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Background: Duchenne muscular dystrophy (DMD) is associated with impaired muscle regeneration, progressive muscle weakness, damage, and wasting. While the cause of DMD is an X-linked loss of function mutation in the gene encoding dystrophin, the exact mechanisms that perpetuate the disease progression are unknown. Our laboratory has demonstrated that pannexin 1 (Panx1 in rodents; PANX1 in humans) is critical for the development, strength, and regeneration of male skeletal muscle. In normal skeletal muscle, Panx1 is part of a multiprotein complex with dystrophin. We and others have previously shown that Panx1 levels and channel activity are dysregulated in various mouse models of DMD. Methods: We utilized myoblast cell lines derived from DMD patients to assess PANX1 expression and function. To investigate how Panx1 dysregulation contributes to DMD, we generated a dystrophic (mdx) mouse model that lacks Panx1 (Panx1−/−/mdx). In depth characterization of this model included histological analysis, as well as locomotor, and physiological tests such as muscle force and grip strength assessments. Results: Here, we demonstrate that PANX1 levels and channel function are reduced in patient-derived DMD myoblast cell lines. Panx1−/−/mdx mice have a significantly reduced lifespan, and decreased body weight due to lean mass loss. Their tibialis anterior were more affected than their soleus muscles and displayed reduced mass, myofiber loss, increased centrally nucleated myofibers, and a lower number of muscle stem cells compared to that of Panx1+/+/mdx mice. These detrimental effects were associated with muscle and locomotor functional impairments. In vitro, PANX1 overexpression in patient-derived DMD myoblasts improved their differentiation and fusion. Conclusions: Collectively, our findings suggest that PANX1/Panx1 dysregulation in DMD exacerbates several aspects of the disease. Moreover, our results suggest a potential therapeutic benefit to increasing PANX1 levels in dystrophic muscles. [ABSTRACT FROM AUTHOR]

Emotion affects postural control during quiet standing. Emotional states can be defined as two-dimensional models comprising valence (pleasant/unpleasant) and arousal (aroused/calm). Most previous studies have investigated the effects of valence on postural control without considering arousal. In addition, studies have focused on the center of pressure (COP) trajectory to examine emotional effects on the quiet standing control; however, the relationship between neuromuscular mechanisms and the emotionally affected quiet standing control is largely unknown. This study aimed to investigate the effects of arousal and valence on the COP trajectory and ankle muscle activity during quiet standing. Twenty-two participants were instructed to stand on a force platform and look at affective pictures for 72 seconds. The tasks were repeated six times, according to the picture conditions composed of arousal (High and Low) and valence (Pleasant, Neutral, and Unpleasant). During the task, the COP, electromyogram (EMG) of the tibialis anterior and soleus muscles, and electrocardiogram (ECG) were recorded. The heart rate calculated from the ECG was significantly affected by valence; the value was lower in Unpleasant than that in Neutral and Pleasant. The 95% confidence ellipse area and standard deviation of COP in the anterior-posterior direction were lower, and the mean power frequency of COP in the anterior-posterior direction was higher in Unpleasant than in Pleasant. Although the mean velocity of the COP in the medio-lateral direction was significantly lower in Unpleasant than in Pleasant, the effect was observed only when arousal was low. Although the EMG variables were not significantly affected by emotional conditions, some EMG variables were significantly correlated with the COP variables that were affected by emotional conditions. Therefore, ankle muscle activity may be partially associated with postural changes triggered by emotional intervention. In conclusion, both valence and arousal affect the COP variables, and ankle muscle activity may be partially associated with these COP changes. [ABSTRACT FROM AUTHOR]

Treadmill running is a common method of exercise and to study human locomotion. Research has examined the kinematics and kinetics of overground and treadmill running, but there has been less focus on the levels of muscle activity during treadmill running. We investigated if muscle activity is different while running overground compared to running on a variety of treadmills. A total of 11 healthy individuals ran at 3 speeds (2.6, 3.6, 4.5 m/s) under 4 different running conditions (3 treadmills, overground). The three treadmills included a typical home exercise treadmill, a midsize commercial research treadmill, and a large, instrumented research treadmill. Surface EMG of the tibialis anterior (TA), gastrocnemius medialis (GM), rectus femoris (RF) and biceps femoris (BF) muscles were measured for each running condition. The integrated EMG was computed for each running condition for the stance and swing phase, as well as 100ms before and after the heel-strike. Friedman analysis revealed significant effects during the stance phase for GM and RF at all speeds, such that muscle activation was lower on the treadmills relative to overground. During the stance phase at faster speeds, themuscle activity was higher for the TA and lower for the BF while running on the different treadmills compared to overground running. Before heel-strike, the TA was significantly less active during treadmill compared to overground running at 2.6 m/s and the RF showed significantly higher activity at 3.6 m/s and 4.5 m/s while running on the different treadmills. Summarizing, differences were mainly observed between the different treadmill conditions relative to overground running. Muscle activation differences between the different treadmill conditions were observed at faster running speeds for RF during the pre-heel-strike phase only. Different types of treadmills with different mechanical properties affects the muscle activity during stance phase as well as in preparation to heel-strike. Additionally, the muscle activity is greater during overground compared to treadmill running during the stance phase for the GM, BF, and RF. [ABSTRACT FROM AUTHOR]

5‐HT2 receptors on motoneurones play a critical role in facilitating persistent inward currents (PICs). Although facilitation of PICs can enhance self‐sustained firing after periods of excitation, the relationship between 5‐HT2 receptor activity and self‐sustained firing in human motor units (MUs) has not been resolved. MU activity was assessed from the tibialis anterior of 10 healthy adults (24.9 ± 2.8 years) during two contraction protocols. Both protocols featured steady‐state isometric contractions with constant descending drive to the motoneurone pool. However, one protocol also included an additional phase of superimposed descending drive. Adding and then removing descending drive in the middle of steady‐state contractions altered MU firing behaviour across the motor pool, where newly recruited units in the superimposed phase were unable to switch off (P = 0.0002), and units recruited prior to additional descending drive reduced their discharge rates (P < 0.0001, difference in estimated marginal means (∆) = 2.24 pulses/s). The 5‐HT2 receptor antagonist, cyproheptadine, was then administered to determine whether changes in MU firing were mediated by serotonergic mechanisms. 5‐HT2 receptor antagonism caused reductions in MU discharge rate (P < 0.001, ∆ = 1.65 pulses/s), recruitment threshold (P = 0.00112, ∆ = 1.09% maximal voluntary contraction) and self‐sustained firing duration (P < 0.0001, ∆ = 1.77s) after the additional descending drive was removed in the middle of the steady‐state contraction. These findings indicate that serotonergic neuromodulation plays a key role in facilitating discharge and self‐sustained firing of human motoneurones, where adaptive changes in MU recruitment must occur to meet the demands of the contraction. Key points: Animal and cellular preparations indicate that somato‐dendritic 5‐HT2 receptors regulate the intrinsic excitability of motoneurones.5‐HT2 receptor antagonism reduces estimates of persistent inward currents in motoneurones, which contribute to self‐sustained firing when synaptic inputs are reduced or removed.This human study employed a contraction task that slowly increased (and then removed) the additional descending drive in the middle of a steady‐state contraction where marked self‐sustained firing occurred when the descending drive was removed.5‐HT2 receptor antagonism caused widespread reductions in motor unit (MU) discharge rates during contractions, which was accompanied by reduced recruitment threshold and attenuation of self‐sustained firing duration after the removal of the additional descending drive to motoneurones.These findings support the role that serotonergic neuromodulation is a key facilitator of MU discharge and self‐sustained firing of human motoneurones, where adaptative changes in MU recruitment must occur to meet the demands of the contraction. [ABSTRACT FROM AUTHOR]

Transcutaneous multisegmental spinal cord stimulation (tSCS) has shown superior efficacy in modulating spinal locomotor circuits compared to single-site stimulation in individuals with spinal cord injury (SCI). Building on these findings, we hypothesized that administering a single session of tSCS at multiple spinal segments may yield greater enhancements in muscle strength and gait function during stimulation compared to tSCS at only one or two segments. In our study, tSCS was applied at single segments (C5, L1, and Coc1), two segments (C5-L1, C5-Coc1, and L1-Coc1), or multisegments (C5-L1-Coc1) in a randomized order. We evaluated the 6-m walking test (6MWT) and maximum voluntary contraction (MVC) and assessed the Hmax/Mmax ratio during stimulation in ten individuals with incomplete motor SCI. Our findings indicate that multisegmental tSCS improved walking time and reduced spinal cord excitability, as measured by the Hmax/Mmax ratio, similar to some single or two-site tSCS interventions. However, only multisegmental tSCS resulted in increased tibialis anterior (TA) muscle strength. These results suggest that multisegmental tSCS holds promise for enhancing walking capacity, increasing muscle strength, and altering spinal cord excitability in individuals with incomplete SCI. [ABSTRACT FROM AUTHOR]

