Publications by authors named "David R Woods"

40 Publications

Reproductive and metabolic adaptation to multistressor training in women.

Am J Physiol Endocrinol Metab 2021 Aug 30;321(2):E281-E291. Epub 2021 Jun 30.

University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, grid.4305.2University of Edinburgh, Edinburgh, United Kingdom.

Hypothalamic-pituitary-gonadal (HPG) axis suppression in exercising women can be caused by low energy availability (EA), but the impact of a real-world, multistressor training environment on reproductive and metabolic function is unknown. This study aimed to characterize reproductive and metabolic adaptation in women undertaking basic military training. A prospective cohort study in women undertaking 11-month initial military training ( = 47) was carried out. Dynamic low-dose 1-h gonadotrophin-releasing hormone (GnRH) tests were completed after 0 and 7 mo of training. Urine progesterone was sampled weekly throughout. Body composition (dual X-ray absorptiometry), fasting insulin resistance (homeostatic modeling assessment 2, HOMA2), leptin, sex steroids, anti-Müllerian hormone (AMH), and inhibin B were measured after 0, 7, and 11 mo with an additional assessment of body composition at 3 mo. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses were suppressed after 7 mo (both < 0.001). Among noncontraceptive users ( = 20), 65% had regular (23-35 days) cycles preenrollment, falling to 24% by 7 mo of training. Of women in whom urine progesterone was measured ( = 24), 87% of cycles showed no evidence of ovulation. There was little change in AMH, LH, and estradiol, although inhibin B and FSH increased ( < 0.05). Fat mass fluctuated during training but at was unchanged from baseline. Fat-free mass did not change. Visceral adiposity, HOMA2, and leptin increased (all < 0.001). HPG axis suppression with anovulation occurred in response to training without evidence of low EA. Increased insulin resistance may have contributed to the observed pituitary and ovarian dysfunction. Our findings are likely to represent an adaptive response of reproductive function to the multistressor nature of military training. We characterized reproductive endocrine adaptation to prolonged arduous multistressor training in women. We identified marked suppression of hypothalamic-pituitary-gonadal (HPG) axis function during training but found no evidence of low energy availability despite high energy requirements. Our findings suggest a complex interplay of psychological and environmental stressors with suppression of the HPG axis via activation of the hypothalamic-pituitary adrenal (HPA) axis. The neuroendocrine impact of nonexercise stressors on the HPG axis during arduous training should be considered.
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http://dx.doi.org/10.1152/ajpendo.00019.2021DOI Listing
August 2021

Marching to the Beet: The effect of dietary nitrate supplementation on high altitude exercise performance and adaptation during a military trekking expedition.

Nitric Oxide 2021 Sep 27;113-114:70-77. Epub 2021 May 27.

Carneige School of Sport, Leeds Beckett University, Leeds, LS16 5LF, UK.

Purpose: The aim was to investigate the effect of dietary nitrate supplementation (in the form of beetroot juice, BRJ) for 20 days on salivary nitrite (a potential precursor of bioactive nitric oxide), exercise performance and high altitude (HA) acclimatisation in field conditions (hypobaric hypoxia).

Methods: This was a single-blinded randomised control study of 22 healthy adult participants (12 men, 10 women, mean age 28 ± 12 years) across a HA military expedition. Participants were randomised pre-ascent to receive two 70 ml dose per day of either BRJ (~12.5 mmol nitrate per day; n = 11) or non-nitrate calorie matched control (n = 11). Participants ingested supplement doses daily, beginning 3 days prior to departure and continued until the highest sleeping altitude (4800 m) reached on day 17 of the expedition. Data were collected at baseline (44 m altitude), at 2350 m (day 9), 3400 m (day 12) and 4800 m (day 17).

Results: BRJ enhanced the salivary levels of nitrite (p = 0.007). There was a significant decrease in peripheral oxygen saturation and there were increases in heart rate, diastolic blood pressure, and rating of perceived exertion with increasing altitude (p=<0.001). Harvard Step Test fitness scores significantly declined at 4800 m in the control group (p = 0.003) compared with baseline. In contrast, there was no decline in fitness scores at 4800 m compared with baseline (p = 0.26) in the BRJ group. Heart rate recovery speed following exercise at 4800 m was significantly prolonged in the control group (p=<0.01) but was unchanged in the BRJ group (p = 0.61). BRJ did not affect the burden of HA illness (p = 1.00).

Conclusions: BRJ increases salivary nitrite levels and ameliorates the decline in fitness at altitude but does not affect the occurrence of HA illness.
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http://dx.doi.org/10.1016/j.niox.2021.05.002DOI Listing
September 2021

Tibial Macrostructure and Microarchitecture Adaptations in Women During 44 Weeks of Arduous Military Training.

J Bone Miner Res 2021 Jul 15;36(7):1300-1315. Epub 2021 Apr 15.

Army Health and Performance Research, Army Headquarters, Andover, UK.

Bone adapts to unaccustomed, high-impact loading but loses mechanosensitivity quickly. Short periods of military training (≤12 weeks) increase the density and size of the tibia in women. The effect of longer periods of military training, where the incidence of stress fracture is high, on tibial macrostructure and microarchitecture in women is unknown. This observational study recruited 51 women (age 19 to 30 years) at the start of 44 weeks of British Army Officer training. Tibial volumetric bone mineral density (vBMD), geometry, and microarchitecture were measured by high-resolution peripheral quantitative computed tomography (HRpQCT). Scans of the right tibial metaphysis (4% site) and diaphysis (30% site) were performed at weeks 1, 14, 28, and 44. Measures of whole-body areal bone mineral density (aBMD) were obtained using dual-energy X-ray absorptiometry (DXA). Blood samples were taken at weeks 1, 28, and 44, and were analyzed for markers of bone formation and resorption. Trabecular vBMD increased from week 1 to 44 at the 4% site (3.0%, p < .001). Cortical vBMD decreased from week 1 to 14 at the 30% site (-0.3%, p < .001). Trabecular area decreased at the 4% site (-0.4%); trabecular bone volume fraction (3.5%), cortical area (4.8%), and cortical thickness (4.0%) increased at the 4% site; and, cortical perimeter increased at the 30% site (0.5%) from week 1 to 44 (p ≤ .005). Trabecular number (3.5%) and thickness (2.1%) increased, and trabecular separation decreased (-3.1%), at the 4% site from week 1 to 44 (p < .001). Training increased failure load at the 30% site from week 1 to 44 (2.5%, p < .001). Training had no effect on aBMD or markers of bone formation or resorption. Tibial macrostructure and microarchitecture continued to adapt across 44 weeks of military training in young women. Temporal decreases in cortical density support a role of intracortical remodeling in the pathogenesis of stress fracture. © 2021 Crown copyright. Journal of Bone and Mineral Research © 2021 American Society for Bone and Mineral Research (ASBMR). This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.
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http://dx.doi.org/10.1002/jbmr.4290DOI Listing
July 2021

Echocardiographic changes following active heat acclimation.

