Early Human Pathophysiological Responses to Exertional Hypobaric Decompression Stress.

INTRODUCTION: Consistent blood biomarkers of hypobaric (altitude) decompression stress remain elusive. Recent laboratory investigation of decompression sickness risk at 25,000 ft (7620 m) enabled evaluation of early pathophysiological responses to exertional decompression stress.METHODS: In this study, 15 healthy men, aged 20-50 yr, undertook 2 consecutive (same-day) ascents to 25,000 ft (7620 m) for 60 and 90 min, breathing 100% oxygen, each following 1 h of prior denitrogenation. Venous blood was sampled at baseline (T0), immediately after the second ascent (T8), and next morning (T24). Analyses encompassed whole blood hematology, endothelial microparticles, and soluble markers of cytokine response, endothelial function, inflammation, coagulopathy, oxidative stress, and brain insult, plus cortisol and creatine kinase.RESULTS: Acute hematological effects on neutrophils (mean 72% increase), eosinophils (40% decrease), monocytes (37% increase), and platelets (7% increase) normalized by T24. Consistent elevation (mean five-fold) of the cytokine interleukin-6 (IL-6) at T8 was proinflammatory and associated with venous gas emboli (microbubble) load. Levels of C-reactive protein and complement peptide C5a were persistently elevated at T24, the former by 100% over baseline. Additionally, glial fibrillary acidic protein, a sensitive marker of traumatic brain injury, increased by a mean 10% at T24.CONCLUSIONS: This complex composite environmental stress, comprising the triad of hyperoxia, decompression, and moderate exertion at altitude, provoked pathophysiological changes consistent with an IL-6 cytokine-mediated inflammatory response. Multiple persistent biomarker disturbances at T24 imply incomplete recovery the day after exposure. The elevation of glial fibrillary acidic protein similarly implies incomplete resolution following recent neurological insult.Connolly DM, Madden LA, Edwards VC, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Early human pathophysiological responses to exertional hypobaric decompression stress. Aerosp Med Hum Perform. 2023; 94(10):738-749.

The effect of sex and protein supplementation on bone metabolism during a 36-h military field exercise in energy deficit.

This study investigated sex differences in, and the effect of protein supplementation on, bone metabolism during a 36-h military field exercise. Forty-four British Army Officer cadets (14 women) completed a 36-h field exercise. Participants consumed either their habitual diet [n = 14 women (Women) and n = 15 men (Men Controls)] or the habitual diet with an additional 46.6 g·day-1 of protein for men [n = 15 men (Men Protein)]. Women and Men Protein were compared with Men Controls to examine the effect of sex and protein supplementation. Circulating markers of bone metabolism were measured before, 24 h after (postexercise), and 96 h after (recovery) the field exercise. Beta C-telopeptide cross links of type 1 collagen and cortisol were not different between time points or Women and Men Controls (P ≥ 0.094). Procollagen type I N-terminal propeptide decreased from baseline to postexercise (P < 0.001) and recovery (P < 0.001) in Women and Men Controls. Parathyroid hormone (PTH) increased from baseline to post-exercise (P = 0.006) and decreased from postexercise to recovery (P = 0.047) in Women and Men Controls. Total 25(OH)D increased from baseline to postexercise (P = 0.038) and recovery (P < 0.001) in Women and Men Controls. Testosterone decreased from baseline to post-exercise (P < 0.001) and recovery (P = 0.007) in Men Controls, but did not change for Women (all P = 1.000). Protein supplementation in men had no effect on any marker. Men and women experience similar changes to bone metabolism-decreased bone formation and increased PTH-following a short-field exercise. Protein had no protective effect likely because of the energy deficit.NEW & NOTEWORTHY Energy deficits are common in arduous military training and can cause disturbances to bone metabolism. This study provides first evidence that short periods of severe energy deficit and arduous exercise-in the form of a 36-h military field exercise-can suppress bone formation for at least 96 h, and the suppression in bone formation was not different between men and women. Protein feeding does not offset decreases in bone formation during severe energy deficits.

Association between external training loads and injury incidence during 44 weeks of military training.

