Variable stress contributes to cardiovascular morbidity by impairing endothelial function through oxidative stress, inflammation and hormonal imbalance. These effects depend on sex-specific physiological responses. While aerobic exercise is recognized for its vascular benefits, the mechanisms underlying these adaptations may differ between sexes. This study investigated the sex-specific effects of aerobic training on vascular function in Wistar rats subjected to variable stress. For this, male and female Wistar rats (n=8/group) were assigned to control or stress groups (8 days using four different types of stressor stimuli), with or without aerobic training (treadmill, moderate intensity, 30 min/day for 8 weeks). Thoracic aortic endothelial function was evaluated by acetylcholine-induced relaxation and phenylephrine-induced contraction. Antioxidant enzyme activity, nitrite concentration and protein expression of eNOS, p-eNOSser1177, catalase and superoxide dismutase were measured. Stress impaired endothelium-dependent relaxation and increased vascular collagen content in both sexes. In females, stress reduced eNOS phosphorylation and nitrite bioavailability, while increasing antioxidant enzyme activity. In males, no significant changes in the eNOS-NO pathway were observed, but SOD activity increased. Aerobic training attenuated stress-induced vascular injury, predominantly through the upregulation of the eNOS-NO signaling pathway in females, while in males, possibly through another pathway related to oxidative status. These findings demonstrate the protective effects of aerobic exercise on vascular health in rats subjected to variable stress and underscore the existence of sex-specific mechanisms, with distinct molecular pathways mediating vascular adaptations in males and females. Furthermore, histological analysis revealed that aerobic training reversed collagen deposition and enhanced elastic fiber content.

Infrared radiation (IR) has previously been demonstrated to activate signalling pathways involved in mitochondrial biogenesis and angiogenesis. We tested the hypothesis that IR emitting fabric (IREF) would enhance translocation and phosphorylation of proteins, and mRNA expression of genes, associated with mitochondrial biogenesis and angiogenesis in response to high-intensity interval exercise (HIIE) compared to non-IREF. Eleven males (age, 22 ± 4 yrs, V̇O2peak, 48.0 ± 4.6 ml·kg-1·min-1) completed two HIIE sessions consisting of 10 x 3 min intervals at a power output equivalent to 60% of the difference between gas exchange threshold and peak power output. Each interval was interspersed by 3 min at 25 W. In a repeated-measures, counter balanced, single-blind design, participants wore IREF and non-IREF clothing (SHAM) before, during and following HIIE. Muscle biopsies were obtained pre (Baseline), immediately post (PE) and 3 hours post exercise (3hPE). Cytosolic and Nuclear p-CaMKII content were both greater PE in IREF compared to SHAM (P = 0.001 and P = 0.003 respectively). Cytosolic and Nuclear p-p38 MAPK content increased from baseline to PE in IREF (P = 0.008 and P = 0.005, respectively) but not SHAM. NRF1 and TP53 mRNA expression were greater in IREF compared to SHAM PE (P ≤ 0.013) and 3hPE in NRF1 only (P = 0.002). There was no change in the phosphorylated protein content or gene expression of any angiogenesis related target in IREF compared to SHAM. Wearing IREF before, during and following HIIE augments some of the acute cellular signalling cascades associated with mitochondrial biogenesis.

Advanced footwear technology (AFT) improves running economy and is credited with recent performance improvements in road running, with observational analyses consistently demonstrating that women have improved more than men. In contrast, laboratory studies generally report similar running economy responses to AFT in both sexes, leaving the observational-experimental divergence unresolved. A fundamental limitation of observational work is the absence of a control condition, making it impossible to separate AFT-related gains from concurrent performance trends. We addressed this by comparing performances between pre-AFT (2009-2015) and AFT (2017-2024) eras across road-running events (10km, half marathon, marathon) and throwing events, the latter serving as an active control condition subject to the same broad athletic trends but unaffected by footwear technology. The top 50 performances per event, era, and sex were converted to World Athletics points and analysed using linear mixed-effects models. Performances improved between eras (β = 0.294, p < .001), with gains substantially larger in road running than in throwing (β = 0.731, p < .001). The sex-specific pattern of improvement also differed between event categories (era × event type × sex interaction, β = 0.786, p < .001): road-running improvements were greater in women than men (4.51% vs 2.62%), whereas throwing improvements did not differ by sex (0.93% vs 1.14%). These findings suggest that AFT benefits women more than men in competition, whether through a greater physiological response or more effective translation of economy gains to race performance, and suggest current laboratory protocols may be insufficiently sensitive to detect potential sex-specific effects.

