Type 2 diabetes (T2D) is a metabolic disease associated with cardiovascular dysfunction. The myocardium preferentially uses ketones over free fatty acids as a more energy efficient substrate. The primary aim was to assess the effects of ketone monoester (K) ingestion on cardiac output index (). Secondary aims were to assess the effects of K ingestion on markers of cardiac haemodynamics, muscle oxygenation and vascular function at rest, during and following step-incremental cycling. We undertook a double-blind, randomised, crossover design study in 13 adults (age, 66±10 y; BMI, 31.3±7.0 kg·m) with T2D. Participants completed two conditions, where they ingested a K (0.115 g‧kg) or a placebo taste-mathced drink. Cardiac function was measured using thoracic impedance cardiography and muscle oxygenation of the calf was determined via near-infrared spectroscopy. Macrovascular endothelial function was measured by flow mediated dilation (FMD) and microvascular endothelial function was measured via transdermal delivery of acetylcholine (ACh) and insulin. Circulating β-hydroxybutyrate [β-Hb] was measured throughout. K ingestion raised circulating β-Hb throughout the protocol (peak 1.9 mM; =0.001 vs. placebo). K ingestion increased by 0.75±0.5 L∙min∙m (=0.003) stroke volume index by 7.2±4.5 mL∙m (=0.001), and peripheral muscle oxygenation by 9.9±7.1% (=0.001) and reduced systemic vascular resistance index by-420±-225 dyn∙s∙cm∙m (=0.031) compared to placebo condition. There were no differences between K and placebo in heart rate (=0.995), FMD (=0.542), ACh max (=0.800), insulin max (=0.242). Ingestion of K improved , stroke volume index and peripheral muscle oxygenation, but did not alter macro- or microvascular endothelial function in people with T2D.

Proximal limb cuff inflation to 40% arterial occlusion pressure (AOP) is assumed to reduce exercising leg perfusion, creating "blood flow restriction" (BFR). However, no study has validated this assumption. 18 healthy young participants (9F) performed two-legged knee flexion/extension exercise at 25% WRpeak with bilateral cuffs applied to the proximal thigh at 0% AOP (CTL), 20% AOP and 40% AOP. Leg blood flow (LBF; Doppler and echo ultrasound) and cardiac output (CO; finger photoplethysmography) were measured during rest and exercise. LBF values were doubled to account for both exercising legs. 20% and 40% AOP reduced exercising LBF in a dose-response manner (<.01). However, the magnitude of the leg blood flow restriction by 40% AOP was progressively attenuated across the exercise bout (5-15s: 37%, 50-70s: 20%, 240-300s: 16%; <.01) due to compensatory increases in leg vascular conductance (LVC) (<.01). Between 5-15s of exercise, 40% AOP significantly reduced CO compared to CTL and 20% AOP (8.0 ± 1.3 vs. 8.4 ± 1.5 L/min, <.001 and 8.5 ± 1.5, <.001). By 240-300s, there were no significant differences in CO between cuff pressures (all >.13). Pneumatic cuff inflation at 20% and 40% AOP reduces LBF in a dose-response manner, but this impairment was progressively attenuated across the exercise bout by an increase in LVC. Importantly, this compensatory response differed across participants, which may have implications for the degree of adaptations following BFR training. Furthermore, restoration of normal CO during BFR despite compromised limb perfusion suggests other tissue perfusion is increased as part of the response.

High cardiorespiratory fitness (CRF) is associated with reduced cortical thinning and gray matter (GM) shrinkage in older adults. We investigated associations of CRF measured with peak oxygen consumption (V̇ O) with cortical thickness and GM volume across the adult lifespan. We hypothesized that higher CRF is associated with less cortical thinning and GM shrinkage across the adult lifespan, which is associated with better cognitive performance. This cross-sectional study recruited 172 sedentary yet healthy adults (65% women, 22-81 years) who underwent treadmill exercise testing to measure V̇ O, structural MRI to assess cortical thickness and GM volume, and a comprehensive cognitive test battery to assess fluid cognitive function. Linear regression models were used to examine the associations of total and regional cortical thickness and GM volume with age, V̇ O, and age × V̇ O interaction after adjusting for sex, education, and total intracranial volume, and the associations of cortical thickness and GM volume with fluid cognitive performance. Mean and regional cortical thickness and total GM volume were associated negatively with age, while no associations were observed with V̇ O. However, a significant interaction between age and V̇ O on the right superior parietal volume indicated that aging was associated with smaller right superior parietal volume in the lower CRF group, while no association was observed in the higher CRF group. Larger right superior parietal volume was associated with better fluid cognitive performance. These findings highlight the importance of maintaining CRF to prevent or slow brain aging from an adult lifespan perspective.

