Sex differences in iron status during military training: a prospective cohort study of longitudinal changes and associations with endurance performance and musculoskeletal outcomes.

This study investigated sex differences in Fe status, and associations between Fe status and endurance and musculoskeletal outcomes, in military training. In total, 2277 British Army trainees (581 women) participated. Fe markers and endurance performance (2·4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal body mineral density (aBMD) and markers of bone metabolism were measured at week 1. Injuries during training were recorded. Training decreased Hb in men and women (mean change (-0·1 (95 % CI -0·2, -0·0) and -0·7 (95 % CI -0·9, -0·6) g/dl, both P < 0·001) but more so in women (P < 0·001). Ferritin decreased in men and women (-27 (95 % CI -28, -23) and -5 (95 % CI -8, -1) µg/l, both P ≤ 0·001) but more so in men (P < 0·001). Soluble transferrin receptor increased in men and women (2·9 (95 % CI 2·3, 3·6) and 3·8 (95 % CI 2·7, 4·9) nmol/l, both P < 0·001), with no difference between sexes (P = 0·872). Erythrocyte distribution width increased in men (0·3 (95 % CI 0·2, 0·4)%, P < 0·001) but not in women (0·1 (95 % CI -0·1, 0·2)%, P = 0·956). Mean corpuscular volume decreased in men (-1·5 (95 % CI -1·8, -1·1) fL, P < 0·001) but not in women (0·4 (95 % CI -0·4, 1·3) fL, P = 0·087). Lower ferritin was associated with slower 2·4 km run time (P = 0·018), sustaining a lower limb overuse injury (P = 0·048), lower aBMD (P = 0·021) and higher beta C-telopeptide cross-links of type 1 collagen and procollagen type 1 N-terminal propeptide (both P < 0·001) controlling for sex. Improving Fe stores before training may protect Hb in women and improve endurance and protect against injury.

Vitamin D Metabolites Are Associated With Musculoskeletal Injury in Young Adults: A Prospective Cohort Study.

The relationship between vitamin D metabolites and lower body (pelvis and lower limb) overuse injury is unclear. In a prospective cohort study, we investigated the association between vitamin D metabolites and incidence of lower body overuse musculoskeletal and bone stress injury in young adults undergoing initial military training during all seasons. In 1637 men and 530 women (aged 22.6 ± 7.5 years; body mass index [BMI], 24.0 ± 2.6 kg/m- 2 ; 94.3% white ethnicity), we measured serum 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2 D) by high-performance liquid chromatography tandem mass spectrometry, and 1,25-dihydroxyvitamin D (1,25(OH)2 D) by immunoassay during week 1 of training. We examined whether the relationship between 25(OH)D and 1,25(OH)2 D:24,25(OH)2 D ratio was associated with overuse injury. During 12 weeks of training, 21.0% sustained ≥1 overuse musculoskeletal injury, and 5.6% sustained ≥1 bone stress injury. After controlling for sex, BMI, 2.4 km run time, smoking, bone injury history, and Army training course (Officer, standard, or Infantry), lower body overuse musculoskeletal injury incidence was higher for participants within the second lowest versus highest quartile of 24,25(OH)2 D (odds ratio [OR] = 1.62; 95% confidence interval [CI] 1.13-2.32; p = 0.009) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2 D:24,25(OH)2 D (OR = 6.30; 95% CI 1.89-21.2; p = 0.003). Lower body bone stress injury incidence was higher for participants within the lowest versus highest quartile of 24,25(OH)2 D (OR = 4.02; 95% CI 1.82-8.87; p < 0.001) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2 D:24,25(OH)2 D (OR = 22.08; 95% CI 3.26-149.4; p = 0.001), after controlling for the same covariates. Greater conversion of 25(OH)D to 24,25(OH)2 D, relative to 1,25(OH)2 D (ie, low 1,25(OH)2 D:24,25(OH)2 D), and higher serum 24,25(OH)2 D were associated with a lower incidence of lower body overuse musculoskeletal and bone stress injury. Serum 24,25(OH)2 D may have a role in preventing overuse injury in young adults undertaking arduous physical training. © 2023 Crown copyright and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article is published with the permission of the Controller of HMSO and the King's Printer for Scotland.

Greater post-exercise hypotension in healthy young untrained men after exercising in a hot compared to a temperate environment.