Military training is physically arduous and associated with high injury incidence. Unlike in high-performance sport, the interaction between training load and injury has not been extensively researched in military personnel. Sixty-three (43 men, 20 women; age 24 ± 2 years; stature 1.76 ± 0.09 m; body mass 79.1 ± 10.8 kg) British Army Officer Cadets undergoing 44 weeks of training at the Royal Military Academy Sandhurst volunteered to participate. Weekly training load (cumulative 7-day moderate-vigorous physical activity [MVPA], vigorous PA [VPA], and the ratio between MVPA and sedentary-light PA [SLPA; MVPA:SLPA]) was monitored using a wrist-worn accelerometer (GENEActiv, UK). Self-report injury data were collected and combined with musculoskeletal injuries recorded at the Academy medical center. Training loads were divided into quartiles with the lowest load group used as the reference to enable comparisons using odds ratios (OR) and 95% confidence intervals (95% CI). Overall injury incidence was 60% with the most common injury sites being the ankle (22%) and knee (18%). High (load; OR; 95% CI [>2327 mins; 3.44; 1.80-6.56]) weekly cumulative MVPA exposure significantly increased odds of injury. Similarly, likelihood of injury significantly increased when exposed to low-moderate (0.42-0.47; 2.45 [1.19-5.04]), high-moderate (0.48-0.51; 2.48 [1.21-5.10]), and high MVPA:SLPA loads (>0.51; 3.60 [1.80-7.21]). High MVPA and high-moderate MVPA:SLPA increased odds of injury by ~2.0 to 3.5 fold, suggesting that the ratio of workload to recovery is important for mitigating injury occurrence.

Nutrition and Physical Activity During British Army Officer Cadet Training: Part 1-Energy Balance and Energy Availability.

Military training is characterized by high daily energy expenditures which are difficult to match with energy intake, potentially resulting in negative energy balance (EB) and low energy availability (EA). The aim of this study was to quantify EB and EA during British Army Officer Cadet training. Thirteen (seven women) Officer Cadets (mean ± SD: age 24 ± 3 years) volunteered to participate. EB and EA were estimated from energy intake (weighing of food and food diaries) and energy expenditure (doubly labeled water) measured in three periods of training: 9 days on-camp (CAMP), a 5-day field exercise (FEX), and a 9-day mixture of both CAMP and field-based training (MIX). Variables were compared by condition and gender with a repeated-measures analysis of variance. Negative EB was greatest during FEX (-2,197 ± 455 kcal/day) compared with CAMP (-692 ± 506 kcal/day; p < .001) and MIX (-1,280 ± 309 kcal/day; p < .001). EA was greatest in CAMP (23 ± 10 kcal·kg free-fat mass [FFM]-1·day-1) compared with FEX (1 ± 16 kcal·kg FFM-1·day-1; p = .002) and MIX (10 ± 7 kcal·kg FFM-1·day-1; p = .003), with no apparent difference between FEX and MIX (p = .071). Irrespective of condition, there were no apparent differences between gender in EB (p = .375) or EA (p = .385). These data can be used to inform evidenced-based strategies to manage EA and EB during military training, and enhance the health and performance of military personnel.

Nutrition and Physical Activity in British Army Officer Cadet Training Part 2-Daily Distribution of Energy and Macronutrient Intake.

Dietary intake and physical activity impact performance and adaptation during training. The aims of this study were to compare energy and macronutrient intake during British Army Officer Cadet training with dietary guidelines and describe daily distribution of energy and macronutrient intake and estimated energy expenditure. Thirteen participants (seven women) were monitored during three discrete periods of military training for 9 days on-camp, 5 days of field exercise, and 9 days of a mixture of the two. Dietary intake was measured using researcher-led food weighing and food diaries, and energy expenditure was estimated from wrist-worn accelerometers. Energy intake was below guidelines for men (4,600 kcal/day) and women (3,500 kcal/day) during on-camp training (men = -16% and women = -9%), field exercise (men = -33% and women = -42%), and combined camp and field training (men and women both -34%). Carbohydrate intake of men and women were below guidelines (6 g·kg-1·day-1) during field exercise (men = -18% and women = -37%) and combined camp and field training (men = -33% and women = -39%), respectively. Protein intake was above guidelines (1.2 kcal·kg-1·day-1) for men and women during on-camp training (men = 48% and women = 39%) and was below guidelines during field exercise for women only (-27%). Energy and macronutrient intake during on-camp training centered around mealtimes with a discernible sleep/wake cycle for energy expenditure. During field exercise, energy and macronutrient intake were individually variable, and energy expenditure was high throughout the day and night. These findings could be used to inform evidenced-based interventions to change the amount and timing of energy and macronutrient intake around physical activity to optimize performance and adaptations during military training.