The compliant nature of cerebral blood vessels may represent an important mechanical protection for sustained cerebral perfusion during reductions in arterial blood pressure (ABP). However, whether the rise in cerebrovascular compliance (Ci) with falling ABP persists and exhibits a threshold effect remains unknown. Therefore, we analyzed Ci changes during graded head-up tilt (HUT) in individuals with autonomic failure (AF), a group that tolerates graded and progressive reductions in ABP. Finger ABP and middle cerebral artery blood velocity (MCAv) were recorded from five AF patients (61 ± 22 years) at supine rest and during graded-HUT. Tilt gradients increased incrementally between 30, 45, and 60 degrees every 5 minutes until ABP reached a critically low value. The total time in HUT was 11 ± 4 min. Every 5 s during supine and HUT individual ABP and MCAv waveforms were assessed for Ci and cerebrovascular resistance (CVR) using a modified Windkessel model. Pulse pressure (PP) was calculated as systolic ABP - diastolic ABP. A threshold value for the increase in Ci was determined using breakpoint analysis of the linear relationship between changes in Ci and PP or ABP across tilt periods. Graded HUT resulted in reduced ABP, PP, CVR, and mean MCAv, and increased Ci (all P < 0.01). Ci began to increase progressively after PP fell by 22 ± 6 mmHg and ABP fell by 20 ± 11 mmHg. In conclusion, the increase in Ci during progressive hypotension exhibited a threshold effect and persisted as ABP continued to fall.

This study assessed the cardiorespiratory fitness, running biomechanics, muscle architecture and training characteristics of a 76-year-old female runner who currently holds the world record 1500m to marathon in the women's 75-79 age category. maximal oxygen uptake (V̇O), running economy (RE), lactate threshold (LT) and lactate turnpoint (LTP), maximal heart rate (HR), and running biomechanics were measured during a discontinuous treadmill protocol followed by a maximal incremental test. Muscle architecture was assessed using ultrasound. The testing was done in close proximity to her world record marathon performance in 2024. V̇O was 47.9 ml∙kg∙min, and HR was 180 beats∙min. At marathon speed (11.9 km∙h) her RE was 210 ml∙kg.km. Fractional utilisation corresponding to LT (11.1 km∙h) and LTP (12.5 km∙h) occurred at 83% and 92% of V̇O, respectively. Fractional utilisation at marathon speed corresponded to 88% of V̇O. Average weekly distance was 115 and 84 km∙w in the 6 weeks prior to the marathon world record and world-championships track (where she achieved 6 medals out of 6 events), respectively, with on average 90%, 9%, and 1% of training time performed in the moderate, heavy, and severe intensity domain, respectively. The 76-year-old female world-record holder 1500m to marathon showed the highest V̇O ever recorded for a female >75 years old, a very high fractional utilization of V̇O at LT, LTP, and at marathon pace, but RE was modest in comparison to other world-class master athletes and younger elite runners.

Remote Ischemic Preconditioning (RIPC) is a therapy characterized by repeated bouts of limb ischemia and reperfusion. RIPC protects against ischemia-reperfusion injury (IRI), and preclinical studies suggest that this is mediated through release of endogenous opioids. We aimed to interrogate the role of endogenous opioids in RIPC-signaling in humans, using an arm model of IRI. We hypothesized that RIPC would attenuate IRI-induced reductions in brachial artery flow mediated dilation (FMD), and that this would be prevented by systemic opioid receptor blockade. 11 healthy adults (8M/3F, age=28±8y) completed three experimental visits in which IRI was induced via 20-min upper arm ischemia and 20-min reperfusion achieved via upper arm cuff inflation to 250mmHg. FMD was measured at rest and again following IRI. During the control condition, RIPC was not performed. During the RIPC condition, RIPC was performed on the contralateral arm via 4 cycles of 5-min cuff inflation (250mmHg) with 5-min reperfusion. During the opioid receptor blockade condition (Naloxone), RIPC was performed in the presence of systemic opioid receptor blockade via intranasal naloxone (4mg) which was administered during the first 5-min cycle of RIPC. The change in FMD from baseline vs post-IRI were compared between visits via a two-way repeated measures ANOVA (factor 1: , factor 2, ) followed by Tukey post-hoc tests. IRI reduced FMD during the Control (Pre=6.1±2.4%, Post=3.5±2.8%, P<0.001) and Naloxone (Pre=6.6±2.7%, Post=3.5±1.9%, P<0.001) conditions but not during the RIPC condition (Pre=5.9±2.2%, Post=4.9±2.8%, P=0.14). These findings demonstrate that RIPC provides vascular protection from IRI in humans through an opioid-dependent mechanism.

