Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p <2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups

Influence of Cold-Water Immersion on Recovery of Elite Triathletes Following the Ironman World Championship

Objectives: Cold water immersion (CWI) has been widely used for enhancing athlete recovery though its use following an Ironman triathlon has never been examined. The purpose of this paper is to determine the influence of CWI immediately following an Ironman triathlon on markers of muscle damage, inflammation and muscle soreness. Design: Prospective cohort study. Methods: Thirty three (22 male, 11 female), triathletes participating in the Ironman World Championships volunteered to participate (mean ± SD: age = 40 ± 11 years; height = 174.5 ± 9.1 cm; body mass = 70 ± 11.8 kg; percent body fat = 11.4 ± 4.1%, finish time = 11:03.00 ± 01:25.08). Post race, participants were randomly assigned to a 10-min bout of 10 ◦C CWI or no-intervention control group. Data collection occurred pre-intervention (PRE), post-intervention (POST), 16 h (16POST) and 40 h (40POST) following the race. Linear mixed model ANOVA with Bonferroni corrections were performed to examine group by time differences for delayed onset muscle soreness (DOMS), hydration indices, myoglobin, creatine kinase (CK), cortisol, C-reactive protein (CRP), IL-6 and percent body mass loss (%BML). Pearson’s bivariate correlations were used for comparisons with finishing time. Alpha level was set a priori at 0.05. Results: No significant group by time interactions occurred. Significant differences occurred for POST BML (−1.7 ± 0.9 kg) vs. 16POST, and 40POST BML (0.9 ± 1.4, −0.1 ± 1.2 kg, respectively; p \u3c 0.001). Compared to PRE, myoglobin, CRP and CK remained significantly elevated at 40POST. Cortisol returned to PRE values by 16POST and IL-6 returned to PRE values by 40POST. Conclusion:Asingle bout of CWI did not provide any physiological benefit during recovery from a triathlon within 40 h post race. Effect of CWI beyond this time is unknown

Heat Exposure and Hypohydration Exacerbate Physiological Strain During Load Carrying

Heat exposure and hypohydration induce physiological and psychological strain during exercise; however, it is unknown if the separate effects of heat exposure and hypohydration are synergistic when co-occurring during loaded exercise. This study compared separate and combined effects of heat exposure and hypohydration on physiological strain, mood state, and visual vigilance during loaded exercise. Twelve males (mean±SD; age, 20±2 years; body mass, 74.0±8.2 kg; maximal oxygen uptake, 57.0±6.0 mLkg-1min-1) completed 4 trials under the following conditions: euhydrated temperate (EUT), hypohydrated temperate (HYT), euhydrated hot (EUH), and hypohydrated hot (HYH). Exercise was 90 min of treadmill walking (∼50% VO2 max, 5% grade) while carrying a 45 lb rucksack. Profile of Mood States and the Scanning Visual Vigilance Test were completed pre and post exercise. The separate effects of heat exposure (EUH) and hypohydration (HYT) on post-exercise Tre were similar (38.25±0.63°C vs. 38.22±0.29°C, respectively, p\u3e0.05), while in combination (HYH), post-exercise Tre was far greater (39.32±0.43°C). Increase in Tre per 1% body mass loss (BML) for HYH (vs. EUH) was greater than HYT (vs. EUT) (0.32°C vs. 0.04°C, respectively, p=0.02); HR increase per 1% BML for HYH (vs. EUH) was 7 bpm compared to HYT (vs. EUT) at 3 bpm (p=0.30). HYH induced greater mood disturbance (post-pre exercise) (35±21 units) compared to other conditions (EUT=3±9 units; HYT=3±16 units; EUH=16±26 units; p0.05). Independently, heat exposure and hypohydration induced similar physiological strain during loaded exercise; when combined, heat exposure with hypohydration, synergistically exacerbated physiological strain and mood disturbance

Validity of Devices That Assess Body Temperature During Outdoor Exercise in the Heat

