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Introduction: Measuring cortisol during military training offers insights into physiological responses to stress. We attempted precisely timed, cortisol awakening response (CAR) and pre-sleep cortisol (PSC), and diurnal slope (peak morning minus evening cortisol), during a British Army exercise. We aimed to understand cortisol dynamics and evaluate the feasibility of CAR and PSC in this environment., Method: Setting: high-intensity, 10-day infantry exercise. Participants: regular infantry soldiers exercising (EX, n=25) or headquarters-based (HQ, n=6). Participants undertook PSC and WAKE and WAKE+30 min samples after 1-2 days, 5-6 days and 9-10 days. Wrist-worn GENEActiv accelerometers were used to assess sleep duration in EX only. Samples taken ±15 min from prespecified time points were deemed adherent. Validated questionnaires were used to measure resilience and perceived stress. Cortisol and cortisone were measured simultaneously by liquid chromatography tandem mass spectrometry., Results: From adherent participants' samples, CAR was positive and tended to decrease as the exercise progressed. From all available data, HQ demonstrated greater diurnal slope than EX (F=7.68, p=0.02), reflecting higher morning cortisol (F=4.72, p=0.038) and lower PSC (p=0.04). No differences were seen in cortisol:cortisone ratio. 26.1% of CAR samples were adherent, with moderately strong associations between adherence and stress (r=0.41, p=0.009) but no association between adherence and day of exercise (χ 2 =0.27, p=0.8), sleep duration (r=-0.112, p=0.43) or resilience (r=-0.79, p=0.75). Test-retest reliability ratings for CAR were Cronbach's α of 0.48, -11.7 and 0.34 for the beginning, middle and end of the exercise, respectively., Conclusions: We observed a reduction in morning cortisol and decreased diurnal slope during a high-intensity military exercise, compared with the HQ comparator cohort in whom diurnal slope was preserved. A carefully timed CAR was not feasible in this setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Heat adaptation is protective against heat illness; however, its role in heat syncope, due to reflex mechanisms, has not been conclusively established. The aim of this study was to evaluate if heat acclimation (HA) was protective against heat syncope and to ascertain underlying physiological mechanisms., Methods: Twenty (15 males, 5 females) endurance-trained athletes were randomized to either 8 d of mixed active and passive HA (HEAT) or climatically temperate exercise (CONTROL). Before, and after, the interventions participants underwent a head up tilt (HUT) with graded lower body negative pressure (LBNP), in a thermal chamber (32.0 ± 0.3°C), continued until presyncope with measurement of cardiovascular parameters. Heat stress tests (HST) were performed to determine physiological and perceptual measures of HA., Results: There was a significant increase in orthostatic tolerance (OT), as measured by HUT/LBNP, in the HEAT group (preintervention; 28 ± 9 min, postintervention; 40 ± 7 min) compared with CONTROL (preintervention; 30 ± 8 mins, postintervention; 33 ± 5 min) ( P = 0.01). Heat acclimation resulted in a significantly reduced peak and mean rectal and skin temperature ( P < 0.01), peak heat rate ( P < 0.003), thermal comfort ( P < 0.04), and rating of perceived exertion ( P < 0.02) during HST. There was a significantly increased plasma volume (PV) in the HEAT group in comparison to CONTROL ( P = 0.03)., Conclusions: Heat acclimation causes improvements in OT and is likely to be beneficial in patients with heat exacerbated reflex syncope. Heat acclimation-mediated PV expansion is a potential physiological mechanism underlying improved OT., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Introduction: Reflex syncope in the UK Armed Forces is reportedly higher than comparable militaries and civilian populations and is significantly more common in soldiers who take part in State Ceremonial and Public Duties (SCPD) compared with other British Army service personnel (SP). This study aimed to investigate individual susceptibility factors for syncope in soldiers who regularly take part in SCPD., Methods: A retrospective cohort study was performed in 200 soldiers who perform SCPD. A questionnaire was undertaken reviewing soldiers' medical history and circumstances of any fainting episodes. A consented review of participants' electronic primary healthcare medical record was also performed. Participants were divided into two groups (syncope, n=80; control, n=120) based on whether they had previously fainted., Results: In the syncope group orthostasis (61%) and heat (35%) were the most common precipitating factors. The most common interventions used by soldiers were to maintain hydration (59%) and purposeful movements (predominantly 'toe wiggling' ; 55%). 30% of participants who had previously fainted did not seek definitive medical attention. A history of migraines/headaches was found to increase the risk of reflex syncope (OR 8.880, 1.214-218.8), while a history of antihistamine prescription (OR 0.07144, 0.003671-0.4236), non-white ethnicity (OR 0.03401, 0.0007419-0.3972) and male sex (OR 0.2640, 0.08891-0.6915) were protective., Conclusion: This is the first study, in the British Army, to describe, categorise and establish potential risk factors for reflex syncope. Orthostatic-mediated reflex syncope is the most common cause in soldiers who regularly perform SCPD and this is further exacerbated by heat exposure. Soldiers do not use evidence-based methods to avoid reflex syncope. These data could be used to target interventions for SP who have previously fainted or to prevent fainting during SCPD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess how biomarkers indicating central nervous system insult (neurobiomarkers) vary in peripheral blood with exertional-heat stress from prolonged endurance exercise., Design: Observational study of changes in neuron specific enolase (NSE), S100 calcium-binding protein B (S100β), Glial Fibrillary Acid Protein (GFAP) and Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) at Brighton Marathon 2022., Methods: In 38 marathoners with in-race core temperature (Tc) monitoring, exposure (High, Intermediate or Low) was classified by cumulative hyperthermia - calculated as area under curve of Time × Tc > 38 °C - and also by running duration (finishing time). Blood was sampled for neurobiomarkers, cortisol and fluid-regulatory stress surrogates, including copeptin and creatinine (at rested baseline; within 30 min of finishing; and at 24 h)., Results: Finishing in 236 ± 40 min, runners showed stable GFAP and UCH-L1 across the marathon and next-day. Significant (P < 0.05) increases from baseline were shown post-marathon and at 24 h for S100β (8.52 [3.65, 22.95] vs 39.0 [26.48, 52.33] vs 80.3 [49.1, 99.7] ng·L -1 ) and post-marathon only for NSE (3.73 [3.30, 4.32] vs 4.85 [4.45, 5.80] μg·L -1 , P < 0.0001). Whilst differential response to hyperthermia was observed for cortisol, copeptin and creatinine, neurobiomarker responses did not vary. Post-marathon, only NSE differed by exercise duration (High vs Low, 5.81 ± 1.77 vs. 4.69 ± 0.73 μg·L -1 , adjusted P = 0.0358)., Conclusions: Successful marathon performance did not associate with evidence for substantial neuronal insult. To account for variation in neurobiomarkers with prolonged endurance exercise, factors additional to hyperthermia, such as exercise duration and intensity, should be further investigated., Competing Interests: Declaration of Interest Statement YP is the founding member of the Sub2 marathon project (www.sub2hrs.com). All other authors have no conflicts of interest relevant to the content of this article., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Introduction: Reflex syncope is the most common subtype of syncope and, despite not being associated with increased mortality, often results in significant morbidity and costly diagnostics. Reflex syncope can be of concern for certain occupational groups and may be exacerbated by some occupations. Reflex syncope in the military is anecdotally common but the extent in the UK Armed Forces (UKAF) is unknown. The aim of this study was to assess the incidence and prevalence of reflex syncope in the UKAF., Methods: A retrospective search of the Defence Medical Information Capability Programme using prespecified read-codes was performed at defence primary healthcare centres over the period of 1 January 2019 to 1 January 2020. Data were obtained on 76 103 service personnel (SP) (53% of the UKAF)., Results: The overall syncope case rate for the UKAF was 10.5 per 1000 person-years (p-yrs). In comparing services there was a significantly increased risk of syncope in the British Army (10.7 per 1000 p-yrs) compared with the Royal Air Force (8.6 per 1000 p-yrs) (p=0.0365), SP who served overseas (16.7 per 1000 p-yrs) in comparison with UK medical centres (10.3 per 1000 p-yrs) (p<0.0001), and British Army units that regularly took part in State Ceremonial and Public Duties (15.8 per 1000 p-yrs vs 10.2 per 1000 p-yrs) (p=0.0035). Army training units conferred a significantly reduced risk of syncope (p<0.0001)., Conclusions: These data are the first to define the incidence and prevalence of syncope in the UKAF. Orthostasis and heat are probable triggers, although recruits are potentially protected. These data offer opportunities to improve the health and well-being of SP, with economic, logistical and reputational benefits for the UKAF. Further research to identify personnel at risk of future syncopal events may allow for targeted use of countermeasures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