We investigated the associations of ongoing, chronic stress exposure and stress appraisal on vascular endothelial function (VEF) in young adults. In 72 healthy young adults (74% female; age = 25±1 y), we assessed chronic stress exposure and appraisal with a measure that quantified chronic stress exposure and chronic stress appraisal related to 8 specific stressors over the last year. Participants completed the perceived stress scale (PSS) as a measure of global, proximal stress appraisal. VEF was assessed using the brachial artery flow mediated dilation technique. We examined relations among ongoing, chronic stress exposure and stress appraisal versus VEF adjusted for age and sex, and then assessed whether stress appraisal moderated the effect of chronic stress exposure on VEF. Chronic stress exposure (β=-0.24, =.045), but not chronic stress appraisal (β=0.07, =.56) or perceived stress (β=-0.20, =.11), was related to VEF. Perceived stress (p = .046), but not chronic stress appraisal (=.54), moderated the association between chronic stress exposure and VEF. The effect of chronic stress exposure on VEF ceased to be significant at a PSS score of ~22. Subsequent exploratory stratified analysis indicated that those with PSS ≥22 had increased exposure to adverse childhood experiences (+1.6±0.6, =.01), greater depressive symptoms (+10.2±2.7, <.001), and reduced psychological resilience (-7.6±3.5, =.036). Chronic stress exposure significantly predicts impaired VEF among young adults. Further, this relation is influenced by proximal perceived stress, such that the association of chronic stress exposure on VEF may be obscured at high levels of proximal perceived stress.

The original concept of the airway-to-lung size mismatch, termed dysanapsis, was introduced on spirometry and was extended by computed tomography (CT) evaluation of the central airways. CT-assessed dysanapsis allows a risk estimation of lung disease development in healthy subjects, although radiation exposure limits its use, particularly for younger subjects. This study investigated which spirometry indices can be used to estimate CT-assessed central airway dysanapsis in healthy subjects. In consecutive lung cancer screening subjects without active lung diseases, the dysanapsis ratio (DR), forced mid-expiratory flow/forced vital capacity (FEF/FVC), forced expiratory volume in 1 second/FVC (FEV/FVC), and peak expiratory flow/FVC (PEF/FVC) were obtained via spirometry. The airway-to-lung size ratio for 4 locations, including the trachea, both main bronchi, and bronchus intermedius (ALR4), and for 14 locations, including the same 4 airways and 10 segmental and subsegmental airways (ALR14), were obtained via CT. According to the quartiles of the ALR14 or ALR4, 163 male and 190 female subjects were divided into 4 groups. CT-assessed dysanapsis was defined as the lowest quartile of the ALR14 (or ALR4). Among the spirometry indices, the area under the curve (AUC) for detecting the lowest ALR14 group was the highest for DR (0.80 and 0.78 for males and females, respectively). In contrast, the AUC for detecting the lowest ALR4 group was the highest for PEF/FVC (0.67 and 0.77 for males and females, respectively). DR and PEF/FVC on spirometry could be associated with CT-assessed dysanapsis, but the associations varied depending on the airway locations used for the ALR calculation.