Calfactant is an animal-derived surfactant, FDA-approved for endotracheal tube administration. Complications during surfactant administration may be related to the volume being delivered. We conducted a controlled comparison of calfactant against a more concentrated, lower volume calfactant. We compared the efficacy and complications of delivery of the two calfactant formulations to each other, and to no surfactant treatment, in the well-established preterm newborn lamb model of surfactant-deficient respiratory distress syndrome. After initial stabilization, a single dose of liquid calfactant or sham air instillation was given, and animals were maintained on mechanical ventilation for up to 6 hours. Reflux of surfactant into the endotracheal airway occurred in 83% of calfactant-treated lambs versus 33% of a more concentrated, lower volume calfactant-treated lambs. Lambs treated with a more concentrated, lower volume calfactant required less positive pressure breaths to clear refluxed surfactant (4 ± 2 versus 30 ± 8) and less time to deliver surfactant (70 ± 10 seconds, versus 130 ± 29 seconds). Ventilation and oxygenation improved significantly in surfactant-treated lambs, but not in controls. Four of six control lambs met adverse endpoint criteria prior to 6 hours, while surfactant-treated lambs remained stable up to 6 hours. We conclude that a more concentrated, lower volume calfactant has similar efficacy to calfactant but can be delivered more quickly and with less risk of complications.

High doubly labeled water (DLW) derived total energy expenditure (TEE) and water turnover (rH2O) occur during 161km (100-mile) ultramarathons. TEE and rH2O during races exceeding 161km and requiring multiple days to complete constitute an anomalous physiological stressor to further elucidate duration-dependent limits of human endurance. PURPOSE: To quantify TEE and rH2O during a multi-day mountain ultramarathon. METHODS: Two runners (female [R1], male [R2]), completed 322km following DLW (2H218O) consumption. TEE and rH2O were calculated from urinary isotopic elimination rates. Race-provided GPS monitors measured duration, moving time, and non-activity time. RESULTS: R1 finished in 73.6h at a pace of 1.3 m·s-1 with non-activity/rest time totaling 32% of the race (50.3h moving, 23.3h resting). In-race TEE for R1 was 123.9 MJ (29,376 kcals) and 35.5 MJ·d-1 (8,408 kcals·d-1, 5.6 times the basal metabolic rate [×BMR]) when expressed per 24h. In-race rH2O for R1 was 35.2 L (10.1 L·d-1). R2 finished in 89.9h at a pace of 1.0 m·s-1 with non-activity/rest time totaling 52% of the race (43.0h moving, 46.9h resting). In-race TEE for R2 was 164.2 MJ (38,909 kcals) and 41.1 MJ·d-1 (9,737 kcals·d-1, 5.0 ×BMR) when expressed per 24h. In-race rH2O for R2 was 47.5 L (11.9 L·d-1). CONCLUSIONS: Akin to 161km events, multi-day events are exceptional human endurance feats, demonstrating large absolute TEE and rH2O values. However, the daily TEE range of multi-day events appears diluted by unique non-activity time needs (rest, sleep). Thus, the human endurance metabolic ceiling will be largely contingent upon event duration.

