Journal of Applied Physiology

BackgroundThe cardiovascular (CV) benefit of CPAP in OSA remains debated and its effects on new OSA-related CV risk markers are unclear. We aimed to quantify short-term CPAP effects on these markers along with vascular and autonomic phenotypes. MethodsIn a 2-week withdrawal study, patients on long-standing effective CPAP took part in three visits (V1-V3: on/off/back-on CPAP) with overnight polygraphy followed by vascular and autonomic phenotyping. Co-primary endpoints included endothelial function assessed by flow-mediated dilation (FMD) and baroreflex sensitivity (BRS), hypoxic burden (HB), pulse wave amplitude drop index (PWADi) and spontaneous-PWADi (excl. apnoea-triggered drops), and event-related heart-rate response ({Delta}HR). Between-visit differences were tested in adjusted mixed models, with visit or within-participant changes in AHI/HB as fixed effects. ResultsIn 42 participants (61{+/-}10 years, 83% male), CPAP withdrawal reinstated OSA (medians [IQR] V1 to V3: AHI 3.9[1.5, 8.8] to 33.4[19.5, 42.1] to 4.0[2.0, 8.8] events/h, HB 4.3[1.1, 8.7] to 51.3[19.7, 83.7] to 2.0[1.2, 6.5] %{middle dot}min/h, p<0.001) and increased total PWADi (mean{+/-}SD 42.25{+/-}18.73 to 50.22{+/-}17.77 to 41.29{+/-}17.14 drops/h, p<0.001), while spontaneous PWADi decreased as respiratory-events recurred (-1.17 drops/h per 10 events/h, p=0.015) along with FMD (3.7{+/-}1.9% to 3.2{+/-}2.5% to 4.2{+/-}2.7%, V2 vs V3 p=0.047). {Delta}HR and BRS were stable across visits. ConclusionShort-term CPAP re-initiation improved endothelial function (FMD), with no significant effects on autonomic measures (BRS, {Delta}HR) or structural vascular indices. This supports a temporal dissociation between rapidly reversible exposure metrics (AHI, HB) and slower dynamics of autonomic markers. Changes in spontaneous PWADi suggests that it may track physiological CPAP benefits beyond indices driven primarily by respiratory-event frequency.

EMG-based muscle force predictions are often inaccurate following active muscle stretch or shortening because of residual force enhancement (rFE) or depression (rFD), respectively, which can alter the neural drive to a muscle. However, the extent of neural drive modulation due to rFE or rFD remains unknown, making it difficult to correct EMG-based force predictions. Therefore, seventeen participants performed dorsiflexion contractions at 20 and 40% of maximum voluntary torque (MVT) in three conditions: stretch-hold, shortening-hold, and fixed-end reference (REF) conditions. The ankle dorsiflexion torques and angles were matched using dynamometry to the REF condition over a 10-s steady state following a 1-s 25{degrees} stretch or shortening, during which we recorded and decomposed tibialis anterior individual motor unit action potentials from high-density surface EMG recordings to gain insights into neural drive. Normalized EMG amplitudes were 2% lower following stretch and 1 or 3% higher following shortening relative to REF at 20 versus 40% MVT (p[&le;].008), respectively. Discharge rates (DRs) from 19 matched motor units per person on average obtained via DEMUSE and MUedit were similar (p=.871). Following stretch and shortening, DRs were [~]1 Hz lower (p[&le;].004) and 0 (p=.966) to 1 Hz higher relative to REF (p=.003), respectively. More unique motor units were also detected following shortening versus REF and in REF versus following stretch. These findings indicate that to account for rFE or rFD, neural drive is respectively decreased or increased via reduced or additional motor unit recruitment and DR modulation, with a contraction-intensity specific discharge rate modulation following active shortening.

BackgroundMeteorological factors such as barometric pressure, humidity, and temperature have been linked to weather-related symptoms in the general population, yet little is known about their influence on athletes daily well-being and performance. Individual variability in weather sensitivity has been reported in biometeorology research, suggesting that only certain individuals exhibit pronounced physiological responses to environmental fluctuations. However, no studies have examined within-person associations between multiple meteorological factors and daily condition or performance in competitive athletes. MethodsCollegiate baseball players were monitored over 10 randomly selected days during July-August 2025. Subjective condition and performance were assessed daily using a 3-point Likert scale (1 = poor, 2 = normal, 3 = good). Barometric pressure, humidity, and temperature were recorded hourly and summarized for each day using mean values, day-to-day changes, daily ranges, and rapid fluctuation indices. For each player, multivariable linear regression models were constructed to examine within-person associations between the three meteorological variables and daily condition or performance. Model fit (R2), regression coefficients ({beta}), and dominant meteorological factors were extracted. ResultsEighty players were included in the condition model and eighty-six in the performance model. High weather sensitivity (R2 [&ge;] 0.60) was observed in 22.5% of players for condition and 14.0% for performance, whereas low sensitivity (R2 [&le;] 0.20) was found in 26.3% and 16.3%, respectively. Temperature was the dominant explanatory factor in more than 80% of players, although subsets showed dominance of barometric pressure or humidity. Directionality varied across individuals: decreases in barometric pressure were associated with worsening conditions in 62.5% of players but improvement in 37.5%; similar bidirectional patterns were observed for humidity and temperature. ConclusionDaily meteorological fluctuations explain a meaningful proportion of within-person variation in condition and performance for a subset of collegiate baseball players. The substantial individual variability and diverse directional responses highlight weather sensitivity as a personalized characteristic rather than a uniform effect. These findings suggest that meteorological factors may represent a relevant contextual variable for daily readiness monitoring in susceptible athletes.

