Experimental Physiology

This study examined how lower-body lengthened partial (LP) versus full range of motion (FULL) resistance training affects acute post-exercise signaling, chronic hypertrophy, and cellular adaptations of the vastus lateralis (VL) muscle in resistance-trained men. Eight males (22{+/-}1 years old, 5.6{+/-}1.4 years training) completed a crossover study whereby VL biopsies were collected pre-exercise and 0, 3, and 24 hours following LP and FULL leg extension bouts for transcriptomic and anabolic signaling analyses (Experiment 1). Another 16 males (26{+/-}5 years old; 8.0{+/-}4.9 years training) completed an 8-week, twice-weekly lower-body intervention using a within-subject design (Experiment 2). One leg was assigned to FULL and the contralateral leg to LP training across three exercises (leg press, leg extension, and lying leg curl). Pre- and post-intervention outcomes included VL muscle cross-sectional area (mCSA) summed across five equidistant MRI-derived transverse slices and mid-thigh VL biopsy outcomes. As a secondary outcome, other hip and thigh muscles from Experiment 2 MRI scans were assessed. Condition x Time interactions for all outcomes were assessed using linear mixed-effects models. In Experiment 1, both conditions produced similar time-dependent changes in the VL transcriptome and anabolic (mTORC1 and Hippo) signaling, but minimal between-protocol interactions. In Experiment 2, VL summed mCSA significantly increased over time (mean change: 9.3 cm{superscript 2}, 95% CI [6.8, 11.8], P<0.001), but there was no clear evidence of differential change between protocols (LP-FULL change: -1.4 cm{superscript 2}, 95% CI [-6.1, 3.8], P=0.640). Additionally, no significant interactions existed for type I fiber CSA (P=0.476), type II fiber CSA (P=0.350), type I fiber myonuclei (P=0.813), type II fiber myonuclei (P=0.589), type I and II satellite cell number (P=0.102 and P=0.797, respectively), or total RNA content (P=0.537). Despite these null VL-centric findings, secondary Experiment 2 analyses provided some evidence that whole hamstring hypertrophy was greater following LP versus FULL (LP-FULL change: 3.9 cm{superscript 2}, 95% CI [-0.2, 7.9], P=0.058). In conclusion, 8 weeks of LP and FULL resistance training broadly elicit similar acute and chronic VL responses in previously trained men, though secondary hamstring findings suggest that differential responses may depend on exercises included in the resistance training program.

Clinically, burn severity is reported as the size (and depth) of burn wounds relative to total body surface area (TBSA). This nomenclature is also often used in rodent models of burns. Accordingly, accurate determination and reporting of rodent TBSA is required to ensure the rigor and reproducibility of preclinical burn research. Rodent TBSA is typically estimated indirectly as a function of body mass. Further, empirical quantification of rodent TBSA through pelt dissection does not consider differences in rodent and human anatomy, making comparison of relative burn size in rodents and humans a challenge. Here, we compared commonly used approaches to directly determine or indirectly estimate rodent TBSA to demonstrate the impact different approaches can have on the calculation of relative burn size. A total of n=48 C57BL/6J background mice (55% male) ranging from 4 to 45 weeks of age and 17 to 40 grams were used. Mice were weighed prior to euthanasia. After euthanasia, mouse length was measured from the nose to anus. Mice were then placed into clear polypropylene sheet protectors (21.6 x 27.9 cm) to trace the areas of both the dorsal and ventral surfaces as well as all four limbs (dorsal-ventral (DV) tracing). Next, the pelt was carefully excised from the body through cutting a lateral line from the mouth to the genitalia, then again proximally to distally on all four limbs. The pelt was gently placed on a sheet protector and traced when both relaxed and stretched. The ears and tail were removed and traced separately. Photographs were taken of all tracings next to a ruler for scale and analyzed in ImageJ. Stretched pelt measurements of TBSA were 34% (79.4{+/-}7.6 vs. 57.5{+/-}7.5 cm2, P<0.001) and 30% (70.6{+/-}10.9 vs. 52.7{+/-}8.1 cm2, P<0.001) greater than relaxed pelt TBSA measurements in male and female mice respectively. TBSA estimated by DV tracing was 9% greater in males (62.5{+/-}10.9 vs. 57.5{+/-}7.5 cm2) and 15% in females (60.6{+/-}12.3 vs. 52.7{+/-}8.1 cm2) compared to TBSA measurements made on relaxed pelts. Accordingly, empirically derived Meeh constants (k) from DV tracing were greater than those derived from relaxed pelt measurements for both males (7.14{+/-}0.59 vs. 6.58{+/-}0.72) and females (7.72{+/-}0.58 vs. 6.78{+/-}0.80). In contrast k values derived from stretched pelt measures of TBSA were significantly greater than those determined in relaxed pelts for males (8.91{+/-}0.87 vs. 6.58{+/-}0.72, P<0.001) and females (8.85{+/-}1.25 vs. 6.78{+/-}0.80, P>0.001). The combined ears and tail represent approximately 7% and 8% of the TBSA measured by the relaxed pelt approach, respectively. Exclusion of the tail and ears from the calculated TBSA results in derived k values that are [~]16-17% lower. The approach used to determine TBSA in mice significantly influences measured areas and thus derived k values. We suggest that stretching the pelt prior to tracing inflates TBSA values, where measurements made from relaxed pelts or by DV tracing likely provide more accurate estimates of actual TBSA. Further, exclusion of the tail and ears (the latter of which is not typically considered in estimates of TBSA in humans) may be a useful approach relating relative burn sizes of mice to those of humans.

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.

Skeletal muscles secrete a variety of cytokines in response to inflammatory stimuli such as lipopolysaccharide (LPS); however, the contributions of resident macrophages or other non-muscle cells to the secretory responses are not well understood. To determine the potential impact of resident macrophages to inflammatory cytokine production, we tested the LPS responsiveness of isolated mouse soleus muscle when a critical toll receptor adapter protein (Myd88) was knocked down only in myeloid-derived cells within the muscle (e.g. resident macrophages). The phenotype is referred to as LyzMyd88-/- ; the litter mate controls were Myd88fl/fl. In solei from LyzMyd88-/- mice, cytokine secretory rates for interleukin-6 (IL-6) and keratinocyte-derived cytokine (KC, CXCL1) were significantly reduced to 56.3%, and 60.6% of control, respectively, over the first hour of LPS exposure. In the second hour, secretion of granulocyte colony stimulating factor (G-CSF), IL-6, KC(CXCL1) and monocyte chemoattractant protein-1 (MCP-1, CCL2) were greatly elevated by 5-10-fold in both phenotypes compared to the first hour. However, only MCP-1 secretion was decreased to 70.6% of control in the second hour. We also tested the secretory response to buffer containing 1% sterile mouse plasma because dilute plasma is known to amplify the responses of macrophages to LPS. Treatment with 1% plasma alone affected baseline measures of some cytokines but resulted in no further increases in secretion during either hour of exposure. However, small and gradual increases in secretory rates were observed for several cytokines over the study period, with or without plasma, with the largest responses seen in IL-6 and KC. Overall, the results are consistent with a significant early contribution of myeloid-derived, resident immune cells to the cytokine secretory responses of intact oxidative skeletal muscle. In addition, small quantities of plasma in the buffer have no independent stimulatory effects on cytokine secretion

Resistance training lasting a few weeks increases maximal force mainly through neural adaptations that enhance the drive from the nervous system to muscle. While these adaptations have been well documented at the motor unit (MU) level during submaximal force contractions, the mechanisms underlying force increases during maximal voluntary contractions are poorly understood. This is due to a classic technical limitation in tracking MUs longitudinally during maximal force tasks. Here, we solved this technical challenge, enabling the investigation of MU adaptations during MVCs in both the trained and untrained limbs following unilateral resistance training. High-density surface electromyography was recorded from the biceps brachii of both limbs before and after a 4-week unilateral resistance-training intervention, and the same MUs were longitudinally tracked across sessions during MVCs by concatenation of three MVC trials of ~5-s each.Unilateral training increased maximal force in the trained limb (+16%) and induced strength transfer to the untrained limb (+8%). In both limbs, maximal contractions after training were characterized by greater EMG amplitude, faster muscle-fiber conduction velocity, and higher MU discharge rates, indicating enhanced neural drive to the motoneuron pool. These adaptations were strongly associated with improvements in maximal force (R2 > 0.7 for all). Importantly, longitudinal MU tracking revealed a non-uniform adaptation across the MU pool: MUs with higher baseline conduction velocity, indicative of higher recruitment threshold, exhibited the largest pre-post increases in discharge rate, whereas lower-threshold units showed smaller changes. Collectively, these findings demonstrate that gains in maximal force and their transfer to the untrained limb are primarily mediated by enhanced rate coding of higher-threshold MUs during MVCs.

Background and PurposeBadminton imposes considerable cardiovascular and musculoskeletal stress. Physiological profiling can identify modifiable injury risk factors and inform exercise-based prevention and rehabilitation. This study compared cardiovascular recovery, neuromuscular activation, and limb strength between elite and recreational male university badminton players to derive preliminary physiological benchmarks for injury risk stratification and exercise rehabilitation guidance. MethodsForty male athletes (20 elite: national/university representatives with [&ge;]5 years of competitive experience; 20 recreational: <3 years of experience) completed assessments of heart rate recovery (HRR), biceps brachii surface electromyography (sEMG; SENIAM protocol), handgrip strength (JAMAR dynamometry), and maximal bodyweight squat repetitions. Independent-sample t-tests with Cohens d ( = 0.05) and Pearson correlations were applied. ResultsElite players demonstrated significantly greater handgrip strength (49.00{+/-}6.12 vs. 39.00{+/-}5.45 kg, p = 0.001, d = 1.72) and lower-limb (LL) strength (60.35{+/-}11.29 vs. 41.75{+/-}6.72 repetitions, p < 0.001, d = 1.96). Normalized sEMG root mean square (RMS) was higher in elite athletes during flexion (11.56{+/-}4.16% vs. 7.26{+/-}5.15%, p = 0.004, d = 0.94) and extension (12.67{+/-}4.56% vs. 7.85{+/-}5.73%, p = 0.003, d = 0.94). HRR did not differ significantly between groups (p = 0.17, d = 0.43, observed power = 0.34). Elite players nonetheless showed a more favorable recovery distribution. sEMG -HRR correlations were weak and non-significant in both groups. ConclusionsElite badminton players exhibit a distinct physiological profile of greater strength and more efficient neuromuscular activation. These preliminary cross-sectional findings may support the design of exercise-based injury-prevention and rehabilitation in university badminton.

Mass is a fundamental aspect of muscle contractile function, yet the inertial effects of inactive muscle mass is generally neglected in modeling and not quantified in studies on small muscles or isolated fibers. However, during submaximal contractions, inactive muscle tissue may take longer to be accelerated by active fibers, and may be subject to prolonged deceleration, both of which may potentially reduce force development and work output. We sought to test if inactive tissue mass imposes an inertial penalty on muscle performance, using in situ sinusoidal work-loop experiments on rat plantaris muscles. Regional fascicle dynamics, measured across supramaximal and submaximal levels of activation, showed that decreasing activation significantly reduced fascicle strain and increased both shortening and lengthening latency. Contrary to our predictions, however, reductions in work, beyond those explained by decreased fascicle strain, were negligible. Normalized work did not decline disproportionately relative to force, suggesting no clear inertial penalty on work at this muscle size. Our findings suggest that while inactive muscle mass influences the dynamics of submaximal contractions, its impact on work during submaximal contractions at small muscle sizes is limited.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely recognized to potentially interfere with skeletal muscle regeneration. However, current knowledge is based almost exclusively on non-aspirin NSAIDs. Aspirin (ASA) differs from other NSAIDs in its ability to irreversibly acetylate cyclooxygenase-2 (COX-2), thereby redirecting its activity toward a lipoxygenase (LOX)-like function that enables the production of unique ASA-triggered specialized pro-resolving lipid mediators (AT-SPMs). Despite this, the potential impact of ASA on musculoskeletal tissue repair remains poorly understood. This study directly compared the effect of ASA against non-ASA NSAIDs on in vitro myogenesis and in vivo skeletal muscle injury and regeneration. Unlike non-ASA NSAIDs, including indomethacin (INDO), celecoxib, and SC-236, which markedly impaired C2C12 myotube formation at concentrations near their pharmacological ranges, ASA only interfered with myogenesis at overtly supraphysiological concentrations. In mice, an oral dose of 3 mg/kg/day INDO following barium chloride-induced muscle injury reduced regenerating myofiber cross-sectional area and impaired the recovery of muscle force-generating capacity. In contrast, a potency-matched oral treatment with 30 mg/kg/day ASA hastened the resolution of cellular inflammation, promoted myonuclear accretion, and improved recovery of absolute muscle strength. The beneficial effects of ASA on inflammatory resolution and muscle strength--but notably not myonuclear accretion--were reversed in mice co-treated with ASA + INDO. These findings demonstrate that, unlike non-ASA NSAIDs, ASA does not impair skeletal muscle regeneration and may promote a favorable early inflammatory environment for repair via unique COX-dependent pro-resolving and COX-independent anabolic mechanisms.

High intensity and unaccustomed physical activity can induce skeletal muscle damage, while even routine movements can cause similar alterations in patients with neuromuscular disease. However, reliable assessment of muscle damage using indirect markers such as muscle function evaluation, invasive measurements, or imaging techniques is difficult to implement in routine clinical follow-up and sport field settings. Bioimpedance spectroscopy appears as a promising non-invasive, easy-to-use and transportable tool to assess indirect markers of muscle damage. The aim of this study was to determine whether bioimpedance spectroscopy data are sensitive to eccentric exercise-induced muscle damage and if these potential changes mirror responses in muscle function and tissue mechanical properties. Changes in knee extensors maximal isometric contraction torque, muscle soreness, resting rigidity of the quadriceps femoris muscle tissue, and bioimpedance parameters at rest and during maximal isometric contraction were assessed in nine healthy males before, immediately after and in the three days following 120 maximal isokinetic eccentric contractions. Maximal contraction torque was significantly reduced during the three days following the eccentric exercise (up to -24.2%) while muscle soreness and rigidity of the quadriceps femoris were elevated until the second day (+494.4% and +7.6%). Changes in bioimpedance spectroscopy parameters were transiently observed at rest immediately after the damaging exercise, but not in the days that followed. Although the changes in bioimpedance parameters correlated with that of the indirect markers of muscle damage, they had already returned to baseline while functional and mechanical impairments persisted. Therefore, bioimpedance spectroscopy measurements may represent a suitable and cost-effective means of monitoring muscle fatigue.

After myocardial infarction (MI), pathological autonomic remodeling, including vagal dysfunction and sympathoexcitation, occurs and predisposes to ventricular arrhythmias (VT/VF). The underlying factors that drive this remodeling, including the observed neuroinflammation and glial activation, remain unknown. We hypothesized that sympathetic nociceptive afferents underlie this remodeling post-MI. Epidural resiniferatoxin (RTX, to ablate sympathetic cardiac afferent neurons) vs. saline was administered in pigs prior to MI and autonomic and electrophysiological effects assessed four to six weeks post-infarction. Acute effects of afferent ablation after chronic MI were also assessed in a separate group of animals. Baroreflex sensitivity and vagal tone, as measured by parasympathetic neuronal activity and cardiac nociceptive responses, were improved in infarcted animals which received epidural RTX prior to MI. These animals also demonstrated reduced spinal cord inflammation and glial activation, downregulation of circulating stress and inflammatory pathways, and stabilization of electrophysiological parameters, with reduced VT/VF-inducibility. Epidural RTX after chronic MI also acutely restored vagal function and decreased VT/VF. These data suggest that cardiac spinal nociceptive afferents directly contribute to VT/VF susceptibility and MI-induced autonomic remodeling, including oxidative stress, inflammation, glial activation, and reduced vagal function, providing novel insights into the causal role of these afferents in driving sympathovagal imbalance after MI.

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.

Given its well-documented effects on human physiology, hypoxia has garnered increasing interest for its potential to enhance specific adaptations to exercise. However, the molecular response of skeletal muscle to exercise under normobaric hypoxia remains poorly understood. To address this gap in knowledge, ten healthy young males completed a crossover study in which exercise in hypoxia was compared to exercise in normoxia matched by either absolute or relative intensity. This design allowed us to identify shared transcriptomic responses across all three conditions, as well as changes that were specific to exercise intensity or hypoxic exposure. Skeletal muscle biopsies were collected before, immediately after, and at 3 and 24 hours following each exercise session, with RNA sequencing performed to assess changes in gene expression. Following exercise, a greater number of differentially expressed genes were observed in hypoxia compared to normoxia at 24 h post-exercise. This hypoxia-specific response involved the downregulation of multiple mitochondrial pathways and appears to be regulated by a transcriptional network comprising both positive and negative regulators of HIF-1 activity. These findings highlight the ability of normobaric hypoxia to influence exercise-induced gene expression and suggests that it may promote distinct molecular adaptations in skeletal muscle following longer-term training.

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

PurposeThe para-cycling classification system aims to minimize the impact of impairments on competition outcomes with the help of scientific evidence. This study investigated the impact of unilateral and bilateral ankle immobility on cycling performance, quantified by the maximal average mechanical power output (AMPO) over one revolution relative to that without ankle immobility. MethodsTen well-trained non-disabled cyclists performed all-out 6-second sprints on a cycle ergometer at 120 rpm under three conditions: without ankle foot orthoses (AFOs), with 1 AFO and with 2 AFOs immobilizing the ankle joint(s). Mechanical power output, pedal forces, cycling kinematics and surface-electromyography were measured. Maximal AMPO; ankle, knee and hip joint AMPO; and the amount of muscle excitation were calculated. ResultsWith 1 AFO and 2 AFOs, respectively, maximal AMPO was 96% (p<0.05) and 91% (p<0.001) of that without AFOs (1188 W). The decrease in maximal AMPO with ankle immobilization was less than the decrease in ankle joint AMPO (126 W decrease with 2 AFOs; p<0.001), due to an increase in hip joint AMPO (69 W increase with 2 AFOs; p<0.05). The amount of muscle excitation was not significantly different across conditions. ConclusionsThese findings provide a first quantitative and mechanistic indication of the impact of ankle immobility on cycling performance, which may offer valuable evidence to support the development of an evidence-based para-cycling classification system.

The pelvic floor muscles (PFM) are critical for maintaining continence and are a primary target of physiotherapy training to manage urinary incontinence. PFM training relies on voluntarily activating this muscle group, limiting its translation to neurological populations where recovery of bladder function is a priority. Indirect evidence suggests that sensory feedback from the lower limb can modulate PFM activity, which may provide alternative strategies for PFM training. Cutaneous reflexes have been used as a proxy to study how sensory inputs from the skin influence motoneuron excitability. To explore the feasibility of eliciting cutaneous reflexes in the PFM and their role in controlling PFM activity, this study examined: 1) the input-output relationship and 2) the nerve-specificity of PFM cutaneous reflex responses from tibial and superficial peroneal nerve stimulation. Twenty-one neurologically intact adults participated in this study. We recorded PFM and lower leg muscle electromyography while participants received cutaneous stimulation to the right distal tibial nerve, bilateral distal tibial nerve, or right superficial peroneal nerve in a standing position. We delivered stimulation at the intensity below motor threshold (MT), 1.2 x MT and 1.5 x MT and quantified tibial-PFM reflex amplitude over a 50-150 ms window after stimulation. PFM reflex responses were evoked from both nerves stimulation. Reflex amplitude increased with stimulus intensity with tibial nerve stimulation but not with superficial peroneal nerve stimulation. Bilateral tibial nerve stimulation evoked larger responses compared to unilateral stimulation. These findings support the existence of neural connections between lower limb afferents and the PFM, and open up possibilities for designing rehabilitation strategies to manage pelvic health conditions in people with neurological disorders. New & NoteworthyO_LICutaneous sensory feedback from the foot, specifically that related to limb loading, can evoke reflex responses in the pelvic floor muscles C_LIO_LINerve-specific modulation was observed. Reflex amplitudes in the pelvic floor muscles increased with tibial nerve stimulation intensity but not with superficial peroneal nerve stimulation. C_LI

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.

Proprioception and reflexive control of muscle tone depend on the activity of muscle spindles, specialized sensory receptors embedded deep within skeletal muscle that detect changes in muscle length. Their location and complex three-dimensional architecture have historically limited morphological analysis to techniques such as silver-impregnation, muscle teasing, or serial sectioning followed by volumetric reconstruction. Here, we describe a workflow for three-dimensional, in situ visualization of muscle spindles in the rabbit tenuissimus muscle, a preparation uniquely enriched in spindles and well suited for whole-mount imaging. The protocol combines fluorescent labeling of spindle sensory and motor innervation, including intrafusal {gamma} neuromuscular junctions labeled with -bungarotoxin, with immunolabeling and solvent-based optical clearing. Optically cleared tenuissimus muscles were compatible with both whole-mount confocal and light-sheet microscopy, enabling volumetric imaging of complete spindle structures and detailed visualization of Ia annulospiral endings at the spindle equator. This approach provides access to spindle morphology and connectivity at multiple spatial scales while avoiding physical sectioning and reconstruction. By enabling reproducible three-dimensional imaging of intact muscle spindles, this workflow offers a practical platform for studying spindle structure and plasticity in health and disease.

Older adults sustain disproportionately severe injuries from trip-induced falls during obstacle crossing. Such falls depend partly on forward momentum when the foot crosses the obstacle. MOSAP, an index of passive dynamic gait stability, reflects this momentum. We quantified MOSAP and a synergy index from uncontrolled manifold analysis of step length and extrapolated center of mass in 25 young (21.6 {+/-} 3.5 yr) and 23 older adults (68 {+/-} 4.3 yr) during unobstructed and obstructed walking, to test whether MOSAP increases during obstacle crossing and whether it is actively stabilized at each step. Both groups increased MOSAP progressively over two approach steps by reducing forward momentum and shifting the center of mass posteriorly. Older adults showed greater increases at the crossing steps. The synergy index was positive for all steps, showing that deviations in step length and extrapolated center of mass covaried to stabilize MOSAP at step-specific values. The synergy index was not influenced by age. We conclude that adults actively recruit passive body mechanics while approaching and crossing obstacles to reduce the risk of a trip becoming a fall. Older adults amplify this strategy to compensate for diminished neuromuscular corrective capabilities.

BackgroundIndividuals with spinal cord injury (SCI) experience accelerated atherosclerotic cardiovascular disease that is not fully explained by traditional risk factors. Endothelial dysfunction is a key mechanism in atherosclerosis. We tested the hypothesis that endothelium-dependent vasodilation is impaired in adults with SCI and is due, at least in part, to oxidative stress. MethodsTwenty-four adults (age:19-58 yr) free of overt cardiometabolic disease were studied: 12 non-injured adults (9 M/3 F) and 12 adults with chronic SCI (8 M/4 F; time since injury 1.5 - 25 years). Forearm blood flow was determined (FBF; via strain-gauge plethysmography) in response to intra-arterial infusion of acetylcholine and isoproterenol in the absence and presence of the antioxidant vitamin C as well as the FBF response to sodium nitroprusside. ResultsAdults with SCI demonstrated significantly lower vasodilator response to acetylcholine (from 4.1{+/-}0.6 to 10.7{+/-}2.6 mL/100 mL tissue/min vs 4.1{+/-}1.1 to 15.7{+/-}3.4 mL/100 mL tissue/min) and isoproterenol (4.0{+/-}0.6 to 11.2{+/-}2.2 mL/100 mL tissue/min vs 4.3{+/-}1.0 to 15.0{+/-}2.6 mL/100 mL tissue/min) compared with non-injured adults. FBF response to sodium nitroprusside was not significantly different between the groups. Co-infusion of vitamin C significantly increased the vasodilator response to acetylcholine (~45%) and isoproterenol (~25%) in the adults with SCI to levels comparable with non-injured adults. ConclusionsChronic SCI is associated with endothelial-dependent vasodilator dysfunction. Impaired vasodilation across two distinct endothelial agonists suggests that chronic SCI is associated with endothelial dysfunction not confined to a specific receptor or intracellular signaling pathway. Moreover, oxidative stress is a contributing factor underlying SCI-related endothelial vasodilator dysfunction. NCT06443151 CLINICAL PERSPECTIVEO_LIThe novel finding of this study is that individuals with SCI demonstrate impaired endothelial vasodilator function in absence of traditional cardiovascular risk factors. C_LIO_LIOxidative stress is a contributing factor to SCI-related endothelial vasodilator dysfunction. C_LIO_LIFuture studies are needed to determine the efficacy of therapeutic interventions, either lifestyle or pharmacologic, in improving endothelial function in order to mitigate the elevated ASCVD risk after SCI. C_LI

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.