosis caused by O . lupi , especially for the detection and quantification of low number of mfs. This assay provides a fundamental contribution for the establishment of surveillance strategies aiming at assessing the presence of O . lupi in carnivores and in insect species acting as potential intermediate hosts. The O . lupi qPCR assay will enable disease progress monitoring as well as the diagnosis of apparently clinical healthy dogs and cats.
    Print ISSN: 1935-2727
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  • 69
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-05
    Description: by Marieke Mastop, Nathalie R. Reinhard, Cristiane R. Zuconelli, Fenna Terwey, Theodorus W. J. Gadella Jr., Jakobus van Unen, Merel J. W. Adjobo-Hermans, Joachim Goedhart
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 70
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-05
    Description: by Ming-Qiang Xu, Hao Jiang, Li-Qun Zhang, Xu-Lei Sun, Dan Luo, Yao Fu, Yan Gao, Bao Yuan, Jia-Bao Zhang The regulatory role of miRNAs has been explored in ovarian cells, and their effects on gonadal development, apoptosis, ovulation, steroid production and corpus luteum (CL) development have been revealed. In this study, we analyzed the expression of miR-29b at different stages of bovine CL development and predicted the target genes of miR-29b. We confirmed that miR-29b reduces the expression of the oxytocin receptor (OXTR), affects progesterone (PROG) secretion and regulates the function of the CL. RT-PCR showed that the expression of miR-29b was significantly higher in functional CL phases than in the regressed CL phase. Immunohistochemistry showed that OXTR was expressed in both large and small CL cells and was mainly located in the cell membrane and cytoplasm of these cells. We analyzed the expression levels of OXTR and found that transfection with a miR-29b mimic decreased OXTR expression, but transfection with the inhibitor had a limited effect on the expression of the OXTR protein. At the same time, the secretion of PROG was significantly increased in the miR-29b mimic-transfected group. We also analyzed the effect of miR-29b on the apoptosis of CL cells. Finally, we found that miR-29b could promote the proliferation of bovine CL cells. In conclusion, we found that miR-29b reduces the expression of OXTR and can promote PROG secretion and the proliferation of CL cells via OXTR.
    Electronic ISSN: 1932-6203
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  • 71
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-05
    Description: by Haijiao Dong, Hu Zhao, Shuangle Li, Zhongmin Han, Gang Hu, Chang Liu, Gaiyu Yang, Gongwei Wang, Weibo Xie, Yongzhong Xing As a major component of ideal plant architecture, leaf angle especially flag leaf angle (FLA) makes a large contribution to grain yield in rice. We utilized a worldwide germplasm collection to elucidate the genetic basis of FLA that would be helpful for molecular design breeding in rice. Genome-wide association studies (GWAS) identified a total of 40 and 32 QTLs for FLA in Wuhan and Hainan, respectively. Eight QTLs were commonly detected in both conditions. Of these, 2 and 3 QTLs were identified in the indica and japonica subpopulations, respectively. In addition, the candidates of 5 FLA QTLs were verified by haplotype-level association analysis. These results indicate diverse genetic bases for FLA between the indica and japonica subpopulations. Three candidates, OsbHLH153 , OsbHLH173 and OsbHLH174 , quickly responded to BR and IAA involved in plant architecture except for OsbHLH173 , whose expression level was too low to be detected; their overexpression in plants increased rice leaf angle. Together with previous studies, it was concluded that all 6 members in bHLH subfamily 16 had the conserved function in regulating FLA in rice. A comparison with our previous GWAS for tiller angle (TA) showed only one QTL had pleiotropic effects on FLA and TA, which explained low similarity of the genetic basis between FLA and TA. An ideal plant architecture is expected to be efficiently developed by combining favorable alleles for FLA from indica with favorable alleles for TA from japonica by inter-subspecies hybridization.