Force production relies on the interaction between neural control of spinal motoneurons and the mechanical properties of the muscles. Changes in muscle length provide a useful model for exploring this interaction; however, studies typically assess these properties in the same muscle undergoing length change. This study investigated how altering the length of one muscle influences motor unit discharge behavior of its synergists. Eighteen healthy participants performed submaximal isometric knee extensions with the hip joint positioned at 90{degrees} (shortened rectus femoris, RF) and 180{degrees} (lengthened RF). At each hip position, participants followed trapezoidal force profiles at 10% and 30% of maximal voluntary contraction (MVC), while high-density surface electromyography (HDsEMG) was recorded from the synergistic vastus medialis and vastus lateralis (VL). Motor unit spike trains were decomposed from HDsEMG, tracked across hip positions, and analyzed for mean discharge rate and coefficient of variation of interspike interval (CoV-ISI). Lengthening the RF led to increased discharge rates of vasti motor units at 10% MVC, but not 30% MVC, with no changes in CoV-ISI. To further explore these force-dependent changes in discharge rate, two sets of experiments were conducted. The first showed that the discharge rate at recruitment during ramp-up contractions increased with RF lengthening, but only for vasti units recruited below 20% MVC. In the second, electrically evoked twitch contractions in the vasti revealed reduced twitches at 180{degrees} during low-frequency, but not high-frequency stimulation. These findings collectively suggest that the force-dependent changes in the vasti motor unit discharge rates are likely driven by RF-length dependent changes in the vasti muscles contractile properties.

When running, metabolic cost increases as muscles are simultaneously fatigued. However, the contribution of an individual muscle group to fatigue-related increase in metabolic costs remains unclear. We investigated the metabolic consequence of running with local plantar flexor or knee extensor fatigue and associated neuromuscular control strategies. Recreational and experienced male runners (N=20) completed two sessions (one per muscle group), with each including two 10 min running bouts: without and with local fatigue ([~]20% reduction in peak joint torque). Net metabolic power and muscle activity (initial and final minutes) were determined. Metabolic power was unaffected by plantar flexor (p=0.367) or knee extensor (p=0.607) fatigue in both cohorts. Plantar flexor fatigue recovered during the fatigued run (p=0.033), while knee extensor fatigue only recovered for the recreational cohort (p=0.009; experienced: p=0.826). With plantar flexor fatigue, plantar flexor muscle activity was unchanged between runs (p[&ge;]0.312), however initial soleus activity was greater in the unfatigued than fatigued run for experienced runners (p=0.022), and initial medial gastrocnemius activity was greater in the unfatigued than fatigued run for the combined cohort (p=0.009). With knee extensor fatigue, knee extensor muscle activity was mostly lower in the unfatigued than fatigued run (p[&le;]0.009), except for final vastus lateralis activity, which was unchanged between runs (p=0.061). Therefore, muscle groups respond with different activation strategies when fatigued. Running with plantar flexor or knee extensor fatigue, at levels like those induced by prolonged running (10-42 km), does not increase metabolic power and thus, submaximal running energetics may be maintained despite local muscle fatigue. NEW & NOTEWORTHYWhile muscle fatigue is suggested to increase the metabolic cost of running, the individual contributions of key lower limb muscle groups have not been explored. We examined responses after fatigue of only the plantar flexors or the knee extensors. Results indicate that local fatigue did not affect the metabolic power of male runners for either fatigued muscle group. These findings enhance our understanding of running performance and the interaction between fundamental criteria dictating human locomotion.

