Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol-1; aged 64.2 ± 9.4 years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [ F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ] = 0.155; ∼2500 m simulated altitude) or normoxic conditions ( F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$  = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor-1α]; [interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon-like peptide-1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect-size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. KEY POINTS: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single-blind, randomised sham-controlled, cross-over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

Habituation of the cold shock response: A systematic review and meta-analysis.

Cold water immersion (CWI) evokes the life-threatening reflex cold shock response (CSR), inducing hyperventilation, increasing cardiac arrhythmias, and increasing drowning risk by impairing safety behaviour. Repeated CWI induces CSR habituation (i.e., diminishing response with same stimulus magnitude) after ∼4 immersions, with variation between studies. We quantified the magnitude and coefficient of variation (CoV) in the CSR in a systematic review and meta-analysis with search terms entered to Medline, SportDiscus, PsychINFO, Pubmed, and Cochrane Central Register. Random effects meta-analyses, including effect sizes (Cohen's d) from 17 eligible groups (k), were conducted for heart rate (HR, n = 145, k = 17), respiratory frequency (fR, n = 73, k = 12), minute ventilation (Ve, n = 106, k = 10) and tidal volume (Vt, n = 46, k=6). All CSR variables habituated (p < 0.001) with large or moderate pooled effect sizes: ΔHR -14 (10) bt. min-1 (d: -1.19); ΔfR -8 (7) br. min-1 (d: -0.78); ΔVe, -21.3 (9.8) L. min-1 (d: -1.64); ΔVt -0.4 (0.3) L -1. Variation was greatest in Ve (control vs comparator immersion: 32.5&24.7%) compared to Vt (11.8&12.1%). Repeated CWI induces CSR habituation potentially reducing drowning risk. We consider the neurophysiological and behavioural consequences.

The peripheral vascular responses in non-freezing cold injury and matched controls.

NEW FINDINGS: What is the central question of this study? Does non-freezing cold injury (NFCI) alter normal peripheral vascular function? What is the main finding and its importance? Individuals with NFCI were more cold sensitive (rewarmed more slowly and felt more discomfort) than controls. Vascular tests indicated that extremity endothelial function was preserved with NFCI and that sympathetic vasoconstrictor response might be reduced. The pathophysiology underpinning the cold sensitivity associated with NFCI thus remains to be identified. ABSTRACT: The impact of non-freezing cold injury (NFCI) on peripheral vascular function was investigated. Individuals with NFCI (NFCI group) and closely matched controls with either similar (COLD group) or limited (CON group) previous cold exposure were compared (n = 16). Peripheral cutaneous vascular responses to deep inspiration (DI), occlusion (PORH), local cutaneous heating (LH) and iontophoresis of acetylcholine and sodium nitroprusside were investigated. The responses to a cold sensitivity test (CST) involving immersion of a foot in 15°C water for 2 min followed by spontaneous rewarming, and a foot cooling protocol (footplate cooled from 34°C to 15°C), were also examined. The vasoconstrictor response to DI was lower in NFCI compared to CON (toe: 73 (28)% vs. 91 (17)%; P = 0.003). The responses to PORH, LH and iontophoresis were not reduced compared to either COLD or CON. During the CST, toe skin temperature rewarmed more slowly in NFCI than COLD or CON (10 min: 27.4 (2.3)°C vs. 30.7 (3.7)°C and 31.7 (3.9)°C, P < 0.05, respectively); however, no differences were observed during the footplate cooling. NFCI were more cold-intolerant (P < 0.0001) and reported colder and more uncomfortable feet during the CST and footplate cooling than COLD and CON (P < 0.05). NFCI showed a decreased sensitivity to sympathetic vasoconstrictor activation than CON and greater cold sensitivity (CST) compared to COLD and CON. None of the other vascular function tests indicated endothelial dysfunction. However, NFCI perceived their extremities to be colder and more uncomfortable/painful than the controls.

Plasma biomarkers of endothelial function, inflammation and oxidative stress in individuals with non-freezing cold injury.