J Therm Biol 2020 Oct 2;93:102705. Epub 2020 Sep 2.

Research and Clinical Innovation, Royal Centre for Defence Medicine, Birmingham, UK; Research Institute for Sport, Physical Activity and Leisure, Carnegie School of Sport, Leeds Beckett University, UK. Electronic address:

Heat adaption through acclimatisation or acclimation improves cardiovascular stability by maintaining cardiac output due to compensatory increases in stroke volume. The main aim of this study was to assess whether 2D transthoracic echocardiography (TTE) could be used to confirm differences in resting echocardiographic parameters, before and after active heat acclimation (HA). Thirteen male endurance trained cyclists underwent a resting blinded TTE before and after randomisation to either 5 consecutive daily exertional heat exposures of controlled hyperthermia at 32°C with 70% relative humidity (RH) (HOT) or 5-days of exercise in temperate (21°C with 36% RH) environmental conditions (TEMP). Measures of HA included heart rate, gastrointestinal temperature, skin temperature, sweat loss, total non-urinary fluid loss (TNUFL), plasma volume and participant's ratings of perceived exertion (RPE). Following HA, the HOT group demonstrated increased sweat loss (p = 0.01) and TNUFL (p = 0.01) in comparison to the TEMP group with a significantly decreased RPE (p = 0.01). On TTE, post exposure, there was a significant comparative increase in the HOT group in left ventricular end diastolic volume (p = 0.029), SV (p = 0.009), left atrial volume (p = 0.005), inferior vena cava diameter (p = 0.041), and a significant difference in mean peak diastolic mitral annular velocity (e') (p = 0.044). Cardiovascular adaptations to HA appear to be predominantly mediated by improvements in increased preload and ventricular compliance. TTE is a useful tool to demonstrate and quantify cardiac HA.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467033PMC
October 2020

Measuring the Exercise Component of Energy Availability during Arduous Training in Women.

Med Sci Sports Exerc 2021 04;53(4):860-868

University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UNITED KINGDOM.

Introduction: Low energy availability (EA) may impede adaptation to exercise, suppressing reproductive function and bone turnover. Exercise energy expenditure (EEE) measurements lack definition and consistency. This study aimed to compare EA measured from moderate and vigorous physical activity from accelerometry (EEEmpva) with EA from total physical activity (EEEtpa) from doubly labeled water in women. The secondary aim was to determine the relationship of EA with physical fitness, body composition by dual-energy x-ray absorptiometry, heart rate variability (HRV), and eating behavior (Brief Eating Disorder in Athletes Questionnaire [BEDA-Q]).

Methods: This was a prospective, repeated-measures study, assessing EA measures and training adaptation during 11-month basic military training. Forty-seven women (23.9 ± 2.6 yr) completed three consecutive 10-d assessments of EEEmvpa, EEEtpa, and energy intake (EI). EA measures were compared using linear regression and Bland-Altman analyses; relationships of EA with fat mass, HRV, 1.5-mile run times, and BEDA-Q were evaluated using partial correlations.

Results: EA from EEEmvpa demonstrated strong agreement with EA from EEEtpa across the measurement range (R2 = 0.76, r = 0.87, P < 0.001) and was higher by 10 kcal·kg-1 FFM·d-1. However, EA was low in absolute terms because of underreported EI. Higher EA was associated with improved 1.5-mile run time (r = 0.28, P < 0.001), fat mass loss (r = 0.38, P < 0.001), and lower BEDA-Q score (r = -0.37, P < 0.001) but not HRV (all P > 0.10).

Conclusion: Accelerometry-based EEE demonstrated validity against doubly labeled water during multistressor training, the difference representing 10 kcal·kg-1 FFM·d-1 EEE from nonexercise activity. Beneficial physical but not autonomic adaptations were associated with higher EA. EAmvpa and BEDA-Q warrant consideration for low EA assessment and screening.
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http://dx.doi.org/10.1249/MSS.0000000000002527DOI Listing
April 2021

The Effects of Apnea Training, Using Voluntary Breath Holds, on High Altitude Acclimation: Breathe-High Altitude Study.

High Alt Med Biol 2020 06 8;21(2):152-159. Epub 2020 Apr 8.

Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, United Kingdom.

There is evidence that intermittent hypoxic exposure (IHE) may improve high altitude (HA) performance. In this study, the effects of short-term IHE through voluntary apnea training on HA-related symptoms, including acute mountain sickness (AMS), were examined for the first time. Forty healthy adults were randomized to a self-administered apnea training ( = 19) or control ( = 21 no apnea training) group before ascent to an altitude of 5100 m in the Himalayas over 14 days. The apnea training was conducted at sea level (SL) and consisted of five breath holds per day in week 1, seven in week 2, followed by 10 per day from weeks 3 to 6 and until HA exposure. Saturation of arterial oxygen (SpO), heart rate, sleep quality (Insomnia Severity Index [ISI]), rating of perceived exertion (RPE), blood pressure, and Lake Louise scores were measured at SL (in the United Kingdom) and at HA at 1400, 2700, 3400-3700, 4050-4200, 4800, and 5100-5200 m. Anxiety (Generalized Anxiety Disorder-7 [GAD-7]) scores were examined at SL, 1400, and 5100-5200 m. Apnea training led to a significant increase in the mean longest breath-hold times from baseline (80.42 ± 32.49 [median 87.00] seconds) to the end of week 6 (107.02 ± 43.65 [113.00] seconds), respectively ( = 0.009). There was no significant difference in the prevalence of AMS (8/19 = 42.1% vs. 11/21 = 52.4%; RR 0.80; 95% confidence interval 0.41-1.57:  = 0.80) or in GAD-7, ISI and RPE, SpO heart rate, or blood pressure among the apnea versus control groups, respectively, at HA. Apnea training does not lessen HA-related symptoms in healthy adults traveling up to 5200 m. Larger studies using more challenging apnea protocols and at higher altitudes should be considered.
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http://dx.doi.org/10.1089/ham.2019.0087DOI Listing
June 2020

Mapping the Steroid Response to Major Trauma From Injury to Recovery: A Prospective Cohort Study.

J Clin Endocrinol Metab 2020 03;105(3)

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.

Context: Survival rates after severe injury are improving, but complication rates and outcomes are variable.

Objective: This cohort study addressed the lack of longitudinal data on the steroid response to major trauma and during recovery.

Design: We undertook a prospective, observational cohort study from time of injury to 6 months postinjury at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) > 15).

Main Outcome Measures: We measured adrenal and gonadal steroids in serum and 24-hour urine by mass spectrometry, assessed muscle loss by ultrasound and nitrogen excretion, and recorded clinical outcomes (ventilator days, length of hospital stay, opioid use, incidence of organ dysfunction, and sepsis); results were analyzed by generalized mixed-effect linear models.