IntroductionCardiopulmonary exercise testing (CPET) quantifies exercise limitation and helps differentiate cardiovascular dysfunction from deconditioning in patients with exertional dyspnoea. In mild pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), traditional CPET oxygen delivery parameters may not adequately distinguish cardiac limitation. We evaluated whether oxygen pulse (O2 pulse) kinetics and the ratio of ventilation-carbon dioxide slope to peak oxygen uptake (VEVCO2/peakVO2) improve identification of cardiovascular limitation and prognostication. MethodsWe retrospectively analysed 289 consecutive patients referred for CPET. Patients were categorised into pre-capillary PH, no PH, or "unclassified" PH based on haemodynamics. O2 pulse slopes were calculated across exercise phases, and qualitative curve patterns were classified. VEVCO2/peakVO2 was derived from standard CPET parameters. Logistic regression assessed predictors of cardiac dysfunction (peak O2 pulse <65% predicted). Survival was evaluated using Kaplan-Meier and Cox regression analyses. ResultsPre-capillary PH patients demonstrated more impaired aerobic capacity and ventilatory efficiency than those without PH. Abnormal O2 pulse patterns (early plateauing or down-sloping) were associated with shallower slopes, lower peak O2 pulse, and greater chronotropic index. A work-phase O2 pulse slope < 0.40 identified impaired oxygen delivery but was not independently predictive in multivariable analysis. VEVCO2/peakVO2 independently predicted cardiac dysfunction (OR 3.9 [2.6-6.2], p < 0.001) and showed strong discrimination (AUC 0.83). VEVCO2/peakVO2 [&ge;] 2.7 independently predicted mortality (HR 13.6, 95% CI 3.8-48.5, p<0.001) outperforming peak O2 pulse and VE/VCO2 slope. ConclusionO2 pulse kinetics, particularly a work-phase slope < 0.40 and plateauing or decreasing trajectories, are associated with cardiac dysfunction in patients with pre-capillary PH. VEVCO2/peakVO2 appears to be a marker of cardiovascular limitation and mortality and may aid differentiation between cardiac dysfunction and deconditioning in this population when conventional CPET parameters are inconclusive.

BackgroundQuadriceps weakness may reduce sagittal plane shock absorption during landing, shifting load toward the frontal plane and increasing knee abduction moment (KAM), a biomechanical risk factor for anterior cruciate ligament (ACL) injuries. PurposeThe purpose of this study was to evaluate the association between isokinetic quadriceps strength and peak KAM during drop vertical jump landing in adolescent athletes. Study DesignSecondary analysis of previously collected data. MethodsHealthy adolescent athletes completed quadriceps strength testing using an isokinetic dynamometer and a biomechanical assessment during a drop vertical jump task. Quadriceps strength was quantified as peak concentric torque and the peak external KAM was calculated during the landing phase on the dominant limb. Both strength and KAM were normalized to body mass. Linear regression was used to examine the association between normalized quadriceps strength and peak external KAM on the dominant limb. ResultsThe association between quadriceps strength and peak normalized KAM on the dominant limb was not statistically significant ({beta} = -0.053 (95% CI [-0.137 to 0.030]), F(1,119) = 1.62, R2 = 0.013, p = 0.206). Quadriceps strength explained only 1.3% of the variance in peak KAM, indicating a negligible association between these variables in this cohort. DiscussionQuadriceps strength was not associated with peak normalized KAM during landing, suggesting that frontal-plane knee loading during a drop vertical jump is not meaningfully explained by maximal concentric quadriceps strength alone. KAM appears to be driven more by multi-joint movement strategy and neuromuscular coordination than by the capacity of a single muscle group.

BackgroundIn critically ill patients admitted to the intensive care unit (ICU), rapid skeletal muscle atrophy frequently develops in the acute phase. This ICU-acquired weakness can significantly impair long-term physical function. Although the biceps brachii cross-sectional area (CSA) is commonly used to assess muscle atrophy, its ultrasound imaging can be technically challenging, and the flexor carpi ulnaris may offer a more accessible alternative. Therefore, this study aimed to investigate whether CSA changes of the flexor carpi ulnaris correlate with those of the biceps brachii in critically ill patients admitted to the ICU, as well as whether the flexor carpi ulnaris CSA reflects systemic muscle atrophy in the acute phase of the ICU stay. MethodsTwenty critically ill patients admitted to the ICU underwent serial ultrasound assessment of the biceps brachii and flexor carpi ulnaris CSAs on days 0, 5, 7, and 14 after admission. Longitudinal changes in CSA were analyzed using the Friedman and Wilcoxon signed-rank tests. Correlations between the biceps brachii and flexor carpi ulnaris were examined using Spearmans rank correlation, and structural equation modeling was applied to explore causal relationships between clinical variables and CSA changes. ResultsSignificant CSA reductions were observed in both the flexor carpi ulnaris (-20.6%) and biceps brachii (-16.3%) by day 14, and the relative CSA changes of the biceps brachii and flexor carpi ulnaris showed a moderate positive correlation ({rho} = 0.5489, p = 0.0122). Structural equation modeling analysis revealed that the biceps brachii CSA change had positive effect on that of the flexor carpi ulnaris ({beta} = 0.249, p = 0.0011). Moreover, body mass index was positively associated with the baseline flexor carpi ulnaris CSA ({beta} = 0.042, p = 0.0004). However, the baseline flexor carpi ulnaris CSA was not a significant predictor of subsequent CSA changes. ConclusionUltrasound measurement of the flexor carpi ulnaris CSA offers a practical alternative to that of the biceps brachii for early detection of muscle wasting in ICU patients. Given its anatomical accessibility and high sensitivity to early atrophic changes, it may serve as a feasible screening tool for ICU-acquired weakness and inform timely interventions.