This is an observational study of heat-related illness in UK Service Personnel deployed into summer conditions in Northern Kuwait and Southern Iraq. Among 622 hospitalisations reported during a 9-week period at the historical British Military Hospital, Shaibah, 303 consecutive admissions are reviewed in detail. Several clinical syndromes attributable to thermal stress were observed. These ranged from self-limiting debility to life-threatening failures of homeostasis, with 5.0% developing a critical care requirement. Hyponatraemia was a commonly occurring electrolyte disturbance by which, relative to the local reference range, a majority of heat-attributed admissions were affected. Reductions in measured serum sodium could be profound (<125 mmol/L in 20.1% of all heat-related casualties). Hypokalaemia was observed in half of cases, though only a minority were affected by severely low potassium (<2.5 mmol/L in 4.0%). Despite preventive measures prescribed on hospital discharge, illness and significant biochemical derangements could recur upon return to duties in the heat. We reiterate the need for primary prevention of heat illness wherever possible and importance of early, effective interventions to treat and protect Service Personnel from secondary injury. We also highlight the requirement for comprehensive assessment to inform prognostication and occupational decision-making in relation to extreme climatic heat, including aeromedical evacuation. We draw additional attention to the contribution of psychological factors in select cases and identify research questions to improve understanding of environment-induced incapacitation in general., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Bolus water drinking, at room temperature, has been shown to improve orthostatic tolerance (OT), probably via sympathetic activation; however, it is not clear whether the temperature of the water bolus modifies the effect on OT or the cardiovascular responses to orthostatic stress. The aim of this study was to assess whether differing water temperature of the water bolus would alter time to presyncope and/or cardiovascular parameters during incremental orthostatic stress., Methods: Fourteen participants underwent three head-up tilt (HUT) tests with graded lower body negative pressure (LBNP) continued until presyncope. Fifteen minutes prior to each HUT, participants drank a 500 mL bolus of water which was randomised, in single-blind crossover fashion, to either room temperature water (20 °C) (ROOM), ice-cold water (0-3 °C) (COLD) or warm water (45 °C) (WARM). Cardiovascular parameters were monitored continuously., Results: There was no significant difference in OT in the COLD (33 ± 3 min; p = 0.3321) and WARM (32 ± 3 min; p = 0.6764) conditions in comparison to the ROOM condition (31 ± 3 min). During the HUT tests, heart rate and cardiac output were significantly reduced (p < 0.0073), with significantly increased systolic blood pressure, stroke volume, cerebral blood flow velocity and total peripheral resistance (p < 0.0054), in the COLD compared to ROOM conditions., Conclusions: In healthy controls, bolus cold water drinking results in favourable orthostatic cardiovascular responses during HUT/LBNP without significantly altering OT. Using a cold water bolus may result in additional benefits in patients with orthostatic intolerance above those conferred by bolus water at room temperature (by ameliorating orthostatic tachycardia and enhancing vascular resistance responses). Further research in patients with orthostatic intolerance is warranted., (© 2022. Crown.)