Background: About one third of kids with spastic hemiplegic cerebral palsy also have equinovarus. For equinovarus deformity, the ideal softtissue surgical treatment is a split transfer of the tibialis anterior tendon. Objectives: To evaluate the radiological as well as clinical results of split transfer of tibialis anterior to peroneus brevis in management of equinovarus deformity among children with cerebral palsy. Subjects and methods: This is interventional clinical trial study that was performed on 18 patients presented to orthopedic department at Zagazig University Hospitals with equinovarus foot deformity undergone split tibilais anterior transfer to peroneus brevis with fractional lengthening of tibilais posterior and gastrocnemius recession. Results: The pain and difficulty of shoe-wearing were improved in all the patients (100.0%). There were 15 patients (83.3%) had an excellent outcome, and only 3 patients (16.7%) had a good outcome according to Kling’s score. We found a highly statistically significant decrease (improve) in the GMFC score from (2.3±0.48) to become (1.3±0.47) (p-value<0.001) with a percent of improvement (50.4%) ranging from (43.1%-69.2%). There were 13 patients (72.2%) didn’t have any complications, two cases (11.1%) had dry, flaky skin & itching after the cast and three cases (16.7%) had superficial wound infections which treated by parental antibiotics for 2 weeks. Conclusion: The benefits of split tibialis anterior transfer to peroneus brevis in treating equinovarus foot deformity in cerebral palsy patients have been demonstrated by this research. The procedure is technically simple, with high rates of success and minimal complications [ABSTRACT FROM AUTHOR]

Background. Prolonged joint immobilization causes muscle hypotrophy and joint stiffness, which worsen as the immobilization time increases. Muscle remobilization is essential to restore muscle mass and activity as soon as possible. There are various treatments for muscle remobilization, but therapeutic ultrasound has proved to be a promising technique, with thermal and athermic actions, generating possibilities for increasing tissue extensibility and cell metabolism, helping with the anabolic effects of static stretching. Objective. To evaluate the histopathological changes in the tibialis anterior muscle of Wistar rats after remobilization using therapeutic ultrasound, using the histopathological index. Methods. 21 male Wistar rats were used, divided into 3 groups (n = 7): immobilization group, immobilization and free remobilization group, immobilization and remobilization with ultrasound group. Immobilization was carried out with the knee flexed at 120° and total ankle plantiflexion for three weeks. Ultrasound was used at a frequency of 1.0 MHz with an intensity of 0.5 w/cm², lasting 2 minutes on the knee and a further 2 minutes on the ankle. Analyses were carried out using the histopathological index to measure the level of alterations and lesions in the muscle tissue, classifying them as severe, moderate or mild. Conclusions. It was concluded that the anabolic stimulus of ultrasound was favorable to the trophic recovery of muscle tissue. [ABSTRACT FROM AUTHOR]

Purpose: Outdoor running surfaces are designed with a cross-slope, which can alter kinetic and kinematic gait parameters. The purpose of this study was to evaluate running economy, gait characteristics, and muscle activation while running on a surface with cross-slopes similar to those encountered on roads and trails. Methods: Eleven recreational runners (females n = 6) completed 5-min running trials on a treadmill at 10 km h−1 with cross-slopes of 0, 1.15, 2.29, and 6 deg in a randomized order. Results: There were no significant differences in VO2, HR, RER, or VE across cross-slope conditions. Compared to 0 deg of cross-slope, ground contact time and duty factor increased at 2.29 and 6 deg, with significant decreases in absolute and relative flight times. Rear foot angles increased in the upslope leg at 2.29 and 6 deg cross-slopes and decreased in the downslope leg at 6 deg compared to 0 deg of cross-slope, with differences between legs for the 2.29 and 6 deg conditions. Knee flexion at foot strike increased in the upslope leg at a 6 deg cross-slope. Vastus lateralis, biceps femoris, gastrocnemius, and tibialis anterior activation were not affected by the cross-slope conditions. While cross-slopes up to 6 deg result in changes to some gait kinematics, these effects do not impact running economy at moderate running velocity. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to a deficiency in dystrophin production and consequent progressive degeneration of skeletal muscle fibres, through oxidative stress and an exacerbated inflammatory process. The flavonoid trilobatin (TLB) demonstrates antioxidant and anti‐inflammatory potential. Its high safety profile and effective action make it a potent therapy for the process of dystrophic muscle myonecrosis. Thus, we sought to investigate the action of TLB on damage in a DMD model, the mdx mouse. Eight‐week‐old male animals were treated with 160 mg/kg/day of trilobatin for 8 weeks. Control animals were treated with saline. Following treatment, muscle strength, serum creatine kinase (CK) levels, histopathology (necrotic myofibres, regenerated fibres/central nuclei, Feret's diameter and inflammatory area) and the levels of catalase and NF‐κB (western blotting) of the quadriceps (QUA), diaphragm (DIA) and tibialis anterior (TA) muscles were measured. TLB was able to significantly increase muscle strength and reduce serum CK levels in dystrophic animals. The QUA of mdx mice showed a reduction in catalase and the number of fibres with a centralized nucleus after treatment with TLB. In the DIA of dystrophic animals, TLB reduced the necrotic myofibres, inflammatory area and NF‐κB and increased the number of regenerated fibres and the total fibre diameter. In TA, TLB increased the number of regenerated fibres and reduced catalase levels in these animals. It is concluded that in the mdx experimental model, treatment with TLB was beneficial in the treatment of DMD. [ABSTRACT FROM AUTHOR]

Introduction: Today, disabled sports have become one of the most important categories in the world of sports. In the meantime, exercising the blind and visually impaired is essential. Therefore, the present study aimed to examine the effect of clothing weight on the range of lower limb muscle activities during the execution of archery skills in blind people. Methods: The current research is semi-experimental and laboratory-type. The statistical sample of the present study included 30 blind boys from Ardabil City who were selected purposefully and voluntarily. The subjects were randomly divided into two groups. The shooting target was placed at a distance of 10 meters from the subject. A two-way analysis of variance and a t-test at a significance level of 0.05 were used for statistical analysis of the data. Results: According to the obtained results, the effect of the time factor on the electrical activity of the vastus medialis muscle when releasing the bowstring was statistically significant. The impact of the group factor on the electrical activity of the tibialis anterior muscle when releasing the bowstring had a statistically significant difference. Also, the effect of the group factor when taking the bow in the rectus femoris muscle and biceps muscle had a statistically significant difference. Conclusions: Finally, according to all the obtained results, it can be said that probably using shooting clothes by affecting the electrical activity of the muscles of the lower limbs can improve balance during shooting, which can be one of the influential reasons, and become efficient in the success of archers. [ABSTRACT FROM AUTHOR]

Fibrosis is associated with respiratory and limb muscle atrophy in Duchenne muscular dystrophy (DMD). Current standard of care partially delays the progression of this myopathy but there remains an unmet need to develop additional therapies. Adiponectin receptor agonism has emerged as a possible therapeutic target to lower inflammation and improve metabolism in mdx mouse models of DMD but the degree to which fibrosis and atrophy are prevented remain unknown. Here, we demonstrate that the recently developed slow-release peptidomimetic adiponectin analog, ALY688-SR, remodels the diaphragm of murine model of DMD on DBA background (D2.mdx) mice treated from days 7–28 of age during early stages of disease. ALY688-SR also lowered interleukin-6 (IL-6) mRNA but increased IL-6 and transforming growth factor-β1 (TGF-β1) protein contents in diaphragm, suggesting dynamic inflammatory remodeling. ALY688-SR alleviated mitochondrial redox stress by decreasing complex I-stimulated H2O2 emission. Treatment also attenuated fibrosis, fiber type-specific atrophy, and in vitro diaphragm force production in diaphragm suggesting a complex relationship between adiponectin receptor activity, muscle remodeling, and force-generating properties during the very early stages of disease progression in murine model of DMD on DBA background (D2.mdx) mice. In tibialis anterior, the modest fibrosis at this young age was not altered by treatment, and atrophy was not apparent at this young age. These results demonstrate that short-term treatment of ALY688-SR in young D2.mdx mice partially prevents fibrosis and fiber type-specific atrophy and lowers force production in the more disease-apparent diaphragm in relation to lower mitochondrial redox stress and heterogeneous responses in certain inflammatory markers. These diverse muscle responses to adiponectin receptor agonism in early stages of DMD serve as a foundation for further mechanistic investigations. NEW & NOTEWORTHY: There are limited therapies for the treatment of Duchenne muscular dystrophy. As fibrosis involves an accumulation of collagen that replaces muscle fibers, antifibrotics may help preserve muscle function. We report that the novel adiponectin receptor agonist ALY688-SR prevents fibrosis in the diaphragm of D2.mdx mice with short-term treatment early in disease progression. These responses were related to altered inflammation and mitochondrial functions and serve as a foundation for the development of this class of therapy. [ABSTRACT FROM AUTHOR]