NEW FINDINGS: What is the central question of this study? Are biomarkers of endothelial function, oxidative stress and inflammation altered by non-freezing cold injury (NFCI)? What is the main finding and its importance? Baseline plasma [interleukin-10] and [syndecan-1] were elevated in individuals with NFCI and cold-exposed control participants. Increased [endothelin-1] following thermal challenges might explain, in part, the increased pain/discomfort experienced with NFCI. Mild to moderate chronic NFCI does not appear to be associated with either oxidative stress or a pro-inflammatory state. Baseline [interleukin-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosis of NFCI. ABSTRACT: Plasma biomarkers of inflammation, oxidative stress, endothelial function and damage were examined in 16 individuals with chronic NFCI (NFCI) and matched control participants with (COLD, n = 17) or without (CON, n = 14) previous cold exposure. Venous blood samples were collected at baseline to assess plasma biomarkers of endothelial function (nitrate, nitrite and endothelin-1), inflammation [interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor alpha and E-selectin], oxidative stress [protein carbonyl, 4-hydroxy-2-nonenal (4-HNE), superoxide dismutase and nitrotyrosine) and endothelial damage [von Willebrand factor, syndecan-1 and tissue type plasminogen activator (TTPA)]. Immediately after whole-body heating and separately, foot cooling, blood samples were taken for measurement of plasma [nitrate], [nitrite], [endothelin-1], [IL-6], [4-HNE] and [TTPA]. At baseline, [IL-10] and [syndecan-1] were increased in NFCI (P < 0.001 and P = 0.015, respectively) and COLD (P = 0.033 and P = 0.030, respectively) compared with CON participants. The [4-HNE] was elevated in CON compared with both NFCI (P = 0.002) and COLD (P < 0.001). [Endothelin-1] was elevated in NFCI compared with COLD (P < 0.001) post-heating. The [4-HNE] was lower in NFCI compared with CON post-heating (P = 0.032) and lower than both COLD (P = 0.02) and CON (P = 0.015) post-cooling. No between-group differences were seen for the other biomarkers. Mild to moderate chronic NFCI does not appear to be associated with a pro-inflammatory state or oxidative stress. Baseline [IL-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosing NFCI, but it is likely that a combination of tests will be required.

The effects of manipulating the visual environment on thermal perception: A structured narrative review.

When exposed to ambient temperatures that cause thermal discomfort, a human's behavioral responses are more effective than autonomic ones at compensating for thermal imbalance. These behavioral thermal responses are typically directed by an individual's perception of the thermal environment. Perception of the environment is a holistic amalgamation of human senses, and in some circumstances, humans prioritize visual information. Existing research has considered this in the specific case of thermal perception, and this review investigates the state of the literature examining this effect. We identify the frameworks, research rationales, and potential mechanisms that underpin the evidence base in this area. Our review identified 31 experiments, comprising 1392 participants that met the inclusion criteria. Methodological heterogeneity was observed in the assessment of thermal perception, and a variety of methods were employed to manipulate the visual environment. However, the majority of the included experiments (80%) reported a difference in thermal perception after the visual environment was manipulated. There was limited research exploring any effects on physiological variables (e.g. skin and core temperature). This review has wide-ranging implications for the broad discipline of (thermo)physiology, psychology, psychophysiology, neuroscience, ergonomics, and behavior.

Myths and methodologies: Degrees of freedom - limitations of infrared thermographic screening for Covid-19 and other infections.

Around the planet, in many different scenarios, skin temperature is being used as a surrogate measure of deep body (core) temperature in the assessment of whether an individual is infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (Covid-19), as indicated by the presence of fever. The key question is whether this is a valid methodology. If it is not, we run the risk of falsely excluding individuals from places they may want, or need, to go. We also run the risk of falsely allowing people into places where they can spread the undetected infection they have. In this review, we explore these and associated questions. We establish the limited utility of the current methodology for the mass screening of individuals for Covid-19 related fever using infrared thermography. We propose the development of an alternative method that may prove to be more sensitive.

Predicting Deep Body Temperature (Tb) from Forehead Skin Temperature: Tb or Not Tb?