Short duration heat acclimation (HA) (≤5 daily heat exposures) elicits incomplete adaptation compared to longer interventions, possibly due to the lower accumulated thermal 'dose'. It is unknown if matching thermal 'dose' over a shorter timescale elicits comparable adaptation to a longer intervention. Using a parallel-groups design, we compared: i) 'condensed' HA (CHA; =17 males) consisting of 4×75 min∙day heat exposures (target rectal temperature ()=38.5°C) for 2 consecutive days, with; ii) 'traditional' HA (THA; =15 males) consisting of 1×75 min∙day heat exposure (target =38.5°C) for 8 consecutive days. Physiological responses to exercise heat-stress, hypoxia, and normoxic exercise performance were evaluated pre- and post-intervention. Thermal ( over final 45 min: CHA=38.45±0.17°C, THA=38.53±0.13°C, =0.126) and cardiovascular strain were not different during interventions, indicating similar thermal 'dose', although CHA had lower sweating rate, higher starting , and greater inflammation, gastrointestinal permeability and renal stress (<0.05). However, CHA elicited an array of thermophysiological adaptations that did not differ from THA (reduced indices of peak thermal [, Δ peak CHA=- 0.28±0.26°C, THA=-0.36±0.17°C, =0.303] and cardiovascular strain, inflammation and renal stress; blood and plasma volume expansion; improved perceptual indices), although improvements in resting thermal strain (, Δ resting CHA=-0.14±0.21°C, THA=- 0.35±0.29°C, =0.027) and sweating rate were less with CHA. Both interventions improved aspects of hypoxic tolerance, but effects on temperate normoxic exercise indices were limited. The diminished thermal strain was well-maintained over a 22-day decay period. In conclusion, CHA could represent a viable acclimation option for time-restricted young healthy-males preparing for a hot, and possibly high-altitude, environment.

Impaired glycemic control increases the risk for type 2 diabetes (T2D) and Alzheimer's Disease (AD). Heat therapy (HT), via hot water immersion (HWI), has shown promise in improving shared mechanisms implicated in both T2D and AD, like blood glucose regulation, insulin sensitivity, and inflammation. The potential for HT to improve brain health in individuals at risk for AD has not been examined. This pilot study aimed to assess the feasibility and adherence of utilizing HT in cognitively healthy older individuals at risk for AD due to existing metabolic risk factors. Participants underwent four weeks of HT (three sessions/week) via HWI, alongside cognitive screening, self-reported sleep characterization, glucose tolerance tests, and MRI scans pre- and post-intervention. A total of 18 participants (9 male, 9 female; mean age: 71.1 ± 3.9 years), demonstrating metabolic risk, completed the intervention. Participant adherence for the study was 96% (8 missed sessions out of 216 total sessions), with one study related mild adverse event (mild dizziness/nausea). Overall, the research participants responded to a post-intervention survey saying they enjoyed participating in the study and it was not a burden on their schedules. Secondary outcomes of the HT intervention demonstrated significant changes in mean arterial pressure, diastolic blood pressure, and cerebral blood flow p<0.05), with a trend toward improved body mass index (p=0.06). Future studies, including longer durations and a thermoneutral control group, are needed to fully understand heat therapy's impact on glucose homeostasis and potential to improve brain health.

Violation of the National Institute of Occupational Safety and Health (NIOSH) heat stress recommendations by exceeding the allowable wet bulb globe temperature (WBGT) for a given work intensity and work-rest ratio augments acute kidney injury (AKI) risk. Here we tested the hypothesis that exceeding the allowable work intensity at a given WBGT and work-rest ratio would also worsen AKI risk. Twelve healthy adults completed two NIOSH recommendation compliant trials and one noncompliant trial consisting of a 4 h (half workday) exposure. Work-rest ratio was fixed at 30 min of walking and 30 min of rest each hour. Work intensity (metabolic heat production) was prescribed as a function of WBGT- 412±51 W (27.3±0.3°C; high intensity compliant [C]), 290±75 W (31.6±0.2°C; low intensity compliant [C]), and 410±61 W (31.7±0.2°C; high intensity noncompliant [NC]). AKI risk was quantified by the product of urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinase 2 normalized to urine specific gravity ([IGFBP7•TIMP-2]). Peak core temperature was higher in NC trial (38.3±0.4°C) compared to the compliant trials (C: 38.0±0.3°C; C: 37.8±0.4°C; p≤0.0095). [IGFBP7•TIMP-2] increased from pre- to immediately postexposure in all trials (time effect: p=0.0454) but the peak increase was not different between trials (C: 0.89±1.7 [ng/mL]/1000; C: 0.78±1.7 [ng/mL]/1000; NC: 1.0±1.4 [ng/mL]/1000; p=0.7811). Violating the NIOSH recommendations by exceeding either the allowable work intensity (i.e., NC versus C) or WBGT (i.e., NC versus C) resulted in a modest elevation in peak core temperature but did not modify AKI risk.