The "Repeated Bout Effect" (RBE) occurs when a skeletal muscle is preconditioned with a few lengthening contractions (LC) prior to exposing the muscle to a greater number of LC. The preconditioning (PC) results in significantly less damage and preservation of force. Since it takes only a few LC to increase muscle heat shock protein (HSP) content, it was of interest to examine the relationship between HSPs and the RBE. To do this, one tibialis anterior (TA) muscle from Sprague–Dawley rats (n = 5/group) was preconditioned with either 0, 5, or 15 lengthening contractions (LC) and exposed to a treatment of 60 LC 48 h later. Preconditioning TA muscles with 15 LC, but not 5 LC, significantly elevated muscle αB-crystallin (p < 0.05), HSP25 (p < 0.05), and HSP72 content (p < 0.001). These preconditioned TA muscles also showed a significantly (p < 0.05) reduced loss of active torque throughout the subsequent 60 LC. While there was a trend for all preconditioned muscles to maintain higher peak torque levels throughout the 60 LC, no significant differences were detected between the groups. Morphologically, preconditioned muscles appeared to show less discernible muscle fiber damage. In conclusion, an elevated skeletal muscle HSP content from preconditioning may contribute to the RBE. [ABSTRACT FROM AUTHOR]

Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to limit scarring around peripheral nerves. Thirty rats were divided into three groups: glutaraldehyde-induced sciatic nerve injury treated with FG (GA + FG), sciatic nerve injury with no treatment (GA), and no sciatic nerve injury (Sham). Neural regeneration was assessed with weekly measurements of the visual static sciatic index as a parameter for sciatic nerve function across a 12-week period. After 12 weeks, qualitative and quantitative histological analysis of scar tissue formation was performed. Furthermore, histomorphometric analysis and wet muscle weight analysis were performed after the postoperative observation period. The GA + FG group showed a faster functional recovery (6 versus 9 weeks) compared to the GA group. The FG-treated group showed significantly lower perineural scar tissue formation and significantly higher fiber density, myelin thickness, axon thickness, and myelinated fiber thickness than the GA group. A significantly higher wet muscle weight ratio of the tibialis anterior muscle was found in the GA + FG group compared to the GA group. Our results suggest that applying FG to injured nerves is a promising scar tissue prevention strategy associated with improved regeneration both at the microscopic and at the functional level. Our results can serve as a platform for innovation in the field of perineural regeneration with immense clinical potential. [ABSTRACT FROM AUTHOR]

This variation was observed in the left lower extremity of a 75-year-old male cadaver fixed with formalin, ethanol and glycerol solution. The common peroneal nerve was divided into six terminal branches. These branches were identified as deep peroneal nerve, superficial peroneal nerve, two muscular branches to the tibialis anterior and two muscular branches to the peroneus longus. Knowledge of the variations of the common peroneal nerve and its branches is important in knee and proximal leg operations [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the effects of exercises on sand on the frequency content of the lower limb muscles in individuals with anterior cruciate ligament reconstruction and pronated feet during walking. Methods: This was a semi-experimental and laboratory-type study. The study samples included 28 male students with pronated feet and anterior... [ABSTRACT FROM AUTHOR]

Skeletal muscle adaptation to external stimuli, such as regeneration following injury and hypertrophy in response to resistance exercise, are blunted with advanced age. The accumulation of senescent cells, along with defects in myogenic progenitor cell (MPC) proliferation, have been strongly linked as contributing factors to age-associated impairment in muscle adaptation. p53 plays an integral role in all these processes, as upregulation of p53 causes apoptosis in senescent cells and prevents mitotic catastrophe in MPCs from old mice. The goal of this study was to determine if a novel pharmaceutical agent (BI01), which functions by upregulating p53 through inhibition of binding to MDM2, the primary p53 regulatory protein, improves muscle regeneration and hypertrophy in old mice. BI01 effectively reduced the number of senescent cells in vitro but had no effect on MPC survival or proliferation at a comparable dose. Following repeated oral gavage with 2 mg/kg of BI01 (OS) or vehicle (OV), old mice (24 months) underwent unilateral BaCl2 injury in the tibialis anterior (TA) muscle, with PBS injections serving as controls. After 7 days, satellite cell number was higher in the TA of OS compared to OV mice, as was the expression of genes involved in ATP production. By 35 days, old mice treated with BI01 displayed reduced senescent cell burden, enhanced regeneration (higher muscle mass and fiber cross-sectional area) and restoration of muscle function relative to OV mice. To examine the impact of 2 mg/kg BI01 on muscle hypertrophy, the plantaris muscle was subjected to 28 days of mechanical overload (MOV) in OS and OV mice. In response to MOV, OS mice had larger plantaris muscles and muscle fibers than OV mice, particularly type 2b + x fibers, associated with reduced senescent cells. Together our data show that BI01 is an effective senolytic agent that may also augment muscle metabolism to enhance muscle regeneration and hypertrophy in old mice. [ABSTRACT FROM AUTHOR]

Whether eccentric exercise involves active fascicle stretch is unclear due to muscle-tendon unit (MTU) series compliance. Therefore, this study investigated the impact of changing the activation timing and level (i.e., preactivation) of the contraction on muscle fascicle kinematics and kinetics of the human tibialis anterior during dynamometer-controlled maximal voluntary MTU-stretch-hold contractions. B-mode ultrasound and surface electromyography were used to assess muscle fascicle kinematics and muscle activity levels, respectively. Although joint kinematics were similar among MTU-stretch-hold contractions (∼40° rotation amplitude), increasing preactivation increased fascicle shortening and stretch amplitudes (9.9–23.2 mm, P ≤ 0.015). This led to increasing positive and negative fascicle work with increasing preactivation. Despite significantly different fascicle kinematics, similar peak fascicle forces during stretch occurred at similar fascicle lengths and joint angles regardless of preactivation. Similarly, residual force enhancement (rFE) following MTU stretch was not significantly affected (6.5–7.6%, P = 0.559) by preactivation, but rFE was strongly correlated with peak fascicle force during stretch (rrm = 0.62, P = 0.003). These findings highlight that apparent eccentric exercise causes shortening-stretch contractions at the fascicle level rather than isolated eccentric contractions. The constant rFE despite different fascicle kinematics and kinetics suggests that a passive element was engaged at a common muscle length among conditions (e.g., optimal fascicle length). Although it remains unclear whether different fascicle mechanics trigger different adaptations to eccentric exercise, this study emphasizes the need to consider MTU series compliance to better understand the mechanical drivers of adaptation to exercise. NEW & NOTEWORTHY: Apparent eccentric exercises do not result in isolated eccentric contractions, but shortening-stretch contractions at the fascicle level. The amount of fascicle shortening and stretch depends on the preactivation during the exercise and cannot be estimated from the muscle-tendon unit (MTU) or joint kinematics. As different fascicle mechanics might trigger different adaptations to eccentric exercise, muscle-tendon unit series compliance and muscle preactivation need to be considered when eccentric exercise protocols are designed. [ABSTRACT FROM AUTHOR]

Background: Excessive body weight is associated with gait alterations. In none of previous studies, body fat distribution has been considered as a factor that could change gait parameters and induce different neuromuscular adaptations. Objective: This multicenter, analytical, and cross-sectional study aimed to investigate the influence of the body mass distribution on gait parameters and ankle muscle coactivation in obese individuals. Methods: Three distinct groups were included in the study: a non-obese control group (CG, n = 15, average age = 32.8 ± 6.5 years, BMI = 21.4 ± 2.2 kg/m2), an obese-android group characterized by a Waist to Hip Ratio (WHR) greater than 1 (OAG, n = 15, age = 32.4 ± 3.9 years, BMI = 41.4 ± 3.9 kg/m2, WHR = 1.2 ± 0.2), and an obese-gynoid group with a WHR less than 1 (OGG, n = 15, age = 35.4 ± 4.1 years, BMI = 40.0 ± 5.7 kg/m2, WHR = 0.82 ± 0.3). All participants walked on an instrumented gait analysis treadmill at their self-selected walking speed for one minute. Spatiotemporal parameters, walking cycle phases, vertical ground reaction force (GRFv) and center of pressure (CoP) velocity were sampled from the treadmill software. Electromyography (EMG) activity of the gastrocnemius medialis (GM), the soleus (SOL) and tibialis anterior (TA) were collected during walking and used to calculate coactivation indexes (CI) between ankle plantar and dorsal flexors (GM/TA and SOL/TA) for the different walking cycle phases. Results: Compared to OAG, OGG walked with shorter and larger strides, lower CoP velocity and GRFv. During the single support phase, SOL/TA coactivation was higher in OAG compared to OGG (p <.05). During the propulsion phase, SOL/TA coactivation was higher in OGG compared to OAG (p <.05). Conclusion: Gait parameters and ankle muscle coactivation in obese individuals seem to be strongly dependent on body mass distribution. From the biomechanical point of view, body mass distribution changes gait strategies in obese individuals inducing different neuromuscular adaptations during the single support and propulsion phases. [ABSTRACT FROM AUTHOR]