There is a need to rapidly screen individuals for heat strain and fever using skin temperature (Tsk) as an index of deep body temperature (Tb). This study's aim was to assess whether Tsk could serve as an accurate and valid index of Tb during a simulated heatwave. Seven participants maintained a continuous schedule over 9-days, in 3-day parts; pre-/post-HW (25.4 °C), simulated-HW (35.4 °C). Contact thermistors measured Tsk (Tforehead, Tfinger); radio pills measured gastrointestinal temperature (Tgi). Proximal-distal temperature gradients (ΔTforehead-finger) were also measured. Measurements were grouped into ambient conditions: 22, 25, and 35 °C. Tgi and Tforehead only displayed a significant relationship in 22 °C (r: 0.591; p < 0.001) and 25 °C (r: 0.408; p < 0.001) conditions. A linear regression of all conditions identified Tforehead and ΔTforehead-finger as significant predictors of Tgi (r2: 0.588; F: 125.771; p < 0.001), producing a root mean square error of 0.26 °C. Additional residual analysis identified Tforehead to be responsible for a plateau in Tgi prediction above 37 °C. Contact Tforehead was shown to be a statistically suitable indicator of Tgi in non-HW conditions; however, an error of ~1 °C makes this physiologically redundant. The measurement of multiple sites may improve Tb prediction, though it is still physiologically unsuitable, especially at higher ambient temperatures.

Previous recreational cold exposure does not alter endothelial function or sensory thermal thresholds in the hands or feet.

NEW FINDINGS: What is the central question of this study? Does recreational cold exposure result in cold sensitivity and is this associated with endothelial dysfunction and impaired sensory thermal thresholds? What is the main finding and its importance? Previous cold exposure was correlated with cold sensitivity of the foot, which might indicate the development of a subclinical non-freezing cold injury. Endothelial function and thermal detection were not impaired in cold-sensitive individuals; therefore, further research is required to understand the pathophysiology of subclinical and clinical forms of non-freezing cold injury. ABSTRACT: In this study, we investigated whether cold-sensitive (CS) individuals, who rewarm more slowly after a mild cold challenge, have impaired endothelial function and sensory thermal thresholds (STTs) and whether this is related to reported cold exposure. Twenty-seven participants with varying previous cold exposure undertook three tests: an STT test, i.e. determination of warm and cold STTs of the fingers and dorsal foot; an endothelial function test, i.e. measurement of cutaneous vascular conductance (CVC) during iontophoresis of ACh on the forearm, finger and foot; and a CS test, involving immersion of a foot for 2 min in water at 15°C followed by 10 min of rewarming in air at 30°C. Toe skin temperature (Tsk ) measured during the CS test was used to form a CS group (<32°C before and 5 min after immersion) and an otherwise closely matched control group [Tsk >32°C; n = 9 (four women) for both groups]. A moderate relationship was found between cold exposure ranking and Tsk rewarming (r = 0.408, P = 0.035, n = 27) but not STT or endothelial function. The Tsk and blood flow were lower in CS compared with control subjects before and after foot immersion [Tsk , mean (SD): 30.3 (0.9) versus 34.8 (0.8) and 27.9 (0.8) versus 34.3 (0.8)°C, P < 0.001; and CVC: 1.08 (0.79) versus 3.82 (1.21) and 0.79 (0.52) versus 3.45 (1.07) flux mmHg-1 , n = 9, P < 0.001, respectively]. However, no physiologically significant differences were observed between groups for endothelial function or STT. A moderate correlation between previous cold exposure and toe Tsk rewarming after foot immersion was observed; however, CS was not associated with impaired endothelial function or reduced thermal detection.

The eye in extreme environments.

NEW FINDINGS: What is the topic of this review? This review describes the effect of extreme environments on the visual system. What advances does it highlight? The review highlights the way in which environmental stressors affect the eye and vision, both directly and indirectly. ABSTRACT: Much is known about the physiology and anatomy of the eye. Much less is known about the impact of different environments on the eye, and yet it is the pathophysiology that results from this interaction that is often the precursor to disaster. The present review focuses on the effect of different extreme environments on the visual system; in particular, the way in which such environments affect the sensory mechanism of that system.

A network physiology approach to oxygen saturation variability during normobaric hypoxia.