BackgroundPreserving muscle function is essential for maintaining independence during aging, but muscle force-generating capacity is not commonly measured clinically due to a lack of accessible, sensitive tools. Magnetic resonance imaging (MRI) provides gold-standard measures of muscle volume and microstructure, which reflect force-generating capacity, while dynamometry quantifies peak joint moments during voluntary contraction. Both modalities are time-consuming and costly, so clinical and large-scale studies often rely on low-fidelity measures such as the time to complete the five times sit-to-stand test (5xSTS). OpenCap, a tool for quantifying musculoskeletal dynamics from smartphone videos, may provide an accessible and more informative approach to assessing muscle function. We evaluated whether OpenCap-derived knee extension moments during chair rise relate to MRI-based measures of quadriceps muscle volume and microstructure, using dynamometry as a comparator. MethodsNineteen healthy adults of various ages (63.2% female, 57.8 {+/-} 15.4 y, 30-78 y) underwent quadriceps MRI, dynamometry, and 5xSTS time with concurrent OpenCap data collection. Using MRI, we computed quadriceps volume and radial diffusivity (a measure related to fiber size). We standardized these features and summed to create a composite MRI score, reflecting muscle quantity and quality. We estimated peak knee extension moment using OpenCap during chair rise and via both isometric and isokinetic dynamometry. We compared OpenCap kinematics (torso angle) and dynamics (knee moment), 5xSTS time, and dynamometry to MRI measures of muscle function using linear regression; false discovery rate was controlled using the Benjamini-Hochberg procedure. ResultsThe OpenCap-derived knee extension moment was associated with quadriceps muscle volume (r=0.63, p=0.014) and radial diffusivity (r=0.61, p=0.016). Peak knee extension moments measured by both isometric and isokinetic dynamometry were correlated with muscle volume (r=0.66-0.75, p=0.002-0.009), but not with radial diffusivity (r=0.04-0.52, p=0.054-0.91). Both OpenCap and isokinetic dynamometry showed their strongest associations with the composite MRI score (r=0.77, p=0.002 and r=0.73, p=0.002, respectively). 5xSTS time and a kinematic feature (torso angle) were not associated with any MRI-derived measures (r=-0.16-0.35, p=0.22-0.97). ConclusionsSmartphone video-based joint moments associate with muscle size and microstructure, unlike time or kinematic features. OpenCap offers a scalable assessment of muscle force-generating capacity that can be conducted rapidly without specialized equipment, enabling higher-fidelity assessments of muscle function in the clinic and in large-scale studies where imaging and dynamometry are impractical.

Hypoxemia occurs in intermittent forms, such as obstructive sleep apnea, and in continuous forms, such as at high altitude, and is increasingly recognized as a modulator of cardiometabolic risk. Although hypoxemia alters postprandial glucose and lipid metabolism, its effects on ketone bodies remain unclear. Using a randomized crossover design, we examined whether six hours of normoxemia or intermittent hypoxemia (15 hypoxemic cycles/hour targeting [~]85% peripheral oxyhemoglobin saturation with 100% medical-grade nitrogen) alters plasma {beta}-hydroxybutyrate (BHB) concentrations in 12 young adult females (mean [SD]: 21 [3] years) following a high-fat meal (33% of estimated daily energy requirements; 59% of calories from fat). In a follow-up session, a subset (n = 8) completed six hours of continuous hypoxemia (fraction of inspired oxygen [~]12.0% in a normobaric chamber). Postprandial data were analyzed using baseline-adjusted linear mixed-effects models, with Bonferroni post hoc tests. A time x condition interaction (P = 0.010) indicated that BHB concentrations at 360 minutes were higher during continuous hypoxemia (0.247 mmol/L; 95% CI: 0.218-0.275) than normoxemia (0.176 mmol/L; 95% CI: 0.153-0.200; PBonferroni = 0.029) and intermittent hypoxemia (0.163 mmol/L; 95% CI: 0.139-0.186; PBonferroni = 0.002), representing increases of 13.0% and 14.2% in estimated marginal means, respectively. This response was accompanied by higher postprandial plasma glucose and triglyceride concentrations during continuous hypoxemia than during normoxemia and intermittent hypoxemia (PBonferroni [&le;] 0.002), despite similar plasma insulin and non-esterified fatty acid responses across conditions (P [&ge;] 0.081). These findings indicate that continuous hypoxemia increases late postprandial plasma BHB concentrations in young adult females. New FindingsO_ST_ABSWhat is the central question of this study?C_ST_ABSWhat are the effects of normoxemia, intermittent hypoxemia, and continuous hypoxemia on plasma {beta}-hydroxybutyrate (BHB) concentrations in young adult females after a high-fat meal? What is the main finding and its importance?Compared to normoxemia, young adult females showed higher postprandial plasma BHB concentrations during continuous hypoxemia, but not during intermittent hypoxemia, despite similar changes in plasma concentrations of two main regulators of BHB production (non-esterified fatty acids and insulin) across experimental conditions. These findings suggest that continuous hypoxemia modifies postprandial BHB concentrations through mechanisms not fully explained by circulating non-esterified fatty acids or insulin concentrations alone.

ObjectiveTandem cycling requires a coordinated effort between the pilot and the stoker. Previous research suggests that randomly paired tandem cyclists produce lower power output than when cycling solo. This study examined how a cyclists individual ability and their position on the tandem (pilot or stoker) affects pair performance, when partners are either closely matched or differ substantially in solo cycling capacity, as this might be relevant for training and selection. MethodsTwenty-three trained cyclists completed three 10-minute time trials: solo, equal-capacity tandem ([&le;]25 W difference in solo performance), and unequal-capacity tandem ([&ge;]40 W difference). Mean power output, heart rate, cadence, and rating of perceived exertion (RPE) were recorded. Positions (pilot or stoker) were counterbalanced. Linear mixed-effects models assessed effects of capacity and position. ResultsRelative to solo cycling, equal-capacity tandem pairs revealed lower power output (-3.9%), lower heart rate (-2.3%), and lower RPE (-11.5%). Unequal-capacity tandems differed from solo only in heart rate (-2.7%). Stokers produced lower power relative to solo (-5.3%) and relative to pilots (-3.7%) and reported lower RPE relative to solo (-13.9%), while pilots matched their solo power at a lower heart rate (-2.9%). Cadence did not differ across conditions. Total tandem power averaged 95.6% of combined solo power, and differences in partner capacity did not significantly affect combined power output. ConclusionThis study provides the first known experimental data on how partner matching affects individual and combined power output in tandem cycling. Equal- and unequal-capacity tandem pairs showed similar performance. Lower power and RPE among stokers suggest reduced engagement or a redistribution of effort between riders. These findings highlight that effective tandem performance depends on physiological capacity and rider position on the tandem, but not on the difference in capacity between partners.

PurposeDetrended fluctuation analysis alpha-1 (DFAa1) has emerged as a promising non-invasive biomarker for exercise intensity assessment. However, the standard 2-min analysis window lacks temporal resolution necessary for real-time training applications. This study systematically investigated the validity of shortened DFAa1 windows (30s and 1min) versus the 2-min reference across different intensities. MethodsPhysically active males completed three continuous cycling protocols: low-intensity training at the first lactate threshold (LOW, n=19), moderate-intensity training at the second lactate threshold (MOD, n=19), and a 30-min self-paced time trial (TT30, n=18). DFAa1 was calculated using 30-s, 1-min, and 2-min moving windows, advancing in 1s increments. Validity was assessed using intraclass correlation coefficients (ICC), Bland-Altman analysis, and standard error of measurement (SEM). ResultsDuring LOW, both shortened windows showed poor agreement with the 2-min reference (30s: ICC=0.02, mean bias of -0.05; 1min: ICC=0.37, -0.02). During MOD, the 30-s window remained unreliable (ICC=0.32, -0.01), while the 1-min window achieved moderate reliability (ICC=0.63, 0.00). During TT30, both shortened windows substantially improved performance (30s: ICC=0.78, -0.02; 1min: ICC=0.95, -0.01), with the 1-min window achieving excellent reliability. ConclusionDFAa1 analysis window validity is intensity-dependent, with shortened windows showing progressively improved agreement as exercise intensity and heart rate increases. While the 2-min window remains essential for low-intensity monitoring, 1-min or 30-s windows provide appropriate validity during high-intensity exercise, enabling more-responsive real-time feedback. These results support adaptive windowing strategies that dynamically adjust window length based on exercise intensity and the number of included data points, to optimize the analytical validity-temporal responsiveness trade-off.