Findings: We screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed all male survivors <50 years not treated with steroids (N = 60; median age 27 [interquartile range 24-31] years; median NISS 34 [29-44]). Urinary nitrogen excretion and muscle loss peaked after 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 months, respectively, to recover; opioid treatment delayed dehydroepiandrosterone recovery in a dose-dependent fashion. Androgens and precursors correlated with SOFA score and probability of sepsis.

Conclusion: The catabolic response to severe injury was accompanied by acute and sustained androgen suppression. Whether androgen supplementation improves health outcomes after major trauma requires further investigation.
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http://dx.doi.org/10.1210/clinem/dgz302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043227PMC
March 2020

Heat Adaptation in Military Personnel: Mitigating Risk, Maximizing Performance.

Front Physiol 2019 17;10:1485. Epub 2019 Dec 17.

Academic Department of Military Medicine, Research and Clinical Innovation, Royal Centre for Defence Medicine, Birmingham, United Kingdom.

The study of heat adaptation in military personnel offers generalizable insights into a variety of sporting, recreational and occupational populations. Conversely, certain characteristics of military employment have few parallels in civilian life, such as the imperative to achieve mission objectives during deployed operations, the opportunity to undergo training and selection for elite units or the requirement to fulfill essential duties under prolonged thermal stress. In such settings, achieving peak individual performance can be critical to organizational success. Short-notice deployment to a hot operational or training environment, exposure to high intensity exercise and undertaking ceremonial duties during extreme weather may challenge the ability to protect personnel from excessive thermal strain, especially where heat adaptation is incomplete. Graded and progressive acclimatization can reduce morbidity substantially and impact on mortality rates, yet individual variation in adaptation has the potential to undermine empirical approaches. Incapacity under heat stress can present the military with medical, occupational and logistic challenges requiring dynamic risk stratification during initial and subsequent heat stress. Using data from large studies of military personnel observing traditional and more contemporary acclimatization practices, this review article (1) characterizes the physical challenges that military training and deployed operations present (2) considers how heat adaptation has been used to augment military performance under thermal stress and (3) identifies potential solutions to optimize the risk-performance paradigm, including those with broader relevance to other populations exposed to heat stress.
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http://dx.doi.org/10.3389/fphys.2019.01485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928107PMC
December 2019

Fuel Use during Exercise at Altitude in Women with Glucose-Fructose Ingestion.

Med Sci Sports Exerc 2019 12;51(12):2586-2594

Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM.

Purpose: This study compared the coingestion of glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at terrestrial high altitude (HA) versus sea level, in women.

Method: Five women completed two bouts of cycling at the same relative workload (55% Wmax) for 120 min on acute exposure to HA (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min of glucose (enriched with C glucose) and 0.6 g·min of fructose (enriched with C fructose) before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen.

Results: The rates and absolute contribution of exogenous carbohydrate oxidation was significantly lower at HA compared with sea level (effect size [ES] > 0.99, P < 0.024), with the relative exogenous carbohydrate contribution approaching significance (32.6% ± 6.1% vs 36.0% ± 6.1%, ES = 0.56, P = 0.059) during the second hour of exercise. In comparison, no significant differences were observed between HA and sea level for the relative and absolute contributions of liver glucose (3.2% ± 1.2% vs 3.1% ± 0.8%, ES = 0.09, P = 0.635 and 5.1 ± 1.8 vs 5.4 ± 1.7 g, ES = 0.19, P = 0.217), and muscle glycogen (14.4% ± 12.2% vs 15.8% ± 9.3%, ES = 0.11, P = 0.934 and 23.1 ± 19.0 vs 28.7 ± 17.8 g, ES = 0.30, P = 0.367). Furthermore, there was no significant difference in total fat oxidation between HA and sea level (66.3 ± 21.4 vs 59.6 ± 7.7 g, ES = 0.32, P = 0.557).

Conclusions: In women, acute exposure to HA reduces the reliance on exogenous carbohydrate oxidation during cycling at the same relative exercise intensity.
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http://dx.doi.org/10.1249/MSS.0000000000002072DOI Listing
December 2019

Variation in renal responses to exercise in the heat with progressive acclimatisation.

J Sci Med Sport 2019 Sep 4;22(9):1004-1009. Epub 2019 May 4.

Department of Military Medicine, Royal Centre for Defence Medicine, United Kingdom; Department of Surgery and Cancer, Imperial College London, United Kingdom. Electronic address:

Objectives: To investigate changes in renal status from exercise in the heat with acclimatisation and to evaluate surrogates markers of Acute Kidney Injury.

Design: Prospective observational cohort study.

Methods: 20 male volunteers performed 60 min standardised exercise in the heat, at baseline and on four subsequent occasions during a 23-day acclimatisation regimen. Blood was sampled before and after exercise for serum creatinine, copeptin, interleukin-6, normetanephrine and cortisol. Fractional excretion of sodium was calculated for corresponding urine samples. Ratings of Perceived Exertion were reported every 5 min during exercise. Acute Kidney Injury was defined as serum creatinine rise ≥26.5 μmol L or fall in estimated glomerular filtration rate >25%. Predictive values of each candidate marker for developing Acute Kidney Injury were determined by ROC analysis.

Results: From baseline to Day 23, serum creatinine did not vary at rest, but showed a significant (P<0.05) reduction post-exercise (120 [102, 139] versus 102 [91, 112] μmol L). Acute Kidney Injury was common (26/100 exposures) and occurred most frequently in the unacclimatised state. Log-normalised fractional excretion of sodium showed a significant interaction (exercise by acclimatization day), with post-exercise values tending to rise with acclimatisation. Ratings of Perceived Exertion predicted AKI (AUC 0.76, 95% confidence interval 0.65-0.88), performing at least as well as biochemical markers.

Conclusions: Heat acclimatization is associated with reduced markers of renal stress and AKI incidence, perhaps due to improved regional perfusion. Acclimatisation and monitoring Ratings of Perceived Exertion are practical, non-invasive measures that could help to reduce renal injury from exercise in the heat.
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http://dx.doi.org/10.1016/j.jsams.2019.04.010DOI Listing
September 2019

Response to "Letter to the Editors" regarding the article "Risk of heat illness in men and women: A systematic review and meta-analysis".

Environ Res 2019 05 21;172:723. Epub 2019 Feb 21.

University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK. Electronic address:

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http://dx.doi.org/10.1016/j.envres.2019.01.057DOI Listing
May 2019

Skeletal responses to an all-female unassisted Antarctic traverse.

Bone 2019 04 5;121:267-276. Epub 2019 Feb 5.

Army Personnel Research Capability, Army Headquarters, Andover, UK. Electronic address:

Purpose: To investigate the skeletal effects of the first all-female trans-Antarctic traverse.