Residual force depression (rFD) following active muscle shortening is assumed to correlate most strongly with muscle work, but this has not been tested during voluntary contractions in humans. Using dynamometry, we compared steady‐state ankle joint torques (N = 16) following tibialis anterior (TA) muscle–tendon unit (MTU) lengthening and shortening to the time‐matched torque during submaximal voluntary fixed‐end dorsiflexion reference contractions (REF) at a matched MTU length and EMG amplitude. Ultrasound revealed significantly reduced (P < 0.001) TA fascicle shortening amplitudes during MTU lengthening without a preload over small and medium amplitudes, respectively, relative to REF. MTU lengthening with a preload over a large amplitude significantly (P < 0.001) increased fascicle shortening relative to REF, as well as stretch amplitudes relative to MTU lengthening without a preload (P = 0.001). Significant (P = 0.028) steady‐state fascicle force enhancement relative to REF was observed following MTU lengthening, and was similar among MTU lengthening‐hold conditions (3–5%). MTU shortening with and without a preload over small and large amplitudes significantly (P < 0.001) increased positive fascicle and MTU work relative to REF, but significant (P = 0.006) rFD was observed following MTU shortening with a preload (7–10%) only. rFD was linearly related to positive MTU work [rrm(47) = 0.48, P < 0.001], but not positive fascicle work [rrm(47) = 0.16, P = 0.277]. Our findings indicate that MTU lengthening without substantial fascicle stretch enhances steady‐state force output, which might arise from less shortening‐induced rFD. Our findings also indicate similar rFD following different amounts of positive fascicle/MTU work, which cautions against using work to predict rFD during submaximal voluntary contractions. Key points: Accurately predicting muscle force is challenging because active muscle shortening depresses force output.The residual force depression (rFD) that exists following active muscle shortening is commonly assumed to correlate strongly and positively with muscle work.We found that tibialis anterior muscle fascicle work and muscle–tendon unit work did not accurately predict rFD during submaximal voluntary dorsiflexion contractions.Fascicle shortening during fixed‐end reference contractions also potentially induced rFD of 3–5%, which was similar to the rFD following muscle–tendon unit shortening without a preload.A higher number of active muscle fibres during shortening probably increased rFD, which suggests that motor unit recruitment during shortening might predict rFD. [ABSTRACT FROM AUTHOR]

Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to contract multiple muscle groups simultaneously. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly through mitochondrial biosynthesis. This study examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for one week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague–Dawley rats using belt electrodes attached to both ankle joints. After acute stimulation, a significant decrease in the glycogen content was observed in the left and right TA and GAS, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN + electrically stimulated with B-SES (DEN + ES) groups. After seven days of treatment, the wet weight (n = 8–11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN + ES groups compared with that in the CON group. The DEN + ES group showed significantly higher muscle weight and CSA than those in the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial biogenesis is a critical event in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 18S (n = 6) levels in the DEN + ES group were higher than those in the DEN group, even though RNA-seq showed that the ribosome biogenesis pathway was reduced by electrical stimulation. The mRNA levels of the muscle proteolytic molecules atrogin-1 and MuRF1 were significantly higher in DEN than those in CONT. However, they were more suppressed in DEN + ES than those in DEN. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes effectively reduced denervation-induced atrophy in multiple muscle groups. Furthermore, ribosomal biosynthesis plays a vital role in this phenomenon. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of different durations of lower limb static stretching (SS) on the performance of long jump (LJ) athletes. Methods: A crossover randomized controlled trial was conducted with 20 athletes, submitted to 4 conditions: 3 experimental conditions, performing the usual warm-up plus SS of quadriceps, hamstrings, gastrocnemius and tibialis anterior during 30 s, 1 min or 3 min; and a control condition, of only the usual warm-up. LJ performance was assessed before and immediately after the interventions/control. Results: There was a significant change after the 3 min SS, with an improvement in the distance achieved (p = 0.012). However, there were no differences between the 4 conditions (p = 0.154). Conclusion: Results suggest that SS performed for 30 s, 1 min or 3 min, seem not to influence the LJ performance, since despite an improvement in the distance reached after the 3 min SS, there were no significant differences between conditions. [ABSTRACT FROM AUTHOR]

To adequately evaluate the corticospinal and spinal plasticity in health and disease, it is essential to understand whether and to what extent the corticospinal and spinal responses fluctuate systematically across multiple measurements. Thus, in this study, we examined the session-to-session variability of corticospinal excitability for the ankle dorsiflexor tibialis anterior (TA) in people with and without incomplete spinal cord injury (SCI). In neurologically normal participants, the following measures were obtained across 4 days at the same time of day (N = 13) or 4 sessions over a 12-h period (N = 9, at 8:00, 12:00, 16:00, and 20:00): maximum voluntary contraction (MVC), maximum M-wave and H-reflex (Mmax and Hmax), motor evoked potential (MEP) amplitude, and silent period (SP) after MEP. In participants with chronic incomplete SCI (N = 17), the same measures were obtained across 4 days. We found no clear diurnal variation in the spinal and corticospinal excitability of the TA in individuals with no known neurological conditions, and no systematic changes in any experimental measures of spinal and corticospinal excitability across four measurement days in individuals with or without SCI. Overall, mean deviations across four sessions remained in a range of 5–13% for all measures in participants with or without SCI. The study shows the limited extent of non-systematic session-to-session variability in the TA corticospinal excitability in individuals with and without chronic incomplete SCI, supporting the utility of corticospinal and spinal excitability measures in mechanistic investigation of neuromodulation interventions. The information provided through this study may serve as the reference in evaluating corticospinal plasticity across multiple experimental sessions. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the influence of contraction history on force steadiness and the associated EMG activity during submaximal isometric contractions performed with the dorsiflexor muscles. The key feature of the protocol was a triangular ramp contraction performed in the middle of a steady contraction at a lower target force. The target force during the ramp contraction was 20% MVC greater than that during the steady contraction. Thirty-seven healthy individuals (21 men and 16 women) performed the submaximal tasks with the ankle dorsiflexors. Electromyography (EMG) signals were recorded from tibialis anterior with a pair of surface electrodes. The coefficient of variation for force was significantly greater during the second steady contraction compared with the first one at each of the seven target forces (p < 0.015; d = 0.38–0.92). Although the average applied force during the steady contractions before and after the triangular contraction was the same (p = 0.563), the mean EMG amplitude for the steady contractions performed after the triangular contraction was significantly greater at each of the seven target forces (p < 0.0001; d = 0.44–0.68). Also, there were significant differences in mean EMG frequency between the steady contractions performed before and after the triangular contraction (p < 0.01; d = 0.13–0.82), except at 10 and 20% MVC force. The greater force fluctuations during a steady submaximal contraction after an intervening triangular contraction indicate a change in the discharge characteristics of the involved motor units. [ABSTRACT FROM AUTHOR]

• Creation and characterization of muscle-derived extracellular matrix hydrogels from TSP2 KO mice shows altered composition, assembly, and biomechanical properties when compared to WT. • TSP2 KO hydrogels allow greater myocyte spreading and invasion as well increased tube formation by endothelial cells in vitro. • In vivo study showed excellent foreign body response of TSP2 KO hydrogels associated with enhanced cell invasion, innervation, and angiogenesis. • TSP2 KO hydrogels were used to treat VML injury in mice and were found to induce greater recruitment of repair cells and enhanced tissue remodeling. Volumetric muscle loss (VML) represents a clinical challenge due to the limited regenerative capacity of skeletal muscle. Most often, it results in scar tissue formation and loss of function, which cannot be prevented by current therapies. Decellularized extracellular matrix (DEM) has emerged as a native biomaterial for the enhancement of tissue repair. Here, we report the generation and characterization of hydrogels derived from DEM prepared from WT or thrombospondin (TSP)-2 null muscle tissue. TSP2-null hydrogels, when compared to WT, displayed altered architecture, protein composition, and biomechanical properties and allowed enhanced invasion of C2C12 myocytes and chord formation by endothelial cells. They also displayed enhanced cell invasion, innervation, and angiogenesis following subcutaneous implantation. To evaluate their regenerative capacity, WT or TSP2 null hydrogels were used to treat VML injury to tibialis anterior muscles and the latter induced greater recruitment of repair cells, innervation, and blood vessel formation and reduced inflammation. Taken together, these observations indicate that TSP2-null hydrogels enhance angiogenesis and promote muscle repair in a VML model. [ABSTRACT FROM AUTHOR]