NEW FINDINGS: What is the central question of this study? What is the physiological interpretation of SpO2 fluctuations observed during normobaric hypoxia in healthy individuals? What is the main finding and its importance? There is a significant flow of information between SpO2 and other cardio-respiratory time series during graded hypoxia. Analysis of the pattern of SpO2 variations has potential for non-invasive assessment of the engagement of respiratory control system in health and disease. ABSTRACT: Peripheral capillary oxygen saturation ( SpO2 ) exhibits a complex pattern of fluctuations during hypoxia. The physiological interpretation of SpO2 variability is not well understood. In this study, we tested the hypothesis that SpO2 fluctuation carries information about integrated cardio-respiratory control in healthy individuals using a network physiology approach. We explored the use of transfer entropy in order to compute the flow of information between cardio-respiratory signals during hypoxia. Twelve healthy males (mean (SD) age 22 (4) years) were exposed to four simulated environments (fraction of inspired oxygen ( FIO2 ): 0.12, 0.145, 0.17, and 0.2093) for 45 min, in a single blind randomized controlled design. The flow of information between different physiological parameters ( SpO2 , respiratory frequency, tidal volume, minute ventilation, heart rate, end-tidal pressure of O2 and CO2 ) were analysed using transfer entropy. Normobaric hypoxia was associated with a significant increase in entropy of the SpO2 time series. The transfer entropy analysis showed that, particularly at FIO2 0.145 and 0.12, the flow of information between SpO2 and other physiological variables exhibits a bidirectional relationship. While reciprocal interactions were observed between different cardio-respiratory parameters during hypoxia, SpO2 remained the main hub of this network. SpO2 fluctuations during graded hypoxia exposure carry information about cardio-respiratory control. Therefore, SpO2 entropy analysis has the potential for non-invasive assessment of the functional connectivity of respiratory control system in various healthcare settings.

The water incident database (WAID) 2012 to 2019: a systematic evaluation of the documenting of UK drownings.

BACKGROUND: Death by drowning is a leading cause of accidental death in the United Kingdom (UK) and worldwide. The World Health Organization (WHO) states that effective documentation of drowning is required to describe drowning frequency and to underpin effective drowning prevention intervention, thus improving the quality of data describing drowning frequency represents a key initiative. The water incident database (WAID) has been used to document UK fatal and non-fatal water-based incidents since 2009. WAID has not undergone a systematic evaluation of its data or data collection procedures to establish if the database meets the WHO requirements. The present study investigated the characteristics of UK fatal drowning incidents and audited current WAID data capture procedures. METHODS: Data for the fatal drowning cases recorded between 2012 and 2019 were reviewed. Descriptive data were generated 1) to describe fatal drownings in the UK's WAID in this period; 2) a sub-set of drownings were audited i) for completeness of data entry and, based on source documents, ii) for quality of data entry; 3) these processes were used to make recommendations for onward revisions to WAID. RESULTS: A total of 5051 fatalities were recorded between 2012 and 2019. Drowning was most frequent amongst males aged 35 to 60 years (n = 1346), whilst suspected accidents and suicides accounted for 44 and 35% of fatalities. Suicide by drowning was at a peak in the most recent year of data analysed (i.e., 2019; 279 cases) highlighting an urgent need for targeted intervention. Audit part 2i) indicated that 16% of all fields were incomplete, thus indicating potential redundancy, duplication, or the need for onward review. Audit part 2ii) indicated high levels of agreement (80 ± 12%) between audited cases and the 'true' WAID entries. CONCLUSIONS: This study confirms WAID as a rigorous, transparent and effective means of documenting UK drownings thereby meeting WHO requirements for data quality; yet future improvements are recommended. Such findings allow researchers and policy makers to use WAID to further investigate UK drowning with a view to improving public safety measures and drowning prevention interventions. Observations alongside several expert recommendations have informed a revised version of WAID.

ACSM Expert Consensus Statement: Injury Prevention and Exercise Performance during Cold-Weather Exercise.

ABSTRACT: Cold injury can result from exercising at low temperatures and can impair exercise performance or cause lifelong debility or death. This consensus statement provides up-to-date information on the pathogenesis, nature, impacts, prevention, and treatment of the most common cold injuries.

The thermal demands of flood rescue and impacts on task performance.

The aim of this study was to determine the thermal demand of simulated Flood Rescue tasks and impacts on performance. Ten participants undertook two simulations: 'Cold' (4 °C) -participants stood in knee height moving water (4.8 km·h-1), with simulated wind and rain for 60 min. 'Warm' (20 °C) - participants performed 6x7 min walking in knee height moving water (3.2 km·h-1), pulling 10 kg. Grip strength, manual dexterity, and jump height were measured pre and post. The cold resulted in cooling of the great toe and finger (9.98 [0.84]°C and 10.38 [8.21-12.1] °C, respectively). Jump height, manual dexterity and grip strength fell by 20%, 22% and ∼13%, respectively. In the 'Warm': heart rates were 157 (19) b·min-1, oxygen consumption 30.62 (7.83) mL.kg-1·min-1, and sweat loss 1.06 (0.31) L. There were no differences in the physical tests. Flood Rescue represents significant, but different, challenges. Remaining static in the cold resulted in peripheral neuromuscular cooling, whilst exercising in the warm resulted in a significant thermal challenge. Practitioner Summary: Little is known about the physical requirements, thermal profiles and optimum personal protective equipment for flood rescue. Flood rescue represents significant challenges. In the cold, emergency responders may be incapacitated by peripheral cooling. In the heat, they may be incapacitated by heat-related exhaustion. Consideration should be given to these risks.