Background: Medical personnel may find it challenging to distinguish severe Exertional Heat Illness (EHI), with attendant risks of organ-injury and longer-term sequalae, from lesser forms of incapacity associated with strenuous physical exertion. Early evidence for injury at point-of-incapacity could aid the development and application of targeted interventions to improve outcomes. We aimed to investigate whether biomarker surrogates for end-organ damage sampled at point-of-care (POC) could discriminate EHI versus successful marathon performance., Methods: Eight runners diagnosed as EHI cases upon reception to medical treatment facilities and 30 successful finishers of the same cool weather marathon (ambient temperature 8 rising to 12 ºC) were recruited. Emerging clinical markers associated with injury affecting the brain (neuron specific enolase, NSE; S100 calcium-binding protein B, S100β) and renal system (cystatin C, cysC; kidney-injury molecule-1, KIM-1; neutrophil gelatinase-associated lipocalin, NGAL), plus copeptin as a surrogate for fluid-regulatory stress, were sampled in blood upon marathon collapse/completion, as well as beforehand at rest (successful finishers only)., Results: Versus successful finishers, EHI showed significantly higher NSE (10.33 [6.37, 20.00] vs. 3.17 [2.71, 3.92] ug.L-1, P<0.0001), cysC (1.48 [1.10, 1.67] vs. 1.10 [0.95, 1.21] mg.L-1, P = 0.0092) and copeptin (339.4 [77.0, 943] vs. 18.7 [7.1, 67.9] pmol.L-1, P = 0.0050). Discrimination of EHI by ROC (Area-Under-the-Curve) showed performance that was outstanding for NSE (0.97, P<0.0001) and excellent for copeptin (AUC = 0.83, P = 0.0066)., Conclusions: As novel biomarker candidates for EHI outcomes in cool-weather endurance exercise, early elevations in NSE and copeptin provided sufficient discrimination to suggest utility at point-of-incapacity. Further investigation is warranted in patients exposed to greater thermal insult, followed up over a more extended period., Competing Interests: The authors have declared that no competing interests exist.