Analysis of responses on electrical stimulation is one of the experimental paradigms to study the excitability of the nervous system. In particular, the technique of recording muscle responses evoked by electrical epidural stimulation (ES) of the spinal cord (SC) in humans and animals is widely used. In rats decerebrated at the precollicular level, responses of mm. tibialis anterior (TA) and gastrocnemius medialis (GM) on ES of the L2, L4, L6 spinal segments and transvertebral stimulation (TS) of the VL2, VL4, VL6 vertebrae with single and double pulses were analyzed. The currents at which the amplitude of the sensory component of the response for a single pulse and one of the pulses of the pair was maximum were determined. At the minimum of these currents, the ratio of the amplitudes of the sensory component of the response to the first and second pulses to the amplitude of the sensory component of the response to a single pulse was analyzed. For both muscles, a weakening of the response to both pulses of the pair was obtained with TS VL2 and VL4, while when stimulating VL2, the TA response to the second pulse was lower than to the first. On the contrary, with ES of all segments of interest, a facilitation of the response to the second pulse was obtained for both muscles. A similar facilitation was qualitatively observed for two other muscles, mm. iliacus and vastus lateralis. Thus, the use of double pulses during stimulation made it possible to identify the dependence of the response of SC neural networks on the method of their activation (TS or ES). The facilitation of the response to the second pulse during ES is presumably explained by a decrease in presynaptic inhibition due to decerebration. [ABSTRACT FROM AUTHOR]

In skeletal muscle, the Hippo effector Yap promotes satellite cell, myoblast, and rhabdomyoblast proliferation but prevents myogenic differentiation into multinucleated muscle fibres. We previously noted that Yap drives expression of the first enzyme of the serine biosynthesis pathway, phosphoglycerate dehydrogenase (Phgdh). Here, we examined the regulation and function of Phgdh in satellite cells and myoblasts and found that Phgdh protein increased during satellite cell activation. Analysis of published data reveal that Phgdh mRNA in mouse tibialis anterior muscle was highly expressed at day 3 of regeneration after cardiotoxin injection, when markers of proliferation are also robustly expressed and in the first week of synergist-ablated muscle. Finally, siRNA-mediated knockdown of PHGDH significantly reduced myoblast numbers and the proliferation rate. Collectively, our data suggest that Phgdh is a proliferation-enhancing metabolic enzyme that is induced when quiescent satellite cells become activated. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the effects of dietary supplementation with tannic acid (TA) on the growth performance, digestibility, antioxidant status, intestinal morphology and the caecal fermentation and microbiota in rabbits. A total number of 120 Ira rabbits (30 days of age) were randomly allotted to four dietary treatment groups: TA 0 (control), TA 0.75, TA 1.5 and TA 3, administered basal diets with 0, 0.75, 1.5 and 3 g TA/kg of feed for 28 days. Compared to the control group, dietary 3 g TA/kg inclusion decreased the average daily feed intake (p < 0.05). No significant differences were found in the digestibility among the groups (p > 0.05). Serum total antioxidant capacity was significantly higher in the 3 g/kg TA group than in the other groups (p < 0.05). There was a significant increase in the concentration of propionic acid and butyric acid in the 3 g/kg TA group. The addition of TA had no effect on villus height and crypt depth of small intestine (p > 0.05). The 16S rRNA high‐throughput sequencing results showed that at the phylum level, dietary 3 g/kg TA increased the abundance of Bacteroidetes in the caecum of rabbits (p < 0.05). Based on the results, dietary TA is effective in antioxidant capacity of rabbits, improving caecal fermentation and optimizing the caecal microflora. However, the appropriate dosage supplementation of TA in rabbits needs further research. [ABSTRACT FROM AUTHOR]

Researchers commonly use the 'free-fall' paradigm to investigate motor control during landing impacts, particularly in drop landings and depth jumps (DJ). While recent studies have focused on the impact of vision on landing motor control, previous research fully removed continuous visual input, limiting ecological validity. The aim of this investigation was to evaluate the effects of stroboscopic vision on depth jump (DJ) motor control. Ground reaction forces (GRF) and lower-extremity surface electromyography (EMG) were collected for 20 young adults (11 male; 9 female) performing six depth jumps (0.51 m drop height) in each of two visual conditions (full vision vs. 3 Hz stroboscopic vision). Muscle activation magnitude was estimated from EMG signals using root-mean-square amplitudes (RMS) over specific time intervals (150 ms pre-impact; 30–60 ms, 60–85 ms, and 85–120 ms post-impact). The main effects of and interactions between vision and trial number were assessed using two-way within-subjects repeated measures analyses of variance. Peak GRF was 6.4% greater, on average, for DJs performed with stroboscopic vision compared to full vision (p = 0.042). Tibialis anterior RMS EMG during the 60–85 ms post-impact time interval was 14.1% lower for DJs performed with stroboscopic vision (p = 0.020). Vastus lateralis RMS EMG during the 85–120 ms post-impact time interval was 11.8% lower for DJs performed with stroboscopic vision (p = 0.017). Stroboscopic vision altered DJ landing mechanics and lower-extremity muscle activation. The observed increase in peak GRF and reduction in RMS EMG of the tibialis anterior and vastus lateralis post-landing may signify a higher magnitude of lower-extremity musculotendinous stiffness developed pre-landing. The results indicate measurable sensorimotor disruption for DJs performed with stroboscopic vision, warranting further research and supporting the potential use of stroboscopic vision as a sensorimotor training aid in exercise and rehabilitation. Stroboscopic vision could induce beneficial adaptations in multisensory integration, applicable to restoring sensorimotor function after injury and preventing injuries in populations experiencing landing impacts at night (e.g., military personnel). [ABSTRACT FROM AUTHOR]

• We confirm the presence of an increase in internalized nuclei, fibre type 1 hypertrophy and NAHD central clearances/cores. • One third of our FSHD1 samples showed membrane attack complex (MAC) deposits. • Abnormal MHC i expression was observed in 72 % of samples at the membrane but also at cytoplasmic level. • Increased muscle regeneration in FSHD1 correlates with the inflammatory score. The aim of this study was to identify key routinely used myopathologic biomarkers of FSHD1. Needle muscle biopsies were taken in 34 affected muscles (m. quadriceps femoris (QF), n = 20, m. tibialis anterior (TA), n = 13, m. biceps brachii, n = 1) from 22 patients (age, 53.5 (10) years; M = 12, F = 10). Eleven patients had more than one biopsy (2xQF, n = 1; QF+TA, n = 9; 2xQF+TA, n = 1). Histochemistry, immunoperoxidase, and immunofluorescence stainings were performed and compared to age and muscle type matched muscle specimens of 11 healthy controls. Myopathologic features observed in our FSHD1 cohort were internalized nuclei, type 1 fibre hypertrophy and NADH central clearances/cores. We observed a prominent inflammatory response with MAC deposits, MHC I expression, and muscle regeneration that correlated with the inflammatory score. Our up-to-date characterization of FSHD1 points towards MHC I, MAC, and embryonic Myosin Heavy Chain/muscle regeneration as useful myopathologic readouts of FSHD1. [ABSTRACT FROM AUTHOR]

Canoe modality in flatwater canoeing has a clear asymmetrical nature. This study aimed (1) to determine the magnitude and direction of neuromuscular properties, range of motion (ROM) and lower-limb strength asymmetries in female and male canoeists; (2) to establish sex-individualized asymmetry thresholds for canoeists' neuromuscular properties, ROM and lower-limb strength; and (3) to determine the relationship of canoeists' neuromuscular properties, ROM and lower-limb strength asymmetries with a specific canoe–dynamometer performance test. Twenty-one international canoeists were assessed through tensiomyography (TMG), ROM, lower-limb explosive strength, and a specific canoe incremental dynamometric test. The magnitude of asymmetry assessed through TMG and ROM was not modulated either by sex or performance level (international medal vs. non-medal). Females showed greater asymmetry than males on muscle tone of the erector spinae towards non-stroke side (22.75% vs. 9.72%) and the tibialis anterior (30.97% vs. 16.29%), and Fmax in explosive leg press (2.41% vs. 0.63%) towards the stroke side. International medalists showed greater asymmetry in semitendinosus contraction time towards non-stroke side (20.51% vs. 9.43%) and reached Vmax earlier in explosive leg press towards stroke side leg (19.20% vs. 9.40%). A greater asymmetry in Fmax and in Vm, and a smaller asymmetry in Tvmax and in leg press showed a small predictive capacity for canoeists' performance on a specific canoe incremental dynamometry test. Reporting reference data from world-class canoeists' asymmetries can be of great importance for coaches to periodically control lateral asymmetry. [ABSTRACT FROM AUTHOR]

Muscle function is compromised by gravitational unloading in space affecting overall musculoskeletal health. Astronauts perform daily exercise programmes to mitigate these effects but knowing which muscles to target would optimise effectiveness. Accurate inflight assessment to inform exercise programmes is critical due to lack of technologies suitable for spaceflight. Changes in mechanical properties indicate muscle health status and can be measured rapidly and non-invasively using novel technology. A hand-held MyotonPRO device enabled monitoring of muscle health for the first time in spaceflight (> 180 days). Greater/maintained stiffness indicated countermeasures were effective. Tissue stiffness was preserved in the majority of muscles (neck, shoulder, back, thigh) but Tibialis Anterior (foot lever muscle) stiffness decreased inflight vs. preflight (p < 0.0001; mean difference 149 N/m) in all 12 crewmembers. The calf muscles showed opposing effects, Gastrocnemius increasing in stiffness Soleus decreasing. Selective stiffness decrements indicate lack of preservation despite daily inflight countermeasures. This calls for more targeted exercises for lower leg muscles with vital roles as ankle joint stabilizers and in gait. Muscle stiffness is a digital biomarker for risk monitoring during future planetary explorations (Moon, Mars), for healthcare management in challenging environments or clinical disorders in people on Earth, to enable effective tailored exercise programmes. [ABSTRACT FROM AUTHOR]

The effects of jaw clenching on balance has been shown under static steady-state conditions but the effects on dynamic steady-state balance have not yet been investigated. On this basis, the research questions were: 1) if jaw clenching improves dynamic steady-state balance; 2) if the effects persist when the jaw clenching task loses its novelty and the increased attention associated with it; 3) if the improved dynamic steady-state balance performance is associated with decreased muscle activity. A total of 48 physically active healthy adults were assigned to three groups differing in intervention (Jaw clenching and balance training (JBT), only balance training (OBT) or the no-training control group (CON)) and attending two measurement points separated by two weeks. A stabilometer was used to assess the dynamic steady-state balance performance in a jaw clenching and non-clenching condition. Dynamic steady-state balance performance was measured by the time at equilibrium (TAE). The activities of tibialis anterior (TA), gastrocnemius medialis (GM), rectus femoris (RF), biceps femoris (BF) and masseter (MA) muscles were recorded by a wireless EMG system. Integrated EMG (iEMG) was calculated to quantify the muscle activities. All groups had better dynamic steady-state balance performance in the jaw clenching condition than non-clenching at T1, and the positive effects persisted at T2 even though the jaw clenching task lost its novelty and attention associated with it after balance training with simultaneous jaw clenching. Independent of the intervention, all groups had better dynamic steady-state balance performances at T2. Moreover, reductions in muscle activities were observed at T2 parallel to the dynamic steady-state balance performance improvement. Previous studies showed that jaw clenching alters balance during upright standing, predictable perturbations when standing on the ground and unpredictable perturbations when standing on an oscillating platform. This study complemented the previous findings by showing positive effects of jaw clenching on dynamic steady-state balance performance. [ABSTRACT FROM AUTHOR]

Background: Clubfoot, or congenital talipes equinovarus deformity, is a common anomaly affecting the foot in infants. However, clinical equipoise remains between different interventions, especially those based on the Ponseti method. The aim of this study was to examine the clinical outcomes of the various interventions for treating idiopathic clubfoot. Methods: Searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Scopus, and CINAHL were conducted. Randomized controlled trials comparing different interventions, including the Ponseti method, accelerated Ponseti method, Ponseti method with botulinum toxin type A (Botox) injection, Ponseti method with early tibialis anterior tendon transfer (TATT), Kite method, and surgical treatment, were included. Network meta-analyses (NMAs) were conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) reporting guidelines. The primary outcomes were the change in total Pirani score and maximal ankle dorsiflexion. Secondary outcomes were the number of casts, time in casts, and rates of tenotomy, total complications, relapse, adverse events, and additional required major surgery. Results: Eleven randomized controlled trials involving 740 feet were included. According to the SUCRA (surface under the cumulative ranking curve)-based relative ranking, the Ponseti method was associated with the best outcomes in terms of Pirani score changes, maximal ankle dorsiflexion, number of casts, adverse events, and total complications, whereas the accelerated Ponseti method was associated with the best outcomes in terms of time in casts and tenotomy rate. Early TATT ranked best in terms of relapse rate. The Ponseti method with Botox injection was associated with the best outcomes in terms of the need for additional major surgery. Conclusions: The NMAs suggest that the Ponseti method is the optimal treatment overall, despite potential drawbacks such as longer time in casts and higher rates of tenotomy, relapse, and the need for additional surgery compared with other modified approaches. Therefore, clinicians should consider how treatments can be tailored individually. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Measurement of the input–output (IO) curves of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) can be used to assess corticospinal excitability and motor recruitment. While IO curves have been used to study disease and pharmacology, few studies have compared the IO curves across the body. This study sought to characterize IO curve parameters across the dominant and non-dominant sides of upper and lower limbs in healthy participants. Laterality preferences were assessed in eight healthy participants and IO curves were measured bilaterally for the first dorsal interosseous (FDI), biceps brachii (BB), and tibialis anterior (TA) muscles. Results show that FDI has lower motor threshold than BB which is, in turn, lower than TA. In addition, both BB and TA have markedly shallower logarithmic IO curve slopes from small to large MEP responses than FDI. After normalizing these slopes by their midpoints to account for differences in motor thresholds, which could result from geometric factors such as the target depth, large differences in logarithmic slopes remain present between all three muscles. The differences in slopes between the muscles could not be explained by differences in normalized IO curve spreads, which relate to the extent of the cortical representation and were comparable across the muscles. The IO curve differences therefore suggest muscle-dependent variations in TMS-evoked recruitment across the primary motor cortex, which should be considered when utilizing TMS-evoked MEPs to study disease states and treatment effects. [ABSTRACT FROM AUTHOR]

The article describes the results of studies on the impulse activity of various groups of afferent fibers and EMG patterns of lower leg antagonist muscles when walking without, during, and after transcutaneous electrical stimulation of the dorsal roots of the lower thoracic spinal cord of a person. Using a mathematical model based on the prediction of the triggering of muscle spindles, variability in the manifestation of impulse activity of various afferents of the tibialis anterior (TA) and gastrocnemius medialis (GM) muscle when walking under different experimental conditions is shown. It was found that walking on a movable treadmill tape in the absence of spinal cord stimulation was accompanied by strong impulse activity of afferents of I (Ia and Ib) and II groups of GM and increased excitability of its motorneuron pool and weakening of afferent activity and excitability of TA. On the contrary, electrical stimulation of the spinal cord during walking caused strong impulsive activity of group II of TA afferents and moderate in GM, while the activity of Ia fibers in TA and GM decreased to moderate impulsivity, Ib afferents of the same muscles had the weakest activity, and the excitability of the GM motor neuron pool was greater than TA. During the postactivation period, walking was accompanied by increased impulses of afferent fibers of group Ib and II of GM, weakening of afferent flows of Ib of TA and Ia afferents of GM, but along with this, afferent signals of group Ia and II to the motor neuron nucleus of TA decreased to moderate impulses, and excitability of the motor neuron pool of GM was higher than TA. The supposed reflex mechanisms of locomotion regulation are discussed on the basis of well-known phenomena associated with the interaction of various afferent inputs to the spinal cord neuronal apparatus in the system of lower leg antagonist muscles. [ABSTRACT FROM AUTHOR]

There is a lack of experimental methods in genetically tractable mouse models to analyze the developmental period at which newborns mature weight-bearing locomotion. To overcome this deficit, we introduce methods to study L-3,4-dihydroxyphenylalanine (L-DOPA)-induced air-stepping in mice at postnatal day (P)7 and P10. Air-stepping is a stereotypic rhythmic behavior that resembles mouse walking overground locomotion but without constraints imposed by weight bearing, postural adjustments, or sensory feedback. We propose that air-stepping represents the functional organization of early spinal circuits coordinating limb movements. After subcutaneous injection of L-DOPA (0.5 mg/g), we recorded air-stepping movements in all four limbs and electromyographic (EMG) activity from ankle flexor (tibialis anterior, TA) and extensor (lateral gastrocnemius, LG) muscles. Using DeepLabCut pose estimation, we analyzed rhythmicity and limb coordination. We demonstrate steady rhythmic stepping of similar duration from P7 to P10 but with some fine-tuning of interlimb coordination with age. Hindlimb joints undergo a greater range of flexion at older ages, indicating maturation of flexion-extension cycles as the animal starts to walk. EMG recordings of TA and LG show alternation but with more focused activation particularly in the LG from P7 to P10. We discuss similarities to neonatal rat L-DOPA-induced air-stepping and infant assisted walking. We conclude that limb coordination and muscle activations recorded with this method represent basic spinal cord circuitry for limb control in neonates and pave the way for future investigations on the development of rhythmic limb control in genetic or disease models with correctly or erroneously developing motor circuitry. [ABSTRACT FROM AUTHOR]

Persistent inward currents (PICs) increase the intrinsic excitability of a-motoneurons. The main objective of this study was to compare estimates of a-motoneuronal PICs between inactive, chronic resistance-trained, and chronic endurance-trained young individuals. We also aimed to investigate whether there is a relationship in the estimates of a-motoneuronal PIC magnitude between muscles. Estimates of PIC magnitude were obtained in three groups of young individuals: resistance-trained (n = 12), endurance-trained (n = 12), and inactive (n = 13). We recorded high-density surface electromyography (HDsEMG) signals from tibialis anterior (TA), gastrocnemius medialis (GM), soleus (SOL), vastus medialis (VM), and vastus lateralis (VL). Then, signals were decomposed with convolutive blind source separation to identify motor unit (MU) spike trains. Participants performed triangular isometric contractions to a peak of 20% of their maximum voluntary contraction. A paired-motor-unit analysis was used to calculate DF, which is assumed to be proportional to PIC magnitude. Despite the substantial differences in physical training experience between groups, we found no differences in DF, regardless of the muscle. Significant correlations of estimates of PIC magnitude were found between muscles of the same group (VLVM, SOL-GM). Only two correlations (out of 8) between muscles of different groups were found (TA-GM and VL-GM). Overall, our findings suggest that estimates of PIC magnitude from lower-threshold MUs at low contraction intensities in the lower limb muscles are not influenced by physical training experience in healthy young individuals. They also suggest muscle-specific and muscle group-specific regulations of the estimates of PIC magnitude. [ABSTRACT FROM AUTHOR]

Lymphatic vessels are actively involved in the recovery process of inflamed tissues. However, the changes in intramuscular lymphatic vessels during inflammation caused by skeletal muscle injury remain unclear. Therefore, the purpose of this study was to clarify the changes in lymphatic vessels after skeletal muscle injury. The left tibialis anterior muscles of male mice were subjected to lengthening contractions (LC) for inducing skeletal muscle injury, and samples were collected on Days 2, 4, and 7 for examining changes in both the skeletal muscles and intramuscular lymphatic vessels. With hematoxylin–eosin staining, the inflammatory response was observed in myofibers on Days 2 and 4 after LC, whereas regeneration of myofibers was found on Day 7 after LC. The number and area of intramuscular lymphatic vessels analyzed by immunohistochemical staining with an antibody against lymphatic vessel endothelial hyaluronan receptor 1 were significantly increased only on Day 4 after LC. Based on the abovementioned results, intramuscular lymphatic vessels undergo morphological changes such as increase under the state of muscle inflammation. This study demonstrated that the morphology of intramuscular lymphatic vessels undergoes significant changes during the initial recovery phase following skeletal muscle injury. [ABSTRACT FROM AUTHOR]

Ankle inversion orientation and peroneal activation insufficiency may contribute to lateral ankle sprains during landing in chronic ankle instability (CAI); however, how anticipation alters these factors is neglected. This study aimed to assess the impact of anticipation on joint orientation and muscle activity during landing in individuals with CAI. Fifteen participants with CAI and 15 healthy participants (control) were recruited to perform single‐leg landings after bilateral countermovement jumps when the landing limb was specified before (planned) or after (unplanned) take‐off. Joint angle (hip, knee, and ankle) and electromyography (gluteus medius, rectus femoris, biceps femoris, gastrocnemius lateral head, tibialis anterior, and peroneal longus) were collected and analyzed with 2 (groups) × 2 (conditions) statistical parametric mapping ANOVA. In the unplanned condition, the CAI group demonstrated a less plantarflexed (maximum difference [MD] = 9.5°, p = 0.047) and more inverted ankle joint (MD = 4.1°, p < 0.001) before ground contact, along with lower peroneal activity at ground contact compared to the control group (MD = 28.9% of peak activation, p < 0.001). No significant differences between groups were observed in the planned condition. In conclusion, anticipation may mask jump landing deficits in people with CAI, including inverted ankle orientation and reduced peroneus longus activity pre‐ and post‐landing, which were observed exclusively in unplanned landings. Clinicians and researchers need to recognize the impact of anticipation on apparent landing deficits and consider the implications for injury prevention and rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve injuries (PNIs) represent a significant clinical problem, and standard approaches to nerve repair have limitations. Recent breakthroughs in 3D printing and stem cell technologies offer a promising solution for nerve regeneration. The main purpose of this study was to examine the biomechanical characteristics in muscle tissue distal to a nerve defect in a murine model of peripheral nerve regeneration from physiological stress to failure. Methods: In this experimental study, we enrolled 18 Wistar rats in which we created a 10 mm sciatic nerve defect. Furthermore, we divided them into three groups as follows: in Group 1, we used 3D nerve guidance conduits (NGCs) and adipose stem cells (ASCs) in seven rats; in Group 2, we used only 3D NGCs for seven rats; and in Group 3, we created only the defect in four rats. We monitored the degree of atrophy at 4, 8, and 12 weeks by measuring the diameter of the tibialis anterior (TA) muscle. At the end of 12 weeks, we took the TA muscle and analyzed it uniaxially at 10% stretch until failure. Results: In the group of animals with 3D NGCs and ASCs, we recorded the lowest degree of atrophy at 4 weeks, 8 weeks, and 12 weeks after nerve reconstruction. At 10% stretch, the control group had the highest Cauchy stress values compared to the 3D NGC group (0.164 MPa vs. 0.141 MPa, p = 0.007) and the 3D NGC + ASC group (0.164 MPa vs. 0.123 MPa, p = 0.007). In addition, we found that the control group (1.763 MPa) had the highest TA muscle stiffness, followed by the 3D NGC group (1.412 MPa), with the best muscle elasticity showing in the group in which we used 3D NGC + ASC (1.147 MPa). At failure, TA muscle samples from the 3D NGC + ASC group demonstrated better compliance and a higher degree of elasticity compared to the other two groups (p = 0.002 and p = 0.008). Conclusions: Our study demonstrates that the combination of 3D NGC and ASC increases the process of nerve regeneration and significantly improves the compliance and mechanical characteristics of muscle tissue distal to the injury site in a PNI murine model. [ABSTRACT FROM AUTHOR]

The MAPK p38α was proposed to be a prominent promoter of skeletal muscle aging. The skeletal muscle tissue is composed of various muscle types, and it is not known if p38α is associated with aging in all of them. It is also not known if p38α is associated with aging of other tissues. JNK and ERK were also proposed to be associated with aging of several tissues. Nevertheless, the pattern of p38α, JNK, and ERK activity during aging was not documented. Here, we documented the levels of phosphorylated/active p38α, Erk1/2, and JNKs in several organs as well as the soleus, tibialis anterior, quadriceps, gastrocnemius, and EDL muscles of 1-, 3-, 6-, 13-, 18-, and 24-month-old mice. We report that in most tissues and skeletal muscles, the MAPKs' activity does not change in the course of aging. In most tissues and muscles, p38α is in fact active at younger ages. The quadriceps and the lungs are exceptions, where p38α is significantly active only in mice 13 months old or older. Curiously, levels of active JNK and ERKs are also elevated in aged lungs and quadriceps. RNA-seq analysis of the quadriceps during aging revealed downregulation of proteins related to the extra-cellular matrix (ECM) and ERK signaling. A panel of mRNAs encoding cell cycle inhibitors and senescence-associated proteins, considered to be aging markers, was not found to be elevated. It seems that the pattern of MAPKs' activation in aging, as well as expression of known 'aging' components, are tissue- and muscle type-specific, supporting a notion that the process of aging is tissue- and even cell-specific. [ABSTRACT FROM AUTHOR]

• Quantifying mirror activity in ALS patients can be readily achieved using a novel algorithm. • Increase of mirror activity seems to precede changes in other measures of motor function and transcallosal inhibition. • Further studies are warranted to evaluate the potential utility of this approach as a biomarker for ALS. To investigate mirror activity in amyotrophic lateral sclerosis (ALS) patients, using a simple paradigm of signal quantification. Patients were asked to perform a brief isometric maximum contraction of the abductor digiti minimi (ADM) or tibialis anterior (TA) on one side, while relaxing the contralateral side of the body. Both sides were investigated. Signals were stored and analyzed offline, for quantification of electromyographic signal. Clinical signs of upper motor neuron (UMN) dysfunction, transcranial magnetic stimulation (TMS) for the upper (UL) and lower limbs (LL), the ADM ipsilateral cortical silent period (iSP) and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) cognitive scale were also investigated. 42 ALS patients were included. In the 4 investigated muscles the amount of mirror activity was significantly higher than in the matched healthy group. The amount of mirror activity was similar between sides, but significantly higher in UL and LL with abnormal TMS results for ADM (p = 0.005) and TA (p = 0.002), as well as in UL with abnormal iSP values (p = 0.009). No association was found between mirror activity and clinical signs of UMN involvement. Mirror activity is a common phenomenon in ALS. Mirror activity intensity corresponds to the severity of UMN dysfunction, as measured by TMS, and probably derives from the abnormal transcallosal inhibition as mirrored by iSP abnormality. Mirror activity is increased in ALS and is associated with abnormal transcallosal inhibition and UMN dysfunction. [ABSTRACT FROM AUTHOR]

Balance involves several sensory modalities including vision, proprioception and the vestibular system. This study aims to investigate vestibulospinal activation elicited by tone burst stimulation in various muscles and how head position influences these responses. We recorded electromyogram (EMG) responses in different muscles (sternocleidomastoid-SCM, cervical erector spinae-ES-C, lumbar erector spinae-ES-L, gastrocnemius-G, and tibialis anterior-TA) of healthy participants using tone burst stimulation applied to the vestibular system. We also evaluated how head position affected the responses. Tone burst stimulation elicited reproducible vestibulospinal reflexes in the SCM and ES-C muscles, while responses in the distal muscles (ES-L, G, and TA) were less consistent among participants. The magnitude and polarity of the responses were influenced by the head position relative to the cervical spine. When the head was rotated or tilted, the polarity of the vestibulospinal responses changed, indicating the integration of vestibular and proprioceptive inputs in generating these reflexes. Overall, our study provides valuable insights into the complexity of vestibulospinal reflexes and their modulation by head position. However, the high variability in responses in some muscles limits their clinical application. These findings may have implications for future research in understanding vestibular function and its role in posture and movement control. [ABSTRACT FROM AUTHOR]

