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  • 1
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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.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 2
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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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  • 3
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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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  • 4
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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
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  • 5
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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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  • 6
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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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  • 7
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 8
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Shin-Hye Kim, Ji-won On, Heesoo Pyo, Kyung Soo Ko, Jong Chul Won, Jiyeon Yang, Mi Jung Park
    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: 2018-12-20
    Description: by Marcin Studnicki, Grażyna Woźniak, Dariusz Stępkowski
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 10
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Rene Westerholt, Enrico Steiger, Bernd Resch, Alexander Zipf
    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: 2018-12-20
    Description: by Limin Li, Yen Yen Woo, Jessie Anne de Bruyne, Anna Marie Nathan, Sze Ying Kee, Yoke Fun Chan, Chun Wei Chiam, Kah Peng Eg, Surendran Thavagnanam, I-Ching Sam
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 12
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Krishna Das, David Eisel, Clarissa Lenkl, Ashish Goyal, Sven Diederichs, Elke Dickes, Wolfram Osen, Stefan B. Eichmüller
    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: 2018-12-20
    Description: by Mirian Sánchez-Morán, Juan Andrés Hernández, Jon Andoni Duñabeitia, Adelina Estévez, Laura Bárcena, Aintzane González-Lahera, María Teresa Bajo, Luis J. Fuentes, Ana M. Aransay, Manuel Carreiras
    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: 2018-12-20
    Description: by The PLOS ONE Staff
    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: 2018-12-20
    Description: by Francisco J. Santiago-Avila, Ari M. Cornman, Adrian Treves
    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: 2018-12-20
    Description: by Haesuk Park, Donghak Jeong, Pauline Nguyen, Linda Henry, Joseph Hoang, Yoona Kim, Edward Sheen, Mindie H. Nguyen
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 17
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    Public Library of Science (PLoS)
    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
    Topics: Medicine , Natural Sciences in General
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  • 18
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    Public Library of Science (PLoS)
    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
    Topics: Medicine , Natural Sciences in General
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  • 19
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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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  • 20
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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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  • 21
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Anat Gesser-Edelsburg, Alon Diamant, Rana Hijazi, Gustavo S. Mesch Background During epidemic crises, some of the information the public receives on social media is misinformation. Health organizations are required to respond and correct the information to gain the public’s trust and influence it to follow the recommended instructions. Objectives (1) To examine ways for health organizations to correct misinformation concerning the measles vaccination on social networks for two groups: pro-vaccination and hesitant; (2) To examine the types of reactions of two subgroups (pro-vaccination, hesitant) to misinformation correction; and (3) To examine the effect of misinformation correction on these two subgroups regarding reliability, satisfaction, self-efficacy and intentions. Methods A controlled experiment with participants divided randomly into two conditions. In both experiment conditions a dilemma was presented as to sending a child to kindergarten, followed by an identical Facebook post voicing the children mothers’ concerns. In the third stage the correction by the health organization is presented differently in two conditions: Condition 1 –common information correction, and Condition 2 –recommended (theory-based) information correction, mainly communicating information transparently and addressing the public’s concerns. The study included (n = 243) graduate students from the Faculty of Social Welfare and Health Sciences at Haifa University. Results A statistically significant difference was found in the reliability level attributed to information correction by the Health Ministry between the Control condition and Experimental condition (sig
    Electronic ISSN: 1932-6203
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  • 22
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-20
    Description: by Helena Wallin, Anna M. Asp, Carin Wallquist, Eva Jansson, Kenneth Caidahl, Britta Hylander Rössner, Stefan H. Jacobson, Anette Rickenlund, Maria J. Eriksson Background The cause of reduced exercise capacity (ExCap) in chronic kidney disease (CKD) is multifactorial. The aim of this study was to investigate determinants of aerobic ExCap in patients with mild to severe CKD not undergoing dialysis. Methods We included 52 individuals with CKD stage 2–3, 47 with stage 4–5, and 54 healthy controls. Peak workload and peak heart rate (HR) were assessed by a maximal cycle exercise test. Cardiac function including stroke volume (SV) and vascular stiffness were evaluated by ultrasound at rest. Handgrip strength, body composition, haemoglobin level and self-reported physical activity were assessed. Results Peak workload (221±60, 185±59, 150±54 W for controls, CKD 2–3 and CKD 4–5 respectively), peak HR (177±11, 161±24, 144±31 beats/min) and haemoglobin level (14.2±1.2, 13.5±1.4, 12.2±1.3 g/dL) were all three significantly lower in CKD 2–3 than in controls, (p = 0.001, 0.001 and 0.03 respectively) and were even lower in stages 4–5 CKD than in CKD 2–3 (p = 0.01, 0.001 and
    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 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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  • 24
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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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  • 25
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Xiaojian Ye, Guoqiang Zhang, Haibin Chen, Yong Li
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 26
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    Public Library of Science (PLoS)
    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
    Electronic ISSN: 1932-6203
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  • 27
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Peng Tang, Jie Wu, Hou Liu, Youcai Liu, Xingding Zhou
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 28
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Aditi Singh, Adrienne Vancura, Rafal K. Woycicki, Daniel J. Hogan, Alan G. Hendrick, Mariusz Nowacki
    Electronic ISSN: 1932-6203
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  • 29
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    Public Library of Science (PLoS)
    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
    Electronic ISSN: 1935-2735
    Topics: Medicine
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  • 30
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Cannan Yi, Kai Way Li, Fan Tang, Huali Zuo, Liang Ma, Hong Hu
    Electronic ISSN: 1932-6203
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  • 31
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    Public Library of Science (PLoS)
    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
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    Topics: Biology
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  • 32
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    Public Library of Science (PLoS)
    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
    Electronic ISSN: 1932-6203
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  • 33
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-21
    Description: by Fernando Caravaggio, Pontus Plavén-Sigray, Granville James Matheson, Eric Plitman, M. Mallar Chakravarty, Jacqueline Borg, Ariel Graff-Guerrero, Simon Cervenka High levels of trait impulsivity are considered a risk factor for substance abuse and drug addiction. We recently found that non-planning trait impulsivity was negatively correlated with post-commissural putamen volumes in men, but not women, using the Karolinska Scales of Personality (KSP). Here, we attempted to replicate this finding in an independent sample using an updated version of the KSP: the Swedish Universities Scales of Personality (SSP). Data from 88 healthy male participants (Mean Age: 28.16±3.34), who provided structural T1-weighted magnetic resonance images (MRIs) and self-reported SSP impulsivity scores, were analyzed. Striatal sub-region volumes were acquired using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Contrary to our previous findings trait impulsivity measured using SSP was not a significant predictor of post-commissural putamen volumes (β = .14, df = 84, p = .94). A replication Bayes Factors analysis strongly supported this null result. Consistent with our previous findings, secondary exploratory analyses found no relationship between ventral striatum volumes and SSP trait impulsivity (β = -.05, df = 84, p = .28). An exploratory analysis of the other striatal compartments showed that there were no significant associations with trait impulsivity. While we could not replicate our previous findings in the current sample, we believe this work will aide future studies aimed at establishing meaningful brain biomarkers for addiction vulnerability in healthy humans.
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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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    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
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    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
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    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.
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    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
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    Publication Date: 2018-12-21
    Description: by Philip E. Bourne, Fran Lewitter, Scott Markel, Jason A. Papin
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 40
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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.
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    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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    Publication Date: 2018-12-21
    Description: by Benjamin D. Lee
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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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    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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  • 45
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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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  • 46
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    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.
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    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.
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    Publication Date: 2018-12-21
    Description: by Sandra F. Lam, Venktesh S. Shirure, Yunli E. Chu, Alan G. Soetikno, Steven C. George Microfluidic devices have been successfully used to recreate in vitro biological microenvironments, including disease states. However, one constant issue for replicating microenvironments is that atmospheric oxygen concentration (21% O 2 ) does not mimic physiological values (often around 5% O 2 ). We have created a microfluidic device that can control both the spatial and temporal variations in oxygen tensions that are characteristic of in vivo biology. Additionally, since the microcirculation is responsive to hypoxia, we used a 3D sprouting angiogenesis assay to confirm the biological relevance of the microfluidic platform. Our device consists of three parallel connected tissue chambers and an oxygen scavenger channel placed adjacent to these tissue chambers. Experimentally measured oxygen maps were constructed using phosphorescent lifetime imaging microscopy and compared with values from a computational model. The central chamber was loaded with endothelial and fibroblast cells to form a 3D vascular network. Four to six days later, fibroblasts were loaded into the side chambers, and a day later the oxygen scavenger (sodium sulfite) was flowed through the adjacent channel to induce a spatial and temporal oxygen gradient. Our results demonstrate that both constant chronic and intermittent hypoxia can bias vessel growth, with constant chronic hypoxia showing higher degrees of biased angiogenesis. Our simple design provides consistent control of spatial and temporal oxygen gradients in the tissue microenvironment and can be used to investigate important oxygen-dependent biological processes in conditions such as cancer and ischemic heart disease.
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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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    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.