Methods: Six women (mean ± SD, age 32 ± 3 years, height 1.72 ± 0.07 m, body mass 72.8 ± 4.0 kg) hauled 80 kg sledges over 1700 km in 61 days from coast-to-coast across the Antarctic. Whole-body areal bone mineral density (aBMD) (dual-energy X-ray absorptiometry) and tibial volumetric BMD (vBMD), geometry, microarchitecture and estimated mechanical properties (high-resolution peripheral quantitative computed tomography) were assessed 39 days before (pre-expedition) and 15 days after the expedition (post-expedition). Serum and plasma markers of bone turnover were assessed pre-expedition, and 4 and 15 days after the expedition.

Results: There were reductions in trunk (-2.6%), ribs (-5.0%) and spine (-3.4%) aBMD from pre- to post-expedition (all P ≤ 0.046); arms, legs, pelvis and total body aBMD were not different (all P ≥ 0.075). Tibial vBMD, geometry, microarchitecture and estimated mechanical properties at the metaphysis (4% site) and diaphysis (30% site) were not different between pre- and post-expedition (all P ≥ 0.082). Bone-specific alkaline phosphatase was higher 15 days post- than 4 days post-expedition (1.7 μg∙l, P = 0.028). Total 25(OH)D decreased from pre- to 4 days post-expedition (-36 nmol∙l, P = 0.008). Sclerostin, procollagen 1 N-terminal propeptide, C-telopeptide cross-links of type 1 collagen and adjusted calcium were unchanged (all P ≥ 0.154).

Conclusion: A decline in aBMD of the axial skeleton may be due to indirect and direct effects of prolonged energy deficit. We propose that weight-bearing exercise was protective against the effects of energy deficit on tibial vBMD, geometry, microarchitecture and strength.
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http://dx.doi.org/10.1016/j.bone.2019.02.002DOI Listing
April 2019

Pre- to postexpedition changes in the energy usage of women undertaking sustained expeditionary polar travel.

J Appl Physiol (1985) 2019 03 20;126(3):681-690. Epub 2018 Dec 20.

Coventry National Institute for Health Research, Clinical Research Facility, Human Metabolic Research Unit, University Hospitals Coventry and Warwickshire, National Health Service Trust , Coventry , United Kingdom.

This paper reports the metabolic energy changes in six women who made the first unsupported traverse of Antarctica, covering a distance of 1,700 km in 61 days, hauling sledges weighing up to 80 kg. Pre- and postexpedition, measurements of energy expenditure and substrate utilization were made on all six members of the expedition over a 36-h period in a whole body calorimeter. During the study, subjects were fed an isocaloric diet: 50% carbohydrate, 35% fat, and 15% protein. The experimental protocol contained pre- and postexpedition measurement, including periods of sleep, rest, and three periods of standardized stepping exercise at 80, 100, and 120 steps/min. A median (interquartile range) decrease in the lean and fat weight of the subjects of 1.4 (1.0) and 4.4 (1.8) kg, respectively (P < 0.05) was found, using air-displacement plethysmography. No statistically significant difference was found between pre- and postexpedition values for sleeping or resting metabolic rate, nor for diet-induced thermogenesis. A statistically significant difference was found in energy expenditure between the pre- and postexpedition values for exercise at 100 [4.7 (0.23) vs. 4.4 (0.29), P < 0.05] and 120 [5.7 (0.46) vs. 5.5 (0.43), P < 0.05] steps/min; a difference that disappeared when the metabolic rate values were normalized to body weight. The group was well matched for the measures studied. Whereas a physiological change in weight was seen, the lack of change in metabolic rate measures supports a view that women appropriately nourished and well prepared can undertake polar expeditions with a minimal metabolic energy consequence. NEW & NOTEWORTHY This is the first study on the metabolic energy consequences for women undertaking expeditionary polar travel. The results show that participant selection gave a "well-matched" group, particularly during exercise. Notwithstanding this, individual differences were observed and explored. The results show that appropriately selected, trained, and nourished women can undertake such expeditions with no change in their metabolic energy requirements during rest or while undertaking moderate exercise over a sustained period of time.
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http://dx.doi.org/10.1152/japplphysiol.00792.2018DOI Listing
March 2019

Epidemiology and etiology of diarrhea in UK military personnel serving on the United Nations Mission in South Sudan in 2017: A prospective cohort study.

Travel Med Infect Dis 2019 Mar - Apr;28:34-40. Epub 2018 Dec 12.

Academic Department of Military Medicine, Clinical Research and Innovation, Defence Medical Services, Birmingham, UK.

Background: . Diarrhea is a well-established problem in travellers, with military personnel at especially high risk. This study aimed to characterise the spectrum of pathogens causing diarrhea in UK military personnel in South Sudan, and assess the utility of culture-independent testing for etiology and antimicrobial resistance in a logistically challenging and austere environment.

Methods: . All military personnel presenting with diarrhea were admitted to the UK Level 2 Medical Treatment Facility in Bentiu, South Sudan. Samples were tested for etiology utilising multiplex PCR-based diagnostics (BioFire FilmArray). In addition, the presence of carbapenemase resistance genes was determined using the geneXpert Carba-R platform.

Results: . Over 5 months, 127 samples were tested. The vast majority of pathogens detected were diarrheagenic Escherichia coli. The presence of either enterotoxigenic (ETEC) or enteropathogenic (EPEC) E. coli was a significant predictor of the other being present. In this study patients presenting with vomiting were 32 times more likely to have norovirus than not (p < 0.001). No carbapenem resistance was detected.

Conclusions: . Diarrhea in UK military personnel in South Sudan was determined to be predominantly bacterial, with norovirus presenting a distinct clinical and epidemiological pattern. Multiplex PCR and molecular resistance point of care testing were robust and effective in this environment.
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http://dx.doi.org/10.1016/j.tmaid.2018.12.004DOI Listing
May 2019

Confirmation of ovulation from urinary progesterone analysis: assessment of two automated assay platforms.

Sci Rep 2018 12 4;8(1):17621. Epub 2018 Dec 4.

MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

Urinary concentrations of the major progesterone (P4) metabolite pregnanediol-3-glucuronide (PDG) are used to confirm ovulation. We aimed to determine whether automated immunoassay of urinary P4 was as efficacious as PDG to confirm ovulation. Daily urine samples from 20 cycles in 14 healthy women in whom ovulation was dated by ultrasound, and serial weekly samples from 21 women in whom ovulation was unknown were analysed. Daily samples were assayed by two automated P4 immunoassays (Roche Cobas and Abbott Architect) and PDG ELISA. Serial samples were assayed for P4 by Architect and PDG by ELISA. In women with detailed monitoring of ovulation, median (95% CI) luteal phase increase was greatest for PDG, 427% (261-661), 278% (187-354) for P4 Architect and least for P4 Cobas, 146% (130-191), p < 0.0001. Cobas P4 also showed marked inaccuracy in serial dilution. Similar ROC AUCs were observed for individual threshold values and two-sample percent rise analyses for P4 Architect and PDG (both >0.92). In serial samples classified as (an)ovulatory by PDG, P4 Architect gave ROC AUC 0.95 (95% CI 0.89 to 1.01), with sensitivity and specificity for confirmation of ovulation of 0.90 and 0.91 at a cutoff of 1.67 μmol/mol. Automated P4 may potentially be as efficacious as PDG ELISA but research from a range of clinical settings is required.
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http://dx.doi.org/10.1038/s41598-018-36051-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279762PMC
December 2018

Recovery time and heart rate variability following extreme endurance exercise in healthy women.