Validity of energy expenditure estimation methods during 10 days of military training.

Wearable physical activity (PA) monitors have improved the ability to estimate free-living total energy expenditure (TEE) but their application during arduous military training alongside more well-established research methods has not been widely documented. This study aimed to assess the validity of two wrist-worn activity monitors and a PA log against doubly labeled water (DLW) during British Army Officer Cadet (OC) training. For 10 days of training, twenty (10 male and 10 female) OCs (mean ± SD: age 23 ± 2 years, height 1.74 ± 0.09 m, body mass 77.0 ± 9.3 kg) wore one research-grade accelerometer (GENEActiv, Cambridge, UK) on the dominant wrist, wore one commercially available monitor (Fitbit SURGE, USA) on the non-dominant wrist, and completed a self-report PA log. Immediately prior to this 10-day period, participants consumed a bolus of DLW and provided daily urine samples, which were analyzed by mass spectrometry to determine TEE. Bivariate correlations and limits of agreement (LoA) were employed to compare TEE from each estimation method to DLW. Average daily TEE from DLW was 4112 ± 652 kcal·day-1 against which the GENEActiv showed near identical average TEE (mean bias ± LoA: -15 ± 851 kcal. day-1 ) while Fitbit tended to underestimate (-656 ± 683 kcal·day-1 ) and the PA log substantially overestimate (+1946 ± 1637 kcal·day-1 ). Wearable physical activity monitors provide a cheaper and more practical method for estimating free-living TEE than DLW in military settings. The GENEActiv accelerometer demonstrated good validity for assessing daily TEE and would appear suitable for use in large-scale, longitudinal military studies.

Use of short tandem repeat fingerprinting to validate sample origins in hepatitis C virus molecular epidemiology studies.

Sequence analysis is used to define the molecular epidemiology and evolution of the hepatitis C virus. Whilst most studies have shown that individual patients harbour viruses that are derived from a limited number of highly related strains, some recent reports have shown that some patients can be co-infected with very distinct variants whose frequency can fluctuate greatly. Whilst co-infection with highly divergent strains is possible, an alternative explanation is that such data represent contamination or sample mix-up. In this study, we have shown that DNA fingerprinting techniques can accurately assess sample provenance and differentiate between samples that are truly exhibiting mixed infection from those that harbour distinct virus populations due to sample mix-up. We have argued that this approach should be adopted routinely in virus sequence analyses to validate sample provenance.

The role of neutralizing antibodies in hepatitis C virus infection.

Hepatitis C virus (HCV) is a blood-borne virus estimated to infect around 170 million people worldwide and is, therefore, a major disease burden. In some individuals the virus is spontaneously cleared during the acute phase of infection, whilst in others a persistent infection ensues. Of those persistently infected, severe liver diseases such as cirrhosis and primary liver cancer may develop, although many individuals remain asymptomatic. A range of factors shape the course of HCV infection, not least host genetic polymorphisms and host immunity. A number of studies have shown that neutralizing antibodies (nAb) arise during HCV infection, but that these antibodies differ in their breadth and mechanism of neutralization. Recent studies, using both mAbs and polyclonal sera, have provided an insight into neutralizing determinants and the likely protective role of antibodies during infection. This understanding has helped to shape our knowledge of the overall structure of the HCV envelope glycoproteins--the natural target for nAb. Most nAb identified to date target receptor-binding sites within the envelope glycoprotein E2. However, there is some evidence that other viral epitopes may be targets for antibody neutralization, suggesting the need to broaden the search for neutralization epitopes beyond E2. This review provides a comprehensive overview of our current understanding of the role played by nAb in HCV infection and disease outcome and explores the limitations in the study systems currently used. In addition, we briefly discuss the potential therapeutic benefits of nAb and efforts to develop nAb-based therapies.