For most individuals residing in Northwestern Europe, maintaining replete vitamin D status throughout the year is unlikely without vitamin D supplementation and deficiency remains common. Military studies have investigated the association with vitamin D status, and subsequent supplementation, with the risk of stress fractures particularly during recruit training. The expression of nuclear vitamin D receptors and vitamin D metabolic enzymes in immune cells additionally provides a rationale for the potential role of vitamin D in maintaining immune homeostasis. One particular area of interest has been in the prevention of acute respiratory tract infections (ARTIs). The aims of this review were to consider the evidence of vitamin D supplementation in military populations in the prevention of ARTIs, including SARS-CoV-2 infection and consequent COVID-19 illness. The occupational/organisational importance of reducing transmission of SARS-CoV-2, especially where infected young adults may be asymptomatic, presymptomatic or paucisymptomatic, is also discussed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Heat stress exacerbates post-exercise hypotension (PEH) and cardiovascular disturbances from elevated body temperature may contribute to exertion-related incapacity. Mast cell degranulation and muscle mass are possible modifiers, though these hypotheses lack practical evidence. This study had three aims: (1) to characterise pre-post-responses in histamine and mast cell tryptase (MCT), (2) to investigate relationships between whole body muscle mass (WBMM) and changes in blood pressure post-marathon, (3) to identify any differences in incapacitated runners., Methods: 24 recreational runners were recruited and successfully completed the 2019 Brighton Marathon (COMPLETION). WBMM was measured at baseline. A further eight participants were recruited from incapacitated runners (COLLAPSE). Histamine, MCT, blood pressure, heart rate, body temperature and echocardiographic measures were taken before and after exercise (COMPLETION) and upon incapacitation (COLLAPSE)., Results: In completion, MCT increased by nearly 50% from baseline (p = 0.0049), whereas histamine and body temperature did not vary (p > 0.946). Systolic (SBP), diastolic (DBP) and mean (MAP) arterial blood pressures and systemic vascular resistance (SVR) declined (p < 0.019). WBMM negatively correlated with Δ SBP (r = - 0.43, p = 0.046). For collapse versus completion, there were significant elevations in MCT (1.77 ± 0.25 μg/L vs 1.18 ± 0.43 μg/L, p = 0.001) and body temperature (39.8 ± 1.3 °C vs 36.2 ± 0.8 °C, p < 0.0001) with a non-significant rise in histamine (9.6 ± 17.9 μg/L vs 13.7 ± 33.9 μg/L, p = 0.107) and significantly lower MAP, DBP and SVR (p < 0.033)., Conclusion: These data support the hypothesis that mast cell degranulation is a vasodilatory mechanism underlying PEH and exercise associated collapse. The magnitude of PEH is inversely proportional to the muscle mass and enhanced by concomitant body heating.

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 Parsons, Stacey and Woods.)

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 -1 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 -1 ). 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., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Joint problems commonly occur in people with diabetes. Cheiroarthropathy affects the hands and results in painless limited finger joint extension, appearing to be associated with longer diabetes duration and the presence of microvascular complications. The prevalence of cheiroarthropathy seems to be falling, perhaps as a result of improvements in glycaemic management. Non-enzymatic glycation of collagen results in abnormally crosslinked protein resistant to degradation with subsequent increased build-up of collagen in joints. The management of cheiroarthropathy is predominantly conservative, with occupational and hand therapy at the forefront. Tendinopathy is more common in people with diabetes than those without, and is associated with obesity and insulin resistance. As with cheiroarthropathy, the exact causative mechanism of tendinopathy in diabetes is not known, but may be linked to inflammation, apoptosis and increased vascularity of affected tendons, driven by hyperinsulinaemia. Local fat pads have also been suggested to play a role in the pathogenesis of tendinopathy., (© 2019 Diabetes UK.)

Objectives: We sought to establish the effects of professionalism, which officially began in 1995, on the body mass and height of northern hemisphere male international rugby union (RU) players. We hypothesised that mass would significantly increase following professionalism. We also investigated the changes in size of players according to their playing position, and we compared changes to rugby league (RL) players and the public., Methods: The body mass and height of players representing their international team for that country's first game of the Five Nations in 1955, 1965, 1975, 1985 and 1995 and, for 2005 and 2015, the Six Nations, were collected from matchday programmes. RL players' data were collected from the Challenge Cup final games played in the same years., Results: International RU player body mass has significantly increased since 1995. In 1955 mean (±SD) player body mass was 84.8  kg (±8.2); in 2015, it was 105.4  kg (±12.1), an increase of 24.3%. Between 1955 and 2015, the body mass of forwards increased steadily, whereas that of backs has mostly gone up since 1995. RU player body mass gain has exceeded that of RL, but the age-matched difference between RU players and the public has remained relatively constant., Conclusions: The factors influencing the gain in body mass of rugby players are legion; however, we believe that the interpretation of the law relating to the scrum put-in and changes allowing substitutions have, at least in part, contributed to the observed changes. Injury severity is increasing, and this may be linked to greater forces (caused by greater body mass) occurring in contact. RU law makers should adjust the rules to encourage speed and skill at the expense of mass., Competing Interests: Competing interests: None declared.

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 2 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 -1 ), did not differ for copeptin (9.6 [6.0, 15.0] vs. 7.9 [4.3, 14.7] pmol·L -1 ) and were reduced for aldosterone (602 [415, 946] vs. 347 [263, 537] pmol·L -1 ). 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., (© 2018 Crown copyright. Physiological Reports © 2018 published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

Purpose: To prevent heat-related illnesses, guidelines recommend limiting core body temperature (T c ) ≤ 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 c 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 c was recorded by radiotelemetry to differentiate volunteers with maximum T c  > 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 -1 , 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 c  > 38 °C (n = 8) vs ≤ 38 °C (n = 7) there were significantly greater elevations in copeptin (10.4 vs. 2.4 pmol L -1 ) and creatinine (10 vs. 2 μmol L -1 ), but no differences in cortisol, free normetanephrine or osmolality., Conclusions: Changes in copeptin reflected T c 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.