Physiol Rep 2018 Nov;6(21):e13905

Defence Medical Services, Lichfield, United Kingdom.

The relationship between autonomic function and recovery following prolonged arduous exercise in women has not been examined. We undertook an exploratory study that aimed to examine the temporal change in linear and nonlinear measures of heart rate variability (HRV) following prolonged arduous exercise in the form of first all-female (mean age 32.7 ± 3.1 years) team to attempt an unassisted Antarctic traverse. HRV analysis was performed before and 1, 4, and 15 days postexpedition. The traverse was completed in 61 days. There was a significant paired reduction in heart rate, LnLF, LF:HF, DFAα1 between baseline and 15 days postexercise in the same environment. Conversely, RMSSD, LnHF and HFnu, SD1:SD2, and SampEn significantly increased. DFAα2 levels significantly fell from baseline to Day 1 postexercise. In conclusion, we observed a significant latent increase in relative parasympathetic dominance and RR interval irregularity at 15 days post prolonged arduous exercise, versus pre-exercise baseline, in a group of very fit and healthy adult women.
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http://dx.doi.org/10.14814/phy2.13905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209688PMC
November 2018

Female Reproductive, Adrenal, and Metabolic Changes during an Antarctic Traverse.

Med Sci Sports Exerc 2019 03;51(3):556-567

Research & Clinical Innovation, Royal Centre for Defence Medicine, Lichfield, UNITED KINGDOM.

Purpose: To explore the effects of the first all-female transantarctic expedition on hormonal axes pertinent to reproductive and metabolic function.

Methods: Six females (age, 28-36 yr; body mass index, 24.2 ± 0.97 kg·m) hauled 80-kg sledges 1700 km in 61 d. Estimated average energy intake was 20.8 ± 0.1 MJ·d (4970 ± 25 kcal·d). Whole and regional body composition was measured by dual-energy x-ray absorptiometry 1 and 2 months before and 15 d after, the expedition. Body fat was also estimated by skinfold and bioimpedance immediately before and after the expedition. Basal metabolic and endocrine blood markers and, after 0.25 mg dexamethasone suppression, 1-h 10-μg gonadorelin and 1.0 μg adrenocortiocotrophin-(1-24) tests were completed, 39-38 d preexpedition and 4 to 5 d and 15 to 16 d postexpedition. Cortisol was assessed in hair (monthly average concentrations) and saliva (five-point day curves and two-point diurnal sampling).

Results: Average body mass loss was 9.37 ± 2.31 kg (P < 0.0001), comprising fat mass only; total lean mass was maintained. Basal sex steroids, corticosteroids, and metabolic markers were largely unaffected by the expedition except leptin, which decreased during the expedition and recovered after 15 d, a proportionately greater change than body fat. Luteinizing hormone reactivity was suppressed before and during the expedition, but recovered after 15 d, whereas follicle-stimulating hormone did not change during or after the expedition. Cortisol reactivity did not change during or after the expedition. Basal (suppressed) cortisol was 73.25 ± 45.23 mmol·L before, 61.66 ± 33.11 mmol·L 5 d postexpedition and 54.43 ± 28.60 mmol·L 16 d postexpedition (P = 0.7). Hair cortisol was elevated during the expedition.

Conclusions: Maintenance of reproductive and hypothalamic-pituitary-adrenal axis function in women after an extreme physical endeavor, despite energy deficiency, suggests high female biological capacity for extreme endurance exercise.
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http://dx.doi.org/10.1249/MSS.0000000000001803DOI Listing
March 2019

Heat acclimatization blunts copeptin responses to hypertonicity from dehydrating exercise in humans.

Physiol Rep 2018 09;6(18):e13851

Institute of Naval Medicine, Alverstoke, Hampshire, United Kingdom.

Acclimatization favors greater extracellular tonicity from lower sweat sodium, yet hyperosmolality may impair thermoregulation during heat stress. Enhanced secretion or action of vasopressin could mitigate this through increased free water retention. Aims were to determine responses of the vasopressin surrogate copeptin to dehydrating exercise and investigate its relationships with tonicity during short and long-term acclimatization. Twenty-three participants completed a structured exercise programme following arrival from a temperate to a hot climate. A Heat Tolerance Test (HTT) was conducted on Day-2, 6, 9 and 23, consisting of 60-min block-stepping at 50% VO peak, with no fluid intake. Resting sweat [Na ] was measured by iontophoresis. Changes in body mass (sweat loss), core temperature, heart rate, osmolality (serum and urine) and copeptin and aldosterone (plasma) were measured with each Test. From Day 2 to Day 23, sweat [Na ] decreased significantly (adjusted P < 0.05) and core temperature and heart rate fell. Over the same interval, HTT-associated excursions were increased for serum osmolality (5 [-1, 9] vs. 9 [5, 12] mosm·kg ), did not differ for copeptin (9.6 [6.0, 15.0] vs. 7.9 [4.3, 14.7] pmol·L ) and were reduced for aldosterone (602 [415, 946] vs. 347 [263, 537] pmol·L ). Urine osmolality was unchanging and related consistently to copeptin at end-exercise, whereas the association between copeptin and serum osmolality was right-shifted (P = 0.0109) with acclimatization. Unchanging urine:serum osmolality argued against increased renal action of vasopressin. In conclusion, where exercise in the heat is performed without fluid replacement, heat acclimatization does not appear to enhance AVP-mediated free water retention in humans.
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http://dx.doi.org/10.14814/phy2.13851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139708PMC
September 2018

The relationship between anxiety and acute mountain sickness.

PLoS One 2018 21;13(6):e0197147. Epub 2018 Jun 21.

Research Institute, for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, United Kingdom.

Introduction: Whilst the link between physical factors and risk of high altitude (HA)-related illness and acute mountain sickness (AMS) have been extensively explored, the influence of psychological factors has been less well examined. In this study we aimed to investigate the relationship between 'anxiety and AMS risk during a progressive ascent to very HA.

Methods: Eighty health adults were assessed at baseline (848m) and over 9 consecutive altitudes during a progressive trek to 5140m. HA-related symptoms (Lake Louise [LLS] and AMS-C Scores) and state anxiety (State-Trait-Anxiety-Score [STAI Y-1]) were examined at each altitude with trait anxiety (STAI Y-2) at baseline.

