50 research outputs found

    Long-term Tennis Participation and Health Outcomes: An Investigation of “Lifetime” Activities

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    International Journal of Exercise Science 13(7): 1251-1261, 2020. Lifetime sports, such as tennis, provide opportunities for participation throughout the lifespan and has been linked with lower risk of cardiovascular disease, obesity, and depression. The objective of this study was to consider the influence of chronic tennis participation on various parameters of health. Members of the International Tennis Federation (ITF) completed a survey consisting of questions from International Physical Activity Questionnaire (IPAQ), Behavior Risk Factor Surveillance System (BRFSS), Satisfaction With Life Survey (SWLS), and specific tennis participation questions. Descriptive characteristics were calculated for all variables and a chi-squared analysis was used to compare prevalence of health variables of this sample and recent BRFSS data. Compared to the BRFSS greater proportion of study participants 45yrs and older frequently reported being in good or better health (χ2=7.946, p = 0.005); lower obesity rates (χ2=19.92, p = 0.0001); and a lower prevalence of heart disease than those of similar age who completed BRFSS (χ2= 8.759, p = 0.003). This study highlights the importance of activities that continue throughout the lifespan such as tennis

    Identification of key residues that confer Rhodobacter sphaeroides LPS activity at horse TLR4/MD-2.

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    The molecular determinants underpinning how hexaacylated lipid A and tetraacylated precursor lipid IVa activate Toll-like receptor 4 (TLR4) are well understood, but how activation is induced by other lipid A species is less clear. Species specificity studies have clarified how TLR4/MD-2 recognises different lipid A structures, for example tetraacylated lipid IVa requires direct electrostatic interactions for agonism. In this study, we examine how pentaacylated lipopolysaccharide from Rhodobacter sphaeroides (RSLPS) antagonises human TLR4/MD-2 and activates the horse receptor complex using a computational approach and cross-species mutagenesis. At a functional level, we show that RSLPS is a partial agonist at horse TLR4/MD-2 with greater efficacy than lipid IVa. These data suggest the importance of the additional acyl chain in RSLPS signalling. Based on docking analysis, we propose a model for positioning of the RSLPS lipid A moiety (RSLA) within the MD-2 cavity at the TLR4 dimer interface, which allows activity at the horse receptor complex. As for lipid IVa, RSLPS agonism requires species-specific contacts with MD-2 and TLR4, but the R2 chain of RSLA protrudes from the MD-2 pocket to contact the TLR4 dimer in the vicinity of proline 442. Our model explains why RSLPS is only partially dependent on horse TLR4 residue R385, unlike lipid IVa. Mutagenesis of proline 442 into a serine residue, as found in human TLR4, uncovers the importance of this site in RSLPS signalling; horse TLR4 R385G/P442S double mutation completely abolishes RSLPS activity without its counterpart, human TLR4 G384R/S441P, being able to restore it. Our data highlight the importance of subtle changes in ligand positioning, and suggest that TLR4 and MD-2 residues that may not participate directly in ligand binding can determine the signalling outcome of a given ligand. This indicates a cooperative binding mechanism within the receptor complex, which is becoming increasingly important in TLR signalling.This work was supported by a project grant from the Horserace Betting Levy Board to CEB and a Horserace Betting Levy Board Veterinary Research Training Scholarship to KLI. This work was also supported by a Wellcome Trust program grant to NJG and CEB. CEB is a BBSRC Research Development Fellow.This is the final version of the article. It first appeared from PLOS at http://dx.doi.org/10.1371/journal.pone.0098776

    Public International Law: Environmental Law

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    Noteworthy international activity relating to the environment occurred in a wide variety of fora in 2000. This chapter provides brief updates on some of the most significant developments. Though by no means a comprehensive review, the chapter reflects the wide sweep of issues and large number of entities now involved in the development of international environmental law, at the start of this new century. It also reflects how critical and complex this international work is, and how much remains to be done

    Phase Ia Clinical Evaluation of the Safety and Immunogenicity of the Plasmodium falciparum Blood-Stage Antigen AMA1 in ChAd63 and MVA Vaccine Vectors

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    Traditionally, vaccine development against the blood-stage of Plasmodium falciparum infection has focused on recombinant protein-adjuvant formulations in order to induce high-titer growth-inhibitory antibody responses. However, to date no such vaccine encoding a blood-stage antigen(s) alone has induced significant protective efficacy against erythrocytic-stage infection in a pre-specified primary endpoint of a Phase IIa/b clinical trial designed to assess vaccine efficacy. Cell-mediated responses, acting in conjunction with functional antibodies, may be necessary for immunity against blood-stage P. falciparum. The development of a vaccine that could induce both cell-mediated and humoral immune responses would enable important proof-of-concept efficacy studies to be undertaken to address this question

    The Somatic Genomic Landscape of Glioblastoma

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    We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    The Impact of an Acute Active Reading Intervention on Physical Activity Levels in Preschoolers: A Comparative Analysis

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    The purpose of this study was to examine the acute effects of an active reading intervention on physical activity (PA) levels in preschoolers. Participants were recruited from the 3–5-year-old classes at two preschools. A total of six classrooms and 37 children participated in three conditions: an active reading book read by a researcher (Act_R) trained in active play techniques, an active reading book read by a preschool classroom teacher (Act_T), and a book about health behavior read by both the researcher and the teacher (Sed_H). The order in which classes received each condition was randomized. The Actigraph accelerometer assessed PA. Motor skills were assessed with the Peabody Motor Development Scale, 2nd Edition. Participants spent significantly more time in sedentary behavior during the Sed_H condition compared to Act_R (p p p = 0.030), Act_T compared to Sed_H (p p < 0.001). The amount of MVPA participation within the active reading sessions was not dependent upon the level of fundamental motor skill competence. Active reading books may provide a feasible method to incorporate physical activity and active play into the preschool day

    The relationship in early childhood body composition and physical activity levels regarding fundamental motor skill development

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    Abstract Background Fundamental motor skills (FMS) are considered essential for sport participation and might be deficit in obese children. While evidence indicates that physical activity (PA) levels impact motor skill development, the relationship between body composition, PA, and motor competence, particularly in early childhood, is not thoroughly understood. We aimed to determine if PA, fat mass (FM), and fat-free mass (FFM) are predictors of FMS. Methods Preschoolers (n = 47) from two preschools were assessed for FMS, PA, and body composition. Peabody Developmental Motor Scales (PDMS-2) subscale scores were used to assess FMS. PA was assessed with a wrist-worn accelerometer for five days during school. FM and FFM were measured with foot-to-foot bioelectrical impedance. Results Linear regressions indicate significant models for stationary skills (SS) (F = 4.57, p = .004) and object manipulation skills (OMS) (F = 4.66, p = .003). FFM was the only significant predictor of SS (t = 3.98, p < .001) and OMS (t = 3.50, p = .001). FM and all intensities of PA were nonsignificant predictors in all models. Conclusions These results indicate that interventions that target improving or maintaining FFM may improve FMS

    Fluoxetine, Smoking, and History of Major Depression: A Randomized Controlled Trial

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    The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine initially enhanced cessation for H+ smokers (p = .02) but subsequently impaired cessation regardless of depressive history. Six months after quit date, fluoxetine-treated participants were 3.3 times more likely to be smoking (p = .02). Further research is warranted to determine why high-dose fluoxetine produces continuing effects that oppose tobacco abstinence
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