Walking speed is widely used to assess gait recovery following stroke, yet it provides limited insight into how walking performance is mechanically organized. This study examined how center of mass (COM) work organization and propulsion-support coupling vary across walking speeds in individuals with post stroke hemiparesis to distinguish recovery of gait organization from recovery of limb level mechanical function. Eleven individuals with post stroke hemiparesis performed treadmill walking across speeds ranging from 0.2 to 0.7 m/s while ground reaction forces were recorded. Limb specific COM power and work were computed using an individual limbs framework, and interlimb asymmetry in net and positive work, along with the propulsion-support ratio (PSR), were quantified. A qualitative transition in gait organization was observed: at lower walking speeds, COM power exhibited a simplified two phase pattern, whereas at higher walking speeds (approximately >=0.5 m/s), a structured four phase COM power pattern emerged, including identifiable push off and preload phases. Despite this recovery of gait organization, interlimb work asymmetry remained elevated and paretic PSR remained reduced across all speeds, indicating persistent limb level mechanical deficits. These findings demonstrate that increases in walking speed and the emergence of typical COM power structure reflect recovery of gait organization rather than restoration of underlying limb level mechanical capacity. Consequently, walking speed alone is insufficient to characterize gait recovery after stroke, and biomechanically informed measures of COM work organization and propulsion-support coupling provide complementary insight by distinguishing organizational recovery from limb-level mechanical recovery.

Skeletal muscle hypertrophy results from the integrated regulation of anabolic and proteolytic processes in response to mechanical loading. Although increases in resistance training (RT) volume are used to increase mechanical stress, it remains uncertain whether large and abrupt volume progressions could exceed muscle adaptive capacity by disrupting the balance between anabolic and catabolic signaling. The present study investigated whether a large increase in weekly RT volume (+120%) leads to impaired hypertrophic outcomes and intracellular regulatory responses compared with a modest increase (+20%). Twenty-five resistance-trained men and women (18-35 years old) completed an 8-week randomized, single-blind, within-subject unilateral intervention. Each participant trained both legs twice weekly, with one leg assigned to the large (VOL120) and the contralateral leg to the modest (VOL20) weekly volume progressions relative to habitual training volume. Vastus lateralis muscle cross-sectional area (mCSA) was assessed by ultrasonography before and after training. Muscle biopsies were obtained at baseline, post-intervention, and 24 h after the last session to quantify muscle fiber cross-sectional area (fCSA), satellite cell myonuclear content, and anabolic/catabolic signaling markers. Both protocols induced increases in mCSA over time (p<0.001), with no protocol vs. time interaction. No significant effects were observed for fCSA nor satellite cell number or myonuclear content. Additionally, molecular responses related to translational regulation and protein degradation were largely similar between protocols. Collectively, these data indicate that a large, abrupt increase in weekly set volume does not impair hypertrophic adaptations or meaningfully alter the anabolic-catabolic signaling profile in resistance-trained individuals.

1BackgroundHuman locomotion is a highly adaptive motor skill that adjusts to new environmental demands through learning. Split-belt treadmill paradigms have advanced our understanding of gait adaptation. Most studies have examined gait when the belts move at different speeds in the same direction. We are studying muscle activation patterns during an asymmetric gait, when the treadmill belts move at equal speed in opposite directions, i.e., bidirectional walking (BDW). MethodsTwelve healthy volunteers performed a single session on a split-belt treadmill. We simultaneously collected ground reaction forces via treadmill force plates, joint kinematics via motion capture, and surface electromyography (EMG) from bilateral soleus (SOL) and tibialis anterior (TA) muscles. Participants started with 2 min of forward walking (FW), followed with four 5-min blocks of BDW separated by 1-min standing rest intervals, and finished the session with 2 min of FW (washout). ResultsAll participants successfully completed the protocol. We analyzed EMG signals for temporal activation patterns (rhythm generation) and amplitude characteristics (pattern formation). EMG recordings revealed antiphasic activation of SOL and TA muscles bilaterally throughout all trials. During BDW, the backward-moving legs TA showed prolonged activation patterns that persisted during washout FW, suggesting retention of adaptive changes. Burst-to-cycle duration ratios showed transient changes during early adaptation but remained relatively stable across conditions, demonstrating robust rhythm generation despite adaptive modulation of activation patterns during BDW. DiscussionThese findings demonstrate that BDW induces asymmetric adjustments in muscle activation patterns. Rhythm generation (timing) did not significantly differ between BDW and FW. However, we did observe changes in pattern formation (i.e., EMG profiles) during FW pre- and post-BDW training. Burst-to-cycle duration ratios, as a measure of rhythm generation, showed changes during early adaptation, particularly the increase in right SOL and right TA during block 1, though these changes did not reach statistical significance and largely returned to baseline during washout. The underlying pattern formation structure, was maintained across all conditions, with selective amplitude modulations rather than fundamental reorganization of activation patterns. The substantial temporal adjustments in the backward-moving legs SOL and phase shifts in TA provide the neuromuscular mechanism driving the bilateral step-length reduction, altered inter-limb phasing, and asymmetric double stance timing. These results extend our understanding of locomotor control by suggesting how the central nervous system (CNS) dynamically recalibrates muscle timing and amplitude to maintain satisfactory locomotion under new environmental demands.