This study compared oxygen consumption and substrate oxidation while exercising in hot and temperate conditions in individuals with different physical activity status (i.e., inactive individuals vs. trained runners). 10 inactive individuals (IA: 26 ± 6 y; 79.1 ± 14.1 kg; 40.7 ± 5.1 ml·kg·min) and 10 trained runners (TR: 25 ± 6 y; 69.5 ± 9.1 kg; 63.1 ± 5.1 ml·kg·min) completed two incremental exercise tests (4 min stages) until exhaustion in temperate (TEMP: 18.7 ± 0.1 °C; 43.2 ± 4.1% relative humidity) and hot (HOT: 34.4 ± 0.2 °C and 42.6 ± 1.6% relative humidity) conditions. Expired gas and blood lactate concentrations were measured at the end of each stage. Peak oxygen consumption similarly decreased in HOT compared to TEMP for IA and TR (-13.2 ± 4.5% vs. -15.2 ± 7%; =0.571; ES=0.25). In HOT compared to TEMP, lipid oxidation, from 30 to 70% of V̇O, was reduced for both groups (IA: =0.023, ES=0.43; TR: <0.001, ES=0.72) while carbohydrate oxidation was increased for TR (=0.011; ES=0.45) but not for IA (=0.268; ES=0.21). Core temperature was different between conditions for TR (higher in HOT, =0.017; ES=0.66) but not for IA (=0.901; ES=0.25). Despite reduced physiological capacities in IA, both populations demonstrated reductions in lipid utilisation and peak oxygen consumption in hot compared to temperate conditions. However, the increased carbohydrate oxidation in HOT for TR were not observed in IA, potentially explained by lower thermal strain.

We tested the hypothesis that power at maximal metabolic steady state is similar between fitness matched men and women. Eighteen participants (9 men, 9 women) performed a cycling graded exercise test for maximal oxygen consumption (V̇O). Men and women were matched for V̇O normalized to fat free mass (FFM), which was 50.4±4.7 ml·min·kg FFM and 52.1±8.2 ml·min·kg FFM, respectively (P=0.62). Participants completed a muscle oxygenation (%SmO) zero-slope prediction trial and a 3-min trial (3MT). The %SmO zero-slope trials included three, 5-min cycling bouts (30 sec rest) spanning intensity domains. Linear regression of trial work rate and %SmO slope over the final three minutes established the work rate occurring at the predicted zero slope in %SmO2. The 3MT requires all-out cycling, where end test power (ETP) was calculated as the mean power output over the last 30 sec and work above end test power (WEP) as the power-time integral above ETP. Independent of method, mean (±SD) absolute power at the maximal metabolic steady state was similar between fitness matched women and men (P=0.72), yet became higher in women when expressed relative to FFM (P=0.02). V̇O at the power associated with %SmO2 zero-slope represented a significantly higher fraction of V̇O for women compared to men (P=0.03). Normalized WEP (Watts/kg FFM) remained higher in men (P<0.01). Although highly correlated (r=0.88, P<0.01), ETP was ~8% higher than %SmO zero-slope power (P=0.03). Compared to fitness matched men, women displayed higher FFM normalized power associated with the heavy-severe exercise domain boundary.

We sought to examine how resistance training (RT) status in young healthy individuals, either well resistance trained (T, n=10) or untrained (UT, n=11), affected molecular markers with leg immobilization followed by recovery RT. All participants underwent two weeks of left leg immobilization via a locking leg brace. Afterwards, all participants underwent eight weeks (3 d/week) of knee extensor focused progressive RT. Vastus lateralis (VL) ultrasound-derived thickness and muscle cross-sectional area were measured at baseline (PRE), immediately after disuse (MID), and after RT (POST) with VL muscle biopsies also being collected at these time points. Both groups presented lower ultrasound derived VL size metrics at MID versus PRE (p<0.001), and values increased in both groups from MID to POST (p<0.05); however, VL size increased from PRE to POST in UT only (p<0.001). Mean and type II myofiber cross-sectional area values were greater at PRE and POST versus MID (p<0.05), with T being greater than UT throughout (P<0.012). In both groups, satellite cell number was not affected by leg immobilization but increased in response to RT (p<0.014), with T being greater than UT throughout (p=0.004). Total RNA (ribosome content) decreased (p=0.010) from PRE to MID, while total RNA and certain endoplasmic reticulum stress proteins increased from MID to POST regardless of training status. Immobilization-induced muscle atrophy and recovery RT hypertrophy outcomes are similar between UT and T participants, and the lack of molecular signature differences between groups supports these findings. However, results are limited to younger adults undergoing non-complicated disuse.