Background: Heat illness in the Armed Forces is considered preventable. The UK military relies upon dual Command and Medical reporting for case ascertainment, investigation of serious incidents and improvement of preventive practices and policy. This process could be vulnerable to under-reporting., Objectives: To establish whether heat illness in the British Army has been under-reported, by reviewing concordance of reporting to the Army Incident Notification Cell (AINC) and the Army Health Unit (AHU) and to characterise the burden of heat illness reported by these means., Methods: Analysis of anonymised reporting databases held by the AHU and AINC, for the period 2009-2013., Results: 565 unique cases of heat illness were identified. Annual concordance of reporting ranged from 9.6% to 16.5%. The overall rate was 13.3%. July was the month with the greatest number of heat illness reports (24.4% of total reporting) and the highest concordance rate (30%). Reports of heat illness from the UK (n=343) exceeded overseas notifications (n=221) and showed better concordance (17.1% vs 12.8%). The annual rate of reported heat illness varied widely, being greater in full-time than reservist personnel (87 vs 23 per100 000) and highest in full-time untrained personnel (223 per100 000)., Conclusions: The risk of heat illness was global, year-round and showed dynamic local variation. Failure to dual-report casualties impaired case ascertainment of heat illness across Command and Medical chains. Current preventive guidance, as applied in training and on operations, should be critically evaluated to ensure that risk of heat illness is reduced as low as possible. Clear procedures for casualty notification and surveillance are required in support of this and should incorporate communication within and between the two reporting chains., Competing Interests: None., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Heat illness is a preventable disorder in military populations. Measures that protect vulnerable individuals and contribute to effective Immediate Treatment may reduce the impact of heat illness, but depend upon adequate understanding and awareness among Commanders and their troops., Objective: To assess risk factors for heat illness in British soldiers deployed to the hot Collective Training Environment (CTE) and to explore awareness of Immediate Treatment responses., Methods: An anonymous questionnaire was distributed to British soldiers deployed in the hot CTEs of Kenya and Canada. Responses were analysed to determine the prevalence of individual (Intrinsic) and Command-practice (Extrinsic) risk factors for heat illness and the self-reported awareness of key Immediate Treatment priorities (recognition, first aid and casualty evacuation)., Results: The prevalence of Intrinsic risk factors was relatively low in comparison with Extrinsic risk factors. The majority of respondents were aware of key Immediate Treatment responses. The most frequently reported factors in each domain were increased risk by body composition scoring, inadequate time for heat acclimatisation and insufficient briefing about casualty evacuation., Conclusions: Novel data on the distribution and scale of risk factors for heat illness are presented. A collective approach to risk reduction by the accumulation of 'marginal gains' is proposed for the UK military. This should focus on limiting Intrinsic risk factors before deployment, reducing Extrinsic factors during training and promoting timely Immediate Treatment responses within the hot CTE., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

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.

Although recognized as a vulnerable population, there is no national population size estimate for sex workers in South Africa. A rapid sex worker enumeration exercise was undertaken in twelve locations across the country based on principles of participatory mapping and Wisdom of the Crowd. Sites with a range of characteristics were selected, focusing on level of urbanisation, trucking, mining and borders. At each site, sex worker focus groups mapped local hotspots. Interviews with sex workers at identified hotspots were used to estimate the numbers and genders of sex workers working in each. Estimates provided in the literature were combined with enumeration exercise results to define assumptions that could be applied to a national extrapolation. A working estimate was reached of between 131,000 and 182,000 sex worker in South Africa, or between 0.76 and 1 % of the adult female population. The success of the exercise depended on integral involvement of sex worker peer educators and strong ethical considerations.

For the military doctor, an understanding of the metabolic effects of high altitude (HA) exposure is highly relevant. This review examines the acute metabolic challenge and subsequent changes in nutritional homeostasis that occur when troops deploy rapidly to HA. Key factors that impact on metabolism include the hypoxic-hypobaric environment, physical exercise and diet. Expected metabolic changes include augmentation of basal metabolic rate (BMR), decreased availability of oxygen in peripheral metabolic tissues, reduction in VO2 max, increased glucose dependency and lactate accumulation during exercise. The metabolic demands of exercise at HA are crucial. Equivalent activity requires greater effort and more energy than it does at sea level. Soldiers working at HA show high energy expenditure and this may exceed energy intake significantly. Energy intake at HA is affected adversely by reduced availability, reduced appetite and changes in endocrine parameters. Energy imbalance and loss of body water result in weight loss, which is extremely common at HA. Loss of fat predominates over loss of fat-free mass. This state resembles starvation and the preferential primary fuel source shifts from carbohydrate towards fat, reducing performance efficiency. However, these adverse effects can be mitigated by increasing energy intake in association with a high carbohydrate ration. Commanders must ensure that individuals are motivated, educated, strongly encouraged and empowered to meet their energy needs in order to maximise mission-effectiveness.