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  • 72
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-05
    Description: by Arya Zandvakili, Ian Campbell, Lisa M. Gutzwiller, Matthew T. Weirauch, Brian Gebelein Cells use thousands of regulatory sequences to recruit transcription factors (TFs) and produce specific transcriptional outcomes. Since TFs bind degenerate DNA sequences, discriminating functional TF binding sites (TFBSs) from background sequences represents a significant challenge. Here, we show that a Drosophila regulatory element that activates Epidermal Growth Factor signaling requires overlapping, low-affinity TFBSs for competing TFs (Pax2 and Senseless) to ensure cell- and segment-specific activity. Testing available TF binding models for Pax2 and Senseless, however, revealed variable accuracy in predicting such low-affinity TFBSs. To better define parameters that increase accuracy, we developed a method that systematically selects subsets of TFBSs based on predicted affinity to generate hundreds of position-weight matrices (PWMs). Counterintuitively, we found that degenerate PWMs produced from datasets depleted of high-affinity sequences were more accurate in identifying both low- and high-affinity TFBSs for the Pax2 and Senseless TFs. Taken together, these findings reveal how TFBS arrangement can be constrained by competition rather than cooperativity and that degenerate models of TF binding preferences can improve identification of biologically relevant low affinity TFBSs.
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  • 73
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by Gretl Hendrickx, Vere M. Borra, Ellen Steenackers, Timur A. Yorgan, Christophe Hermans, Eveline Boudin, Jérôme J. Waterval, Ineke D. C. Jansen, Tolunay Beker Aydemir, Niels Kamerling, Geert J. Behets, Christine Plumeyer, Patrick C. D’Haese, Björn Busse, Vincent Everts, Martin Lammens, Geert Mortier, Robert J. Cousins, Thorsten Schinke, Robert J. Stokroos, Johannes J. Manni, Wim Van Hul Hyperostosis Cranialis Interna (HCI) is a rare bone disorder characterized by progressive intracranial bone overgrowth at the skull. Here we identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 ( ZIP14 ). We show that L441R ZIP14 is no longer trafficked towards the plasma membrane and excessively accumulates intracellular zinc, resulting in hyper-activation of cAMP-CREB and NFAT signaling. Conditional knock-in mice overexpressing L438R Zip14 in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients. Remarkably, L438R Zip14 also generates an osteoporotic trabecular bone phenotype. The effects of osteoblastic overexpression of L438R Zip14 therefore mimic the disparate actions of estrogen on cortical and trabecular bone through osteoblasts. Collectively, we reveal ZIP14 as a novel regulator of bone homeostasis, and that manipulating ZIP14 might be a therapeutic strategy for bone diseases.
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  • 74
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by Lichao Li, Weifeng Gu
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  • 75
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by Zaida Herrador, Amalia Fernandez-Martinez, Agustín Benito, Rogelio Lopez-Velez Background Cysticercosis (CC) is a tissue infection caused by the larval cysts of the pork tapeworm Taenia solium . It is usually acquired by eating contaminated food or drinking water. CC Cysts can develop in the muscles, the eyes, the brain, and/or the spinal cord. T . solium is found worldwide, but its prevalence has decreased in developed countries due to stricter meat inspection and better hygiene and sanitation. Nevertheless, CC is still a leading cause of seizures and epilepsy. In Spain, The disease is not nationally reportable and data on CC infected animals are also missing, despite the European Directive 2003/99/EC. Methodology/Principal findings We performed a retrospective descriptive study using the Spanish Hospitalization Minimum Data Set (CMBD). Data with ICD-9 CM cysticercosis code (“123.1”) placed in first or second diagnostic position from 1997 to 2014 were analyzed. Hospitalization rates were calculated and clinical characteristics were described. Spatial distribution of cases and their temporal behavior were also assessed. A total of 1,912 hospital discharges with clinical cysticercosis were identified. From 1998 to 2008, an increasing trend in the number of CC hospitalizations was observed, decreasing afterwards, in parallel with a decrease in the external migration rate. The Murcia region had the highest median hospitalization rate (13.37 hospitalizations/100,000 population), followed by Navarra and Madrid. The 16–44 age group was the most represented (63.6%). The three most frequent associated diagnoses were epilepsy and convulsions (49.5%), hydrocephalus (11.8%) and encephalitis/myelitis/meningitis (11.6%). Conclusions/Significance There is a need for a common strategy on data collection, monitoring and reporting, which would facilitate a more accurate picture on the CC epidemiological scenario. Even if most cases might be imported, improving the human and animal CC surveillance will result useful both in gaining extended disease knowledge and reducing morbidity and related-costs.