Exercise affects the immune function and induces pro- and anti-inflammatory effects. The alterations concerning the immune system linked to physical activity have been documented across various studies with complex exercise tests. However, the characterization of the non-pathological, exercise-induced immunological stress regulation is highly relevant in numerous clinical and non-clinical areas for a better understanding of normal physiological adaptations and differentiation from non-healthy adaptations. Thus, it is valuable and necessary to establish simple immune-metabolic response triggering exercise tests for use in clinical and non-clinical settings. The aim of this study was to examine the effects of the 1-minute sit-to-stand test (STST) on immune-metabolic stress indices and to determine whether it elicits a sufficiently high intensity to qualify as an anaerobic exercise test, thereby supporting its application in investigating exercise-induced immunological stress regulation. 28 study participants performed the 1-minute STST. Capillary blood was taken 20 and 10 minutes before the test, immediately after, and 5, 10, 15, 30, and 45 minutes after exercise. Lactate, glucose and blood counts were determined. Lactate concentration increased significantly immediately after the STST (p < 0.001) and remained significantly elevated until 45 minutes post-exercise. Glucose concentration was significantly decreased after 10 minutes post-exercise (p < 0.05) and again 30 and 45 minutes post-exercise (p < 0.01 for both). Leucocyte count increased significantly post-exercise (p < 0.001) and returned to baseline levels 30 minutes afterwards. Lymphocyte and granulocyte count increased significantly after the test (p < 0.001 for both) and lymphocyte count slightly decreased below baseline values 30 minutes post-exercise (p = 0.07) while granulocyte count remained significantly elevated (p < 0.05). Furthermore, decreased NLR (p < 0.001) and SII (p < 0.01) immediately after the test and increased levels of NLR, SII and SIRI post-exercise could be observed. The 1-minute STST caused an increase in lactate level above the anaerobic threshold, therefore the test can be evaluated as an anaerobic exercise test. Furthermore, it was demonstrated that the STST induced shifts in leucocyte, lymphocyte, and granulocyte counts, which means that even a short intense anaerobic exercise, such as the STST causes changes in immune cell counts and therefore, the test is suitable for analyzing the exercise-induced immunological stress response.

RationaleRegular aerobic exercise protects against vascular aging and reshapes the circulating molecular milieu, but the relation between vascular function, circulating molecules, and exercise dose at extreme volumes remains poorly defined. The vascular and molecular consequences of chronic, multi-stage ultra-endurance running are particularly unclear. ObjectiveTo define circulating molecular signatures associated with vascular dysfunction following the 64-stage, 4,486-km Trans Europe Foot Race (TEFR). Methods and ResultsIntegrated multiomics analysis (proteomics, lipidomics, metabolomics) of plasma from 27 finishers revealed a coordinated systemic shift driving an oxidative phenotype. Specifically, we identified altered arginine metabolism and a universal upregulation of lipotoxic ceramides consistent with incomplete fatty acid oxidation. In conjunction, we identified upregulation of innate immune system pathways including the acute phase response and the complement system. Central pulse wave velocity (cPWV) increased significantly after the race, consistent with arterial stiffening. To test whether the post-race circulating milieu could directly influence vascular mechanics, naive murine aortic rings were incubated with participant plasma. Post-race plasma acutely increased aortic elastic modulus, and this effect was attenuated by the superoxide dismutase mimetic TEMPOL, supporting a ROS-dependent component. In human aortic endothelial cells (HAECs), post-race plasma increased reactive oxygen species generation without detectable changes in eNOS phosphorylation, total eNOS abundance, or stimulated nitric oxide production. Endothelial ROS responses were associated with components of the terminal complement pathway. ConclusionsExtreme multi-stage ultra-endurance exercise induces a distinct systemic milieu associated with arterial stiffening through ROS-sensitive mechanisms. This response is characterized by remodeling of arginine-related metabolism, ceramide accumulation, innate immune activation, and oxidative stress, without evidence of reduced measured eNOS abundance or stimulated NO production. These findings identify candidate molecular pathways linking prolonged metabolic stress to vascular dysfunction.

