The Gastrointestinal Exertional Heat Stroke Paradigm: Efficacy Of Acute Oral Glutamine Supplementation

Exertional heat stroke (EHS) is the most severe form of heat related illness. In military settings, it is considered a largely preventable cause of morbidity, however, prevalence has remained high into the 21st Century. To support disease management, various policy documents provide occupational guidance on effective risk mitigation strategies, however, these can be criticised for focussing solely on the thermoregulatory pathology of the disease. The gastrointestinal (GI) EHS paradigm is a novel pathophysiological model that links EHS to luminal microbial translocation (MT) downstream of structural GI barrier integrity disturbance. Whilst this model is still in its infancy, recent investigations have established practical nutritional interventions that can support GI barrier integrity in populations at risk of EHS. The aims of this thesis were therefore to: (1) characterise the response of GI barrier integrity biomarkers to exertional�heat stress; and (2) examine the efficacy of acute oral L-glutamine (GLN) as a nutritional countermeasure to protect GI barrier integrity. From the experimental evidence reported in this thesis, several major conclusions were derived. First, GI barrier integrity can be reliably examined in blood samples taken at rest and following exertional-heat stress using the dual-sugar absorption test, intestinal�fatty acid binding protein and claudin-3 (chapter 4). Second, GI MT can be reliably examined in blood samples taken at rest and following exertional-heat stress using lipopolysaccharide binding protein and total 16S bacterial DNA, but not Bacteroides/total 16S DNA (chapter 4). Third, individuals with high-aerobic fitness experience blunted small intestinal epithelial injury and MT compared with untrained individuals during a fixed load exertional-heat stress test (chapter 5). Fourth, acute GLN supplementation (0.30, 0.60, 0.90 g·kg·FFM-1) causes mild dose-dependent GI symptoms at rest that generally lasted < 4 hours (chapter 6). Fifth, 0.30 g·kg·FFM-1 acute GLN supplementation does not protect GI permeability, small intestinal epithelial injury or MT when consumed 1-hour before either a low-intensity (chapter 7) or high-intensity (chapter 8) exertional-heat stress test. Taken together, GI barrier integrity loss reliably occurred in response to exertional-heat stress, a response that was blunted in individuals with high-aerobic fitness, but not following acute oral GLN supplementation

Reliability of gastrointestinal barrier integrity and microbial translocation biomarkers at rest and following exertional heat stress

Purpose:Exertional heat stress adversely distrupts (GI) barrier integrity and, through subsequent microbial translocation (MT), negativly impacts health. Despite widespread application, the temporal reliability of popular GI barrier integity and MT biomarkers is poorly characterised. Method: Fourteen males completed two 80‐min exertional heat stress tests (EHST) separated by 7–14 days. Venous blood was drawn pre, immediately‐ and 1‐hr post both EHSTs. GI barrier integrity was assessed using the serum Dual‐Sugar Absorption Test (DSAT), Intestinal Fatty‐Acid‐Binding Protein (I‐FABP) and Claudin‐3 (CLDN‐3). MT was assessed using plasma Lipopolysaccharide Binding Protein (LBP), total 16S bacterial DNA and Bacteroides DNA. Results: No GI barrier integrity or MT biomarker, except absolute Bacteroides DNA, displayed systematic trial order bias (p ≥ .05). I‐FABP (trial 1 = Δ 0.834 ± 0.445 ng ml−1; trial 2 = Δ 0.776 ± 0.489 ng ml−1) and CLDN‐3 (trial 1 = Δ 0.317 ± 0.586 ng ml−1; trial 2 = Δ 0.371 ± 0.508 ng ml−1) were increased post‐EHST (p ≤ .01). All MT biomarkers were unchanged post‐EHST. Coefficient of variation and typical error of measurement post‐EHST were: 11.5% and 0.004 (ratio) for the DSAT 90‐min postprobe ingestion; 12.2% and 0.004 (ratio) at 150‐min postprobe ingestion; 12.1% and 0.376 ng ml−1 for I‐FABP; 4.9% and 0.342 ng ml−1 for CLDN‐3; 9.2% and 0.420 µg ml−1 for LBP; 9.5% and 0.15 pg µl−1 for total 16S DNA; and 54.7% and 0.032 for Bacteroides/total 16S DNA ratio. Conclusion: Each GI barrier integrity and MT translocation biomarker, except Bacteroides/total 16S ratio, had acceptable reliability at rest and postexertional heat stress

