Tibialis Anterior Research Articles

Symptomatic Accessory Navicular Treated With Endoscopic Accessory Navicular and Partial Navicular Resection.

This study aims to report the results of the patients with symptomatic accessory navicular (AN) who underwent endoscopic AN and partial navicular resection. The medical records of patients with type 2 symptomatic AN who underwent the aforementioned surgery at our hospital from November 2019 to May 2022 with a follow-up of >2 years were reviewed. Data on clinical, radiographic, and patient-reported outcomes were obtained. The analysis included 29 patients (20 females; mean age, 19.6 years; mean body mass index, 21.5) with a mean follow-up duration of 39.5 months. Comparing the preoperative and postoperative scores, visual analog scale score improved from 74.6 to 5.4, and the Japanese Society for Surgery of the Foot score improved from 63.0 to 95.9. We had one wound dehiscence and no other recognized complications. Magnetic resonance and ultrasonographic imaging done 1 year postoperatively revealed that the empty space that remained after resection of the AN was filled with tendonlike tissue. Endoscopic AN and partial navicular resection for treating symptomatic AN resulted in good outcomes and only one case with wound complications.

Basic research for ultrasound-guided injection into skeletal muscle lesions in an experimental animal model.

Ultrasound-guided injection techniques are expected to enhance therapeutic efficacy for skeletal muscle injuries and disorders, but basic knowledge is lacking. The purpose of this study was to examine the diagnostic accuracy of ultrasound for abnormal skeletal muscle lesions, and to examine the distribution patterns of solution and cells injected into abnormal muscle lesions under ultrasound guidance. A cardiotoxin (CTX)-induced muscle injury model was used. Briefly, CTX was injected into tibialis anterior muscle in rats under ultrasound observation. First, the diagnostic accuracy of abnormal muscle lesions on ultrasound was examined by comparing ultrasound findings and histology. Next, Fast Green solution and green fluorescent protein (GFP)-labelled cells were simultaneously injected into the abnormal muscle lesions under ultrasound guidance, and their distribution was evaluated. Evaluation of short-axis ultrasound images and cross-sectional histological staining showed a strong correlation (r = 0.927; p < 0.001) between the maximum muscle damage area in ultrasound and haematoxylin and eosin (H&E) staining evaluations. Histological analysis showed that ultrasound-guided injection could successfully deliver Fast Green solution around the myofibres at the site of injury. In contrast, the distribution of injected cells was very localized compared to the area stained with Fast Green. This experimental animal study demonstrated the potential of ultrasound to quantitatively visualize abnormalities of skeletal muscle. It also showed that ultrasound-guided injections allowed for highly accurate distribution of solution and cells in abnormal muscle tissue, but the patterns of solution and cell distribution were markedly different. Although future studies using a more clinically relevant model are necessary, these results are important findings when considering biological therapies for skeletal muscle injuries and disorders.

Clinical and imaging spectrum of non-congenital dominant ACTN2 myopathy.

Alpha-actinin-2, a protein with high expression in cardiac and skeletal muscle, is located in the Z-disc and plays a key role in sarcomere stability. Mutations in ACTN2 have been associated with both hypertrophic and dilated cardiomyopathy and, more recently, with skeletal myopathy. Genetic, clinical, and muscle imaging data were collected from 37 patients with an autosomal dominant ACTN2 myopathy belonging to 11 families from Spain and Belgium. Haplotypes were studied to confirm a common ancestry for the two most common recurrent variants identified in this study. A trained machine learning model was used to compare muscle MRI scans in ACTN2 myopathy with other neuromuscular diseases to identify a specific pattern of muscle involvement. The clinical phenotype ranged from asymptomatic to limb-girdle weakness and facial involvement and was depending on genotype. Cardiac and respiratory involvement were not common. Belgian families carrying the p.Ile134Asn variant and Basque-Spanish families carrying the p.Cys487Arg variant each showed unique haplotypes supporting respective common ancestry. Available muscle biopsies showed non-specific changes. In muscle imaging, the most affected muscles were the glutei minor, glutei medius, hamstrings, tibialis anterior, and soleus. A machine learning model showed that the most differentiating features in dominant ACTN2 myopathy were the involvement of the tibialis anterior and gluteus medius muscles and preservation of the quadratus femoris, gastrocnemius lateralis, and tensor fasciae latae muscles. We provide new insights into genetic, clinical, and muscle imaging characteristics of non-congenital dominant ACTN2 myopathy, broadening the phenotypic spectrum of muscle disorders caused by ACTN2 variants.