    Print ISSN: 1935-2727
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  • 76
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by Jae Chol Yoon, Youn-Jung Kim, You-Jin Lee, Seung Mok Ryoo, Chang Hwan Sohn, Dong-Woo Seo, Yoon-Seon Lee, Jae Ho Lee, Kyoung Soo Lim, Won Young Kim Objective This study was aimed at a serial evaluation and comparison of the prognostic values of Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores for neurologic outcomes in comatose, out-of-hospital cardiac arrest (OHCA) survivors, treated with targeted temperature management (TTM). Methods We analysed a prospective cohort of comatose OHCA patients, with TTM, admitted to an emergency intensive care unit (ICU), between January 2010 and December 2015. SOFA and APACHE II scores were calculated initially, and then at day 1, 2, 3, 5, and 7 after ICU admission. Primary and secondary outcomes were the 28-day neurologic outcome and the 28-day mortality, respectively. Prognostic value of the SOFA and APACHE II scores was analysed using the receiver operating characteristic curve. Results Of the 143 selected patients, 62 survived and 34 had good neurologic outcomes at day 28. There was no significant difference in the SOFA and extracerebral SOFA scores between the good and poor neurologic outcome groups. However, the APACHE II scores were significantly higher in the good outcome group; they displayed good discriminatory power in predicting poor outcomes, unlike the SOFA scores. The APACHE II score at day 3 had the highest prognostic value for predicting poor neurologic outcomes with an area under the cure of 0.793, and with a cut-off value of 20, the APACHE II score predicted poor neurologic outcomes with a sensitivity of 43.75%, a specificity of 94.12%, a positive predictive value of 94.59%, and a negative predictive value of 41.56%. Conclusions Identifying APACHE II score might assist as one piece of multimodal prognostic approach for the assessment of neurologic outcomes in OHCA survivors treated with TTM.
    Electronic ISSN: 1932-6203
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  • 77
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by Juliette Moreau, Toufic Khalil, Guillaume Dupic, Emmanuel Chautard, Jean-Jacques Lemaire, Florian Magnier, Véronique Dedieu, Michel Lapeyre, Pierre Verrelle, Julian Biau In the present study, we have evaluated the efficacy and toxicity of repeated brain metastases (BM) stereotactic radiosurgery (SRS2) following local failure of a prior radiosurgical procedure (SRS1). Between December 1996 and August 2015, 30 patients with 36 BM underwent SRS2 with a median dose of 18Gy. All BM were located outside critical structures. Following SRS2, local control at 6 months and one year were respectively 82.9% (IC 95%: 67.6–91.9) and 67.8% (IC 95%: 51–81). On multivariate analysis, planning target volume (PTV) 〈 3cc (HR: 0.19 (0.1–0.52)) and whole brain radiotherapy (WBRT) prior to SRS2 (HR: 0.25 (0.1–0.64)) were significantly associated with a better local control. One- and two-year overall survival rates after SRS2 were respectively 65.5% (IC 95%: 47.3–80%) and 27.6% (IC 95%: 14.7–45.7). Median overall survival following SRS2 was 14.2 months (range 1–106). Nineteen (63%) patients died from progressive systemic disease. Three (10%) patients died from out-field progressive brain disease and 8 (27%) in-field. Concerning toxicities, edema, radionecrosis, and hemorrhages were identified in 5 (12.8%), 4 (10.2%), and 5 (12.8%) patients respectively. No toxicity resulted in a neurological deficit. On univariate analysis, toxicities were significantly associated with PTV 〉 7cc (p = 0.02) and all patients had a WBRT before SRS2. A second course of SRS for locally recurrent brain metastases showed encouraging rates of local control. This treatment led to acceptable toxicities, especially for brain metastases smaller than 7cc, in our selected cohort of patients with BM located outside critical structures. Further studies are needed.