Exertional heat stroke: nutritional considerations

Exertional heat stroke (EHS) is a life-threatening illness and an enduring problem among athletes, military servicemen and -women, and occupational labourers who regularly perform strenuous activity, often under hot and humid conditions or when wearing personal protective equipment. Risk factors for EHS and mitigation strategies have generally focused on the environment, health status, clothing, heat acclimatization and aerobic conditioning, but the potential role of nutrition is largely underexplored. Various nutritional and dietary strategies have shown beneficial effects on exercise performance and health and are widely used by athletes and other physically active populations. There is also evidence that some of these practices may dampen the pathophysiological features of EHS, suggesting possible protection or abatement of injury severity. Promising candidates include carbohydrate ingestion, appropriate fluid intake and glutamine supplementation. Conversely, some nutritional factors and low energy availability may facilitate the development of EHS, and individuals should be cognizant of these. Therefore, the aims of this review are to present an overview of EHS along with its mechanisms and pathophysiology, discuss how selected nutritional considerations may influence EHS risk focusing on their impact on the key pathophysiological processes of EHS, and provide recommendations for future research. With climate change expected to increase EHS risk and incidence in the coming years, further investigation on how diet and nutrition may be optimized to protect against EHS would be highly beneficial

Gastrointestinal Tolerance of Low, Medium and High Dose Acute Oral l-Glutamine Supplementation in Healthy Adults: A Pilot Study

l-Glutamine (GLN) is a conditionally essential amino acid which supports gastrointestinal (GI) and immune function prior to catabolic stress (e.g., strenuous exercise). Despite potential dose-dependent benefits, GI tolerance of acute high dose oral GLN supplementation is poorly characterised. Fourteen healthy males (25 ± 5 years; 1.79 ± 0.07 cm; 77.7 ± 9.8 kg; 14.8 ± 4.6% body fat) ingested 0.3 (LOW), 0.6 (MED) or 0.9 (HIGH) g·kg·FFM−1 GLN beverages, in a randomised, double-blind, counter-balanced, cross-over trial. Individual and accumulated GI symptoms were recorded using a visual analogue scale at regular intervals up to 24-h post ingestion. GLN beverages were characterised by tonicity measurement and microscopic observations. 24-h accumulated upper- and lower- and total-GI symptoms were all greater in the HIGH, compared to LOW and MED trials (p 0.05). All beverages were isotonic and contained a dose-dependent number of GLN crystals. Acute oral GLN ingestion in dosages up to 0.9 g·kg·FFM−1 are generally well-tolerated. However, the severity of mild GI symptoms appeared dose-dependent during the first two hours post prandial and may be due to high-concentrations of GLN crystals

Characterization of Genome-Wide Association-Identified Variants for Atrial Fibrillation in African Americans

Despite a greater burden of risk factors, atrial fibrillation (AF) is less common among African Americans than European-descent populations. Genome-wide association studies (GWAS) for AF in European-descent populations have identified three predominant genomic regions associated with increased risk (1q21, 4q25, and 16q22). The contribution of these loci to AF risk in African American is unknown.We studied 73 African Americans with AF from the Vanderbilt-Meharry AF registry and 71 African American controls, with no history of AF including after cardiac surgery. Tests of association were performed for 148 SNPs across the three regions associated with AF, and 22 SNPs were significantly associated with AF (P<0.05). The SNPs with the strongest associations in African Americans were both different from the index SNPs identified in European-descent populations and independent from the index European-descent population SNPs (r(2)<0.40 in HapMap CEU): 1q21 rs4845396 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.13-0.67, P = 0.003), 4q25 rs4631108 (OR 3.43, 95% CI 1.59-7.42, P = 0.002), and 16q22 rs16971547 (OR 8.1, 95% CI 1.46-45.4, P = 0.016). Estimates of European ancestry were similar among cases (23.6%) and controls (23.8%). Accordingly, the probability of having two copies of the European derived chromosomes at each region did not differ between cases and controls.Variable European admixture at known AF loci does not explain decreased AF susceptibility in African Americans. These data support the role of 1q21, 4q25, and 16q22 variants in AF risk for African Americans, although the index SNPs differ from those identified in European-descent populations