There is growing interest in understanding the complex relationship between psychosocial stress and the human gastrointestinal microbiome (GIM). This review explores the potential physiological pathways connecting these two and how they contribute to a pro-inflammatory environment that can lead to the development and progression of the disease. Exposure to psychosocial stress triggers the activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary axis (HPA), leading to various physiological responses essential for survival and coping with the stressor. However, chronic stress in susceptible individuals could cause sustained activation of HPA and SNS, leading to immune dysregulation consisting of redistribution of NK cells in the bloodstream, decreased function of T and B cells, and elevation of proinflammatory cytokines such as IL-1, IL-6, TNF-ɑ, IFN-γ. It also leads to disruption of the GIM composition and increased intestinal barrier permeability, contributing to GIM dysbiosis. The GIM dysbiosis and elevated cytokines can lead to reciprocal effects and further stimulate the HPA and SNS, creating a positive feedback loop that results in a pro-inflammatory state underlying the pathogenesis and progression of stress-associated cardiovascular, gastrointestinal, autoimmune, and psychiatric disorders. Understanding these relationships is critical for developing new strategies for managing stress-related health disorders.

Serotonin (5-HT) is integral to signalling in areas of the brainstem controlling ventilation and is involved in central chemoreception. Selective serotonin reuptake inhibitors (SSRIs), used to effectively increase 5-HT concentrations, are commonly prescribed for depression. The effects of SSRIs on the control of breathing and the potential influence of cerebral blood flow (CBF) have not been directly assessed. We hypothesized that a single SSRI dose in healthy adults would not impact resting ventilation, global CBF, or brainstem blood flow reactivity to CO, but would steepen the slope of the hypercapnic ventilatory response (HCVR). In 15 young, healthy adults (6 female, 25±5years, 70±10kg, 172±15cm, 24±4kg/cm), using a placebo-controlled, double-blind, randomized design, we assessed baseline cardiorespiratory and CBF (duplex ultrasound) responses to SSRI (40 mg citalopram), as well as to hyperoxic hypercapnic rebreathing (as an index of central chemoreception). Baseline measures of mean arterial pressure, heart rate, minute ventilation, CBF and the pressures of end-tidal oxygen and carbon dioxide, were all not influenced by SSRI. Likewise, the sum of blood flowing through both vertebral arteries (as an index of brainstem blood flow) during hypercapnia was also unchanged. In contrast, basal ventilation (during rebreathing following hyperventilation and during hyperoxia) was elevated from 9.5±4.1 to 11.5±5.5 L/min (interaction p=0.023); and, counter to our hypothesis, the central chemoreceptor-mediated ventilatory response to CO was reduced following SSRI from 7.5±5.3 to 5.1±4.1 L/min/mmHg (interaction p=0.027). The implications of these findings in health and pathology remain to be determined.

Disruption of the blood supply to a limb in conjunction with active movement boosts muscle growth, aids in rehabilitation, and allows controlled exploration of the sensorimotor system. Yet, the underlying neuromechanical changes have not been observed in great detail. This study aims to report the acute neuromuscular effects of temporary blood flow restriction (BFR) through behavioral changes at the level of motor units (MUs) using high-density surface electromyography on the abductor digiti minimi muscle during 20 trapezoidal and sinusoidal isometric force tracking tasks (5 pre-BFR, 5 during BFR, and 10 post-BFR). Unsurprisingly, during BFR, reported discomfort levels increased significantly ( < 0.001) regardless of the task (+239% trapezoidal, +228% sinusoidal). However, BFR had very little impact on task tracking performance, though the reconstructed force derived from the underlying neural drive (smoothed cumulative spike train of MUs) deviated substantially during BFR (-40% in trapezoidal, -47% in sinusoidal). Regardless of the condition, the numbers of extracted MUs were consistent (20-26 in trapezoidal, 23-29 in sinusoidal). Interestingly, the inter-spike interval (ISI) of these units increased by 28% in trapezoidal and 24% in sinusoidal tasks during BFR, with ISI steadily returning to original values post-BFR. These results indicate that acute BFR transiently alters the active MU pool, and MU firing behavior, yet only slightly affects the resulting task performance. However, pre-BFR motor function is gradually restored after BFR release. These findings provide insights into the resulting effects of acute BFR administration and the complex response it elicits from the sensorimotor system.