This research examined the effects of exercising in a hot compared to a temperate environment on post-exercise hemodynamics in untrained men. We hypothesized exercise in a hot compared to a temperate environment would elicit greater post-exercise hypotension, and this would be attributable to higher cutaneous vascular conductance and sweat loss, and lower heart rate variability (HRV) and cardiac baroreflex sensitivity (cBRS). In a randomized counterbalanced order, 12 untrained healthy men completed two trials involving 40-min leg-cycling exercise at either 23 °C (CON) or 35 °C (HOT). Post-exercise participants rested supine for 60 min at 23 °C whilst hemodynamic and thermoregulatory measurements were assessed. Post-exercise hypotension was greater after exercising in a hot than a temperate environment as indicated by a lower mean arterial pressure at 60 min recovery (CON 83 ± 5 mmHg, HOT 78 ± 5 mmHg, Mean difference [95% confidence interval], -5 [-8, -3] mmHg). Throughout recovery, cutaneous vascular conductance was higher, and cBRS and HRV were lower after exercising in a hot than in a temperate environment (P < 0.05). Sweat loss was greater on HOT than on CON (P < 0.001). Post-exercise hypotension after exercising in the hot environment was associated with sweat loss (r = 0.66, P = 0.02), and changes in cutaneous vascular conductance (r = 0.64, P = 0.03), and HRV (Root mean square of the successive difference in R-R interval [RMSSD]) r=0.75, P = 0.01 and and log high frequency [HF] r=0.66, P = 0.02), but not cBRS (all, r ≤ 0.2, P > 0.05). Post-exercise hypotension was greater after exercise in a hot compared to a temperate environment and may be partially explained by greater sweat loss and cutaneous vascular conductance, and lower HRV.

Five Days of Tart Cherry Supplementation Improves Exercise Performance in Normobaric Hypoxia.

Previous studies have shown tart cherry (TC) to improve exercise performance in normoxia. The effect of TC on hypoxic exercise performance is unknown. This study investigated the effects of 5 days of tart cherry (TC) or placebo (PL) supplementation on hypoxic exercise performance. Thirteen healthy participants completed an incremental cycle exercise test to exhaustion (TTE) under two conditions: (i) hypoxia (13% O2) with PL and (ii) hypoxia with TC (200 mg anthocyanin per day for 4 days and 100 mg on day 5). Pulmonary gas exchange variables, peripheral arterial oxygen saturation (SpO2), deoxygenated hemoglobin (HHb), and tissue oxygen saturation (StO2) assessed by near-infrared spectroscopy in the vastus lateralis muscle were measured at rest and during exercise. Urinary 8-hydro-2' deoxyguanosine (8-OHdG) excretion was evaluated pre-exercise and 1 and 5 h post-exercise. The TTE after TC (940 ± 84 s, mean ± standard deviation) was longer than after PL (912 ± 63 s, p < 0.05). During submaximal hypoxic exercise, HHb was lower and StO2 and SpO2 were higher after TC than PL. Moreover, a significant interaction (supplements × time) in urinary 8-OHdG excretion was found (p < 0.05), whereby 1 h post-exercise increases in urinary 8-OHdG excretion tended to be attenuated after TC. These findings indicate that short-term dietary TC supplementation improved hypoxic exercise tolerance, perhaps due to lower HHb and higher StO2 in the working muscles during submaximal exercise.

Good perceived sleep quality protects against the raised risk of respiratory infection during sleep restriction in young adults.

STUDY OBJECTIVES: Prospectively examine the association between sleep restriction, perceived sleep quality (PSQ) and upper respiratory tract infection (URTI). METHODS: In 1318 military recruits (68% males) self-reported sleep was assessed at the beginning and end of a 12-week training course. Sleep restriction was defined as an individualized reduction in sleep duration of ≥2 hours/night compared with civilian life. URTIs were retrieved from medical records. RESULTS: On commencing training, approximately half of recruits were sleep restricted (52%; 2.1 ± 1.6 h); despite the sleep debt, 58% of recruits with sleep restriction reported good PSQ. Regression adjusted for covariates showed that recruits commencing training with sleep restriction were more likely to suffer URTI during the course (OR = 2.93, 95% CI 1.29-6.69, p = .011). Moderation analysis showed this finding was driven by poor PSQ (B = -1.12, SE 0.50, p = .023), as no significant association between sleep restriction and URTI was observed in recruits reporting good PSQ, despite a similar magnitude of sleep restriction during training. Associations remained in the population completing training, accounting for loss to follow-up. Recruits reporting poor PSQ when healthy at the start and end of training were more susceptible to URTI (OR = 3.16, 95% CI 1.31-7.61, p = .010, vs good PSQ). CONCLUSION: Good perceived sleep quality was associated with protection against the raised risk of respiratory infection during sleep restriction. Studies should determine whether improvements in sleep quality arising from behavioral sleep interventions translate to reduced respiratory infection during sleep restriction.