Factors influencing nurses' compliance with Standard Precautions in order to avoid occupational exposure to microorganisms: A focus group study

<p>Abstract</p> <p>Background</p> <p>Nurses may acquire an infection during the provision of nursing care because of occupational exposure to microorganisms. Relevant literature reports that, compliance with Standard Precautions (a set of guidelines that can protect health care professionals from being exposed to microorganisms) is low among nurses. Additionally, high rates of exposure to microorganisms among nurses via several modes (needlesticks, hand contamination with blood, exposure to air-transmitted microorganisms) occur. The aim of the study was to study the factors that influence nurses' compliance with Standard Precaution in order to avoid occupational exposure to pathogens, by employing a qualitative research design.</p> <p>Method</p> <p>A focus group approach was used to explore the issue under study. Four focus groups (N = 30) were organised to elicit nurses' perception of the factors that influence their compliance with Standard Precautions. The Health Belief Model (HBM) was used as the theoretical framework and the data were analysed according to predetermined criteria.</p> <p>Results</p> <p>Following content analysis, factors that influence nurses' compliance emerged. Most factors could be applied to one of the main domains of the HBM: benefits, barriers, severity, susceptibility, cues to action, and self-efficacy.</p> <p>Conclusions</p> <p>Changing current behavior requires knowledge of the factors that may influence nurses' compliance with Standard Precautions. This knowledge will facilitate in the implementation of programs and preventive actions that contribute in avoiding of occupational exposure.</p

Influence of aerobic fitness on gastrointestinal barrier integrity and microbial translocation following a fixed-intensity military exertional heat stress test

Purpose: Exertional-heat stress adversely disrupts gastrointestinal (GI) barrier integrity, whereby subsequent microbial translocation (MT) can result in potentially serious health consequences. To date, the influence of aerobic fitness on GI barrier integrity and MT following exertional-heat stress is poorly characterised. Method: Ten untrained (UT; VO2max = 45 ± 3 ml·kg−1·min−1) and ten highly trained (HT; VO2max = 64 ± 4 ml·kg−1·min−1) males completed an ecologically valid (military) 80-min fixed-intensity exertional-heat stress test (EHST). Venous blood was drawn immediately pre- and post-EHST. GI barrier integrity was assessed using the serum dual-sugar absorption test (DSAT) and plasma Intestinal Fatty-Acid Binding Protein (I-FABP). MT was assessed using plasma Bacteroides/total 16S DNA. Results: UT experienced greater thermoregulatory, cardiovascular and perceptual strain (p < 0.05) than HT during the EHST. Serum DSAT responses were similar between the two groups (p = 0.59), although Δ I-FABP was greater (p = 0.04) in the UT (1.14 ± 1.36 ng·ml−1) versus HT (0.20 ± 0.29 ng·ml−1) group. Bacteroides/Total 16S DNA ratio was unchanged (Δ; -0.04 ± 0.18) following the EHST in the HT group, but increased (Δ; 0.19 ± 0.25) in the UT group (p = 0.05). Weekly aerobic training hours had a weak, negative correlation with Δ I-FABP and Bacteroides/total 16S DNA responses. Conclusion: When exercising at the same absolute workload, UT individuals are more susceptible to small intestinal epithelial injury and MT than HT individuals. These responses appear partially attributable to greater thermoregulatory, cardiovascular, and perceptual strain

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio