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Journal of Applied Physiology

American Physiological Society

Preprints posted in the last 90 days, ranked by how well they match Journal of Applied Physiology's content profile, based on 32 papers previously published here. The average preprint has a 0.04% match score for this journal, so anything above that is already an above-average fit.

1
Unimanual fatigue increases muscle excitation and local metabolic activity in the resting contralateral forearm

Hinkle, L. J.; Scheuermann, B. C.; Ade, C. J.; Barstow, T. J.; Carr, J. C.

2026-07-06 physiology 10.64898/2026.06.30.735603 medRxiv
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Intense unilateral muscle contractions evoke measurable activity within the contralateral neuroaxis, which can be detected with surface electromyographic activity in the resting homologous muscle. Physiological mirror activity (PMA), the unintentional increase in contralateral muscle excitation, has been implicated in cross-limb interactions and adaptations. Despite longstanding observations of PMA, it remains unknown whether this low-level muscle excitation influences local muscle metabolism. We addressed this question using a vascular occlusion test in 10 healthy adults. Surface electromyography and near-infrared spectroscopy-derived measures of tissue oxygen saturation and muscle oxygen consumption (mVO2) were obtained from the resting left forearm during vascular occlusion at rest and during fatiguing unimanual contractions of the right hand. PMA in the contralateral resting arm was greater during unimanual fatigue than during rest (mean difference: 8.9%AA, 95% CI: 4.1 to 13.8; p = 0.002, g = 1.20). This increase was accompanied by a steeper rate of tissue oxygen desaturation (mean difference: -0.132 %{middle dot}s-1, 95% CI: -0.227 to -0.037; p = 0.012, g = -0.91) and greater mVO2 (mean difference: 0.188 mL O2{middle dot}min-1{middle dot}100 g-1, 95% CI: 0.057 to 0.320; p = 0.010, g = 0.94). Greater PMA was associated with both a faster rate of oxygen desaturation (r = -0.85, 95% CI: -0.96 to -0.46, p = 0.002) and greater mVO2 (r = 0.78, 95% CI: 0.28 to 0.94, p = 0.008). These findings suggest that PMA is accompanied by increased local metabolic demand, consistent with a coupling between unintentional muscle excitation and oxygen extraction in the resting limb.

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Effect of Match-Play Fatigue on Muscle Stiffness and Explosive Force Asymmetries in Soccer Players Post-Anterior Cruciate Ligament Reconstruction

Bari, M. H.; Bhalli, A. Z.; Sattar, H.

2026-07-21 sports medicine 10.64898/2026.07.18.26357476 medRxiv
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ABSTRACT Background: Athletes who return to soccer after anterior cruciate ligament reconstruction (ACLR) remain at elevated risk of secondary injury despite meeting conventional discharge criteria, and neuromuscular deficits in the reconstructed limb are known to be exposed by fatigue. Objective: To determine whether match-play fatigue differentially affects muscle stiffness, countermovement jump (CMJ) force symmetry, and rate of force development (RFD) asymmetry between soccer players with a history of ACLR and uninjured teammates. Methods: A prospective, cross-sectional, matched-control study enrolled 128 competitive soccer players (64 ACLR, 6-22 months post-surgery; 64 uninjured controls) across five recruitment waves (February-June 2026). Bilateral CMJ peak vertical force, jump height, RFD, and myotonometric stiffness of the rectus femoris (RF), vastus medialis (VM), and biceps femoris (BF) were recorded immediately before and after a standardized competitive match. Fatigue was quantified from second-half heart rate (percentage of age-predicted maximum) and end-match rating of perceived exertion (RPE). Within-group pre-to-post changes were evaluated with paired t-tests, between-group differences in the magnitude of change with independent-samples t-tests, and associations between fatigue indices and asymmetry changes with Pearson correlations. Results: Match play reduced CMJ limb symmetry index (LSI) in both groups, but the decline was more than three-fold greater in the ACLR group, 92.6% (SD 5.4%) to 85.1% (SD 7.1%), than in control group, 97.3% (SD 3.9%) to 95.0% (SD 4.2%), group-by-time difference, p < 0.001, (d = 0.64). RFD asymmetry approximately doubled in the ACLR group, 10.6% (SD 4.1%) to 17.6% (SD 6.5%), compared with a smaller rise in control group, 4.6% (SD 2.4%) to 6.3% (SD 3.7%); p < 0.001, d = 0.77). Involved-limb stiffness losses in the ACLR group exceeded those of controls for the RF (-21.2 vs. -9.2 N/m, p < 0.001), VM (-17.7 vs. -6.1 N/m, p < 0.001), and BF (-13.3 vs. -6.6 N/m, p < 0.001), whereas uninvolved-limb stiffness losses did not differ between groups (all p > 0.05). Fatigue markers (heart rate, RPE) were not significantly correlated with the magnitude of individual asymmetry change (|r| [&le;] 0.18, p > 0.15). Conclusions: In competitive soccer players 6-22 months after ACLR, match-play fatigue selectively compromises stiffness and explosive force output of the reconstructed limb, widening inter-limb asymmetries beyond what is seen in uninjured teammates, even though global cardiovascular and perceptual fatigue were comparable between groups. These findings suggest that return-to-sport testing performed only in a rested state may underestimate residual neuromuscular deficits, and support fatigue-inclusive assessment protocols before athletes are cleared for unrestricted competition. Abbreviations: ACL: anterior cruciate ligament, ACLR: anterior cruciate ligament reconstruction, BF: biceps femoris, CMJ: countermovement jump, HRmax: maximum heart rate, LSI: limb symmetry index, RF: rectus femoris, RFD: rate of force development, RPE: rating of perceived exertion, RTS: return to sport, VM: vastus medialis, SD: standard deviation. Keywords: Anterior cruciate ligament reconstruction, muscle fatigue, muscle stiffness, countermovement jump, limb symmetry index, rate of force development, soccer, return to sport.

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Chronic adaptations following eccentric cycling training at different cadences

Mater, A.; Martin, A.; Laroche, D.; Lepers, R.

2026-07-10 sports medicine 10.64898/2026.07.07.26356024 medRxiv
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Pedalling cadence during an acute eccentric cycling exercise altered physiological and perceptual responses. We examined the influence of cycling cadence on neuromuscular adaptation induced by a 6-week eccentric cycling training period. Eighteen participants performed training (eighteen sessions) at a cadence of 30 or 60 rpm over six weeks. Power output was the same between the two groups. Perceived effort and heart rate were recorded at each training session. Muscle pain and fatigue were reported the day after each session. Maximal voluntary contractions torque, as well as concentric and eccentric cycling efficiency, were assessed before and after training. Additionally, the loss of maximal voluntary isometric torque was assessed after the first and last training sessions. Heart rate and perceived effort increased in the second week of training and then plateaued, with no difference between groups. Muscle pain and fatigue remained low throughout the training, with no difference between groups. Isometric (+28%) and eccentric (+13%) maximal voluntary torque of knee extensor muscles increased regardless of training cadence. Concentric maximal voluntary torque increased for the group pedalling at 60 rpm only (+21%). Cycling efficiency was improved in eccentric mode only (+43%), with no difference between the two training groups. Finally, the voluntary isometric torque loss induced by the first and last sessions were similar. While six weeks of eccentric cycling training improved neuromuscular and functional capacities, cadence had no observable effect. This finding suggest that patients could choose their preferred cadence to obtain better adherence to the rehabilitation program without altering the adaptations.

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Acute Effects of Coherence Breathing on cardiopulmonary and autonomic responses: a randomized crossover study protocol.

Diclemente, G. S.; Sole, S.; Pigman, J.; Rial-Faigenbaum, T.

2026-07-01 sports medicine 10.64898/2026.06.30.26356965 medRxiv
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Background. Cardiopulmonary exercise testing (CPET) is a gold-standard test used to evaluate cardiopulmonary fitness and overall health by measuring physiological responses such as oxygen consumption during exercise. While traditional CPET warm-ups are typically low-intensity aerobic activities, alternative methods like coherence breathing may also prepare the body by influencing autonomic regulation. Breathing-based interventions have shown potential to improve heart rate recovery and performance, and heart rate variability (HRV) serves as a useful non-invasive indicator of autonomic nervous system activity. However, there is limited research on how brief breathing exercises before CPET affect outcomes. This study aims to investigate the effects of coherence breathing on oxygen uptake, HRV, and post-exercise heart rate recovery Objective. This study will aim to compare the acute cardiopulmonary and autonomic responses of coherence breathing versus spontaneous breathing immediately preceding cardiopulmonary exercise testing (CPET) in recreationally active healthy adults. Methods. This study will be a randomized counterbalanced crossover design. Healthy adults aged between 19 and 45 years of age will complete two separate CPETs over two non-consecutive test days (between 48 hours and 7days). During each visit, participants will complete five minutes of slow-paced coherence breathing (6 breaths per minute) or spontaneous breathing at normal breathing rate, followed by an incremental treadmill CPET protocol up to maximal exertion. HRV will be assessed at baseline, during the breathing interventions, and during cool-down for 5 minutes using the Emwave Pro Plus software. Gas exchange during the CPET protocol will be measured continuously using the VO2 Master Pro system. immediately after, and after 5 minutes of resting. The primary outcomes will be peak oxygen consumption and heart rate variability indices. Secondary outcomes will include heart rate recovery, peak heart rate, time to exhaustion, rate of perceived exertion and readiness, blood pressure, tidal volume, peak ventilation, and respiration rate. Analyses will use linear mixed-effects models and paired comparisons. Discussion. This protocol will determine whether pre-exercise coherence breathing can improve cardiopulmonary and autonomic nervous system responses to maximal performance. Findings may have practical implications for exercise testing and performance procedures as well as improving our understanding of pre-exercise breathing strategies for priming the autonomic and cardiopulmonary systems.

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Human decompression in real time: programmable ultrasound imaging during hyperbaric exposure

Currens, J.; Natoli, M. J.; Eltz, K.; Morales, G.; Bautista, K. J. B.; Dayton, P. A.; Lance, R.; Oralkan, O.; Yamaner, F. Y.; Moon, R. E.; Papadopoulou, V.

2026-07-27 physiology 10.64898/2026.07.22.737513 medRxiv
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The formation of inert gas bubbles during decompression can lead to decompression sickness (DCS), a major operational risk for divers, compressed-gas workers, astronauts, and high-altitude aviators. In diving, DCS risk is typically inferred from post-dive ultrasound detection of venous gas emboli (VGE), precluding modification of decompression schedules based on real-time physiological feedback. Two-dimensional ultrasound imaging could provide additional insight into decompression-related physiological changes; however, its use in hyperbaric environments has been largely precluded by fire risk associated with elevated oxygen partial pressures (ppO2) in enclosed spaces. Here, we developed a workflow for operating a programmable ultrasound system under hyperbaric conditions and acquiring ultrasound data from the subclavian vein and calf muscle during decompression. A total of 42 dives were conducted by 26 individuals using a previously characterized dive profile to 132 feet seawater (FSW) for 20 min with 9 min of decompression. Three exposure conditions were evaluated: non-exercising, exercising, and a brief pause at 20 FSW during compression. Twelve dives included programmable ultrasound imaging during decompression. Post-dive VGE responses were consistent with prior reports while demonstrating substantial inter-individual variability and sensitivity to modest profile modifications. VGE were detected in the subclavian vein during decompression in two participants and subsequently confirmed by post-dive echocardiography. Calf muscle ultrasound brightness typically increased from pre-dive to decompression measurements, before decreasing below baseline in the 120 min post dive measurement period. These findings demonstrate the feasibility of programmable ultrasound imaging during human decompression and establish a practical framework for ultrasound operation under hyperbaric conditions. This approach may support future physiological studies and development of automated decompression monitoring technologies. New and NoteworthyThis study demonstrates the first use of a programmable ultrasound system to acquire and quantitatively analyze ultrasound data during human decompression. The approach enabled direct visualization of venous gas emboli during decompression and revealed calf muscle ultrasound signal changes, providing a new tool for investigating physiological responses during decompression that are not accessible through conventional post-dive monitoring.

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Inherent Biomechanical Properties of the Lung: In vivo-Ex vivo Comparisons in Mice

Di Palo, J.; Ibinson, J. T.; Lin, L.; Suh, B.; Gwin, M. S.; Zaeh, S.; Szafron, J. M.; Manning, E. P.

2026-06-29 physiology 10.64898/2026.06.24.734270 medRxiv
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Mammalian lungs operate within a thoracic cage composed of parietal pleura, rib cage, skeletal muscle, and diaphragm, yet clinical ventilator metrics largely reflect the combined mechanics of lung and surrounding structures and the thoracic cage. We hypothesized that thoracic boundary conditions selectively alter measured lung biomechanics. We performed paired pulmonary function testing (FlexiVent) in C57BL6 mice of both sexes spanning development through adulthood, measuring quasi-static pressure-volume behavior and dynamic forced-oscillation parameters in vivo (supine, mechanically ventilated) and again ex vivo in the same lungs. In a subset, we additionally compared in vivo and ex vivo microCT-derived lung volumes, including a pressure-fixed ex vivo protocol using snap freezing at controlled inflation pressure. Quasi-static pressure-volume curves were similar between conditions, with near-identity at higher pressures and only modest divergence at low pressures, consistent with thoracic structures primarily modulating recruitment/de-recruitment rather than intrinsic elastic recoil. Maximal volume at 30 cmH2O showed strong in vivo-ex vivo correlation and minimal bias, and static compliance and PV-loop hysteresis exhibited small biases relative to reported disease-model effect sizes. In contrast, dynamic mechanics demonstrated a clear in vivo elevation of tissue damping (G) with only modest change in tissue elastance (H) and little change in Newtonian resistance (Rn), producing a meaningful increase in hysteresivity (G/H). This dissociation implicates frequency-dependent mechanical heterogeneity (time-constant mismatch/pendelluft) imposed or amplified by nonuniform thoracic loading. Ex vivo microCT enabled reliable whole-lung segmentation and correlated with ex vivo PFT volumes at matched pressures, whereas in vivo volumetry showed weaker agreement. These results indicate that thoracic structures contribute modest restriction but disproportionately increase dynamic dissipation and heterogeneity, suggesting that ex vivo functional testing and oscillometry-like metrics may better detect biomechanical changes inherent to lung parenchyma.

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Resistive Load During CPAP and Automatic Tube Compensation (ATC): A Bench Comparison of ICU Ventilators

Fabry, B.; Kuster, C.; Francis, R.

2026-07-13 intensive care and critical care medicine 10.64898/2026.07.08.26357537 medRxiv
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Background: Automatic tube compensation (ATC) was designed to compensate for the additional resistive load imposed by the endotracheal tube during spontaneous breathing. In ATC mode, the ventilator adds or subtracts the flow-dependent pressure drop across the tube during both inspiration and expiration so that tracheal pressure remains close to PEEP. Early prototype ventilators achieved true tracheal-pressure control and showed physiological and clinical benefits, but clinical studies with commercial systems have failed to confirm these earlier findings. A 2003 bench study found that commercial ventilators provided, at best, only partial tube compensation, unlikely to result in meaningful clinical benefit. We therefore tested whether this limitation has been remedied in contemporary ICU ventilators. Methods: We performed a bench comparison of five commercial ICU ventilators and an ATC prototype ventilator designed to accurately compensate for the flow-dependent resistance over a wide range of flow rates. An active lung simulator generated spontaneous breathing patterns with weak, moderate, and strong inspiratory efforts at different PEEP levels. We tested each breathing pattern through endotracheal tubes with inner diameters of 7 and 8 mm, and measured airway pressure, tracheal pressure, and flow during CPAP with and without ATC. Breathing through the tube against open atmosphere served as a zero-PEEP/T-piece reference. Results: In CPAP mode, the commercial ventilators showed flow-dependent airway-pressure deviations, amounting to a substantial added resistance of 1.5 - 6.5 mbar/(L/s), whereas the ATC prototype ventilator imposed an added resistance of only 0.6 mbar/(L/s). In ATC mode, the commercial ventilators reduced the resistive load by no more than by 25%, and large tracheal-pressure deviations remained, especially at higher inspiratory effort and during expiration. In some cases, the residual load during ATC was even greater than the load during unsupported breathing through the tube. By contrast, the ATC prototype ventilator maintained tracheal pressure close to PEEP throughout the breathing cycle and eliminated on average 79% of the tube-related resistive load. Conclusions: In the commercial ventilators evaluated in this study, the defining physiological objective of ATC was only partially achieved. Therefore, clinical benefits previously reported for tracheal-pressure control support should be interpreted with caution when applied to commercial ATC implementations, unless effective tube compensation has been demonstrated under relevant conditions. These findings suggest that more advanced control approaches, such as those implemented in the ATC prototype ventilator, may be required to achieve consistent and physiologically accurate tube compensation.

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Acute Aerobic Exercise in Individuals with Obesity Abolishes Amino Acid-Stimulated Muscle Protein Synthesis in the Immediate Postexercise Period

Johnsson, K. A.; Freitas, E. D.; Roust, L. R.; De Filippis, E.; Gu, H.; Buras, M.; Katsanos, C. S.

2026-06-18 physiology 10.64898/2026.06.14.732200 medRxiv
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Obesity alters protein metabolism in skeletal muscle, and although exercise and amino acids act synergistically to regulate muscle anabolism in healthy humans, this interaction may be impaired in obesity. We examined whether acute aerobic exercise alters amino acid-stimulated muscle protein synthesis during the immediate postexercise period in subjects with obesity. Sixteen sedentary adults with a body mass index >30 kg/m2 underwent stable-isotope tracer infusion studies to determine mixed-muscle fractional synthesis rate (FSR) in the basal (fasted) state and under two experimental conditions: eight subjects received an amino acid infusion (AA), while another eight performed 45 min of cycling at [~]65% heart rate reserve immediately prior to the amino acid infusion (EX+AA). Amino acid infusion significantly increased muscle protein FSR in AA (P < 0.0001). In contrast, no significant increase was observed in EX+AA (P > 0.05), and the amino acid-stimulated increase in muscle protein FSR in EX+AA was 78% lower than that in the AA (P < 0.01). Amino acid infusion increased plasma amino acid concentrations in both conditions (P < 0.05); however, plasma concentrations of essential and branched-chain amino acids, including leucine, were lower in the EX+AA condition (P < 0.05). Changes in muscle protein FSR were positively associated with plasma leucine concentrations during the amino acid infusion (P < 0.05). These findings suggest that, in humans with obesity, aerobic exercise may abolish amino acid-stimulated muscle protein synthesis during the immediate postexercise period, with implications when considering nutritional strategies designed to optimize muscle anabolism in this population. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/732200v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1c9d4e3org.highwire.dtl.DTLVardef@1b7c399org.highwire.dtl.DTLVardef@18a99aborg.highwire.dtl.DTLVardef@6ed880_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Multimodal Phenotyping of Myofascial Pain Syndrome Using Rotational Shear Wave Elastography and Clinical Network Analysis

Jahani Jirsaraei, M.; Hsu, Y.-l.; Akhwand, R.; Aher, A.; Lee, S.; DeStefano, S.; Srbely, J.; Shah, J.; Rosenberger, W.; Acuna, S.; Assefa, Y.; Gerber, L. H.; Sikdar, S.

2026-07-27 rehabilitation medicine and physical therapy 10.64898/2026.07.23.26358787 medRxiv
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Myofascial pain syndrome (MPS) is characterized by increased muscle stiffness, trigger points, and functional limitations, yet clinical diagnosis remains largely subjective. Shear wave elastography (SWE) provides quantitative assessment of muscle mechanical properties, but its value for identifying biomechanical and clinical phenotypes of MPS is not fully established. This study evaluated whether stiffness parameters derived from multi-angle SWE can reliably characterize upper-trapezius anisotropy, and whether integrating SWE with bioimpedance spectroscopy (BIS), range of motion (ROM), and patient-reported outcomes (PROs) improves differentiation of MPS subgroups. Seventy-one adults completed upper-trapezius SWE, BIS, ROM assessments, and PRO measures. Clinically, 18 were classified as active MPS, 36 as latent, and 17 as normal. Shear wave speed measurements were modeled to estimate longitudinal (uL), transverse (uT), and anisotropy (uE) components. Reliability was examined using intraclass correlation coefficients. Unsupervised clustering and partial-correlation network analysis were applied to biomechanical and clinical variables. uT showed the strongest associations with BIS frequency parameters and ROM measures, indicating sensitivity to fascial composition, and mobility. Multimodal clustering incorporating uT with Fc or ROM identified subgroups with distinct tissue-level and functional characteristics. Network analysis demonstrated a progression in connectivity patterns, shifting from localized mechanical relationships to broader symptom-level coupling involving pain interference, sleep disturbance, emotional distress, and physical function. These findings indicate that SWE-derived stiffness parameters provide reliable, direction-specific quantification of trapezius mechanical properties. Combining SWE with impedance and mobility measures yields physiologically coherent MPS phenotypes that differ in both biomechanical features and clinical network structure, supporting more objective framework for characterizing MPS.

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Cardiovascular and autonomic responses to transcutaneous spinal cord stimulation combined with activity-based therapy after chronic spinal cord injury: An exploratory study from the MACHINE trial

Balthazaar, S. J. T.; Shackleton, C. L.; Williams, A. M. M.; Samejima, S.; Malik, R. N.; Hodgkiss, D. D.; Nightingale, T. E.; Sachdeva, R.; Elliott, S. L.; Berger, M. J.; Lam, T.; Krassioukov, A. V.

2026-08-14 rehabilitation medicine and physical therapy 10.64898/2026.08.11.26359978 medRxiv
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Objective: To describe cardiovascular and autonomic responses to body weight-supported treadmill training (BWSTT) combined with active or sham transcutaneous spinal cord stimulation (TSCS) in individuals with chronic, motor-complete spinal cord injury (SCI). Design and setting: Exploratory case series from randomized, sham-controlled clinical trial in a tertiary Rehabilitation Centre in Vancouver, Canada. Participants: Eight adults with chronic ([&ge;]1 year post-injury) traumatic, motor-complete (American Spinal Injury Association Impairment Scale A-B) SCI at or above T6 Interventions: Participants were randomized to 12 weeks of BWSTT plus lumbosacral TSCS or BWSTT plus sham stimulation, delivered 3 sessions/week. TSCS was delivered at T11-L1 using 30 Hz stimulation with a 10 kHz carrier frequency. Five participants completed the intervention, and four completed full cardiovascular testing (TSCS n=2; sham n=2). Outcome measures: Ambulatory blood pressure (BP) monitoring, participant-reported symptoms of AD and OH (via ADFSCI questionnaire), BP variability, orthostatic hemodynamics, echocardiography, electrocardiography (ECG)- and heart rate variability (HRV)-derived indices, and baroreflex function. Results: Among complete cases, several cardiovascular indices changed over time, including reduced daytime hypotensive burden in TSCS participants, preserved nocturnal dipping, and small changes in stroke volume and ECG-derived variability indices; however, responses were heterogeneous and overlapped with Sham. Both TSCS and Sham participants showed reduced autonomic symptom scores, while low-frequency blood pressure variability responses during orthostatic stress were heterogeneous and did not indicate a pattern that was specific to a cohort. Conclusion: Although preliminary, this exploratory complete-case analysis suggests that cardiovascular responses to BWSTT with active or sham TSCS are measurable but highly individualized after chronic motor-complete SCI. Given the small sample and overlapping Sham responses, findings are exploratory and larger trials are needed to determine whether TSCS augments cardiovascular autonomic adaptations to locomotor training.

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Contractile and Hemodynamic Modulation of Skeletal Muscle Viscoelasticity Quantified In Vivo by Ultrasound Time-Harmonic Elastography

Meyer, T.; Kurz, E.; Klemmer Chandia, S.; Engl, P.; Valli, G.; Wu, Y.; Jenderka, K.; Bartels, T.; Schwesig, R.; Guo, J.; Sack, I.; Aghamiry, H. S.

2026-06-29 radiology and imaging 10.64898/2026.06.25.26356543 medRxiv
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Skeletal muscle is a living, perfused soft tissue whose viscoelastic behavior is shaped by both voluntary contraction and hemodynamic state. However, the independent and superimposed contributions of contractile loading and blood flow restriction (BFR) have not been quantified simultaneously in real time. Twenty-six healthy adults underwent multi-frequency ultrasound time-harmonic elastography (THE, 60-80 Hz) of the vastus lateralis under six conditions: rest, 15% and 30% maximal voluntary contraction (MVC) before BFR, passive BFR after 4 min of cuff inflation, and 15% and 30% MVC shortly after cuff release. Shear wave speed (SWS), reflecting elasticity, and penetration rate (PR), reflecting inverse viscous damping, were extracted using the k-MDEV inversion algorithm. BFR significantly elevated SWS at all three contraction levels relative to the corresponding pre-BFR measurements (Holm-corrected p [&le;] 0.011; dz = 0.54-2.13). PR decreased during resting BFR (dz = 1.34, p < 0.001) and at 15% MVC after cuff release (dz = 0.94, p < 0.001), but not at 30% MVC (dz = 0.21, p = 0.294). BFR-related changes reduced the SWS-force slope by 14.5% and the PR-force slope by 40.7%. Men exhibited a greater BFR-induced increase in resting SWS than women. These findings show that THE can distinguish contractile and hemodynamic contributions to skeletal-muscle viscoelasticity and provide complementary information on elastic and dissipative tissue behavior in vivo.

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Three-dimensional imaging reveals preserved intrinsic contractile function in aging human skeletal muscle fibers

Zepeda, C. S.; Teigen, L. E.; Dobrzycki, I.; Wen, Y.; Sundberg, C. W.

2026-06-12 physiology 10.64898/2026.06.09.730973 medRxiv
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Age-related reductions in muscle fiber size and contractile function, particularly in fibers expressing fast myosin heavy chains, contribute to declines in whole-muscle power. However, methodological limitations in estimating fiber size during contractile experiments have likely contributed to conflicting findings regarding whether reduced single-fiber force and power in older adults reflects their smaller size and/or impaired intrinsic contractile function. To address this, we coupled single-fiber contractile experiments with 3D-imaging in 7 young (19-40yrs) and 6 older (69-84yrs) males to assess intrinsic contractile function and compare agreement between 3D-derived cross-sectional area (CSA) and CSA estimates obtained either in air or solution. Fast fiber CSA from older males were [~]28-45% smaller across measurement conditions compared with young, whereas slow fiber CSA did not differ. Accordingly, absolute force and power of fast fibers were 41% and 37% lower. When normalized to CSA from measurements in air or 3D-imaging, size-specific force and power either did not differ or were greater in older adults, indicating preserved intrinsic contractile function in both fiber types. This was supported by no age-related differences in the rate of tension redevelopment (ktr), a size-independent measure of intrinsic contractile function. In contrast, size-specific force and power calculated using solution-based CSA estimates were lower in older compared with young adults, and Bland-Altman analyses demonstrated the poorest agreement between solution-based and 3D CSA measurements. These findings indicate that intrinsic contractile function is preserved with aging and suggest that methodological differences in CSA measurement contributes to the disparate findings in the literature.

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Revisional augmentation of residual neuromusculature and training facilitate embodiment and control of a bionic knee prosthesis

Shu, T.; McCullough, J.; Riccio-Ackerman, F.; Qiao, J.; Landis, C.; Tie, Y.; Rigolo, L.; Carty, M.; Sullivan, C.; Weischhoff, G.; Myers, P.; Shallal, C.; Levine, D.; Yeon, S. H.; Chun, E.; Nawrot, M.; Carney, M.; Herr, H.

2026-08-27 rehabilitation medicine and physical therapy 10.64898/2026.08.24.26343866 medRxiv
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Conventional transfemoral amputation disrupts native neuromuscular pathways, limiting prosthetic joint control, sensory feedback, and the perception of the prosthesis as part of the body. To ameliorate these pathologies, we restored the agonist-antagonist relationship of residual muscles in two individuals with above-knee amputation through an interventional surgical revision. Participants trained with a bionic knee prosthesis before and after the surgical revision while generating neuromuscular, cortical, functional, and affective data. Both individuals demonstrated improvements after the revision that could not readily be attributed to training effects, including: 1) increased proprioceptive afferents and stronger activation in cortical regions associated with sensorimotor integration of their missing joints, 2) improved control of the bionic knee during functional tasks including sit-to-stand and stair ascent, and 3) generally greater prosthesis embodiment, proprioception, and phantom limb definition as assessed through questionnaires and interviews. In contrast, training outcomes were more participant-specific and more variably correlated with amount of exposure, especially before the revision. These pilot findings suggest that revisional augmentation of residual neuromuscular tissues to restore agonist-antagonist dynamics may promote sensorimotor coherence and enhance both functional and perceptual integration with a bionic prosthesis, and remaining participant-specific heterogeneities may be attributable to inter-individual difference in residual limbs neuromuscular system, amputation history, and personal beliefs about prosthesis usage.

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Force sharing between plantarflexor muscles in sheep during treadmill gait

Ross, S. A.; Schumacher, F. S.; Machado, E.; Sawatsky, A.; Leonard, T. R.; Hopfner, K.; Scott, W. M.; Bossuyt, F. M.; Taylor, W. R.; Herzog, W.

2026-06-24 bioengineering 10.64898/2026.06.23.734066 medRxiv
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Muscle force sharing during locomotion is influenced by the mechanical demands of movement and the contractile properties of synergistic muscles. In cats, plantarflexor muscles exhibit distinct functional specialization, with the slow-fibred soleus maintaining relatively constant force across conditions while faster muscles such as the plantaris and gastrocnemius increase force production with increasing locomotor demand. However, it remains unclear whether similar force-sharing patterns occur in larger animals with different musculoskeletal designs. Therefore, the purpose of this study was to examine force sharing between the superficial digital flexor (SDF) and medial gastrocnemius (MG) muscles during treadmill locomotion in sheep. Tendon buckle force transducers were surgically implanted on the SDF and MG tendons of seven sheep, and in vivo muscle forces were recorded during walking and trotting across different speeds and inclines. Both muscles increased force with increasing speed and incline; however, speed had a substantially greater effect than incline. The SDF consistently produced greater absolute force than the MG across all conditions, whereas the MG exhibited slightly larger relative increases in force with increasing speed. Time to peak force decreased with increasing speed in both muscles, although the SDF reached peak force later in stance than the MG across conditions. In contrast to the distinct specialization observed in cats, neither muscle displayed a relatively condition-independent, soleus-like force contribution. These findings suggest that force sharing in sheep is more distributed across synergistic muscles and may reflect the influence of musculoskeletal design, tendon compliance, and mixed fibre-type composition on muscle function in larger species.

15
Effect of joint velocity and pre-activation on the torque-fascicle length relationship of the vastus lateralis

Tallio, T.; Nordez, A.; Lecarpentier, L.; Dorel, S.

2026-06-29 physiology 10.64898/2026.06.23.734014 medRxiv
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Fascicle operating length during dynamic tasks is often compared to the isometric torque-length relationship, but there is a lack of evidence regarding the influence of joint velocity on optimal fascicle length. Moreover, there is no consensus in the literature regarding the influence of contraction initiation (pre-activation or passive start), although it could alter the interaction between fascicles and the tendon. This study aimed to investigate the effect of joint velocity and pre-activation on the torque-angle and torque-length relationships of the vastus lateralis during mono-articular isokinetic knee extensions. Twenty-one participants performed isometric, isokinetic (50{degrees}.s-1 to 450{degrees}.s-1), and isokinetic knee extensions with maximal isometric or eccentric pre-activation at 100{degrees}.s-1 and 300{degrees}.s-1. Torque, joint angle, fascicle length, and electromyographic activity of the quadriceps femoris muscles were recorded during contractions and then used to model the torque-angle and torque-length relationships. We were able to successfully fit the torque-angle and torque-length relationships (R{superscript 2}=0.93 and R{superscript 2}=0.92, respectively). A main effect of velocity was detected regarding the optimal angle (p<0.05), but no significant change was observed for the optimal fascicle length. Isometric pre-activation induced a reduction in maximal torque production compared with eccentric pre-activation and passive conditions at both isokinetic velocities (p<0.001), with no change in muscle activity. Our results suggest that muscle-tendon interactions may permit a dissimilar behavior between the torque-angle and the torque-fascicle length relationships. The reduction in torque following isometric pre-activation may be related to a contraction history-dependent phenomenon. NEW & NOTEWORTHYWe demonstrated that, at a given joint angle, increasing velocity altered fascicle operating length without shifting optimal fascicle length, likely because of muscle-tendon interactions. We also showed that maximal isometric pre-activation before a concentric contraction reduced mean and maximal torque during the isokinetic phase compared with eccentric pre-activation or no pre-activation. This effect may be linked to contraction history, since muscle activity did not differ between conditions.

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Motor impairment, balance, and muscle coactivation limit the effectiveness of voluntary corrections of asymmetry during walking after stroke

Kuch, A.; Jeffcoat, S.; Aguirre-Ramirez, A.; Hashiguchi, H.; Shrier, E.; Hooyman, A.; Schweighofer, N.; Winstein, C.; McKenzie, A.; Sanchez, N.

2026-07-29 rehabilitation medicine and physical therapy 10.64898/2026.07.27.26359033 medRxiv
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Introduction: Several gait rehabilitation approaches after stroke rely on explicit feedback to promote task-specific voluntary corrections of walking patterns. While these approaches show effectiveness at a group level, individual responses to voluntary corrections can differ, limiting the benefits and translation of task-specific gait interventions. Our goal is to identify biomechanical, neuromuscular, and cognitive characteristics associated with the ability to perform voluntary corrections of walking using explicit visual feedback in people with chronic stroke. Methods: Twenty-eight individuals with chronic stroke completed a single-session treadmill walking protocol, consisting of baseline walking, a voluntary correction condition guided by real-time visual feedback, and a short retention trial without feedback. Reducing step length asymmetry was used as the target to guide voluntary corrections. Clinical assessments included measures of motor impairment, balance, gait function, cognition, and walking capacity. Muscle coactivation was characterized using dimensionality reduction. Associations of clinical assessments with baseline step length asymmetry and residual error in step length asymmetry during voluntary correction were examined using univariate analyses and multivariate regression with LASSO-based variable selection. Results: Eighteen participants successfully reduced step length asymmetry using visual feedback, while ten participants did not reduce asymmetry. Greater residual asymmetry during voluntary correction was independently associated with greater baseline asymmetry, greater lower extremity motor impairment, reduced balance, and increased paretic muscle coactivation (adjusted R2 = 0.46). Neither the direction of asymmetry nor cognitive outcome measures were associated with the ability to correct asymmetry during walking. Immediate retention after feedback removal was limited, with only 4 participants maintaining improvements. Discussion: The ability to perform voluntary corrections of the walking pattern using voluntary corrections after stroke is constrained by motor impairment, balance function, and muscle coactivation. These findings suggest that explicit, feedback-based gait interventions to guide voluntary corrections may benefit individuals with mild to moderate impairments, while individuals with more severe impairments require alternative strategies to guide corrections of the walking pattern.

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Recovery Trends Show Greater Quadriceps Weakness After Patellar Tendon Versus Hamstring Autografts in ACL Reconstruction

Wilebski, B.; Bond, C. W.; Noonan, B. C.

2026-06-10 sports medicine 10.64898/2026.06.08.26355177 medRxiv
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Context: Although knee extensor and flexor strength deficits are well-documented after anterior cruciate ligament reconstruction, limited data exist characterizing how strength recovery evolves over time. Understanding the temporal patterns of recovery, and how they differ by autograft type, is critical for optimizing rehabilitation and return-to-sport decision-making. Objective: To characterize temporal trends in knee extensor and flexor strength recovery during the first year post-ACLR and evaluate differences between patellar tendon and hamstring tendon autografts. Design: Case series. Setting: Sports physical therapy clinics within a large health system. Participants: Five hundred three patients (17.8 {+/-} 3.0 y) who underwent primary reconstruction with either patellar tendon or hamstring tendon autografts and completed a combined 730 return-to-sport tests within 12 months postoperatively. Main Outcome Measures: Normalized peak isokinetic concentric knee extension and flexion torques for involved and uninvolved limbs, and normalized symmetry indices for knee extension and flexion strength. Results: Knee extension strength on both limbs and extension strength symmetry improved over time. Patients with hamstring autografts demonstrated superior involved leg knee extension strength and better extension strength symmetry compared with those receiving patellar tendon autografts, although uninvolved leg strength was similar between autografts. Knee flexion strength on both limbs and flexion strength symmetry also improved over time. Patellar tendon autograft patients exhibited greater strength symmetry, despite no between autografts for flexion strength for the involved or uninvolved limb. Conclusions: Autograft significantly influences muscle strength recovery following anterior cruciate ligament reconstruction. Hamstring tendon autografts are associated with superior recovery of knee extension strength and strength symmetry compared to patellar tendon autografts. These findings underscore the need for graft-specific rehabilitation strategies and earlier identification of patients at risk for delayed recovery.