Control of blood pressure in the cold: differentiation of skin and skeletal muscle vascular resistance.

NEW FINDINGS: What is the central question of this study? Why does blood pressure increases during cold air exposure? Specifically, what is the contribution of skin and skeletal muscle vascular resistance during whole body versus isolated face cooling? What is the main finding and its importance? Whole-body cooling caused an increase in blood pressure through an increase in skeletal muscle and cutaneous vascular resistance. However, isolated mild face cooling caused an increase in blood pressure predominately via an increase in cutaneous vasoconstriction. ABSTRACT: The primary aim of this investigation was to determine the individual contribution of the cutaneous and skeletal muscle circulations to the cold-induced pressor response. To address this, we examined local vascular resistances in the cutaneous and skeletal muscle of the arm and leg. Thirty-four healthy individuals underwent three different protocols, whereby cold air to clamp skin temperature (27°C) was passed over (1) the whole-body, (2) the whole-body, but with the forearm pre-cooled to clamp cutaneous vascular resistance, and (3) the face. Cold exposure applied to the whole body or isolated to the face increased mean arterial pressure (all, P < 0.001) and total peripheral resistance (all, P < 0.047) compared to thermal neutral baseline. Whole-body cooling increased femoral (P < 0.005) and brachial artery resistance (P < 0.003) compared to thermoneutral baseline. Moreover, when the forearm was pre-cooled to remove the contribution of cutaneous resistance (P = 0.991), there was a further increase in lower arm vasoconstriction (P = 0.036) when whole-body cooling was superimposed. Face cooling also caused a reflex increase in lower arm cutaneous (P = 0.009) and brachial resistance (P = 0.050), yet there was no change in femoral resistance (P = 0.815) despite a reflex increase in leg cutaneous resistance (P = 0.010). Cold stress causes an increase in blood pressure through a change in total peripheral resistance that is largely due to cutaneous vasoconstriction with face cooling, but there is additional vasoconstriction in the skeletal muscle vasculature with whole-body cooling.

A comparison of medium-term heat acclimation by post-exercise hot water immersion or exercise in the heat: adaptations, overreaching, and thyroid hormones.

This research compared thermal and perceptual adaptations, endurance capacity, and overreaching markers in men after 3, 6, and 12 days of post-exercise hot water immersion (HWI) or exercise heat acclimation (EHA) with a temperate exercise control (CON), and examined thyroid hormones as a mechanism for the reduction in resting and exercising core temperature (Tre) after HWI. HWI involved a treadmill run at 65% V̇o2peak at 19°C followed by a 40°C bath. EHA and CON involved a work-matched treadmill run at 65% V̇o2peak at 33°C or 19°C, respectively. Compared with CON, resting mean body temperature (Tb), resting and end-exercise Tre, Tre at sweating onset, thermal sensation, and perceived exertion were lower and whole-body sweat rate (WBSR) was higher after 12 days of HWI (all P ≤ 0.049, resting Tb: CON -0.11 ± 0.15°C, HWI -0.41 ± 0.15°C). Moreover, resting Tb and Tre at sweating onset were lower after HWI than EHA (P ≤ 0.015, resting Tb: EHA -0.14 ± 0.14°C). No differences were identified between EHA and CON (P ≥ 0.157) except WBSR that was greater after EHA (P = 0.013). No differences were observed between interventions for endurance capacity or overreaching markers (mood, sleep, Stroop, P ≥ 0.190). Thermal adaptations observed after HWI were not related to changes in thyroid hormone concentrations (P ≥ 0.086). In conclusion, 12 days of post-exercise hot water immersion conferred more complete heat acclimation than exercise heat acclimation without increasing overreaching risk, and changes in thyroid hormones are not related to thermal adaptations after post-exercise hot water immersion.

Vitamin D Metabolites Are Associated with Physical Performance in Young Healthy Adults.

PURPOSE: This study aimed to determine vitamin D metabolites and vitamin D receptor (VDR) single-nucleotide polymorphism (SNP) relationships with physical performance. METHODS: In 1205 men and 322 women (94.8% White Caucasian, 22.0 ± 2.8 yr) commencing military training, we measured serum vitamin D metabolites (25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH) 2 D) by high-performance liquid chromatography tandem mass spectrophotometry and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) by immunoassay), VDR SNPs (rs2228570, rs4516035, and rs7139166 by polymerase chain reaction genotyping), and endurance performance by 2.4-km run, muscle strength by maximal dynamic lift, and muscle power by maximal vertical jump. RESULTS: Serum 25(OH)D was negatively associated with 2.4-km run time and positively associated with muscle power ( ß = -12.0 and 90.1), 1,25(OH) 2 D was positively associated with run time and negatively associated with strength and muscle power ( ß = 5.6, -1.06, and -38.4), and 24,25(OH) 2 D was negatively associated with run time ( ß = -8.9; P < 0.01), after controlling for age, sex, smoking, alcohol, physical activity, time outdoors, season, and body mass index. Vitamin D metabolites (25(OH)D, 1,25(OH) 2 D, and 24,25(OH) 2 D) together explained variances of 5.0% in run time, 0.7% in strength, and 0.9% in muscle power (Δ F P < 0.001). All performance measures were superior with low 1,25(OH) 2 D:24,25(OH) 2 D ratio ( P < 0.05). VDR SNPs were not associated with physical performance (Δ FP ≥ 0.306). CONCLUSIONS: Vitamin D metabolites accounted for a small portion of variance in physical performance. Associations between vitamin D metabolites and run time were the most consistent. VDR SNPs explained no variance in performance. Greater conversion of 25(OH)D to 24,25(OH) 2 D, relative to 1,25(OH) 2 D (i.e., low 1,25(OH) 2 D:24,25(OH) 2 D ratio), was favorable for performance, indicating 24,25(OH) 2 D may have a role in optimizing physical performance.

Hypoxia alters posterior cingulate cortex metabolism during a memory task: A 1H fMRS study.

Environmental hypoxia (fraction of inspired oxygen (FIO2) ∼ 0.120) is known to trigger a global increase in cerebral blood flow (CBF). However, regionally, a heterogeneous response is reported, particularly within the posterior cingulate cortex (PCC) where decreased CBF is found after two hours of hypoxic exposure. Furthermore, hypoxia reverses task-evoked BOLD signals within the PCC, and other regions of the default mode network, suggesting a reversal of neurovascular coupling. An alternative explanation is that the neural architecture supporting cognitive tasks is reorganised. Therefore, to confirm if this previous result is neural or vascular in origin, a measure of neural activity that is not haemodynamic-dependant is required. To achieve this, we utilised functional magnetic resonance spectroscopy to probe the glutamate response to memory recall in the PCC during normoxia (FIO2 = 0.209) and after two hours of poikilocapnic hypoxia (FIO2 = 0.120). We also acquired ASL-based measures of CBF to confirm previous findings of reduced CBF within the PCC in hypoxia. Consistent with previous findings, hypoxia induced a reduction in CBF within the PCC and other regions of the default mode network. Under normoxic conditions, memory recall was associated with an 8% increase in PCC glutamate compared to rest (P = 0.019); a change which was not observed during hypoxia. However, exploratory analysis of other neurometabolites showed that PCC glucose was reduced during hypoxia compared to normoxia both at rest (P = 0.039) and during the task (P = 0.046). We conclude that hypoxia alters the activity-induced increase in glutamate, which may reflect a reduction in oxidative metabolism within the PCC. The reduction in glucose in hypoxia reflects continued metabolism, presumably by non-oxidative means, without replacement of glucose due to reduced CBF.

Dietary nitrate supplementation effect on dynamic cerebral autoregulation in normoxia and acute hypoxia.

We tested the hypothesis that increasing the nitric oxide (NO) bioavailability by dietary nitrate would recover the hypoxia-induced reduction in dynamic cerebral autoregulation (CA). Twelve healthy males (age 21 ± 2 years) completed four days of dietary supplementation with a placebo or inorganic nitrate drink (140-ml beetroot juice per day) followed by 60-min of normoxia or hypoxia (fraction of inspired oxygen [FiO2] = 13%). Duplex ultrasonography was used to perform volumetric change-based assessment of dynamic CA in the internal carotid artery (ICA). Dynamic CA was assessed by rate of regulation (RoR) of vascular conductance using the thigh-cuff method. Four days of beetroot supplementation increased circulating nitrate by 208 [171,245] µM (mean difference [95% confidence interval]) compared with placebo. Dynamic CA was lower in hypoxia than normoxia (RoR Δ-0.085 [-0.116, -0.054]). Compared with placebo, nitrate did not alter dynamic CA in normoxia (RoR Δ-0.022 [-0.060, 0.016]) or hypoxia (RoR Δ0.017 [-0.019, 0.053]). Further, nitrate did not affect ICA vessel diameter, blood velocity or flow in either normoxia or hypoxia. Increased bioavailability of NO through dietary nitrate supplementation did not recover the hypoxia-induced reduction in dynamic CA. This suggests the mechanism of hypoxia-induced reduction in dynamic CA does not relate to the availability of NO.

The influence of short-term high-altitude acclimatization on cerebral and leg tissue oxygenation post-orthostasis.

PURPOSE: Orthostasis at sea level decreases brain tissue oxygenation and increases risk of syncope. High altitude reduces brain and peripheral muscle tissue oxygenation. This study determined the effect of short-term altitude acclimatization on cerebral and peripheral leg tissue oxygenation index (TOI) post-orthostasis. METHOD: Seven lowlanders completed a supine-to-stand maneuver at sea level (450 m) and for 3 consecutive days at high altitude (3776 m). Cardiorespiratory measurements and near-infrared spectroscopy-derived oxygenation of the frontal lobe (cerebral TOI) and vastus lateralis (leg TOI) were measured at supine and 5-min post-orthostasis. RESULTS: After orthostasis at sea level, cerebral TOI decreased [mean Δ% (95% confidential interval): - 4.5%, (- 7.5, - 1.5), P < 0.001], whilst leg TOI was unchanged [- 4.6%, (- 10.9, 1.7), P = 0.42]. High altitude had no effect on cerebral TOI following orthostasis [days 1-3: - 2.3%, (- 5.3, 0.7); - 2.4%, (- 5.4, 0.6); - 2.1%, (- 5.1, 0.9), respectively, all P > 0.05], whereas leg TOI decreased [days 1-3: - 12.0%, (- 18.3, - 5.7); - 12.1%, (- 18.4, - 5.8); - 10.2%, (- 16.5, - 3.9), respectively, all P < 0.001]. This response did not differ with days spent at high altitude, despite evidence of cardiorespiratory acclimatization [increased peripheral oxygen saturation (supine: P = 0.01; stand: P = 0.02) and decreased end-tidal carbon dioxide (supine: P = 0.003; stand: P = 0.01)]. CONCLUSION: Cerebral oxygenation is preferentially maintained over leg oxygenation post-orthostasis at high altitude, suggesting different vascular regulation between cerebral and peripheral circulations. Short-term acclimatization to high altitude did not alter cerebral and leg oxygenation responses to orthostasis.

A comparison of heat acclimation by post-exercise hot water immersion and exercise in the heat.

OBJECTIVES: To compare heat acclimation adaptations after three and six days of either post-exercise hot water immersion (HWI) or exercise-heat-acclimation (EHA) in recreationally active individuals. DESIGN: Randomised, mixed model, repeated measures. METHODS: Post-exercise HWI involved a daily 40-min treadmill-run at 65% V̇O2peak in temperate conditions (19 °C, 45% RH) followed by HWI (≤40 min, 40 °C water; n = 9). Daily EHA involved a ≤60-min treadmill-run in the heat (65% V̇O2peak; 33 °C, 40% RH; n = 9), chosen to elicit a similar endogenous thermal stimulus to HWI. A thermoneutral exercise intervention (TNE, 19 °C, 45% RH; n = 9), work-matched to EHA, was also included to determine thermoregulatory adaptations to daily exercise in temperate conditions. An exercise-heat-stress-test was performed before and after three and six intervention days and involved a 40-min treadmill-run and time-to-exhaustion (TTE) at 65% V̇O2peak in the heat (33 °C, 40% RH). RESULTS: ANCOVA, using baseline values as the covariate, revealed no interaction effects but significant group effects demonstrated that compared to EHA, HWI elicited larger reductions in resting rectal temperature (Tre; p = 0.021), Tre at sweating onset (p = 0.011), and end-exercise Tre during exercise-heat-stress (-0.47 °C; p = 0.042). Despite a similar endogenous thermal stimulus to HWI, EHA elicited a modest reduction in end-exercise Tre (-0.26 °C), which was not different from TNE (-0.25 °C, p = 1.000). There were no main effects or interaction effects for end-exercise Tsk, heart rate, physiological strain index, RPE, thermal sensation, plasma volume, or TTE (all p ≥ 0.154). CONCLUSIONS: Compared with conventional short-term exercise heat acclimation, short-term post-exercise hot water immersion elicited larger thermal adaptations.

The deleterious effects of acute hypoxia on microvascular and large vessel endothelial function.

NEW FINDINGS: What is the central question of this study? The aim was primarily to determine the effect of hypoxia on microvascular function and secondarily whether superior cardiorespiratory fitness is protective against hypoxia-induced impairment in vascular function. What is the main finding and its importance? Hypoxia reduced endothelium-dependent but not endothelium-independent microvascular function. The extent of impairment was twofold higher in the microcirculation compared with the large blood vessels. This study suggests that individuals with superior cardiorespiratory fitness might preserve microvascular function in hypoxia. These findings highlight the sensitivity of the microvascular circulation to hypoxia. ABSTRACT: Hypoxia is associated with diminished bioavailability of the endothelium-derived vasodilator, nitric oxide (NO). Diminished NO bioavailability can have deleterious effects on endothelial function. The endothelium is a heterogeneous tissue; therefore, a comprehensive assessment of endothelial function is crucial to understand the significance of hypoxia-induced endothelial dysfunction. We hypothesized that acute hypoxia would have a deleterious effect on microvascular and large vessel endothelial function. Twenty-nine healthy adults [24 (SD = 4 ) years of age] completed normoxic and hypoxic [inspired O2  fraction = 0.209] trials in this double-blinded, counterbalanced crossover study. After 30 min, we assessed the laser Doppler imaging-determined perfusion response to iontophoresis of ACh as a measure of endothelium-dependent microvascular function and iontophoresis of sodium nitroprusside as a measure of endothelium-independent microvascular function. After 60 min, we assessed brachial flow-mediated dilatation as a measure of large vessel endothelial function. Thirty minutes of hypoxia reduced endothelium-dependent microvascular function determined by the perfusion response to ACh (median difference (x̃∆) = -109% {interquartile range: 542.7}, P < 0.05), but not endothelium-independent microvascular function determined by the perfusion response to sodium nitroprusside (x̃∆ = 69% {interquartile range: 453.7}, P = 0.6). In addition, 60 min of hypoxia reduced allometrically scaled flow-mediated dilatation compared with normoxia ( x¯Δ=-1.19 [95% CI = -1.80, -0.58 (Confidence Intervals)]%, P < 0.001). The decrease in microvascular endothelial function was associated with cardiorespiratory fitness (r  = 0.45, P = 0.02). In conclusion, acute exposure to normobaric hypoxia significantly reduced endothelium-dependent vasodilatory capacity in small and large vessels. Collectively, these findings highlight the sensitivity of the microvascular circulation to hypoxic insult, particularly in those with poor cardiorespiratory fitness.

Bilateral regional extracranial blood flow regulation to hypoxia and unilateral duplex ultrasound measurement error.

NEW FINDINGS: What is the central question of this study? Is blood flow regulation to hypoxia different between the internal carotid arteries (ICAs) and vertebral arteries (VAs), and what is the measurement error in unilateral extracranial artery assessments compared to bilateral? What is the main finding and its importance? ICA and VA blood flow regulation to hypoxia is comparable when factoring for vessel type and vessel side. Compared to bilateral assessment, vessels assessed unilaterally had individual measurement errors of up to 37%. Assessing the vessel with the larger resting blood flow, not the left or right vessel, reduces unilateral measurement error. ABSTRACT: Whether blood flow regulation to hypoxia is similar between left and right internal carotid arteries (ICAs) and vertebral arteries (VAs) is unclear. Extracranial blood flow is regularly calculated by doubling a unilateral assessment; however, lateral artery differences may lead to measurement error. This study aimed to determine extracranial blood flow regulation to hypoxia when factoring for vessel type (ICAs or VAs) and vessel side (left or right) effects, and to investigate unilateral assessment measurement error compared to bilateral assessment. In a repeated-measures crossover design, extracranial arteries of 44 participants were assessed bilaterally by duplex ultrasound during 90 min of normoxic and poikilocapnic hypoxic (12.0% fraction of inspired oxygen) conditions. Linear mixed model analyses revealed no Condition × Vessel Type × Vessel Side interaction for blood flow, vessel diameter and flow velocity (all P > 0.05) indicating left and right ICA and VA blood flow regulation to hypoxia was similar. Bilateral hypoxic reactivity was comparable (ICAs, 1.4 (1.0) vs. VAs, 1.7 (1.1) Δ%·Δ SpO2-1 ; P = 0.12). Compared to bilateral assessment, unilateral mean measurement error of the relative blood flow response to hypoxia was up to 5%, but individual errors reached 37% and were greatest in ICAs and VAs with the smaller resting blood flow due to a ratio-scaling problem. In conclusion, left and right ICA and VA regulation to hypoxia is comparable when factoring for vessel type and vessel side. Assessing the ICA and VA vessels with the larger resting blood flow, not the left or right vessel, reduces unilateral measurement error.

Influence of Vitamin D Supplementation by Simulated Sunlight or Oral D3 on Respiratory Infection during Military Training.