Cognitive performance is associated with cerebral oxygenation and peripheral oxygen saturation, but not plasma catecholamines, during graded normobaric hypoxia.

NEW FINDINGS: What is the central question of this study? What are the mechanisms responsible for the decline in cognitive performance following exposure to acute normobaric hypoxia? What are the main findings and their importance? We found that (1) performance of a complex central executive task (n-back) was reduced at FIO2 0.12; (2) there was a strong correlation between performance of the n-back task and reductions in SpO2 and cerebral oxygenation; and (3) plasma adrenaline, noradrenaline, cortisol and copeptin were not correlated with cognitive performance. ABSTRACT: It is well established that hypoxia impairs cognitive function; however, the physiological mechanisms responsible for these effects have received relatively little attention. This study examined the effects of graded reductions in fraction of inspired oxygen ( FIO2 ) on oxygen saturation ( SpO2 ), cerebral oxygenation, cardiorespiratory variables, activity of the sympathoadrenal system (adrenaline, noradrenaline) and hypothalamic-pituitary-adrenal axis (cortisol, copeptin), and cognitive performance. Twelve healthy males [mean (SD), age: 22 (4) years, height: 178 (5) cm, mass: 75 (9) kg, FEV1 /FVC ratio: 85 (5)%] completed a four-task battery of cognitive tests to examine inhibition, selective attention (Eriksen flanker), executive function (n-back) and simple and choice reaction time (Deary-Liewald). Tests were completed before and following 60 min of exposure to FIO2 0.2093, 0.17, 0.145 and 0.12. Following 60 min of exposure, response accuracy in the n-back task was significantly reduced in FIO2 0.12 compared to baseline [82 (9) vs. 93 (5)%; P < 0.001] and compared to all other conditions at the same time point [ FIO2 0.2093: 92 (3)%; FIO2 0.17: 91 (6)%; FIO2 0.145: 85 (10)%; FIO2 12: 82 (9)%; all P < 0.05]. The performance of the other tasks was maintained. Δaccuracy and Δreaction time of the n-back task was correlated with both Δ SpO2 [r(9) = 0.66, P < 0.001 and r(9) = -0.36, P = 0.037, respectively] and Δcerebral oxygenation [r(7) = 0.55, P < 0.001 and r(7) = -0.38, P = 0.045, respectively]. Plasma adrenaline, noradrenaline, cortisol and copeptin were not significantly elevated in any condition or correlated with any of the tests of cognitive performance. These findings suggest that reductions in peripheral oxygen saturation and cerebral oxygenation, and not increased activity of the sympathoadrenal system and hypothalamic-pituitary-adrenal axis, as previously speculated, are responsible for a decrease in cognitive performance during normobaric hypoxia.

Development of a physical employment standard for a branch of the UK military.

A Physical Employment Standard (PES) was developed for the British Royal Air Force Regiment (RAF Regt). Twenty-nine RAF Regt personnel completed eight critical tasks wearing Combat Equipment Fighting Order (31.5 kg) while being monitored for physical and perceptual effort. A PES was developed using task simulations, measured on 61 incumbents. The resultant PES consists of: 1) a battlefield test involving task simulations: single lift and point-of-entry (psss/fail); timed elements (react to effective enemy fire and crawl) set at 95th performance percentile; casualty evacuation (CASEVAC) casualty drag and CASEVAC simulated stretcher carry completed without stopping. 2) a Multi Stage Fitness Test level 9.10 to assess aerobic fitness to complete a tactical advance to battle. The task-based PES should ensure RAF Regt personnel have a baseline level of fitness to perform and withstand the physical demands of critical tasks to at least a minimum acceptable standard. Practitioner summary: A Physical Employment Standard (PES) was developed for the British RAF Regiment by measuring the physiological demands of critical tasks on a representative cohort of incumbent personnel. A task-based PES should ensure that only those candidates, irrespective of gender, race or disability, with the necessary physical attributes to succeed in training and beyond, are selected.