Results: The average age was 32.1 ± 8.3 years (67.5% men). STAI Y-1 scores fell from 848m to 3619m, before increasing to above baseline scores (848m) at ≥4072m (p = 0.01). STAI Y-1 scores correlated with LLS (r = 0.31; 0.24-0.3; P<0.0001) and AMS-C Scores (r = 0.29; 0.22-0.35; P<0.0001). There was significant main effect for sex (higher STAI Y-1 scores in women) and altitude with no sex-x-altitude interaction on STAI Y-1 Scores. Independent predictors of significant state anxiety included female sex, lower age, higher heart rate and increasing LLS and AMS-C scores (p<0.0001). A total of 38/80 subjects (47.5%) developed AMS which was mild in 20 (25%) and severe in 18 (22.5%). Baseline STAI Y-2 scores were an independent predictor of future severe AMS (B = 1.13; 1.009-1.28; p = 0.04; r2 = 0.23) and STAI Y-1 scores at HA independently predicted AMS and its severity.

Conclusion: Trait anxiety at low altitude was an independent predictor of future severe AMS development at HA. State anxiety at HA was independently associated with AMS and its severity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197147PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013200PMC
November 2018

High Altitude Affects Nocturnal Non-linear Heart Rate Variability: PATCH-HA Study.

Front Physiol 2018 16;9:390. Epub 2018 Apr 16.

The Defence Medical Services, Lichfield, United Kingdom.

High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have been barely examined at HA. This study sought to examine this relationship at terrestrial HA. Sixteen healthy British military servicemen were studied at baseline (800 m, first night) and over eight consecutive nights, at a sleeping altitude of up to 3600 m. A disposable cardiac patch monitor was used, to record the nocturnal cardiac inter-beat interval data, over 1 h (0200-0300 h), for offline HRV assessment. Non-linear HRV measures included Sample entropy (SampEn), the short (α1, 4-12 beats) and long-term (α2, 13-64 beats) detrend fluctuation analysis slope and the correlation dimension (D2). The maximal rating of perceived exertion (RPE), during daily exercise, was assessed using the Borg 6-20 RPE scale. All subjects completed the HA exposure. The average age of included subjects was 31.4 ± 8.1 years. HA led to a significant fall in SpO and increase in heart rate, LLS and RPE. There were no significant changes in the ECG-derived respiratory rate or in any of the time domain measures of HRV during sleep. The only notable changes in frequency domain measures of HRV were an increase in LF and fall in HFnu power at the highest altitude. Conversely, SampEn, SD1/SD2 and D2 all fell, whereas α1 and α2 increased ( < 0.05). RPE inversely correlated with SD1/SD2 ( = -0.31; = 0.002), SampEn ( = -0.22; = 0.03), HFnu ( = -0.27; = 0.007) and positively correlated with LF ( = 0.24; = 0.02), LF/HF ( = 0.24; = 0.02), α1 ( = 0.32; = 0.002) and α2 ( = 0.21; = 0.04). AMS occurred in 7/16 subjects (43.8%) and was very mild in 85.7% of cases. HRV failed to predict AMS. Non-linear HRV is more sensitive to the effects of HA than time and frequency domain indices. HA leads to a compensatory decrease in nocturnal HRV and complexity, which is influenced by the RPE measured at the end of the previous day. HRV failed to predict AMS development.
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http://dx.doi.org/10.3389/fphys.2018.00390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911497PMC
April 2018

Changes in balance and joint position sense during a 12-day high altitude trek: The British Services Dhaulagiri medical research expedition.

PLoS One 2018 17;13(1):e0190919. Epub 2018 Jan 17.

Institute for Sport, Physical Activity & Leisure, Leeds Beckett University, Leeds, United Kingdom.

Postural control and joint position sense are essential for safely undertaking leisure and professional activities, particularly at high altitude. We tested whether exposure to a 12-day trek with a gradual ascent to high altitude impairs postural control and joint position sense. This was a repeated measures observational study of 12 military service personnel (28±4 years). Postural control (sway velocity measured by a portable force platform) during standing balance, a Sharpened Romberg Test and knee joint position sense were measured, in England (113m elevation) and at 3 research camps (3619m, 4600m and 5140m) on a 12-day high altitude trek in the Dhaulagiri region of Nepal. Pulse oximetry, and Lake Louise scores were also recorded on the morning and evening of each trek day. Data were compared between altitudes and relationships between pulse oximetry, Lake Louise score, and sway velocity were explored. Total sway velocity during standing balance with eyes open (p = 0.003, d = 1.9) and during Sharpened Romberg test with eyes open (p = 0.007, d = 1.6) was significantly greater at altitudes of 3619m and 5140m when compared with sea level. Anterior-posterior sway velocity during standing balance with eyes open was also significantly greater at altitudes of 3619m and 5140m when compared with sea level (p = 0.001, d = 1.9). Knee joint position sense was not altered at higher altitudes. There were no significant correlations between Lake Louise scores, pulse oximetry and postural sway. Despite a gradual ascent profile, exposure to 3619 m was associated with impairments in postural control without impairment in knee joint position sense. Importantly, these impairments did not worsen at higher altitudes of 4600 m or 5140 m. The present findings should be considered during future trekking expeditions when developing training strategies targeted to manage impairments in postural control that occur with increasing altitude.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190919PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771604PMC
February 2018

Copeptin reflects physiological strain during thermal stress.

Eur J Appl Physiol 2018 Jan 27;118(1):75-84. Epub 2017 Oct 27.

Department of Military Medicine, Royal Centre for Defence Medicine, ICT Building, Birmingham Research Park, Vincent Drive, Edgbaston, Birmingham, B15 2SQ, UK.

Purpose: To prevent heat-related illnesses, guidelines recommend limiting core body temperature (T ) ≤ 38 °C during thermal stress. Copeptin, a surrogate for arginine vasopressin secretion, could provide useful information about fluid balance, thermal strain and health risks. It was hypothesised that plasma copeptin would rise with dehydration from occupational heat stress, concurrent with sympathoadrenal activation and reduced glomerular filtration, and that these changes would reflect T responses.

Methods: Volunteers (n = 15) were recruited from a British Army unit deployed to East Africa. During a simulated combat assault (3.5 h, final ambient temperature 27 °C), T was recorded by radiotelemetry to differentiate volunteers with maximum T  > 38 °C versus ≤ 38 °C. Blood was sampled beforehand and afterwards, for measurement of copeptin, cortisol, free normetanephrine, osmolality and creatinine.

Results: There was a significant (P < 0.05) rise in copeptin from pre- to post-assault (10.0 ± 6.3 vs. 16.7 ± 9.6 pmol L, P < 0.001). Although osmolality did not increase, copeptin correlated strongly with osmolality after the exposure (r = 0.70, P = 0.004). In volunteers with maximum T  > 38 °C (n = 8) vs ≤ 38 °C (n = 7) there were significantly greater elevations in copeptin (10.4 vs. 2.4 pmol L) and creatinine (10 vs. 2 μmol L), but no differences in cortisol, free normetanephrine or osmolality.