PURPOSE: This study aimed to determine the relationship between vitamin D status and upper respiratory tract infection (URTI) of physically active men and women across seasons (study 1) and then to investigate the effects on URTI and mucosal immunity of achieving vitamin D sufficiency (25(OH)D ≥50 nmol·L-1) by a unique comparison of safe, simulated sunlight or oral D3 supplementation in winter (study 2). METHODS: In study 1, 1644 military recruits were observed across basic military training. In study 2, a randomized controlled trial, 250 men undertaking military training received placebo, simulated sunlight (1.3× standard erythemal dose, three times per week for 4 wk and then once per week for 8 wk), or oral vitamin D3 (1000 IU·d-1 for 4 wk and then 400 IU·d-1 for 8 wk). URTI was diagnosed by a physician (study 1) and by using the Jackson common cold questionnaire (study 2). Serum 25(OH)D, salivary secretory immunoglobulin A (SIgA), and cathelicidin were assessed by liquid chromatography-mass spectrometry LC-MS/MS and enzyme-linked immunosorbent assay. RESULTS: In study 1, only 21% of recruits were vitamin D sufficient during winter. Vitamin D-sufficient recruits were 40% less likely to suffer URTI than recruits with 25(OH)D <50 nmol·L-1 (OR = 0.6, 95% confidence interval = 0.4-0.9), an association that remained after accounting for sex and smoking. Each URTI caused, on average, three missed training days. In study 2, vitamin D supplementation strategies were similarly effective to achieve vitamin D sufficiency in almost all (≥95%). Compared with placebo, vitamin D supplementation reduced the severity of peak URTI symptoms by 15% and days with URTI by 36% (P < 0.05). These reductions were similar with both vitamin D strategies (P > 0.05). Supplementation did not affect salivary secretory immunoglobulin A or cathelicidin. CONCLUSION: Vitamin D sufficiency reduced the URTI burden during military training.

Integrative crosstalk between hypoxia and the cold: Old data and new opportunities.

NEW FINDINGS: What is the topic of this review? The aim was to examine the influence of hypoxia on thermoregulatory and cardiovascular control in the cold. What advances does it highlight? Exposure to hypoxia seems to alter both thermoregulatory and cardiovascular control, but these conclusions are based on limited data, and this review highlights the need for future research in this area. ABSTRACT: Cold stress and hypoxia have been the subject of research for decades; however, humans often encounter these stressors together, such as in the alpine environment. Therefore, this review summarizes previous data with respect to the influence of hypoxia on thermoregulatory and cardiovascular control in the cold and presents new ideas for the future. Altogether, little to no evidence is available on the integrative and adaptive mechanisms by which the human body regulates heat conservation, oxygen delivery and maintenance of blood pressure.

Vitamin D and the hepatitis B vaccine response: a prospective cohort study and a randomized, placebo-controlled oral vitamin D3 and simulated sunlight supplementation trial in healthy adults.

PURPOSE: To determine serum 25(OH)D and 1,25(OH)2D relationship with hepatitis B vaccination (study 1). Then, to investigate the effects on hepatitis B vaccination of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol/L) by a unique comparison of simulated sunlight and oral vitamin D3 supplementation in wintertime (study 2). METHODS: Study 1 involved 447 adults. In study 2, 3 days after the initial hepatitis B vaccination, 119 men received either placebo, simulated sunlight (1.3 × standard-erythema dose, 3 × /week for 4 weeks and then 1 × /week for 8 weeks) or oral vitamin D3 (1000 IU/day for 4 weeks and 400 IU/day for 8 weeks). We measured hepatitis B vaccination efficacy as percentage of responders with anti-hepatitis B surface antigen immunoglobulin G ≥ 10 mIU/mL. RESULTS: In study 1, vaccine response was poorer in persons with low vitamin D status (25(OH)D ≤ 40 vs 41-71 nmol/L mean difference [95% confidence interval] - 15% [- 26, - 3%]; 1,25(OH)2D ≤ 120 vs ≥ 157 pmol/L - 12% [- 24%, - 1%]). Vaccine response was also poorer in winter than summer (- 18% [- 31%, - 3%]), when serum 25(OH)D and 1,25(OH)2D were at seasonal nadirs, and 81% of persons had serum 25(OH)D < 50 nmol/L. In study 2, vitamin D supplementation strategies were similarly effective in achieving vitamin D sufficiency from the winter vitamin D nadir in almost all (~ 95%); however, the supplementation beginning 3 days after the initial vaccination did not effect the vaccine response (vitamin D vs placebo 4% [- 21%, 14%]). CONCLUSION: Low vitamin D status at initial vaccination was associated with poorer hepatitis B vaccine response (study 1); however, vitamin D supplementation commencing 3 days after vaccination (study 2) did not influence the vaccination response. CLINICAL TRIAL REGISTRY NUMBER: Study 1 NCT02416895; https://clinicaltrials.gov/ct2/show/study/NCT02416895 ; Study 2 NCT03132103; https://clinicaltrials.gov/ct2/show/NCT03132103 .