Wearing body armour and backpack loads increase the likelihood of expiratory flow limitation and respiratory muscle fatigue during marching.

The effect of load carriage on pulmonary function was investigated during a treadmill march of increasing intensity. 24 male infantry soldiers marched on six occasions wearing either: no load, 15 kg, 30 kg, 40 kg or 50 kg. Each loaded configuration included body armour which was worn as battle-fit or loose-fit (40 kg only). FVC and FEV1 were reduced by 6 to 15% with load. Maximal mouth pressures were reduced post load carriage by up to 11% (inspiratory) and 17% (expiratory). Increased ventilatory demands associated with carrying increased mass were met by increases in breathing frequency (from 3 to 26 breaths·min-1) with minimal changes to tidal volume. 72% of participants experienced expiratory flow limitation whilst wearing the heaviest load. Loosening the armour had minimal effects on pulmonary function. It was concluded that as mass and exercise intensity are increased, the degree of expiratory flow limitation also increases. Practitioner Summary: This study investigated the effect of soldier load carriage on pulmonary function, to inform the trade-off between protection and burden. Load carriage caused an inefficient breathing pattern, respiratory muscle fatigue and expiratory flow limitation during marching. These effects were exacerbated by increases in mass carried and march intensity.

Autonomic conflict exacerbates long QT associated ventricular arrhythmias.

This study tested the hypothesis that concomitant sympathetic and parasympathetic stimulation ("autonomic conflict") may act as a trigger for arrhythmias in long QT syndrome (LQTS). Studies were performed in isolated innervated rabbit hearts treated with clofilium (100 nmol/L); a potassium channel blocker. The influence of vagus nerve stimulation (VNS) on spontaneous ventricular arrhythmias was assessed in the absence/presence of sustained noradrenaline perfusion (100 nmol/L) and with sudden adrenergic stress (injections of noradrenaline into the perfusion line). Hearts were instrumented for a pseudo-electrocardiogram and monophasic action potential recordings. VNS, which slows heart rate, was associated with a stimulation frequency-dependent incidence of spontaneous early after-depolarisations (EADs) and ventricular tachycardia (VT), best predicted by the duration of the electrocardiographic T-wave and by triangulation of the ventricular action potential. In the presence of sustained (steady-state) noradrenaline perfusion, the incidence of EADs and VT with VNS was decreased from 73/55% to 45/27%, respectively. However, sudden adrenergic stress, imposed during periods of sustained VNS, was associated with a transient increase in the incidence of severity of observed arrhythmias, as indicated by an increase in the average arrhythmias score (1.6 ±â€¯0.4 vs. 2.1 ±â€¯0.7, p = .01). Analysis of electrophysiological parameters suggests that sudden adrenergic stress is associated with a transient prolongation, and increased triangulation, of the ventricular action potential, which may predispose to triggered activity. This study demonstrates that autonomic conflict is a pro-arrhythmic stimulus in LQTS. However, combined adrenergic and parasympathetic stimulation has a complex relationship with arrhythmogenicity, with differences in the effects of steady-state adrenergic activation vs. sudden adrenergic stress.

Effects of acute or chronic heat exposure, exercise and dehydration on plasma cortisol, IL-6 and CRP levels in trained males.

This study examined the acute and chronic effects of euhydrated and hypohydrated heat exposure, on biomarkers of stress and inflammation. Eight trained males [mean (SD) age: 21 (3) y; mass: 77.30 (4.88) kg; V̇O2max: 56.9 (7.2) mL kg-1 min-1] undertook two heat acclimation programmes (balanced cross-over design), once drinking to maintain euhydration and once with restricted fluid-intake (permissive dehydration). Days 1, 6, and 11 were 60 min euhydrated exercise-heat stress tests (40 °C; 50% RH, 35% peak power output), days 2-5 and 7-10 were 90 min, isothermal-strain (target rectal temperature: 38.5 °C) exercise-heat sessions. Plasma was obtained pre- and post- exercise on day 1, 2, and 11 and analysed for cortisol, interleukin-6 (IL-6), and C-reactive protein (CRP). Cortisol and CRP were also assessed on day 6. IL-6 was elevated following the initial (acute) 90 min isothermal heat strain exercise-heat exposure (day 2) with permissive dehydration ((pre exercise: 1.0 pg mL-1 [0.9], post-exercise: 1.8 pg mL-1 [1.0], P = .032) and when euhydrated (pre-exercise: 1.0 pg mL-1 [1.4], post-exercise: 1.6 pg mL-1 [2.1], P = .048). Plasma cortisol levels were also elevated but only during permissive dehydration (P = .032). Body mass loss was strongly correlated with Δcortisol (r = -0.688, P = .003). Although there was a trend for post-exercise cortisol to be decreased following both heat acclimation programmes (chronic effects), there were no within or between intervention differences in IL-6 or CRP. In conclusion, acute exercise in the heat increased IL-6 and cortisol only when fluid-intake is restricted. There were no chronic effects of either intervention on biomarkers of inflammation as evidenced by IL-6 and CRP returning to basal level at the end of heat acclimation.