: Cerebrovascular disease and dementia risk increases with age and lifetime risk is greater in women. Cerebrovascular dysfunction likely precedes cerebrovascular disease and dementia but the mechanisms are incompletely understood. We hypothesized that oxidative stress mediates cerebrovascular dysfunction with human aging. : Internal carotid artery dilation (ICA dilation) and middle cerebral artery cerebrovascular reactivity (MCA CVR) in response to hypercapnia (5% CO) was measured in 20 young (10F/10M; age 23±3 years [mean±SD]) and 21 older (11F/10M; age 69±9 years) adults during intravenous infusions of saline (control) and vitamin C (acutely reduced oxidative stress condition). : ICA dilation increased in response to vitamin C infusion in older adults (saline=4.3±2.4%; vitamin C=6.7±3.3%) but was unchanged in young adults (saline=6.1±2.7%; vitamin C=5.5±1.9%) (group*condition: p=0.004). MCA CVRCO2 was not different in response to vitamin C in either group (group*condition: p=0.341). However, when separated by sex, older female participants exhibited increased MCA CVR with vitamin C (saline=0.85±0.79cm/s/mmHg; vitamin C=1.33±1.01cm/s/mmHg) compared to older male participants (saline=1.21±0.57cm/s/mmHg; vitamin C=0.99±0.47cm/s/mmHg) (sex*condition: p=0.011). : Oxidative stress selectively impairs cerebrovascular function in older adults in an artery- and sex-specific manner.

The objective of this study was to explore if the time of day (AM vs PM) resistance exercise is performed influences glucose and insulin concentrations, body composition, and muscular strength in adults with prediabetes. A secondary data analysis was conducted using data from the "Resist Diabetes" study, a phase II exercise intervention. Participants (Age:59.9±5.4 yrs; BMI:33±3.7 kg/m) with prediabetes and overweight or obesity were categorized into AM (N=73) or PM (N=80) exercisers based on when they completed all of their supervised exercise sessions during a 12-week, 2x/week resistance exercise intervention. Blood glucose and insulin derived from oral glucose tolerance tests, body composition, and muscular strength were assessed pre and post resistance exercise training. Inverse propensity score weighting approach was used to estimate the efficacy of AM/PM exercise on the change of clinical responses. Paired samples t-test was used to compare pre-/post outcomes within AM/PM group. No differences between AM and PM exercisers were detected in the change in glucose or insulin areas under the curve (AUC), body composition, or muscular strength. When exploring within-group changes, PM exercisers reduced glucose AUC (change: -800.6 mg/dl*120 min; p=0.01), whereas no significant change was detected for AM exercisers (change: -426.9 mg/dl*120 min; p=0.26). Only AM exercisers increased fat-free mass (change: 0.6 kg; p=0.001). The time of day of resistance exercise is performed may have some impact on glucose concentrations and body composition response. Future randomized clinical trials are needed to understand how exercise timing influences cardiometabolic outcomes in at-risk adults.

Characterizing individual muscle behavior is crucial for understanding joint function and adaptations to exercise, diseases, or aging. Shear wave elastography (SWE) is a promising tool for measuring the intrinsic material properties of muscle. This study assessed the passive and active shear modulus of the triceps surae muscle group in 14 volunteers (7 females, 25.9±2.5 years) using SWE. Ankle moment, surface electromyography, and SWE of the gastrocnemius medialis (GM), gastrocnemius lateralis (GL), and soleus (SOL) muscles were measured from 30° plantar flexion (PF) to 15° dorsiflexion (DF) ankle angles during passive and isometric contractions at 25%, 50%, and 75% of maximum voluntary contraction (MVC). Muscle length, passive and active ankle moment, and passive shear modulus increased from PF to DF (p<0.001 for all). At 15° DF, the passive shear modulus of the SOL was 76% lower than that of the GM (p<0.001), suggesting that the SOL operates within a lower strain range. The active shear modulus decreased from PF to DF (e.g., by 36.8% at 75% MVC, p=0.009) and was lowest in SOL. The decreasing active shear modulus suggests the muscles operate at shorter-than-optimal to optimal lengths. Contraction intensity also affected the shear modulus (p<0.001), indicating distinct force-sharing strategies, with GL possibly playing a crucial role at higher-intensity contractions and longer lengths. This study demonstrated SWE's potential to characterize muscle mechanics in vivo. If validated, predictions from SWE could facilitate studying muscle behavior and force-sharing strategies, serving as a diagnostic or monitoring tool for muscle function and performance.