Heat-related illnesses pose a significant public health challenge in Europe, resulting in increased mortality. Although cold water immersion (CWI) is the most effective treatment for heat stroke, its clinical use is limited. A better understanding of temperature changes in the peripheral body regions can lead to more effective CWI application. Nevertheless, most muscle temperature measurement techniques are invasive. This study evaluated magnetic resonance spectroscopy (MRS) for non-invasive assessment of intramuscular temperature during cold stress and rewarming. Nine healthy volunteers (7 men, 2 women) participated in three 3T MRI sessions: baseline (PRE), immediately after 15 minutes of CWI at 10 degrees to the iliac crest (POST-CWI), and following 100-Watt cycling (POST-cycling). Each scan session included T1w and localized spectroscopy acquisitions in the right thigh. Absolute temperature was estimated from the proton resonance frequency shift between water and creatine peaks. The measurements were split into three groups of voxels, defined as follows: close to the top (TL), bottom (BL), or central (DL) thigh positions. Measurement depth showed a location main effect (p<0.001, p^2=0.40), with DL (35.4[5.9] mm) significantly deeper than TL (22.5[4.2] mm) and BL (25.3[5.1] mm), remaining constant across phases. Temperature decreased significantly from PRE to POST-CWI across all locations (TL: p<0.001, d=2.74; BL: p<0.001, d=1.84; DL: p<0.005, d=1.14). Post-cycling temperature increased at all sites compared to POST-CWI (DL: p=0.040, d=1.06; TL: p<0.001, d=1.7; BL: p<0.001, d=1.80), though TL remained lower than PRE (p<0.017, d=1.48). During POST-CWI, DL showed a significantly higher temperature than TL (p<0.001, d=2.13) and BL (p<0.001, d=2.06). These findings demonstrate that MRS-based temperature mapping provides unique anatomical and thermal characterization of muscle during thermoregulatory stress. While results are promising for understanding CWI mechanisms, validation in larger cohorts is necessary to establish clinical reliability and reproducibility for heat illness management.

ContextClinical assessments of landing mechanics often require complex scoring systems or laboratory-based motion analysis, which can limit feasibility in routine practice. A visually based landing-mechanics score centered on a standardized optimal joint-alignment configuration ("Zero Position") may offer a simple, clinically deployable alternative. ObjectiveTo determine the intra- and inter-rater reliability of a landing mechanics score based on standardized optimal joint alignment at the moment of maximal center-of-mass (COM) descent. DesignCross-sectional reliability study. SettingUniversity athletic training facility. Patients or Other ParticipantsNinety healthy male collegiate athletes. Main Outcome MeasuresLanding mechanics were evaluated using frontal- and sagittal-plane video recordings, with scoring performed on the frame corresponding to maximal COM descent. Five criteria reflecting the standardized joint configuration ("Zero Position") were assessed. Intra- and inter-rater reliability were calculated using Cohens kappa coefficients and Kendalls W. ResultsAll five criteria demonstrated moderate to substantial intra-rater reliability and moderate to almost perfect inter-rater reliability. The total landing-mechanics score showed excellent agreement across all comparisons. The scoring system required minimal training and was feasible to implement using standard video recordings. ConclusionsThe landing-mechanics score centered on the Zero Position demonstrated high reliability and strong clinical feasibility. This simple, visually grounded assessment may support routine clinical screening, injury-risk evaluation, and return-to-sport decision-making. Future research should examine its applicability to single-leg landings and sport-specific high-risk movements.

General anesthetics enable invasive experimentation but can affect cardiovascular and respiratory physiology, biasing preclinical outcomes. We compared five anesthetic regimens in adult male Wistar rats, tribromoethanol (TBE, 250 mg/kg i.p.), chloral hydrate (CH, 400 mg/kg i.p.), ketamine-xylazine (KX, 80/10 mg/kg i.p.), thiopental (TP, 80 mg/kg i.p.), and isoflurane (ISO, 4% induction, 2% maintenance), to investigate integrated cardiorespiratory and biochemical markers. Femoral arterial catheterization allowed continuous blood pressure (BP) and derived heart rate (HR) recordings, while ventilation was assessed through pletysmography at baseline (awake), during induction, and recovery phases of anesthesia. Variability was evaluated in the time and frequency domains, including HR, systolic blood pressure (SBP), and spontaneous baroreflex sensitivity. In an independent cohort of rats, butyrylcholinesterase (BChE), CK-MB, cTnI, and LDH were measured. Baseline BP was unchanged by TBE and TP, whereas all anesthetics affected HR. Minute ventilation and breathing frequency were reduced with all agents, while tidal volume decreased with KX and TBE only. LDH and cTnI were unaffected, BChE was reduced by KX, TBE, and ISO, and CK-MB increased with CH and KX. Variability analysis showed that all anesthetics depressed pulse-interval and SBP variability and shifted spectral power toward higher frequencies, while baroreflex sensitivity and effectiveness were consistently reduced. During recovery, KX and TP restored most variability indices, whereas CH, TBE, and ISO showed persistent suppression. These findings highlight distinct profiles of cardiovascular depression and biomarker responses across anesthetics and underscore the importance of accounting for autonomic variability when selecting different anesthetics in experimental protocols. HighlightsO_LIFive anesthetic regimens were tested in rats. C_LIO_LIAll anesthetics reduced ventilation, and KX and TBE also reduced tidal volume. C_LIO_LICH and KX increased CKMB, while KX, TBE and ISO reduced BChE. C_LIO_LIAll anesthetics reduced blood pressure variability and baroreflex sensitivity. C_LIO_LIVariability recovered with TP and KX, whereas CH, TBE and ISO showed persistent suppression. C_LI