Global REACH 2018: Andean highlanders, chronic mountain sickness and the integrative regulation of resting blood pressure.

NEW FINDINGS: What is the central question of this study? Does chronic mountain sickness (CMS) alter sympathetic neural control and arterial baroreflex regulation of blood pressure in Andean (Quechua) highlanders? What is the main finding and its importance? Compared to healthy Andean highlanders, basal sympathetic vasomotor outflow is lower, baroreflex control of muscle sympathetic nerve activity is similar, supine heart rate is lower and cardiovagal baroreflex gain is greater in mild CMS. Taken together, these findings reflect flexibility in integrative regulation of blood pressure that may be important when blood viscosity and blood volume are elevated in CMS. ABSTRACT: The high-altitude maladaptation syndrome chronic mountain sickness (CMS) is characterized by excessive erythrocytosis and frequently accompanied by accentuated arterial hypoxaemia. Whether altered autonomic cardiovascular regulation is apparent in CMS is unclear. Therefore, during the 2018 Global REACH expedition to Cerro de Pasco, Peru (4383 m), we assessed integrative control of blood pressure (BP) and determined basal sympathetic vasomotor outflow and arterial baroreflex function in eight Andean natives with CMS ([Hb] 22.6 ± 0.9 g·dL-1 ) and seven healthy highlanders ([Hb] 19.3 ± 0.8 g·dL-1 ). R-R interval (RRI, electrocardiogram), beat-by-beat BP (photoplethysmography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest and during pharmacologically induced changes in BP (modified Oxford test). Although [Hb] and blood viscosity (7.8 ± 0.7 vs. 6.6 ± 0.7 cP; d = 1.7, P = 0.01) were elevated in CMS compared to healthy highlanders, cardiac output, total peripheral resistance and mean BP were similar between groups. The vascular sympathetic baroreflex MSNA set-point (i.e. MSNA burst incidence) and reflex gain (i.e. responsiveness) were also similar between groups (MSNA set-point, d = 0.75, P = 0.16; gain, d = 0.2, P = 0.69). In contrast, in CMS the cardiovagal baroreflex operated around a longer RRI (960 ± 159 vs. 817 ± 50 ms; d = 1.4, P = 0.04) with a greater reflex gain (17.2 ± 6.8 vs. 8.8 ± 2.6 ms·mmHg-1 ; d = 1.8, P = 0.01) versus healthy highlanders. Basal sympathetic vasomotor activity was also lower compared to healthy highlanders (33 ± 11 vs. 45 ± 13 bursts·min-1 ; d = 1.0, P = 0.08). In conclusion, our findings indicate adaptive differences in basal sympathetic vasomotor activity and heart rate compensate for the haemodynamic consequences of excessive erythrocyte volume and contribute to integrative blood pressure regulation in Andean highlanders with mild CMS.

Reversal of neurovascular coupling in the default mode network: Evidence from hypoxia.

Local changes in cerebral blood flow are thought to match changes in neuronal activity, a phenomenon termed neurovascular coupling. Hypoxia increases global resting cerebral blood flow, but regional cerebral blood flow (rCBF) changes are non-uniform. Hypoxia decreases baseline rCBF to the default mode network (DMN), which could reflect either decreased neuronal activity or altered neurovascular coupling. To distinguish between these hypotheses, we characterized the effects of hypoxia on baseline rCBF, task performance, and the hemodynamic (BOLD) response to task activity. During hypoxia, baseline CBF increased across most of the brain, but decreased in DMN regions. Performance on memory recall and motion detection tasks was not diminished, suggesting task-relevant neuronal activity was unaffected. Hypoxia reversed both positive and negative task-evoked BOLD responses in the DMN, suggesting hypoxia reverses neurovascular coupling in the DMN of healthy adults. The reversal of the BOLD response was specific to the DMN. Hypoxia produced modest increases in activations in the visual attention network (VAN) during the motion detection task, and had no effect on activations in the visual cortex during visual stimulation. This regional specificity may be particularly pertinent to clinical populations characterized by hypoxemia and may enhance understanding of regional specificity in neurodegenerative disease pathology.