Ankle muscle strength and activation are associated with walking patterns in preschool and school-age children.

Walking patterns can differ between children and adults, both kinematically and kinetically. However, the detailed nature of the ankle pattern has not been clarified. We investigated musculature, biomechanics, and muscle activation strategies and their relevance to walking performance in preschool (PS) and school children (SC), with adults (AD) as reference. Twenty-six PS (3-5 yr), 20 SC (6-8 yr), and 17 AD (18-30 yr) participated. Tibialis anterior (TA) and medial gastrocnemius (MG) thicknesses, fascicle lengths, and maximal voluntary dorsi- and plantar flexion isometric torques were measured. Hip, knee, and ankle kinematics, ground reaction forces (GRFs), and TA and MG electromyographic activities were recorded during shod walking at each participant's preferred speed. Walking speed, step length, and cadence were correlated with age in PS. These walking performance measures were also correlated with muscle thickness and fascicle length, showing higher speed in individuals with thicker muscles and longer TA and MG fascicles (conversely, higher cadence with thinner muscles and shorter fascicles). AD demonstrated the largest values for muscle thickness (p<0.001), fascicle length (p<0.001), strength (p<0.001), and walking performance (speed p = 0.004; step length p<0.001; cadence p<0.001), followed by SC then PS. Both PS and SC exhibited higher TA activities than AD during the stance phase, resulting in a higher co-activation index. The GRFs relative to body weight were lower in both horizontal and vertical components in PS compared to SC and AD, while the relative lateral force during stance was greatest in PS followed by SC and then AD. Differences in preferred walking speed and step length were associated with age and muscle size. Children, particularly preschool-aged, employed a co-activation strategy of dorsi- and plantar flexors for stabilization, which resulted in sideways steps even at a preferred walking speed.

CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor

Sarcopenia corresponds to a decrease in muscle mass and strength. CCL5 is a new myokine whose expression, along with the CCR5 receptor, is increased in sarcopenic muscle. Therefore, we evaluated whether CCL5 and CCR5 induce a sarcopenic-like effect on skeletal muscle tissue and cultured muscle cells. Electroporation in the tibialis anterior (TA) muscle of mice was used to overexpress CCL5. The TA muscles were analyzed by measuring the fiber diameter, the content of sarcomeric proteins, and the gene expression of E3-ligases. C2C12 myotubes and single-isolated flexor digitorum brevis (FDB) fibers were also treated with recombinant CCL5 (rCCL5). The participation of CCR5 was evaluated using the antagonist maraviroc (MVC). Protein and structural analyses were performed. The results showed that TA overexpression of CCL5 led to sarcopenia by reducing muscle strength and mass, muscle-fiber diameter, and sarcomeric protein content, and by upregulating E3-ligases. The same sarcopenic phenotype was observed in myotubes and FDB fibers. We showed increased reactive oxygen species (ROS) production and carbonylated proteins, denoting oxidative stress induced by CCL5. When the CCR5 was antagonized, the effects produced by rCCL5 were prevented. In conclusion, we report for the first time that CCL5 is a novel myokine that exerts a sarcopenic-like effect through the CCR5 receptor.

Combined exercise-induced modulation of Notch pathway and muscle quality in senescence-accelerated mice.

The Notch signaling pathway is crucial for skeletal muscle development, regeneration, inflammation, and aging. This study investigated the association between interleukin-10 (IL-10) and the Notch pathway in C2C12 cells, as well as explored the effects of combined endurance and resistance exercise on the Notch and autophagy pathways in the skeletal muscle of senescence-accelerated mouse-resistant 1 Sedentary (SAMR1 CT), SAMR1 exercised (SAMR1 EX), senescence-accelerated prone mouse 8 Sedentary (SAMP8 CT), and SAMP8 exercised (SAMP8 EX). C2C12 myoblasts were transfected with siIL-10. Histological analysis, reverse transcription-quantitative polymerase chain reaction, and immunoblotting were performed on the quadriceps and tibialis anterior muscles. A publicly available dataset was analyzed to assess the Notch pathway in older men. In summary, IL-10 knockdown in myoblasts reduced the Notch pathway gene and protein expression. In SAMP8 mice, combined exercise improved muscle fiber organization, enhanced balance and coordination, and increased Notch2 and Hes1 mRNA levels. NOTCH2 mRNA levels were also higher in older men compared to young subjects with similar physical activity levels. These findings suggest that combined physical exercise enhances muscle regeneration via the Notch pathway in aged muscle.