Conclusions: Changes in copeptin reflected T response more closely than sympathoadrenal markers or osmolality. Dynamic relationships with tonicity and kidney function may help to explain this finding. As a surrogate for integrated physiological strain during work in a field environment, copeptin assay could inform future measures to prevent heat-related illnesses.
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http://dx.doi.org/10.1007/s00421-017-3740-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754412PMC
January 2018

A comparison of substrate oxidation during prolonged exercise in men at terrestrial altitude and normobaric normoxia following the coingestion of 13C glucose and 13C fructose.

Physiol Rep 2017 Jan;5(1)

Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, United Kingdom.

This study compared the effects of coingesting glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at altitude and sea level, in men. Seven male British military personnel completed two bouts of cycling at the same relative workload (55% W) for 120 min on acute exposure to altitude (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min of glucose (enriched with C glucose) and 0.6 g·min of fructose (enriched with C fructose) directly before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen. Total carbohydrate oxidation during the exercise period was lower at altitude (157.7 ± 56.3 g) than sea level (286.5 ± 56.2 g, P = 0.006, ES = 2.28), whereas fat oxidation was higher at altitude (75.5 ± 26.8 g) than sea level (42.5 ± 21.3 g, P = 0.024, ES = 1.23). Peak exogenous carbohydrate oxidation was lower at altitude (1.13 ± 0.2 g·min) than sea level (1.42 ± 0.16 g·min, P = 0.034, ES = 1.33). There were no differences in rates, or absolute and relative contributions of plasma or liver glucose oxidation between conditions during the second hour of exercise. However, absolute and relative contributions of muscle glycogen during the second hour were lower at altitude (29.3 ± 28.9 g, 16.6 ± 15.2%) than sea level (78.7 ± 5.2 g (P = 0.008, ES = 1.71), 37.7 ± 13.0% (P = 0.016, ES = 1.45). Acute exposure to altitude reduces the reliance on muscle glycogen and increases fat oxidation during prolonged cycling in men compared with sea level.
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http://dx.doi.org/10.14814/phy2.13101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256160PMC
January 2017

Hematopoiesis Shows Closer Correlation with Calculated Free Testosterone in Men than Total Testosterone.

J Appl Lab Med 2017 Jan;1(4):441-444

Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Trust, Newcastle-upon-Tyne, UK.

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http://dx.doi.org/10.1373/jalm.2016.022012DOI Listing
January 2017

Nutritional status and the gonadotrophic response to a polar expedition.

Appl Physiol Nutr Metab 2015 Mar;40(3):292-7

Polar expeditions have been associated with changes in the hypothalamic-pituitary-testicular axis consistent with central hypogonadism (i.e., decreased testosterone, luteinising hormone (LH), and follicle stimulating hormone (FSH)). These changes are typically associated with body mass loss. Our aim was to evaluate whether maintenance of body mass during a polar expedition could mitigate against the development of central hypogonadism. Male participants (n = 22) from a 42-day expedition (British Services Antarctic Expedition 2012) volunteered to take part in the study. Body mass, body composition, and strength data were recorded pre- and postexpedition in addition to assessment of serum testosterone, LH, FSH, thyroid hormones, insulin-like growth factor 1 (IGF-1), and trace elements. Energy provision and energy expenditure were assessed at mid- and end-expedition. Daily energy provision was 6335 ± 149 kcal·day(-1). Estimated energy expenditure midexpedition was 5783 ± 1690 kcal·day(-1). Body mass and percentage body fat did not change between pre- and postexpedition. Total testosterone (nmol·L(-1)) (14.0 ± 4.9 vs. 17.3 ± 4.0, p = 0.006), calculated free testosterone (pmol·L(-1)) (288 ± 82 vs. 350 ± 70, p = 0.003), and sex hormone binding globulin (nmol·L(-1)) (33 ± 12 vs. 36 ± 11, p = 0.023) concentrations increased. LH and FSH remained unchanged. Thyroid stimulating hormone (TSH; IU·L(-1)) (2.1 ± 0.8 vs. 4.1 ± 2.1, p < 0.001) and free triiodothyronine (FT3; IU·L(-1)) (5.4 ± 0.4 vs. 6.1 ± 0.8, p < 0.001) increased while free thyroxine, IGF-1, and trace elements remained unchanged. Hand-grip strength was reduced postexpedition but static lift strength was maintained. Maintenance of body mass and nutritional status appeared to negate the central hypogonadism previously reported from polar expeditions. The elevated TSH and free FT3 were consistent with a previously reported "polar T3 syndrome".
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http://dx.doi.org/10.1139/apnm-2014-0418DOI Listing
March 2015

High Altitude and Acute Mountain Sickness and Changes in Circulating Endothelin-1, Interleukin-6, and Interleukin-17a.

High Alt Med Biol 2016 Mar 17;17(1):25-31. Epub 2015 Dec 17.

4 Defence Medical Services , Lichfield, United Kingdom .

Introduction: Hypoxia induces an inflammatory response, which is enhanced by exercise. High altitude (HA) leads to endothelial activation and may be proinflammatory. The relationship between endothelial activation, inflammation, and acute mountain sickness (AMS) and its severity has never been examined.

Methods: Forty-eight trekkers were studied during a progressive trek at 3833, 4450, and 5129 m at rest postascent (exercise), and then again at rest 24 hours later. Twenty of the subjects were also tested at rest pre- and postexercise at sea level (SL) at 6 weeks preascent. We examined plasma levels of the interleukin 6 (IL-6), 17a (IL-17a), and endothelin-1 (ET-1) along with oxygen saturation (SpO2) and Lake Louise scores (LLS).

Results: ET-1 (5.7 ± 2.1 vs. 4.3 ± 1.9 pg/mL; p < 0.001), IL-6 (3.3 ± 3.3 vs. 2.4 ± 2.3 pg/mL; p = 0.007), and IL-17a (1.3 ± 3.0 vs. 0.46 ± 0.4 pg/mL; p < 0.001) were all overall significantly higher at HA versus SL. There was a paired increase in ET-1 and IL-6 with exercise versus rest at SL, 3833, 4450, and 5129 m (p < 0.05). There was a negative correlation between LLS and SpO2 (r = -0.32; 95% confidence interval [CI] -0.21 to -0.42; p < 0.001) and a positive correlation between LLS and IL-6 (r = 0.16; 0.0-0.27; p = 0.007) and ET-1 levels (r = 0.29; 0.18-0.39; p < 0.001. Altitude, ET-1, IL-6, and SpO2 were all univariate predictors of AMS. On multivariate analysis, ET-1 (p = 0.002) and reducing SpO2 (p = 0.02) remained as the only independent predictors (overall r(2) = 0.16; p < 0.001) of AMS. ET-1 (p = 03) and SpO2 were (p = 0.01) also independent predictors of severe AMS (overall r(2) = 0.19; p < 0.001).