Sex differences in exercise hyperemia remain unclear, and the role of β-adrenergic receptors (β-AR) in this response is unknown. Accordingly, we examined the role of β-AR in modulating central and peripheral hemodynamic responses to rhythmic handgrip exercise in 10 females and 7 males under control conditions (CON) and during β-AR blockade with oral propranolol (PROP). Participants completed a low-intensity (10% MVC) and incremental (40, 80, 120 N) rhythmic handgrip exercise. Hemodynamic variables, including heart rate (HR), mean arterial pressure (MAP), brachial artery diameter (BAD), forearm blood flow (Q̇ARM), and vascular conductance (VCARM) were assessed at baseline and during steady state exercise for each intensity. The overall hyperemia response was assessed as the slope of the relationship between Q̇ARM and VCARM over exercise intensity. β-AR blockade was achieved with two 80mg doses of oral HCl propranolol administered 7.5 and 1.5 hours prior to the PROP visit. β-adrenergic blockade reduced HR and absolute Q̇ARM in males and females (both, p<0.05), but not MAP (p=0.49). The overall exercise hyperemia slope response for Q̇ARM and VCARM did not differ by sex or with β-AR blockade (both p>0.05), even after adjusting to maximal handgrip strength (both, p>0.05). The relative increase in BAD from baseline was blunted in females (p=0.03) but not males (p=0.96) during PROP. In conclusion, the exercise hyperemia response is preserved in males and females with systemic β-adrenergic receptor blockade. However, young females appear to have a greater reliance on β-AR relative to males in mediating macrovascular tone during exercise.

After adaptation to weightlessness, astronauts will experience head-to-foot accelerations (G) during descent to and ascent from the lunar surface that may provoke symptoms of orthostatic intolerance (OI). There were no reports consistent with OI among Apollo astronauts who experienced up to 10 minutes of 0.4-0.6 G, while standing without OI countermeasures during dynamic flight phases, though heart rate (HR) was elevated. The likelihood of developing OI in future Artemis crews, which will include females, may be greater given observations of increased OI in females and potentially greater acceleration requirements. We assessed orthostatic tolerance and cardiovascular responses in 34 healthy individuals (16 females) during 20 minutes of 30, 50 and 80° head-up tilt (HUT), simulating sustained accelerations (0.50-, 0.75, 1.00-G) after pharmacologically-induced hypovolemia (~10% plasma volume loss) as a short-duration spaceflight model. On a separate day using the same model, we evaluated the efficacy of a lower body orthostatic intolerance garment (OIG), to prevent OI. Tilt tolerance time without OIG was 4.6 minutes greater in males than females during 80° HUT (p=0.003). Without OIG, hypovolemic females demonstrated lower mean arterial pressures prior to and during HUT at 80° compared to males (p=0.038). OIG use increased tolerance by 4.2 (P<0.001) and 1.6 minutes (P=0.007) for 80 and 50° HUT, respectively, and attenuated the increase in HR and decrease in SV, which was greater in females (P<0.001). Hypovolemic females demonstrated an increased cardiovascular response to HUT contributing to differences in OI throughout 20-minute exposures and the OIG demonstrates protection in all participants.

Previous studies have reported that non-Hispanic Black males exhibit augmented blood pressure (BP) responses to dynamic exercise relative to White males; however, the underlying mechanism(s) remain unclear. To our knowledge, no studies have examined the muscle sympathetic nerve activity (MSNA) response to dynamic exercise in BL adults. The purpose of this study was to examine potential racial differences in the sympathoinhibition that occurs at the onset of dynamic exercise. We hypothesized that cardiopulmonary baroreflex-mediated inhibition of sympathetic vasomotor outflow during the onset of low-intensity dynamic exercise is diminished in BL individuals. MSNA was recorded via microneurography of the left radial nerve in nine non-Hispanic Black (BL; 20±3 years, mean±SD) and eleven non-Hispanic White (WH; 22±4 years) males. BP was measured by finger photoplethysmography, which was verified by automated brachial BP measures. Participants performed 3 minutes of bilateral leg cycling at 15 watts on a cycle ergometer in the 70-degree semirecumbent position. MSNA burst frequency (BF) decreased during cycling in both groups; however, the decrease was significantly smaller (P<0.001) in the BL group (-4.7±3.7 bursts/min) than in the WH group (-11.3±5.0 bursts/min). Mean BP increased during cycling in both groups, with no significant difference between the two groups (BL, +7.4±4.2 vs. WH, +6.9±7.1 mmHg, P=0.958). These findings suggest that cardiopulmonary baroreflex-mediated inhibition of sympathetic vasomotor outflow at the onset of dynamic exercise is diminished in BL males compared to WH males.