The encapsulated sensory endings of mammalian skeletal muscles are all mechanoreceptors. At the most basic functional level they serve as length sensors (muscle spindle primary and secondary endings), tension sensors (tendon organs), and pressure or vibration sensors (lamellated corpuscles). At a higher functional level, the differing roles of individual muscles in, for example, postural adjustment and locomotion might be expected to be reflected in characteristic complements of the various end-organs, their sensory endings and afferent nerve fibres. This has previously been demonstrated with regard to the number of muscle-spindle capsules; however, information on the other types of end-organ, as well as the complements of primary and secondary endings of the spindles themselves, is sporadic and inconclusive regarding their comparative provision in different muscles. Our general conclusion that muscle-specific variability in the provision of encapsulated sensory endings does exist demonstrates the necessity for the acquisition of more data of this type if we are to understand the underlying adaptive relationships between motor control and the structure and function of skeletal muscle. The present quantitative and comparative analysis of encapsulated muscle afferents is based on teased, silver-impregnated preparations. We begin with a statistical analysis of the number and distribution of muscle-spindle afferents in hind-limb muscles of the cat, particularly tenuissimus. We show that: (i) taking account of the necessity for at least one primary ending to be present, muscles differ significantly in the mean number of additional afferents per spindle capsule; (ii) the frequency of occurrence of spindles with different sensory complements is consistent with a stochastic, rather than deterministic, developmental process; and (iii) notwithstanding the previous finding, there is a differential distribution of spindles intramuscularly such that the more complex ones tend to be located closer to the main divisions of the nerve. Next, based on a sample of tendon organs from several hind-foot muscles of the cat, we demonstrate the existence in at least a large proportion of tendon organs of a structural substrate to account for multiple spike-initiation sites and pacemaker switching, namely the distribution of sensory terminals supplied by the different first-order branches of the Ib afferent to separate, parallel, tendinous compartments of individual tendon organs. We then show that the numbers of spindles, tendon organs and paciniform corpuscles vary independently in a sample of (mainly) hind-foot muscles of the cat. Grouping muscles by anatomical region in the cat indicated the existence of a gradual proximo-distal decline in the overall average size of the afferent complement of muscle spindles from axial through hind limb to intrinsic foot muscles, but with considerable muscle-specific variability. Finally, we present some comparative data on muscle-spindle afferent complements of rat, rabbit and guinea pig, one particularly notable feature being the high incidence of multiple primary endings in the rat.

Infestation of the eye by larval fly forms (ophthalmomyiasis) is rarely seen in the Western world. We present the case of a 21 year old British soldier who developed external ophthalmomyiasis during an operational tour of southern Afghanistan. This case report and discussion illustrates the potential for ophthalmomyiasis in personnel deployed to this theatre; the possibility of infestation without an identifiable episode of exposure; the importance of proper assessment and follow-up in order to identify sight-threatening complications; and the balance between optimal patient care and the risks inherent to casualty evacuation demanded by modern day stability operations.

1. We have used the glycogen-depletion technique, combined with myofibrillar ATPase (mATPase) staining for muscle fibre type, to study the fibre-type composition of four skeleto-fusimotor (beta) units in cat peroneus tertius, namely, one beta dynamic (beta d) unit and three beta static (beta s) units. 2. Depletion of glycogen was observed in serial cross-sections of thirty-four beta-unit extrafusal muscle fibres of various types traced from origin to insertion. No fibre was depleted of glycogen throughout its length; depletion was restricted to a number of zones, usually about five. Oxidative (type I) and oxidative-glycolytic (type IIA) fibres were depleted for a significantly greater proportion of their total length than glycolytic IIB fibres. 3. The fibre-type composition of the beta d unit was determined by tracing its fibres from end to end. The muscle unit consisted of one intrafusal bag1 fibre and ninety-three extrafusal muscle fibres comprising seventy-six type I fibres, eleven IIC fibres, and six fibres that changed from IIC to I during the course of their length (IIC/I fibres). The extrafusal fibre-type composition was thus 81.7% I plus 18.3% IIC and IIC/I. 4. The three beta s units (beta s1, beta s2, beta s3) were all fast-contracting and fatigued rapidly. Identification of their extrafusal fibre types, made in 1 mm2 areas sampled from different parts of each unit, gave mixed compositions as follows: beta s1, IIB + 6.7% IIA; beta s2, IIB + 5.8% IIA; beta s3, IIB + 29.9% IIA. The intrafusal component of each unit included either one or two long chain fibres. 5. In a discussion of the results, the fact that the continuous stimulation of extrafusal muscle fibres does not deplete them of glycogen throughout their length is examined in relation to the work of others who have assumed that it did. With regard to the finding of mixed extrafusal fibre types in the beta units, a distinction is drawn between minimal (around 5%) and moderate mixing. It is suggested that minimal mixing may occur in any motor unit as the outcome of endplate degeneration with foreign replacement, but that moderate mixing indicates an on-going process of conversion from one fibre type to another which in the adult may prove to occur only among beta units.