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    Publication Date: 2018-12-21
    Description: by Ana Maria Ravena Severino Carvalho, Tiago Antônio de Oliveira Mendes, Eduardo Antonio Ferraz Coelho, Mariana Costa Duarte, Daniel Menezes-Souza Visceral leishmaniasis (VL) still represents a serious public health problem in Brazil due to the inefficiency of the control measures currently employed, that included early diagnosis and treatment of human cases, vector control, euthanasia of infected dogs and, recently approved in Brazil, treatment with Milteforam drug. Effective clinical management depend largely on early and unequivocal diagnosis, however, cross-reactivity have also been described in serological tests, especially when it refers to individuals from areas where Chagas’ disease is also present. Thus, to discover new antigens to improve the current serological tests for VL diagnosis is urgently needed. Here, we performed an immunogenomic screen strategy to identify conserved linear B-cell epitopes in the predicted L . infantum proteome using the following criteria: i ) proteins expressed in the stages found in the vertebrate host, amastigote stage, and secreted/excreted, to guarantee greater exposure to the immune system; ii ) divergent from proteins present in other infectious disease pathogens with incidence in endemic areas for VL, as T . cruzi ; iii ) highly antigenic to humans with different genetic backgrounds, independently of the clinical stage of the disease; iv ) stable and adaptable to quality-control tests to guarantee reproducibility; v) using statistical analysis to determine a suitable sample size to evaluate accuracy of diagnostic tests established by receiver operating characteristic strategy. We selected six predicted linear B-cell epitopes from three proteins of L . infantum parasite. The results demonstrated that a mixture of peptides (Mix IV: peptides 3+6) were able to identify VL cases and simultaneously able to discriminate infections caused by T . cruzi parasite with high accuracy (100.00%) and perfect agreement (Kappa index = 1.000) with direct methods performed by laboratories in Brazil. The results also demonstrated that peptide-6, Mix III (peptides 2+6) and I (peptides 2+3+6) are potential antigens able to used in VL diagnosis, represented by high accuracy (Ac = 99.52%, 99.52% and 98.56%, respectively). This study represents an interesting strategy for discovery new antigens applied to serologic diagnosis which will contribute to the improvement of the diagnosis of VL and, consequently, may help in the prevention, control and treatment of the disease in endemic areas of Brazil.
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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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    Publication Date: 2018-12-19
    Description: by Tormod Rebnord, Truls Østbye, Blandina Theophil Mmbaga, Bariki Mchome, Rolv Terje Lie, Anne Kjersti Daltveit
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-19
    Description: by Katharine Kripke, Marjorie Opuni, Elijah Odoyo-June, Mathews Onyango, Peter Young, Kennedy Serrem, Vincent Ojiambo, Melissa Schnure, Peter Stegman, Emmanuel Njeuhmeli Background Kenya is 1 of 14 priority countries in Africa scaling up voluntary medical male circumcision (VMMC) for HIV prevention following the recommendations of the World Health Organization and the Joint United Nations Programme on HIV/AIDS. To inform VMMC target setting, we modeled the impact of circumcising specific client age groups across several Kenyan geographic areas. Methods The Decision Makers’ Program Planning Tool, Version 2 (DMPPT 2) was applied in Kisumu, Siaya, Homa Bay, and Migori counties. Initial modeling done in mid-2016 showed coverage estimates above 100% in age groups and geographic areas where demand for VMMC continued to be high. On the basis of information obtained from country policy makers and VMMC program implementers, we adjusted circumcision coverage for duplicate reporting, county-level population estimates, migration across county boundaries for VMMC services, and replacement of traditional circumcision with circumcisions in the VMMC program. To address residual inflated coverage following these adjustments we applied county-specific correction factors computed by triangulating model results with coverage estimates from population surveys. Results A program record review identified duplicate reporting in Homa Bay, Kisumu, and Siaya. Using county population estimates from the Kenya National Bureau of Statistics, we found that adjusting for migration and correcting for replacement of traditional circumcision with VMMC led to lower estimates of 2016 male circumcision coverage especially for Kisumu, Migori, and Siaya. Even after addressing these issues, overestimation of 2016 male circumcision coverage persisted, especially in Homa Bay. We estimated male circumcision coverage in 2016 by applying correction factors. Modeled estimates for 2016 circumcision coverage for the 10- to 14-year age group ranged from 50% in Homa Bay to approximately 90% in Kisumu. Results for the 15- to 19-year age group suggest almost complete coverage in Kisumu, Migori, and Siaya. Coverage for the 20- to 24-year age group ranged from about 80% in Siaya to about 90% in Homa Bay, coverage for those aged 25–29 years ranged from about 60% in Siaya to 80% in Migori, and coverage in those aged 30–34 years ranged from about 50% in Siaya to about 70% in Migori. Conclusions Our analysis points to solutions for some of the data issues encountered in Kenya. Kenya is the first country in which these data issues have been encountered because baseline circumcision rates were high. We anticipate that some of the modeling methods we developed for Kenya will be applicable in other countries.