Marked inter-individual variability in muscle strength exists among older adults which cannot be fully explained by differences in muscle mass alone. Although motor unit remodeling is a characteristic feature of neuromuscular aging, whether variability in motor unit remodeling contributes to inter-individual differences in muscle strength remains unclear. The purpose of this study was to examine the association between motor unit remodeling and muscle strength in older adults. Forty-nine older adults (25 men and 24 women) participated in this study. Motor unit parameters of the abductor pollicis brevis muscles were estimated using the MScanFit2 program. From the stimulus-response curve, motor unit number estimation (MUNE), A50, the largest surface motor unit potential (L-sMUP) (motor unit size), N50, and N50/MUNE (motor unit size composition) were derived. Associations between motor unit parameters and pinch strength were examined using partial correlation analyses adjusted for age, sex, and body weight. Sex-specific analyses were also performed. Pinch strength was significantly correlated with MUNE (r = .360, P = .014), A50 (rs = -.394, P = .007), L-sMUP (rs = -.389, P = .007), N50 (r = .416, P = .004), and N50/MUNE (r = .439, P = .002). These correlations remained significant only in men in sex-specific analyses. A lower motor unit number and shift toward larger motor unit sizes, reflecting greater motor unit remodeling, were associated with lower pinch strength. These findings suggest that motor unit remodeling may contribute to inter-individual variability in muscle strength among older adults, particularly men.

Physical activity during pregnancy is highly beneficial, but the mechanisms underlying these benefits have not been elucidated. Given its central role in supporting pregnancy, the placenta is a primary target for investigation. We implemented untargeted lipidomic analysis on 36 human placenta samples collected at term from uncomplicated pregnancies. Participant activity levels were objectively measured using accelerometry and participants were categorized as active or inactive. Samples were assessed by LC-MS/MS. The docosahexaenoic acid (DHA) transporter major facilitator superfamily domain-containing 2a (MFSD2a) was analyzed with western blot. A total of 192 lipids were annotated. Among these, 34 lipid species differed significantly between groups (|log2FC| ≥ 0.58; FDR-adjusted p value < 0.05). Multivariate analyses demonstrated modest separation between groups. DHA was identified in 17 lipid species, and seven were higher in the active group. Area under the receiver operating characteristic curve (AUROC) revealed five lipids with perfect group separation. Pathway analysis showed enrichment of the phosphatidylserine decarboxylase (PISD) pathway in the active group. No differences in MFSD2a expression were identified. The results demonstrate a relationship between physical activity and the placental lipidome. Several DHA species are higher in the active group, suggesting improved fetal availability for brain and retinal development. Lipids with perfect group separation may represent biomarkers of physical activity. Multiple lipid species and pathways warranting future targeted investigation are highlighted.

Reduced preferred walking speed (PWS) is a known indicator of increased fall risk, particularly sideways falls in individuals with reduced physical capacity, often attributed to decreased mediolateral stability in the frontal plane. The underlying mechanisms and the impact of walking speed on inter-plane balance control coordination remain unclear. The current study aimed to develop a novel analytical framework for quantifying the sagittal and frontal inter-plane coordination of COM-COP control and its variabilities during level walking via continuous relative phase (CRP) angles and to study the walking speed effects. Fifteen young adults walked at PWS, slower and faster, while the COM-COP inclination angles (IA) and their rates of change (RCIA) were measured to calculate inter-plane CRP patterns. The deviation phases (DP) of CRP curves quantified the variability of inter-plane coordination. The inter-plane balance control coordination and variability were significantly influenced by walking speed, with minimum DP values occurring during double limb support at PWS. Walking at one's PWS represents the best compromise for minimising control variability between the sagittal and frontal planes. This novel approach highlights the role of inter-plane balance control variability in determining PWS in young adults and emphasises the importance of monitoring these variables for fall risk assessment.