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IntroductionA concern expressed by the clinical community is that the constraint of motion provided by an ankle foot orthosis (AFO) may lead the user to become dependent on its stiffness, leading to learned non-use. To examine this, we hypothesized that using an experimental AFO-footwear combination (exAFO-FC) that constrains ankle motion during walking would result in reduced soleus and tibialis anterior EMG compared to free (exAFO-FC) and control (no AFO, footwear only) conditions.MethodA total of 14 healthy subjects walked at their preferred speed (1.34 ± 0.09 m·s-1) for 15 min, in three conditions, namely, control, free, and stop.ResultsDuring the stance phase of walking in the stop condition, ipsilateral soleus integrated EMG (iEMG) declined linearly, culminating in a 32.1% reduction compared to the control condition in the final 5 min interval of the protocol. In contrast, ipsilateral tibialis anterior iEMG declined in a variable fashion culminating in an 11.2% reduction compared to control in the final 5 min interval. During the swing phase, the tibialis anterior iEMG increased by 6.6% compared to the control condition during the final 5 min interval. The contralateral soleus and tibialis anterior exhibited increased iEMG in the stop condition.DiscussionAn AFO-FC functions as a biomechanical motion control device that influences the neural control system and alters the output of muscles experiencing constraints of motion.

Context: Dynamic balance exercises are commonly utilized during ankle sprain and chronic ankle instability (CAI) rehabilitation. Blood flow restriction (BFR) has been used to enhance muscle activity during exercise and improve outcomes of traditional rehabilitation exercises in clinical populations. Objective: Examine the effects of BFR on lower-extremity muscle activation during dynamic balance exercises in individuals with CAI. Design: Crossover study design. Setting: Laboratory. Patients or Other Participants: Twenty-five (N = 25) young adults with a history of CAI. Interventions: Participants performed dynamic balance reaching exercises during 2 randomized order conditions, BFR, and control. For each condition, participants performed 2 trials of balance exercises. Each trial included 4 sets (30 × 15 × 15 × 15) of reaches in anterior, posteromedial, and posterolateral directions. For the BFR condition, the authors placed a cuff around the proximal thigh at 80% of arterial occlusion pressure. For the control condition, no cuff was worn. Main Outcome Measure(s): The authors recorded normalized electromyography muscle activation of the vastus lateralis, soleus, tibialis anterior, and fibularis longus during balance exercise trials and recorded participants' ratings of perceived postural instability and exertion after each trial of balance exercises. Results: The authors observed greater vastus lateralis (P <.001, d = 0.86 [0.28 to 1.44]) and soleus (P =.03, d = 0.32 [−0.24 to 0.87]) muscle activation during balance exercises with BFR than control. The authors observed no differences in tibialis anterior (P =.33, d = 0.09 [−0.46 to 0.65]) or fibularis longus (P =.13, d = 0.06 [−0.50 to 0.61]) muscle activation between the conditions. The authors observed greater ratings of perceived postural instability (P =.004) and exertion (P <.001) during balance exercises with BFR than control. Conclusions: Individuals with CAI demonstrated large increases in vastus lateralis and small increases in soleus muscle activation during dynamic balance exercises with BFR. The BFR had no effect on fibularis longus and tibialis anterior muscle activation. Individuals with CAI perceived greater postural instability and exertion during dynamic balance exercises with BFR. [ABSTRACT FROM AUTHOR]

Postinhibitory excitation is a transient overshoot of a neuron's baseline firing rate following an inhibitory stimulus and can be observed in vivo in human motoneurons. However, the biophysical origin of this phenomenon is still unknown and both reflex pathways and intrinsic motoneuron properties have been proposed. We hypothesized that postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents (h-currents). Using an electrical circuit model, we investigated how h-currents can modulate the postinhibitory response of motoneurons. Further, we analyzed the spike trains of human motor units from the tibialis anterior muscle during reciprocal inhibition. The simulations revealed that the activation of h-currents by an inhibitory postsynaptic potential can cause a short-term increase in a motoneuron's firing probability. This result suggests that the neuron can be excited by an inhibitory stimulus. In detail, the modulation of the firing probability depends on the time delay between the inhibitory stimulus and the previous action potential. Further, the postinhibitory excitation's strength correlates with the inhibitory stimulus's amplitude and is negatively correlated with the baseline firing rate as well as the level of input noise. Hallmarks of h-current activity, as identified from the modeling study, were found in 50% of the human motor units that showed postinhibitory excitation. This study suggests that h-currents can facilitate postinhibitory excitation and act as a modulatory system to increase motoneuron excitability after a strong inhibition. Author summary: Human movement is determined by the activity of specialized nerve cells, the motoneurons. Each motoneuron activates a specific set of muscle fibers. The functional unit consisting of a neuron and muscle fibers is called a motor unit. The activity of motoneurons can be observed noninvasively in living humans by recording the electrical activity of the motor units using the electromyogram. We studied the behavior of human motor units in an inhibitory reflex pathway and found an unexpected response pattern: a rebound-like excitation following the inhibition. This has occasionally been reported for human motor units, but its origin has never been systematically studied. In non-human cells of the neural system, earlier studies reported that a specific membrane protein, the so-called h-channel, can cause postinhibitory excitation. Our study uses a computational motoneuron model to investigate whether h-channels can cause postinhibitory excitation, as observed in the experimental recordings. Using the model, we developed a method to detect features of h-channel activity in human recordings. Because we found these features in half of the recorded motor units, we conclude that h-channels can facilitate postinhibitory excitation in human motoneurons. [ABSTRACT FROM AUTHOR]

Background: Cycling workload is an essential factor in practical cycling training. Saddle height is the most studied topic in bike fitting, but the results are controversial. This study aims to investigate the effects of workload and saddle height on the activation level and coordination of the lower limb muscles during cycling. Methods: Eighteen healthy male participants with recreational cycling experience performed 15 × 2-min constant cadence cycling at five saddle heights of 95%, 97%, 100%, 103%, and 105% of greater trochanter height (GTH) and three cycling workloads of 25%, 50%, and 75% of functional threshold power (FTP). The EMG signals of the rectus femoris (RF), tibialis anterior (TA), biceps femoris (BF), and medial gastrocnemius (MG) of the right lower limb were collected throughout the experiment. Results: Greater muscle activation was observed for the RF and BF at a higher cycling workload, whereas no differences were observed for the TA and MG. The MG showed intensified muscle activation as the saddle height increased. The mean and maximum amplitudes of the EMG signals of the MG increased by 56.24% and 57.24% at the 25% FTP workload, 102.71% and 126.95% at the 50% FTP workload, and 84.27% and 53.81% at the 75% FTP workload, respectively, when the saddle height increased from 95 to 100% of the GTH. The muscle activation level of the RF was minimal at 100% GTH saddle height. The onset and offset timing revealed few significant differences across cycling conditions. Conclusions: Muscle activation of the RF and BF was affected by cycling workload, while that of the MG was affected by saddle height. The 100% GTH is probably the appropriate saddle height for most cyclists. There was little statistical difference in muscle activation duration, which might be related to the small workload. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NADH) is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation (OXPHOS). NADH is autofluorescent, and its fluorescence lifetime can be used to infer metabolic dynamics in living cells. Fiber-coupled time-correlated single photon counting (TCSPC) equipped with an implantable needle probe can be used to measure NADH lifetime in vivo, enabling investigation of changing metabolic demand during muscle contraction or tissue regeneration. This study illustrates a proof of concept for point-based, minimally-invasive NADH fluorescence lifetime measurement in vivo. Volumetric muscle loss (VML) injuries were created in the left tibialis anterior (TA) muscle of male Sprague Dawley rats. NADH lifetime measurements were collected before, during, and after a 30 s tetanic contraction in the injured and uninjured TA muscles, which was subsequently fit to a biexponential decay model to yield a metric of NADH utilization (cytoplasmic vs protein-bound NADH, the A 1 τ 1 /A 2 τ 2 ratio). On average, this ratio was higher during and after contraction in uninjured muscle compared to muscle at rest, suggesting higher levels of free NADH in contracting and recovering muscle, indicating increased rates of glycolysis. In injured muscle, this ratio was higher than uninjured muscle overall but decreased over time, which is consistent with current knowledge of inflammatory response to injury, suggesting tissue regeneration has occurred. These data suggest that fiber-coupled TCSPC has the potential to measure changes in NADH binding in vivo in a minimally invasive manner that requires further investigation. [ABSTRACT FROM AUTHOR]