    Electronic ISSN: 1932-6203
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  • 55
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-19
    Description: by Matthew Fuirst, Richard R. Veit, Megan Hahn, Nolwenn Dheilly, Lesley H. Thorne Larus gull species have proven adaptable to urbanization and due to their generalist feeding behaviors, they provide useful opportunities to study how urban environments impact foraging behavior and host-associated microbiota. We evaluated how urbanization influenced the foraging behavior and microbiome characteristics of breeding herring gulls ( Larus argentatus ) at three different colonies on the east coast of the United States. Study colonies represented high, medium and low degrees of urbanization, respectively. At all colonies, gulls frequently foraged at landfills and in other urban environments, but both the use of urban environments and gull foraging metrics differed with the degree of urbanization. Gulls at the more urban colonies used urban environments more frequently, showed higher rates of site fidelity and took shorter trips. Gulls at less urban colonies used a greater diversity of habitat types and foraged offshore. We observed high microbial diversity at all colonies, though microbial diversity was highest at the least urban colony where gulls used a wider variety of foraging habitats. This suggests that gulls may acquire a wider range of bacteria when visiting a higher variety of foraging sites. Our findings highlight the influence of urban habitats on gull movements and microbiome composition and diversity during the breeding season and represent the first application of amplicon sequence variants, an objective and repeatable method of bacterial classification, to study the microbiota of a seabird species.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 56
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-19
    Description: by Miro-Pekka Jussila, Tiina Remes, Julia Anttonen, Arja Harila-Saari, Jaakko Niinimäki, Tytti Pokka, Päivi Koskenkorva, Anna Sutela, Sanna Toiviainen-Salo, Pekka Arikoski, Pekka Riikonen, Mikko Arola, Päivi Lähteenmäki, Kirsti Sirkiä, Heikki Rantala, Maria Suo-Palosaari, Marja Ojaniemi Purpose Long-term side effects of the treatments are common in survivors of irradiated pediatric brain tumors. Ionizing radiation in combination with surgery and chemotherapy during childhood may reduce vertebral height and bone mineral density (BMD), and cause growth failure. The aim of this study was to evaluate the late consequences of tumor treatments on vertebrae in survivors of childhood brain tumors. Methods 72 adult survivors (mean age 27.8 years, standard deviation 6.7) of irradiated childhood brain tumor were studied by spinal magnetic resonance imaging (MRI) for vertebral abnormalities from the national cohort of Finland. Patients were treated in five university hospitals in Finland between the years 1970 and 2008. Subject height and weight were measured and body mass index (BMI) was calculated. The morphology and height/depth ratio of the vertebrae in the middle of the kyphotic thoracic curvature (Th8) and lumbar lordosis (L3) were examined. Vertebrae were analyzed by Genant’s semiquantative (SQ) method and spinal deformity index (SDI) was calculated. BMD was measured by using dual X-ray absorptiometry. Results 4.2% (3/72) of the patients had undiagnosed asymptomatic vertebral fracture and 5.6% (4/72) of patients had radiation-induced decreased vertebral body height. Male patients had flatter vertebrae compared with females. Patient age at the time of irradiation, BMI and irradiation area correlated to vertebral morphology differentially in males and females. BMD had no association with the vertebral shape. Patients who had received craniospinal irradiation were shorter than the general population. Conclusion Childhood brain tumor survivors had a high number of vertebral abnormalities in young adulthood. Irradiation was associated with abnormal vertebral morphology and compromised final height. Male gender may predispose vertebrae to the side effects of irradiation.
    Electronic ISSN: 1932-6203
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  • 57
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-19
    Description: by Matthijs P. S. van Wijmen, H. Roeline W. Pasman, Jos W. R. Twisk, Guy A. M. Widdershoven, Bregje D. Onwuteaka-Philipsen Background Stating preferences about care beforehand using advance care planning and advance directives has become increasingly common in current medicine. There is still lack of clarity what happens over the course of time in relation to these preferences. We wanted to determine whether the preferences about end-of-life care of a person owning an advance directive stay stable after the experience of a life-event; how often advance directives are altered and discussed with family members and physicians over time. Design A longitudinal cohort study with a population consisting of people owning the most common advance directives in the Netherlands, with a follow-up of 6-years from 2005 until 2011. Respondents were recruited using two associations that provided the advance directives, Right to Die-NL (n = 4463) and the Dutch Patient Organisation (n = 1263). Each 1.5 year a questionnaire was sent. We analyzed the relationship between variables using generalized estimated equations. Results 96.9–98.1% of the respondents who had experienced a life-event had stable preferences. 89.9–93.7% of Right-to-Die-NL-members who had experienced a life-event didn’t make any alterations in their advance directives. During the 6-year course of our study, a minority of both groups didn’t discuss their advance directive with anyone (8.7–16.4%), while a majority didn’t discuss it with physicians (ranging 58.1–95.1%). Factors related to health, such as deterioration in experienced health, increased the odds to discuss advance directives. Conclusion Our results largely dispute criticism concerning usability of advance directives due to lack of stability of preferences. Whereas a change in health status and the experience of other life-events were not related to instability in preferences, they did increase the odds of communication about advance directives.Because our results show that the possession of an advance directive does not necessarily result in frequent discussions between patients and caregivers, a more structured approach like advance care planning might be a solution.