Results are presented of examining the postcrush sensory reinnervation of cat peroneus brevis muscle spindles previously investigated physiologically by Hyde and Scott. It is shown that primary and secondary endings were successfully restored in their final form in the early stages of recovery. The primary endings were shorter than normal and had fewer transverse bands; 12% were judged to be hyperinnervated. Some secondary endings showed signs of growth through the primary region apparently designed to establish secondary terminals in the opposite pole. This is compared with the collateral regeneration of intact motor axons in partially denervated muscle. It is concluded that the defects observed in the regenerated sensory endings had no effect on their functional recovery.

After nerve injury muscles remain denervated until axons return to begin reinnervation and recovery. The delay between injury and recovery in human limb nerves averages 13 weeks after crush, and 16 weeks after transection and suture. In order to assess the effects of such long denervation periods on the recovery of cat muscle receptors, we crushed the common peroneal nerve and denervated peroneus brevis for 10 to 134 days; 39 days were allowed for reinnervation in each experiment. After 50 days denervation, the mean number of terminal bands in the regenerated spindle primary endings was 10.3 compared with a normal mean of 29.0. After 134 days, the mean was 0.6 and spindles were severely atrophied. Despite this most spindle afferent fibers continued to respond normally to ramp-and-hold stretch, abnormal responses being recognized as those that failed to maintain firing during the held phase of the ramp. After 50 days, 21% of spindle afferent fibers responded abnormally and about this proportion did so after all the longer denervation periods. Maximum afferent firing rates were all significantly lower than normal, and many afferent fibers fatigued more rapidly. Tendon organs were atrophied after 113 and 134 days and received fewer terminals, but their afferents fired apparently normally during muscle twitch. These results imply that the consequences of long-term denervation on human muscle spindles would be unlikely to affect the overall pattern of response to stretch of any Ia or II afferent fibers reinnervating them, though the quality of their response might be impaired.

Direct identification of the endings of skeletofusimotor (beta) axons has been made in muscle spindles deprived for their gamma innervation by degeneration. Hindlimb muscles were prepared in which 1--5 fast-conducting motor axons were left intact while the rest of the motor supply was cut and allowed to degenerate for a period of 7 days. In 3 experiments a single beta axons survived supplying tenuissimus, and in 2 experiments beta axons were among 4 or 5 surviving axons that supplied superficial lumbrical and abductor digiti quinti medius muscles. Motor endings identified as p1 plates were found in teased, silver preparations of all experimental muscles, a total of 35 such plates being located in 15 spindles. The plates were all supplied to bag1 fibres. The experiments show that if a spindle innervated by a beta axon is deprived of its gamma supply by degeneration the motor endings that remain intact are p1 plates.

1. Intrafusal muscle fibres of cat tenuissimus spindles have been injected with the fluorescent dye Procion Yellow and identified histologically after recording their changes in membrane potential during 1/sec stimulation of single static or dynamic gamma axons. 2. Thirteen intrafusal muscle fibres innervated by static gamma axons were identified as eight bag2 and five chain fibres. The fact that none proved to be a bag1 fibre is not regarded as significant, for reasons given in the Discussion. 3. In one spindle Procion Yellow was injected into two intrafusal muscle fibres activated by the same static gamma axon; they were identified as a bag2 and a chain fibre. 4. Nine intrafusal muscle fibres innervated by dynamic gamma axons were identified as seven bag1 fibres, one bag2 fibre, and one long chain fibre. 5. In one spindle two bag fibres were injected, one activated by a dynamic gamma axon, the other by a static gamma axon; the former proved to be a bag1 fibre, the latter a bag2 fibre. 6. Stimulation of static gamma axons elicited junctional potentials in seven bag2 fibres and one damaged chain fibre, and action potentials in one bag2 and four chain fibres. In the whole sample of impaled intrafusal muscle fibres (identified and unidentified) activated by static axons, junctional potentials were recorded from twenty-three (62.2%), and action potentials from fourteen (37.8%). Stimulation of dynamic gamma axons always elicited junctional potentials. 7. In a number of instances it was possible to examine the ultrastructure of motor endings belonging to the stimulated gamma axon. The myoneural junctions of trail endings supplied by static gamma axons to bag2 and chain fibres were both smooth and folded; the deepest and most regular folding occurred on chain fibres. The terminals of p2 plates supplied to bag1 fibres by dynamic gamma axons had smooth myoneural junctions.