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Muscle stability deficits are strongly associated with musculoskeletal complaints in football (soccer) players: the AF-Ratio outperforms conventional strength parameters--a cross-sectional study with preliminary follow-up

Schaefer, L. V.; Bittmann, F. N.; Ulrich, J.; Prill, R.; Becker, R.

2026-07-10 sports medicine 10.64898/2026.07.07.26357205 medRxiv
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Objectives: Given the high injury burden in football and the documented limitations of strength-based screening, novel approaches are warranted. Adaptive Force (AF)being closer to injury-prone movements than pushing/pulling strength--offers an alternative. This study examined the association between AF-based muscle stability and musculoskeletal complaints in football players and compared AF-derived and conventional strength parameters in their discriminative capacity, complemented by a preliminary prospective follow-up. Methods: AF and maximal voluntary isometric contraction (MVIC) were measured in 23 male football players across five bilateral muscle groups (knee extensors/flexors; hip flexors/adductors/abductors). AF parameters (maximal isometric AF, maximal AF, AF-Ratio), MVIC and hamstrings-to-quadriceps (H:Q) ratio were compared between players with and without complaints assessed via questionnaire at baseline and six-month follow-up (n=13). Results: Stability deficits were strongly associated with complaints (OR=54.0, 82% side concordance). AF-Ratio discriminated clearly between players with and without complaints (d=-1.47), with hip abductors showing the strongest effect (d=-1.64). Players with subsequent complaints showed lower baseline AF-Ratio (d=-1.45) and more stability deficits (d=1.67). MVIC and H:Q ratio did not discriminate (p>0.430). Conclusion: The findings suggest that muscle stability assessment outperforms conventional strength parameters in discriminating players with and without complaints, with preliminary follow-up data providing tentative support for predictive value. The concept of functional instability syndrome (FIS) provides a mechanistic framework for non-contact injuries and musculoskeletal complaints. AF assessment offers potential for screening, including return-to-sport decisions. Further studies are needed to verify the results, investigate predictive value, and evaluate whether personalised stability-based interventions can reduce injury incidence.

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Older adults do not have a higher metabolic cost than younger adults in outdoor overground walking.

van der Kruk, E.; Jongbloed, K.; Orlandi, M.; Miller, M.; Silverman, A.

2026-07-28 bioengineering 10.64898/2026.07.27.740899 medRxiv
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The metabolic cost of walking is widely used to evaluate human performance and effectiveness of clinical interventions. Decades of laboratory research, largely based on treadmill experiments, have established a canonical relationship between walking speed and metabolic cost, and suggested that ageing shifts this relationship upward, implying reduced efficiency in older adults. However, this relationship has not been well tested during overground walking across matched speeds. We compared healthy younger (n=16; 26{+/-}2yr) and older (n=11; 74{+/-}3yr) adults across eight outdoor overground walking trials at different speeds: preferred walking speed (PWS), three fixed speeds (0.8, 1.2, 1.6 m{middle dot}s-{superscript 1}), and four speeds at {+/-}5% and {+/-}10% of PWS. Contrary to our hypothesis, older adults did not show higher gross or net metabolic cost of walking (GCOW and NCOW) than younger adults at any speed; rather, both trended consistently lower in older adults, reaching significance for GCOW at 0.8 m{middle dot}s-{superscript 1} only. Comparisons of resting metabolic rate and respiratory exchange ratio to prior reference groups did not indicate that our older cohort was unusually fit. Independent of age, GCOW was significantly higher at 0.8 m{middle dot}s-{superscript 1} than at the remaining speeds (1.2-1.6 m{middle dot}s-{superscript 1}), confirming that walking at slower speeds increases GCOW. These findings challenge the view that ageing intrinsically increases the energetic cost of walking, suggesting instead that previously reported upward shifts in cost may reflect treadmill-specific constraints or speed effects. Future work is needed to explore direct comparisons of outdoor, overground walking with treadmill walking at fixed speeds in both younger and older adults.

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Understanding the biomechanical and physiological responses to Advanced Footwear Technology in well-trained male and female runners

Albertus, Y.; Leith, D.; Berg, O.; Barrons, Z. B.; Tam, N.

2026-06-24 physiology 10.64898/2026.06.19.732297 medRxiv
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Advanced footwear technology (AFT) has transformed competitive running, yet individual and sex-specific responses to different AFT models remain unclear, particularly near race pace. This study examined running economy (RE) and gait biomechanics in response to three top-tier AFT models (Shoe A: adidas Pro Evo 2; Shoe B: Nike Alphafly 3; Shoe C: On CloudBoom Strike 2) in 14 male and 12 female well-trained runners at sex-specific submaximal speeds (16 and 14 km{middle dot}h-{superscript 1}). RE, spatiotemporal, and joint kinematic/kinetic data were collected via indirect calorimetry, accelerometry, and three-dimensional motion capture with force platforms. RE was significantly lower in Shoe C than Shoe A (males: 2.1%; females: 1.4%) and Shoe B (males: 1.9%; females: 0.9%), with 73% of runners responding favourably to Shoe C, a more consistent response than previously reported. Despite being lightest, Shoe A produced the poorest RE, challenging conventional mass-economy assumptions. Biomechanically, Shoe C elicited greater impact magnitude, lower ankle quasi-stiffness, and greater ankle angular velocity during early stance. Female runners showed smaller RE improvements, potentially related to lower running velocity and body mass limiting midsole engagement. The most efficient AFT enabled these well-trained runners to be more spring-like through tolerating higher forces and faster angular velocities without greater demand on metabolic cost.