Inter-individual variation in the adaptive response to heat acclimation.

AIM: To investigate inter-individual variance in adaptive responses to heat acclimation (HA). METHODS: 17 males (VO2max=58.8(8.4) mL·kg-1·min-1) undertook 10-days (exercise + heat-stress [40 °C, 50%RH]) HA. Adaptation was assessed by heat stress tests (HST; 60-minutes cycling, 35% peak power output) pre- and post-HA. RESULTS: Inter-individual variability was evident in adaptive responses e.g. mean(range) reduction in end-exercise Tre= -0.70(-0.20 to -1.32)°C, but, in the main, the variance in adaptation was unrelated across indices (thermal, sudomotor, cardiovascular, haematological), indicating independence between adaptation indices. Variance in adaptive responses was not correlated with aerobic capacity, history of previous HA, or the accrued thermal-dose. Some responses to the initial HST were related to the subsequent adaptations e.g. ∆T̅sk during the initial HST and the reduction in the within HST ΔTre after HA (r = -0.676), but responses to the initial HST may also have been influenced by HST design e.g. ΔTre correlated with metabolic heat production (r = 0.609). Metabolic heat production also correlated with the reduction in the within HST ΔTre after HA (r = -0.514). SUMMARY: HA indices are mainly independent; 'low', or 'high', responders on one index do not necessarily demonstrate similar response across other indices. Variance in HA responses was not related to aerobic capacity, previous HA, or thermal-dose. Thermo-physiological responses to a HST might identify individuals who will benefit from HA. However, some initial responses are influenced by HST design, which may also affect the scope for demonstrating adaption. CONCLUSION: Variance in the HA response remains largely unaccounted for and future studies should identify factors contributing to this variance.

Cutaneous Vascular Responses of the Hands and Feet to Cooling, Rewarming, and Hypoxia in Humans.

INTRODUCTION: This study investigated skin vasomotor responses in the fingers and toes during cooling and rewarming with and without normobaric hypoxia. METHODS: Fourteen volunteers (8 males and 6 females) were exposed to gradual air cooling (mean±SD: -0.4±0.1oC·min-1) followed by rewarming (+0.5±0.1oC·min-1) while breathing normoxic air (FIO2 0.21 at 761±3 mm Hg) or hypoxic gas (FIO2 0.12, at 761±3 mm Hg, equivalent to ~5000 m above sea level). Throughout the gradual cooling and rewarming phases, rectal temperature was measured, and skin temperatures and laser Doppler skin blood flow were measured on the thumb, little finger, and great and little toe pads. RESULTS: During gradual cooling, skin temperature but not deep body temperature decreased. No differences in cutaneous vascular conductance were found for the toes or thumb (P=0.169 great toe; P=0.289 little toe; P=0.422 thumb). Cutaneous vascular conductance was reduced in the little finger to a greater extent at the same mean skin temperatures (34.5-33.5oC) in the hypoxic compared with normoxic conditions (P=0.047). The onset of vasoconstriction and release of vasoconstriction in the thumb and little finger occurred at higher mean skin temperatures in hypoxia compared with normoxia (P<0.05). The onset of vasoconstriction and release of vasoconstriction in the toes occurred at similar skin temperatures (P=0.181 and P=0.132, respectively). CONCLUSION: The earlier vasoconstrictor response and later release of vasoconstriction in the finger during hypoxic conditions may result in a greater dose of cold to that digit, taking longer to rewarm following the release of vasoconstriction.