A thin layer chromatographic system is presented for the separation of histamine (H), 1,4-methylhistamine (M), acid metabolites comprising imidazole and methylimidazole acetic acids (A) and N-acetylhistamine (N). The system was applied to separation of the histamine metabolites formed following incubation of rabbit and guinea-pig thoracic aorta segments with labelled histamine. The effects of various agents known to affect histamine uptake, storage and metabolism in vascular tissue were studied on the disposition of histamine metabolites.

Patterns of innervation were examined in tandem muscle spindles teased from silver-stained muscles of the cat neck. Each tandem spindle was composed of two or more encapsulated receptors linked in series by a shared bag2 fiber. In most tandem spindles, two different types of encapsulation were identified according to differences in their intrafusal fiber content. One type, the b1b2c unit, contained typical bag1, bag2, and chain fibers and was structurally similar to single spindles described in other cat muscles. Each b1b2c unit contained a single primary sensory ending and 1-6 secondary endings. Fusimotor innervation was supplied by many axons. Some fusimotor axons ended in trail ramifications on bag2 and chain fibers, others ended in plates on the bag1 or long chain fiber. The other type of tandem encapsulation, the b2c unit, had only bag2 and chain fibers in its intrafusal fiber bundle. The b2c unit was usually supplied by only one sensory axon that ended on the nucleated part of the intrafusal fiber bundle. This single ending had a more variable terminal morphology than the primary ending in b1b2c units. A few b2c units (3/49) were also supplied by a secondary ending. The fusimotor innervation of the b2c unit was relatively simple. A single pole of the b2c unit was usually supplied by only one to three axons, all ending in trail ramifications. No plate endings were found in b2c units. These morphological specializations suggest that b1b2c and b2c units in tandem spindles differ in both their transductive and fusimotor mechanisms. Thus, the tandem spindle is a specialized structure that may provide additional proprioceptive information beyond that available from single muscle spindles.

The presynaptic features of 234 motor endings supplied to cat hindlimb muscle spindles have been studied in teased, silver preparations, and the postsynaptic features of a further 27 endings have been studied in serial, 1 micron thick, transverse sections. In the presynaptic study motor endings received by the three types of intrafusal muscle fibre were compared with the endings supplied to spindles by the various functional categories of motor axon. Three forms of motor ending were found that had significantly different presynaptic features. These forms correspond closely to those previously identified in the literature as p1 (beta), p2 (dynamic gamma) and trail (static gamma). The results of the postsynaptic study showed that the degree of indentation of the intrafusal muscle fibres by motor axon terminals increases with greater distance from the primary ending, irrespective of muscle-fibre type. We conclude that the postsynaptic form of intrafusal motor endings is determined by distance from primary ending and muscle-fibre type. It is not determined by type of motor axon, and cannot be correlated with presynaptic form so as to produce a unified classification of intrafusal motor endings.

A direct correlation of the histochemical and ultrastructural properties of intrafusal muscle fibres has been achieved by cutting frozen serial sections for histochemical applications (15 micron thick sections) and for electron microscopy (60 micron thick sections) in a repeating sequence. Three types of intrafusal fibre were recognized, including two types of nuclear-bag fibre, designated bag1 and bag2. In addition to histochemical and ultrastructural differences, the three types of fibre differed in length and diameter. Regional variations of histochemical and ultrastructural properties were found. The results are compared with previous attempts to correlate histochemical and ultrastructural properties of intrafusal muscle fibres based on indirect methods.

1. Eleven cat tenuissimus spindles have been analysed mainly by cutting serial, transverse, 1 micrometer thick sections following direct observation of the effects of dynamic motor (gamma or beta) stimulation. 2. Histological results from these spindles were also used to interpret the effects of static fusimotor stimulation of other spindles. 3. Dynamic motor stimulation usually produced contractions seen as convergent movements of sarcomeres in single bag fibres, identified as bag1 fibres for reasons given in the text. 4. In one spindle a single dynamic axon produced a translational movement in one pole of a bag1 fibre and a convergent movement in each pole of a bag2 fibre, together with movements in other unidentified (presumably chain) fibres. Subsequent analysis showed that besides innervating both bag fibres the axon also supplied two chain fibres. 5. Contrary to expectation, motor endings on the bag1 fibres seldom occurred at the sites of convergent movement. Only two cases of coincidence occurred among sixteen foci and twenty-one motor endings; otherwise focus and nearest ending were separated by distances of 0.85--2.5 mm. 6. Most of the convergent movements of sarcomeres observed in bag1 fibres occurred in a region of the pole that is ultrastructurally distinct from the region where most of the motor endings were located. The possible relevance of this to the production of contractions in the bag1 fibre is discussed. 7. Convergent movement foci in bag2 fibres produced by the stimulation of static axons occurred largely within the same regions of the pole as the motor endings were located, though, whereas foci were observed in both intra- and extracapsular regions, most of the endings were intracapsular.