    Electronic ISSN: 1932-6203
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  • 58
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-19
    Description: by Maryam Kebbe, Arnaldo Perez, Annick Buchholz, Tara-Leigh F. McHugh, Shannon S. Scott, Caroline Richard, Charmaine Mohipp, Michele P. Dyson, Geoff D. C. Ball Background Many adolescents with obesity do not meet recommendations for nutrition, physical and sedentary activities, and sleep habits, all of which can influence weight management. Objective To explore barriers and enablers that influenced the adoption of lifestyle behavior changes among adolescents receiving multidisciplinary clinical care for pediatric weight management. Methods In this multi-centre, qualitative description study, we used purposeful sampling to recruit 13–17 year olds (body mass index ≥85 th percentile) enrolled in one of two pediatric weight management clinics in Edmonton and Ottawa, Canada. Adolescents participated in one-on-one, in-person, semi-structured interviews in English or French. Interviews lasted 30–60 minutes, were audio-recorded, transcribed verbatim, and managed using NVivo 11. Data were triangulated using transcripts, field notes, and memos and analyzed by two independent researchers using inductive, semantic thematic analysis. Results In total, 19 adolescents (12 Anglophone and 7 Francophone; 15.1±1.7 years old; 3.5±0.6 BMI z-score; n = 11 female; n = 13 Caucasian) participated. Adolescents reported diverse barriers to and enablers of healthy nutrition, physical and sedentary activities, and sleep habits, which we organized into the following themes: physiological mechanisms and physical health status, self-regulation for behavior change, controllability and competence beliefs, social relationships and interactions, and accessibility to and availability of opportunities for lifestyle enhancement. Across these themes and lifestyle areas, we identified three shared barriers and/or enablers, including the degree of controllability, the impact of mental health, and social pressures related to weight management. Conclusions This research provides evidence that can be used to tailor interventions and health services delivery, including a focus on psychosocial well-being, to support adolescents with obesity in making and maintaining healthy lifestyle behavior changes.
    Electronic ISSN: 1932-6203
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  • 59
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-19
    Description: by Alessandro Nesti, Giulio Rognini, Bruno Herbelin, Heinrich H. Bülthoff, Lewis Chuang, Olaf Blanke Current neuroscientific models of bodily self-consciousness (BSC) argue that inaccurate integration of sensory signals leads to altered states of BSC. Indeed, using virtual reality technology, observers viewing a fake or virtual body while being exposed to tactile stimulation of the real body, can experience illusory ownership over–and mislocalization towards—the virtual body (Full-Body Illusion, FBI). Among the sensory inputs contributing to BSC, the vestibular system is believed to play a central role due to its importance in estimating self-motion and orientation. This theory is supported by clinical evidence that vestibular loss patients are more prone to altered BSC states, and by recent experimental evidence that visuo-vestibular conflicts can disrupt BSC in healthy individuals. Nevertheless, the contribution of vestibular information and self-motion perception to BSC remains largely unexplored. Here, we investigate the relationship between alterations of BSC and self-motion sensitivity in healthy individuals. Fifteen participants were exposed to visuo-vibrotactile conflicts designed to induce an FBI, and subsequently to visual rotations that evoked illusory self-motion (vection). We found that synchronous visuo-vibrotactile stimulation successfully induced the FBI, and further observed a relationship between the strength of the FBI and the time necessary for complete vection to arise. Specifically, higher self-reported FBI scores across synchronous and asynchronous conditions were associated to shorter vection latencies. Our findings are in agreement with clinical observations that vestibular loss patients have higher FBI susceptibility and lower vection latencies, and argue for increased visual over vestibular dependency during altered states of BSC.