Hyperhidrosis is characterized by excessive sweating, typically in the palmar and axillary regions. Individuals with severe cases of hyperhidrosis can be treated surgically via endoscopic thoracic sympathectomy to disrupt the neural connection between the spinal cord and the affected regions, thereby attenuating sweating in the hyperhidrotic regions. However, the effects of this procedure on skin blood flow and sweating responses to whole body heat stress in regions not targeted by the sympathectomy, such as the forearm, are unknown. We tested the hypothesis that surgical sympathectomy attenuates the increase in forearm cutaneous vascular conductance and sweating during whole body heat stress. Before and 7 ± 1 wk following bilateral thoracic surgical sympathectomy, forearm skin blood flow (laser-Doppler imaging) and local sweat rate (capacitance hygrometry) were assessed during whole body passive heat stress sufficient to elevate core temperature by ∼1°C (P = 0.74 between trials) in 10 subjects (27 ± 3 yr; 7 females). The mean increase in forearm cutaneous vascular conductance was attenuated following sympathectomy (Δ3.67 ± 1.34 flux·mmHg[-1] vs. Δ1.62 ± 1.19 flux·mmHg[-1]; P < 0.01). Similarly, mean sweat rate was attenuated in the palmar (Δ0.68 ± 0.42 mg·min[-1]·cm[-2] vs. Δ0.20 ± 0.25 mg·min[-1]·cm[-2]; P = 0.015) and forearm (Δ0.62 ± 0.31 mg·min[-1]·cm[-] vs. Δ0.24 ± 0.26 mg·min[-1]·cm[-2]; P = 0.03) regions following sympathectomy. These data suggest that the increase in forearm cutaneous vascular conductance and sweat rate in response to whole body heat stress is attenuated by ∼50% after surgical sympathectomy. However, the implications of these responses on whole body thermoregulation remain unknown.NEW & NOTEWORTHY Thoracic surgical sympathectomy is often performed to attenuate sweating in the palmar and axillary regions in individuals with hyperhidrosis. However, the effect of this procedure on efferent thermoregulatory responses to heat stress is unknown. We show that the increase in forearm cutaneous vascular conductance and local sweat rate is attenuated during whole body passive heating following a surgical sympathectomy.

Purpose: To assess longitudinal changes in official competitive performance in elite runners with androgen-sensitive 46,XY differences of sex development (DSD) during prolonged testosterone suppression. Methods: This retrospective longitudinal study analyzed nine elite 46,XY DSD runners with type II 5α-reductase deficiency who maintained serum testosterone below 2.5 nmol/L after gonadectomy, gonadotropin-releasing hormone agonist treatment, or combined oral contraceptive use. Outdoor performances in sprint, middle-distance, and long-distance events were evaluated. Semester-best performances were compared with pre-suppression personal bests and expressed as percentage change and World Athletics World Ranking points. Results: Before treatment, mean serum testosterone was 22.5 ± 6.5 nmol/L. Follow-up included 16 performance profiles and 44 semester-best observations over 0-1258 days of suppression. Competitive performance declined after testosterone suppression, with mean decrements of 6.0%, 7.1%, 6.5%, 7.2%, 6.6%, and 4.4% across successive semesters. Across the full observation period, the mean performance decrement was 6.5 ± 3.6%, and after two years it remained approximately 6.0 ± 4.5%. No significant difference in percentage decrement was observed between sprint and middle-/long-distance groups, although substantial interindividual variability was present. Conclusion: Sustained testosterone suppression in elite androgen-sensitive 46,XY DSD runners was associated with a clear but heterogeneous reduction in competitive performance. In several athletes, the decrement remained smaller than the expected elite male-female performance gap, suggesting that prior male-range androgen exposure may confer advantages not uniformly abolished by current testosterone suppression.