Conclusions: HA leads to endothelial activation and an inflammatory response. The rise in ET-1 and IL-6 is heavily influenced by the degree of exercise and hypoxia. ET-1 is an independent predictor of both AMS and its severity.
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http://dx.doi.org/10.1089/ham.2015.0098DOI Listing
March 2016

Susceptibility to exertional heat illness and hospitalisation risk in UK military personnel.

BMJ Open Sport Exerc Med 2015 14;1(1):e000055. Epub 2015 Oct 14.

Section of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London, UK; Reader in Critical Care, Centre for Perioperative Medicine and Critical Care Research, Imperial College Healthcare NHS Trust, UK.

Background: Susceptibility to exertional heat illness (EHI) is considered multifactorial in nature. The aims of this study were to (1) review traditional susceptibility factors identified in cases of EHI and (2) determine how they are related to risk of hospitalisation.

Methods: Review of an electronic database of EHI reported in the British Army between 1 September 2007 and 31 December 2014. Cases were categorised by demographic, situational and susceptibility variables. Univariate and multivariate logistic regression was performed for the OR for hospitalisation by risk factor.

Results: 361 reports were included in the analysis. 33.5% of cases occurred in hot climates, 34.6% in temperate climates during summer months and 31.9% in temperate climates outside of summer months. Traditional susceptibility factors were reported in 193 but entirely absent from 168 cases. 137 cases (38.0%) were admitted to hospital. Adjusted OR for hospitalisation was lower for recruits (OR 0.42, 95% CI 0.18 to 0.99, p<0.05) and for personnel wearing occlusive dress (OR 0.56, 95% CI 0.34 to 0.93, p<0.05) or unacclimatised to heat (OR 0.31, 95% CI 0.15 to 0.66, p<0.01).

Conclusions: The global, year-round threat of EHI is highlighted. Absence of susceptibility factors in nearly half of reports highlights the challenge of identifying EHI-prone individuals. Paradoxical association of traditional susceptibility factors with reduced hospitalisation risk may reflect the contemporary contexts in which severe EHI occurs. These findings also suggest a need for better evidence to inform guidelines that aim to prevent severe EHI concurrent to reducing overall morbidity.
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http://dx.doi.org/10.1136/bmjsem-2015-000055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117044PMC
October 2015

Phaeochromocytoma and ACTH-dependent cushing's syndrome: tumour crf secretion can mimic pituitary cushing's disease.

Clin Endocrinol (Oxf) 2016 Feb 20;84(2):177-184. Epub 2015 Nov 20.

Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.

Introduction: 10% of corticotrophin (ACTH)-dependent Cushing's syndrome arises from secretion by extrapituitary tumours, with phaeochromocytoma implicated in a few cases. Ectopic secretion by phaeochromocytoma of corticotropin-releasing hormone (CRF), with secondary corticotroph hyperplasia, is even rarer, with only five cases in the literature hitherto. However, such cases may be classified as 'ectopic ACTH' due to incomplete verification.

Clinical Cases: We describe three patients with phaeochromocytoma and ACTH-dependent Cushing's syndrome in whom biochemical cure was achieved following unilateral adrenalectomy. Although unable to access a validated CRF assay within the timeframe for sample storage, we nevertheless inferred CRF secretion in 2 of 3 cases by tumour immunostaining (positive for CRF; negative for ACTH), supported in one case by pre-operative inferior petrosal sinus sampling (IPSS) indicative of pituitary ACTH source. Both cases were characterized by rapid postoperative wean off glucocorticoids, presumed to reflect the pituitary stimulatory-effect of CRF outweighing central negative feedback inhibition by hypercortisolaemia. By contrast, the tumour excised in a third case exhibited positive immunostaining for ACTH - negative for CRF - and postoperative recovery of hypothalamic-pituitary-adrenal axis took significantly longer.

Discussion: Ectopic CRF production is biochemically indistinguishable from ectopic ACTH secretion, except that IPSS mimics pituitary Cushing's disease and cortisol dynamics may normalize rapidly postadrenalectomy. CRF secretion can be inferred through tumour immunohistochemistry, even if no CRF assay is available. Unrecognized phaeochromocytoma ACTH secretion may underpin some cases of cardiovascular collapse postadrenalectomy through acute hypocortisolaemia. Despite advances in phaeochromocytoma genetics since previous reports, we were unable to identify somatic DNA defects associated with either ACTH or CRF secretion.
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http://dx.doi.org/10.1111/cen.12960DOI Listing
February 2016

Rating of perceived exertion and acute mountain sickness during a high-altitude trek.

Aviat Space Environ Med 2014 Dec;85(12):1214-6

Defence Medical Services and the Academic Department of Anaesthesia and Critical Care, Royal Centre for Defence Medicine, Birmingham, UK.

Background: There is a widely held belief that strenuous exercise should be avoided on arrival at high altitude (HA) and during acclimatization. Data from chamber studies are contradictory and the studies are usually of short duration, therefore differing from the "real world."

Methods: We studied 48 trekkers during a 10-d ascent to 16,827 ft (5129 m) in the Cordillera Real area of Bolivia. Borg Rating of Perceived Exertion (RPE) scores were recorded for the hardest perceived exertion during the day after ascents to 12,576, 14,600, and 16,827 ft (3833, 4450, and 5129 m). Heart rate, Spo2, and Lake Louise Score (LLS) were recorded simultaneously. Statistical testing was performed using SPSS 21 software. A P-value of ≤ 0.05 was deemed significant.

Results: Acute mountain sickness (AMS) rates were higher after trekking days with higher levels of perceived exertion. The LLS was higher in those with a Borg RPE score ≥ 15 both following exercise (mean LLS 2.6 vs. 1.7) and at rest the following day (mean LLS 2.7 vs. 1.7). Heart rate was higher in those with high Borg RPE scores (80 vs. 87) and oxygen saturations lower at rest (86 vs. 83) the following morning.

Discussion: This data lends weight to the advice of moderate exertion during a trek to HA and suggests that reducing perceived exertion may reduce AMS.
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http://dx.doi.org/10.3357/ASEM.4083.2014DOI Listing
December 2014

Neutrophil gelatinase-associated lipocalin: its response to hypoxia and association with acute mountain sickness.

Dis Markers 2013 20;35(5):537-42. Epub 2013 Oct 20.

Defence Medical Services, Lichfield WS14 9PY, UK ; Academic Department of Emergency Medicine, James Cook University Hospital, Middlesbrough TS4 3BW, UK ; Ministry of Defence Hospital Unit, Northallerton DL6 1JG, UK.

Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n = 22) undertaking 6 hours exercise at near sea-level (SL); a cohort (n = 14) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions (n = 52) to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range) rose significantly (P < 0.001) from 68 ± 14 (60-102) at 1300 m to 183 ± 107 (65-519); 143 ± 66 (60-315) and 150 ± 71 (60-357) at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n = 7), mild AMS (n = 16) or no AMS (n = 23): 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively (P = 0.009 for severe versus no AMS; P = 0.026 for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS.
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http://dx.doi.org/10.1155/2013/601214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817649PMC
June 2014
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