    Electronic ISSN: 1932-6203
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  • 60
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    Publication Date: 2018-12-19
    Description: by Leonie de Munter, Nancy C. W. ter Bogt, Suzanne Polinder, Charlie A. Sewalt, Ewout W. Steyerberg, Mariska A. C. de Jongh Introduction The overestimation of survival predictions in the ageing trauma population results in negative benchmark numbers in hospitals that mainly treat elderly patients. The aim of this study was to develop and validate a modified Trauma and Injury Severity Score (TRISS) for accurate survival prediction in the ageing blunt trauma population. Methods This retrospective study was conducted with data from two Dutch Trauma regions. Missing values were imputed. New prediction models were created in the development set, including age (continuous or categorical) and Anesthesiologists Physical Status (ASA). The models were externally validated. Subsets were created based on age (≥75 years) and the presence of hip fracture. Model performance was assessed by proportion explained variance (Nagelkerke R 2 ), discrimination (Area Under the curve of the Receiver Operating Characteristic, AUROC) and visually with calibration plots. A final model was created based on both datasets. Results No differences were found between the baseline characteristics of the development dataset (n = 15,530) and the validation set (n = 15,504). The inclusion of ASA in the prediction models showed significant improved discriminative abilities in the two subsets (e.g. AUROC of 0.52 [95% CI: 0.46, 0.58] vs. 0.74 [95% CI: 0.69, 0.78] for elderly patients with hip fracture) and an increase in the proportion explained variance (R 2 = 0.32 to R 2 = 0.35 in the total cohort). The final model showed high agreement between observed and predicted survival in the calibration plot, also in the subsets. Conclusions Including ASA and age (continuous) in survival prediction is a simple adjustment of the TRISS methodology to improve survival predictions in the ageing blunt trauma population. A new model is presented, through which even patients with isolated hip fractures could be included in the evaluation of trauma care.
    Electronic ISSN: 1932-6203
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  • 61
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    Public Library of Science (PLoS)
    Publication Date: 2018-12-19
    Description: by Nanako Kitanaka, Rei Nakano, Taku Kitanaka, Shinichi Namba, Tadayoshi Konno, Tomohiro Nakayama, Hiroshi Sugiya Inflammatory and microenvironmental factors produced by cancer cells are thought to directly or indirectly promote cancer cell growth. Prostaglandins, including prostaglandin E2, have key roles as a microenvironment factor in influencing the development of tumors, and are produced by the rate limiting enzyme cyclooxygenase 2 (COX-2). In this study, we used canine melanoma cells treated with the proinflammatory cytokine interleukin 1β (IL-1β) and investigated the transcriptional factor nuclear factor-κB (NF-κB) signaling in IL-1β-induced COX-2 expression. IL-1β induced prostaglandin E2 release and COX-2 mRNA expression in a time- and dose-dependent manner. In the cells treated with the NF-κB inhibitors BAY11-7082 and TPC-1, IL-1β-mediated prostaglandin E2 release and COX-2 mRNA expression were inhibited. IL-1β also provoked phosphorylation of p65/RelA and p105/NF-κB1, which are members of the NF-κB families. The IL-1β-induced phosphorylation of p65 and p105 was attenuated in the presence of both NF-κB inhibitors. In melanoma cells transfected with siRNA of p65 or p105, IL-1β-mediated COX-2 mRNA expression was inhibited. These findings suggest that canonical activation of NF-κB signaling plays a crucial role for inflammatory states in melanoma cells.
    Electronic ISSN: 1932-6203
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  • 62
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    Public Library of Science (PLoS)
    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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  • 63
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    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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  • 64
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    Publication Date: 2018-12-20
    Description: by Bencan Yang, Zihao Song, Chaonan Li, Jiahao Jiang, Yangyang Zhou, Ruipu Wang, Qi Wang, Chang Ni, Qing Liang, Haodong Chen, Liu-Min Fan MYB transcription factors are involved in many biological processes, including metabolism, development and responses to biotic and abiotic stresses. RADIALIS-LIKE SANT/MYB 1 (RSM1) belongs to a MYB-related subfamily, and previous transcriptome analysis suggests that RSM1 may play roles in plant development, stress responses and plant hormone signaling. However, the molecular mechanisms of RSM1 action in response to abiotic stresses remain obscure. We show that down-regulation or up-regulation of RSM1 expression alters the sensitivity of seed germination and cotyledon greening to abscisic acid (ABA), NaCl and mannitol in Arabidopsis . The expression of RSM1 is dynamically regulated by ABA and NaCl. Transcription factors ELONGATED HYPOCOTYL 5 (HY5) and HY5 HOMOLOG (HYH) regulate RSM1 expression via binding to the RSM1 promoter. Genetic analyses reveal that RSM1 mediates multiple functions of HY5 in responses of seed germination, post-germination development to ABA and abiotic stresses, and seedling tolerance to salinity. Pull-down and BiFC assays show that RSM1 interacts with HY5/HYH in vitro and in vivo . RSM1 and HY5/HYH may function as a regulatory module in responses to ABA and abiotic stresses. RSM1 binds to the promoter of ABA INSENSITIVE 5 ( ABI5 ), thereby regulating its expression, while RSM1 interaction also stimulates HY5 binding to the ABI5 promoter. However, no evidence was found in the dual-luciferase transient expression assay to support that RSM enhances the activation of ABI5 expression by HY. In summary, HY5/HYH and RSM1 may converge on the ABI5 promoter and independently or somehow dependently regulate ABI5 expression and ABI5-downstream ABA and abiotic stress-responsive genes, thereby improving the adaption of plants to the environment.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 65
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    Publication Date: 2018-12-20
    Description: by Mateusz K. Hołda, Agnieszka Pietsch-Fulbiszewska, Marek Trybus, Mateusz Koziej Smooth septum interatrial septum, patent foramen ovale (PFO) channel and atrial septal pouches (SPs) are commonly described variants in humans. Recent discoveries on the clinical significance of left-sided SP may encourage the creation of new strategies and devices for the management of SPs. However, these strategies may first be tested in the ovine model before implementation in humans. Unfortunately, little is known about the presence of SPs in ovine. In this study a total of 60 ovine ( Ovis aries ) hearts were examined. The interatrial septum morphology was assessed and the PFO channel and SPs were measured. The most commonly occurring variant were PFO channels (25.0%) with channel lengths of 5.4±2.3 mm. Smooth septums were observed in 18.3% of hearts. In the remaining cases, septums had a left septal ridge (15.0%), left SP (11.7%), left septal bridge (10.0%), right SP (10.0%), or had both a right SP and left septal ridge (10.0%). No double SPs were observed. The mean right SP depth was 3.4 ± 1.2 mm, and its mean ostium width and height were 7.9±1.8 mm and 2.8±1.0, respectively. For the left SP, the mean depth was 6.0±1.7mm, the ostium width was 7.9±2.4mm, and the ostium height was 4.1±1.6mm (range: 2.3–6.4mm). In conclusion the interatrial septum of ovine hearts exhibit morphologies that are more similar to humans than they are to swine, which should be taken into account during experimental studies. The presence of a left SP in sheep hearts make ovine models a promising alternative to the human heart for developing left-sided SP management devices and techniques.
    Electronic ISSN: 1932-6203
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    Publication Date: 2018-12-20
    Description: by Bryan M. H. Keng, Fei Gao, Ru San Tan, See Hooi Ewe, Louis L. Y. Teo, Bei Qi Xie, George B. B. Goh, Woon-Puay Koh, Angela S. Koh Ageing-related alterations in cardiovascular structure and function are commonly associated with chronic inflammation. A potential blood-based biomarker indicative of a chronic inflammatory state is N-Terminal Pro C-Type Natriuretic Peptide (NTproCNP). We aim to investigate associations between NTproCNP and ageing-related impairments in cardiovascular function. Community-based participants underwent same-day assessment of cardiovascular function and circulating profiles of plasma NTproCNP. Associations between cardiovascular and biomarker profiles were studied in adjusted models including standard covariates. We studied 93 participants (mean age 73 ± 5.3 years, 36 women), of whom 55 (59%) had impaired myocardial relaxation (ratio of peak velocity flow in early diastole E (m/s) to peak velocity flow in late diastole by atrial contraction A (m/s)
    Electronic ISSN: 1932-6203
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  • 67
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    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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  • 68
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    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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    Public Library of Science (PLoS)
    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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  • 70
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    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.
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  • 71
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    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
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  • 72
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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
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  • 73
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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
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  • 74
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    Publication Date: 2018-12-20
    Description: by Francis Agyemang-Yeboah, Joseph Yorke, Christian Obirikorang, Emmanuella Nsenbah Batu, Emmanuel Acheampong, Emmanuel Amankwaa Frimpong, Enoch Odame Anto, Bright Amankwaa Background Colorectal cancer (CRC) is one of the commonest cancers associated with diverse prognosis times in different parts of the world. Despite medical interventions, the overall clinical outcomes and survival remains very poor for most patients in developing countries. This study therefore investigated the survival rate of colorectal cancer and its prognostic factors among patients at Komfo Anokye Teaching Hospital, Ghana. Methodology In this retrospective cohort study, a total of 221 patients diagnosed with CRC from 2009 to 2015 at the Surgical and Oncological units of Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana were employed. The survival graphs were obtained using the Kaplan–Meier method and compared by the Log-rank test. Cox regression analysis was used to assess prognostic factors. All analyses were performed by SPSS version 22. Results The median survival time was 15 months 95% CI (11.79–18.21). The overall survival rate for CRC over the 5 years period was 16.0%. The survival rates at the 1 st , 2 nd , 3 rd , 4 th and 5 th years were 64% 95% CI (56.2–71.1), 40% 95% CI (32.2–50.1), 21% 95% CI (11.4–30.6) 16% 95% CI (8.9–26.9) and 16% 95% CI (7.3–24.9). There was a significant difference in the survival rate of colorectal cancer according to the different stages (p = 0.0001). Family history [HR = (3.44), p = 0.029)], Chemotherapy [HR = (0.23), p =
    Electronic ISSN: 1932-6203
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  • 75
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    Publication Date: 2018-12-20
    Description: by Alexander J. Q. Parsons, Stuart Gilmour Japan’s ongoing struggle with rapid ageing is well known. Fertility and migration policies have both been proposed as solutions to Japan’s ageing population. We used stock flow population models to estimate the impact of hypothetical fertility and migration policy interventions on measures of aging in Japan from 2015 to 2050. We evaluated policy models based on the Old Age Dependency Ratio (OADR) they produced at the specified end date. Start dates ranged from 2020 to 2030 to assess the time horizons of individual policies. Fertility policies were found to be highly time dependent and only slowed the rate of increase of OADR. It would require a Total Fertility Rate far above replacement levels to compensate for Japan’s already aged demography. Migration policy was less time dependent. However, such measures would require unprecedented, and ultimately unrealistic, volumes of migration over coming decades in order to reduce Japan’s OADR. Our results suggest that fertility and migration based policy responses will be unable to significantly reduce Japan’s OADR or reverse Japan’s ageing population within the next few decades. Japan should focus on activating its human capital through the prolongation of working lives, increasing participation, and improving productivity within the Japanese labour force to mitigate and adapt to the inevitable effects of ageing populations.