    Electronic ISSN: 1932-6203
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  • 78
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by Bin Zhu, Yang Fu, Jinlin Liu, Ying Mao Background China is the largest developing country with a relatively developed public health system. To further prevent and eliminate the spread of infectious diseases, China has listed 39 notifiable infectious diseases characterized by wide prevalence or great harm, and classified them into classes A, B, and C, with severity decreasing across classes. Class A diseases have been almost eradicated in China, thus making class B diseases a priority in infectious disease prevention and control. In this retrospective study, we analyze the spatial distribution patterns of 12 class B notifiable infectious diseases that remain active all over China. Methods Global and local Moran’s I and corresponding graphic tools are adopted to explore and visualize the global and local spatial distribution of the incidence of the selected epidemics, respectively. Inter-correlations of clustering patterns of each pair of diseases and a cumulative summary of the high/low cluster frequency of the provincial units are also provided by means of figures and maps. Results Of the 12 most commonly notifiable class B infectious diseases, viral hepatitis and tuberculosis show high incidence rates and account for more than half of the reported cases. Almost all the diseases, except pertussis, exhibit positive spatial autocorrelation at the provincial level. All diseases feature varying spatial concentrations. Nevertheless, associations exist between spatial distribution patterns, with some provincial units displaying the same type of cluster features for two or more infectious diseases. Overall, high–low (unit with high incidence surrounded by units with high incidence, the same below) and high–high spatial cluster areas tend to be prevalent in the provincial units located in western and southwest China, whereas low–low and low–high spatial cluster areas abound in provincial units in north and east China. Conclusion Despite the various distribution patterns of 12 class B notifiable infectious diseases, certain similarities between their spatial distributions are present. Substantial evidence is available to support disease-specific, location-specific, and disease-combined interventions. Regarding provinces that show high–high/high–low patterns of multiple diseases, comprehensive interventions targeting different diseases should be established. As to the adjacent provincial units revealing similar patterns, coordinated actions need to be taken across borders.
    Electronic ISSN: 1932-6203
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  • 79
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by Yousuke Imai, Taro Kariya, Masaki Iwakiri, Yoshitsugu Yamada, Eiki Takimoto Right ventricular (RV) dysfunction following left ventricular (LV) failure is associated with poor prognosis. RV remodeling is thought initiated by the increase in the afterload of RV due to secondary pulmonary hypertension (PH) to impaired LV function; however, RV molecular changes might occur in earlier stages of the disease. cGMP (cyclic guanosine monophosphate)-phosphodiesterase 5 (PDE5) inhibitors, widely used to treat PH through their pulmonary vasorelaxation properties, have shown direct cardiac benefits, but their impacts on the RV in LV diseases are not fully determined. Here we show that RV molecular alterations occur early in the absence of RV hemodynamic changes during LV pressure-overload and are ameliorated by PDE5 inhibition. Two-day moderate LV pressure-overload (transverse aortic constriction) neither altered RV pressure/ function nor RV weight in mice, while it induced only mild LV hypertrophy. Importantly, pathological molecular features were already induced in the RV free wall myocardium, including up-regulation of gene markers for hypertrophy and inflammation, and activation of extracellular signal-regulated kinase (ERK) and calcineurin. Concomitant PDE5 inhibition (sildenafil) prevented induction of such pathological genes and activation of ERK and calcineurin in the RV as well as in the LV. Importantly, dexamethasone also prevented these RV molecular changes, similarly to sildenafil treatment. These results suggest the contributory role of inflammation to the early pathological interventricular interaction between RV and LV. The current study provides the first evidence for the novel early molecular cross-talk between RV and LV, preceding RV hemodynamic changes in LV disease, and supports the therapeutic strategy of enhancing cGMP signaling pathway to treat heart diseases.
    Electronic ISSN: 1932-6203
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  • 80
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by Stephen A. Stansfeld, Ewan Carr, Melanie Smuk, Charlotte Clark, Emily Murray, Nicola Shelton, Jenny Head Objectives To examine whether psychosocial work characteristics at age 45 years predict exit from the labour market by the age of 50 years in data from the 1958 British Birth Cohort. Methods Psychosocial work characteristics (decision latitude, job demands, job strain and work social support at 45 years and job insecurity at 42 years) measured by questionnaire were linked to employment outcomes (unemployment, retirement, permanent sickness, homemaking) at 50 years in 6510 male and female participants. Results Low decision latitude (RR = 2.01, 95%CI 1.06,3.79), low work social support (RR = 1.96, 95%CI 1.12,3.44), and high job insecurity (RR = 2.27, 95%CI 1.41, 3.67) predicted unemployment at 50, adjusting for sex, housing tenure, socioeconomic status, marital status, and education. High demands were associated with lower risk of unemployment (RR = 0.50, 95%CI 0.29,0.88) but higher risk of permanent sickness (RR = 2.14, 95%CI 1.09,4.21). Conclusions Keeping people in the workforce beyond 50 years may contribute to both personal and national prosperity. Employers may wish to improve working conditions for older workers, in particular, increase control over work, increase support and reduce demands to retain older employees in the workforce.
    Electronic ISSN: 1932-6203
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  • 81
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by José Luis Álvarez-Castillo, Gemma Fernández-Caminero, Hugo González-González In the field of the social psychology of prejudice, John Duckitt's Dual-Process Cognitive-Motivational Model of Ideology and Prejudice has gained a firm grounding over the past decade and a half, while empathy has become one of the most powerful predictors of prejudice, alongside right-wing authoritarianism and social dominance orientation. This study integrates empathy into the dual-process model, exploring the effects of this variable, along with the impact of personality and ideological attitudes, on prejudice in both its blatant and subtle forms. A cross-sectional research design was used to collect data from 260 university students by self-report measures. Despite its cross-sectional nature, a pattern of causal relationships was hypothesized according to experimental and longitudinal findings from previous studies. The path analysis results show that in the model fitted to the data, empathy does not have any direct impact on prejudice, although it plays a significant role in the prediction of prejudice towards a particular immigrant group. On the other hand, the dual-process model is confirmed in the explanation of blatant prejudice and, in a weaker and indirect way, of subtle prejudice; sustaining the distinctive nature of these constructs on some differential predictors and paths. In the discussion, this study proposes that when ideological and personality-based variables are both included in the model, general empathy is not so robust in the explanation of prejudice, since some of the empathetic components might become diluted among other covariates. But even so, its indirect effectiveness through personality and ideological attitudes remains relevant.
    Electronic ISSN: 1932-6203
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  • 82
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    Public Library of Science (PLoS)
    Publication Date: 2018-04-06
    Description: by Youri Yordanov, Agnes Dechartres, Philippe Ravaud Background Cochrane reviewers are strongly encouraged to evaluate the quality of evidence for the most important outcomes by using the GRADE approach and to report these results in a Summary of Findings (SoF) table. We aimed to assess whether outcomes reported in the SoF table of Cochrane reviews could be considered patient-important outcomes (PIOs) and the quality of the available evidence for these outcomes. Methods We performed a methodological review of Cochrane reviews published between March 2011 and September 2014. For a random sample of Cochrane reviews reporting a SoF table, we extracted all outcomes reported in this table and evaluated whether they could be considered PIOs (i.e., mortality, other clinical events, adverse events, function, pain, quality of life and therapeutic decisions). Then, we collected the quality of evidence for every outcome in these SoF tables. Results We included 290 reviews issued by 47 of the 53 Cochrane Review Groups. Every SoF table included a median of 5 outcomes, for a total of 1414 outcomes; 1089 (77%) could be considered PIOs. Almost all reviews (n = 278, 96%) included at least one PIO in their SoF table. The quality of evidence for the outcomes was high for 12% (n = 168), moderate for 28% (n = 402) and low or very low for 45% (n = 640). Less than one quarter of reviews (n = 63) included at least one PIO with high-quality evidence that favoured a benefit of the experimental intervention evaluated in half of them (n = 34 reviews). Conclusions Many outcomes reported in the SoF table of recent Cochrane reviews can be considered PIOs. However, the quality of available evidence remains limited for these outcomes.
    Electronic ISSN: 1932-6203
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  • 83
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    Publication Date: 2018-04-06
    Description: by Bharti Bhatia, Chad Hillman, Valentina Carracoi, Britney N. Cheff, Kit Tilly, Patricia A. Rosa Lyme disease in humans is caused by several genospecies of the Borrelia burgdorferi sensu lato (s.l.) complex of spirochetal bacteria, including B . burgdorferi , B . afzelii and B . garinii . These bacteria exist in nature as obligate parasites in an enzootic cycle between small vertebrate hosts and Ixodid tick vectors, with humans representing incidental hosts. During the natural enzootic cycle, infected ticks in endemic areas feed not only upon naïve hosts, but also upon seropositive infected hosts. In the current study, we considered this environmental parameter and assessed the impact of the immune status of the blood-meal host on the phenotype of the Lyme disease spirochete within the tick vector. We found that blood from a seropositive host profoundly attenuates the infectivity (〉10 4 fold) of homologous spirochetes within the tick vector without killing them. This dramatic neutralization of vector-borne spirochetes was not observed, however, when ticks and blood-meal hosts carried heterologous B . burgdorferi s.l. strains, or when mice lacking humoral immunity replaced wild-type mice as blood-meal hosts in similar experiments. Mechanistically, serum-mediated neutralization does not block induction of host-adapted OspC+ spirochetes during tick feeding, nor require tick midgut components. Significantly, this study demonstrates that strain-specific antibodies elicited by B . burgdorferi s.l. infection neutralize homologous bacteria within feeding ticks, before the Lyme disease spirochetes enter a host. The blood meal ingested from an infected host thereby prevents super-infection by homologous spirochetes, while facilitating transmission of heterologous B . burgdorferi s.l. strains. This finding suggests that Lyme disease spirochete diversity is stably maintained within endemic populations in local geographic regions through frequency-dependent selection of rare alleles of dominant polymorphic surface antigens.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
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  • 84
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    Publication Date: 2018-04-07
    Description: by Álvaro López-Samanes, Jesús G. Pallarés, Alberto Pérez-López, Ricardo Mora-Rodríguez, Juan F. Ortega We sought to measure the response of cortisol concentrations around a professional tennis match and its association with hydration status and neuromuscular performance. Nine professional male tennis players were tested in a rest day, and 2-week after, during the first match of a professional tournament played in a clay-court. Salivary concentrations of cortisol (SalCC) were measured in a resting day (9:00 am and 8:00 pm), at the match day (9:00 am and 8:00 pm) and immediately before and after the match. Hydration status was assessed before the match (urine specific gravity; USG) while fluid turnover was tracked during the match. Finally, counter movement jump (CMJ) and handgrip isometric strength (HS) were measured before and after the match. SalCC, either in the morning (P = 0.161) and afternoon (P = 0.683) was similar in rest and match days. However, SalCC increased after the match (P = 0.033). Participants started the match hypohydrated (USG = 1.026±0.002) and during the match lost 1.0±0.3% of body weight despite 1.035±0.124 L/h of fluid ingested. CMJ and HS did not change post-match (P = 0.210 and P = 0.881, respectively). Correlations between the elevations in SalCC and dehydration (% BW loss) during the match were significant (r = -0.632; P = 0.034). Professional male tennis players did not show an anticipatory increase in SalCC the day of the match and neither signs of neuromuscular fatigue after it. During the match, the mild dehydration (i.e.,
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