Context: Rectal temperature is recommended by the National Athletic Trainers' Association as the criterion standard for recognizing exertional heat stroke, but other body sites commonly are used to measure temperature. Few authors have assessed the validity of the thermometers that measure body temperature at these sites in athletic settings

Letter on the 2023 ACSM Expert Consensus Statement on Exertional Heat Illness

This letter to the editor is in response to the recently (re)published 2023 ACSM Expert Consensus Statement on Exertional Heat Illness: Recognition, Management, and Return to Activity; the associated Corrigendum; and letter to the editor. The Corrigendum noted one author cast a dissenting vote of the final publication regarding four key issues she felt were inaccurate and unsuitable. The authors of this letter concur with her viewpoint and were surprised the dissenting author was not given a forum to defend her reasoning despite two authors being allowed to refute her dissension

The BEST criteria improve sensitivity for detecting positive cultures in residual blood components cultured in suspected septic transfusion reactions

BACKGROUND: Culturing residual blood components after suspected septic transfusion reactions guides management of patients and cocomponents. Current practice, accuracy of provider vital sign assessment, and performance of the AABB culture criteria are unknown. A multicenter international study was undertaken to investigate these issues and develop improved culture criteria. STUDY DESIGN AND METHODS: Retrospective data for all transfusion reactions resulting in residual blood component culture in 2016 were collected from participating hospitals. The performance of the AABB culture criteria were assessed for detection of positive culture results. Modifications to the AABB criteria including 1) recommending culturing in the setting of isolated high fevers, 2) defining hypotension and tachycardia using objective parameters, and 3) incorporating antipyretic use were tested to determine if modifications improved performance. Modifications associated with improvement were incorporate into the BEST criteria. The AABB and the BEST criteria were then tested against a data set enriched for positive culture results to determine which criteria were superior. RESULTS: Data were collected from 20 centers encompassing 779,143 transfusions, 3,187 reported transfusion reactions, and 1,104 cultured components. There was marked variation in reaction reporting and culturing rates (0.0%-100.0%). Of 35 total positive component cultures, only one of 35 (2.9%) had concordant patient cultures; 12 of 34 (35.3%) did not have patient cultures performed. The BEST criteria had better sensitivity for detection of a positive culture result compared to the AABB criteria (74% vs. 41%), although specificity decreased (45% vs. 65%). CONCLUSION: Compared to the AABB criteria, the BEST criteria have improved sensitivity for positive culture detection

The BEST criteria improve sensitivity for detecting positive cultures in residual blood components cultured in suspected septic transfusion reactions

© 2019 AABB BACKGROUND: Culturing residual blood components after suspected septic transfusion reactions guides management of patients and cocomponents. Current practice, accuracy of provider vital sign assessment, and performance of the AABB culture criteria are unknown. A multicenter international study was undertaken to investigate these issues and develop improved culture criteria. STUDY DESIGN AND METHODS: Retrospective data for all transfusion reactions resulting in residual blood component culture in 2016 were collected from participating hospitals. The performance of the AABB culture criteria were assessed for detection of positive culture results. Modifications to the AABB criteria including 1) recommending culturing in the setting of isolated high fevers, 2) defining hypotension and tachycardia using objective parameters, and 3) incorporating antipyretic use were tested to determine if modifications improved performance. Modifications associated with improvement were incorporate into the BEST criteria. The AABB and the BEST criteria were then tested against a data set enriched for positive culture results to determine which criteria were superior. RESULTS: Data were collected from 20 centers encompassing 779,143 transfusions, 3,187 reported transfusion reactions, and 1,104 cultured components. There was marked variation in reaction reporting and culturing rates (0.0%-100.0%). Of 35 total positive component cultures, only one of 35 (2.9%) had concordant patient cultures; 12 of 34 (35.3%) did not have patient cultures performed. The BEST criteria had better sensitivity for detection of a positive culture result compared to the AABB criteria (74% vs. 41%), although specificity decreased (45% vs. 65%). CONCLUSION: Compared to the AABB criteria, the BEST criteria have improved sensitivity for positive culture detection