    Electronic ISSN: 1932-6203
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  • 76
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    Publication Date: 2018-12-20
    Description: by Sang-Tae Kim, Jae-Ryong Yoo, Jong Min Park Purpose To investigate the internal exposure of nuclear medicine practitioners in South Korea. Methods This study selected nuclear medicine practitioners among domestic hospitals and quantitatively measured their degree of internal exposure to radioisotopes, and conducted a dose assessment based on the results. For the dose assessment, 35 nuclear medicine practitioners at seven large hospitals were selected as the measurement subjects, and the measurements were obtained using the thyroid count, total body count, and a urine sample analysis. The internal exposure was measured once every two weeks, and measurements were obtained three to 15 times according to the practitioners. Results As a result of measuring and analyzing the radionuclides with urine samples, one or more detections above the minimum detectable activity (MDA) was identified in 52 (15%) among all 340 cases for 14 of the practitioners (43%). The committed effective doses were evaluated as have a distribution of zero to 5.4 mSv, and were mostly 1 mSv or less. There were four practitioners exceeding 1 mSv based on the whole-body measurements, whose results from a urine sample analysis and thyroid monitoring all showed exposure of 1 mSv or less. All of the practitioners participated directly in the distribution and handling of radioactive sources, and none of the nurses exceeded 1 mSv. Furthermore, it was noteworthy that, among medical assistants who do not directly handle radioisotopes and are mainly involved in the transport of contaminated patients, there was one person who exceeded the whole-body measurement standard of 1 mSv. Conclusions The committed effective dose of most nuclear medicine practitioners who participated in the survey was lower than 1 mSv. However, because the possibility of overexposure under special circumstances cannot be completely excluded, new strict radiation protection rules on the handling of open-source radioisotopes in hospitals are required for non-handling workers.
    Electronic ISSN: 1932-6203
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  • 77
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    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.
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  • 78
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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.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 79
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    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.
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  • 80
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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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  • 81
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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
    Print ISSN: 1935-2727
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  • 82
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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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  • 83
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    Publication Date: 2018-12-21
    Description: by Michele C. Paula, Kamylla B. Michelutti, Aylson D. M. M. Eulalio, Raul C. Piva, Claudia A. L. Cardoso, William F. Antonialli-Junior Most flies of forensic importance are in two superfamilies, the Muscoidea and the Oestroidea, with similar life stages including the puparium. Upon completion of metamorphosis the adult fly emerges from the puparium, leaving behind an exuvia that is of potential significance in forensic investigation. The empty puparium is a durable piece of entomological evidence lasting several years. Through the study of chemical compounds, specifically the hydrocarbons of these puparia, it is possible to identify the species, in addition to how long they have been exposed to weathering and for this reason, these parameters can assist forensic entomologists in estimating long-term postmortem interval (minPMI). In corpses that take a relatively longer time to decompose, insects may use the same corpses for several oviposition cycles. Therefore, the aim of this study was to develop a new method to determine the PMI based on chemical compounds of the puparia from different oviposition cycles of the fly Chrysomya megacephala . The chemical composition of 50 puparia from different cycles of oviposition were evaluated by Gas Chromatography–Mass Spectrometry (GC-MS). In total, 60 compounds were identified ranging from C 18 to C 34 , 38 of those were common to all generations. Our results demonstrate that chemical profiles can be used to differentiate puparia collected from successive cycles, and therefore valuable in the estimation of minPMI.
    Electronic ISSN: 1932-6203
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  • 84
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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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  • 85
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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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  • 86
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    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.
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