Clinical Outcome After Surgical Treatment of Traumatic Peroneal Nerve Injury: An Analysis of Risk Factors After Different Surgical Approaches

Background: This study aims to analyze potential risk factors that may influence the clinical outcomes following surgical treatment of traumatic peroneal nerve lesions. Methods: We conducted a retrospective analysis of patients with traumatic peroneal nerve injuries treated with decompression, split repair, or nerve grafting between 2010 and 2020. Motor function and potential risk factors were evaluated. Results: Out of 93 patients, 42 (45%) underwent decompression, 15 (16%) received split repair, and 36 (39%) required autologous nerve grafting. Up to one year after surgery, weakness of the anterior tibial muscle improved from a median of M0 to M3. After one year following nerve decompression, functional recovery was observed in 28 (65%) cases, in 9 (21%) cases after split repair, and in 7 (16%) cases following autologous nerve grafting. A defect greater than 8 cm was associated with significantly poorer improvement of extensor hallucis longus (p = 0.037, HR 0.109). We found no significant associations between age, diabetes mellitus, arterial hypertension, obesity, and postoperative outcomes. Conclusions: According to the present data, a significant number of patients achieved functional improvement following surgical treatment, indicating that this procedure should be considered an important treatment option in selected cases.

Neuromuscular Strategies in Dominant and Non-Dominant Legs in Dancers During Dynamic Balance Tasks.

Introduction: Ballet-based dance training emphasizes the equal development of both legs. However, dancers often perceive differences between their legs during balance or landing. There still needs to be more consensus on the functional difference between dominant (D) and non-dominant legs (ND). Therefore, this study investigated both legs' neuromuscular strategy in single-leg balance and landing based on leg dominance. Methods: Thirteen female dancers (age: 22.2 ± 2.8 years) with no history of ankle injuries in the past year participated in the study. Based on the questionnaire, the dominant leg was set, which legs were preferred to balance, generate strength, and land. Joint kinematics and ground reaction force (GRF) were analyzed using a three-dimensional motion analysis system and force plates during single-leg balance (SLB), passé balance (PB), sissone simple (SS), and sissone ouverte (SO). The tibialis anterior (TA), medial gastrocnemius (MG), peroneus longus (PL), and gluteus medius (GM) activation were measured by wireless surface electromyography (EMG). Displacement (cm) of the center of pressure and the dynamic postural stability index (DPSI), a balanced score post dynamic tasks, were calculated. Results: Bilateral leg balance ability was observed based on joint kinematics and DPSI during SLB, PB, SS, and SO. Higher TA activity was noted during PB in ND legs than in D legs (P = .038). PL activation was significantly increased in ND legs (69.3 ± 34.4%) than in D legs (45.6 ± 19.2%) before contact during SS and SO (P < .05). After landing with ND legs, dancers regulated postural stability with increasing TA activation (P < .05). Conclusions: Pre-activation of PL before landing with ND legs increases ankle stiffness, enhancing stability. Conversely, D legs achieve balance with lower activation levels. The findings highlight significant differences between legs in dancers, suggesting that leg dominance should be considered in future training and performance strategies.

Feasibility within-subject RCT of neuromuscular electrical stimulation; an Intervention to Maintain and improve neuroMuscular function during period of Immobility (IMMI).

Neuromuscular electrical stimulation (NMES) is a potentially effective intervention to improve outcomes after a fragility fracture, but its feasibility in this group has not been established. A feasibility study was conducted in two phases: 1) in the hospital only, and 2) hospital, rehabilitation centres, and participants' homes. Patients with fragility fracture were randomised to receive NMES for 6weeks/discharge either to the right or left leg, with the other leg serving as control. Patients who had no mobility issues had contraindications to NMES and were unable to give consent were excluded. NMES was applied to quadriceps and tibialis anterior muscles for 30min, 3days/week. Sessions were progressed to achieve 60min, 5-7days/week. Feasibility outcomes included participant characteristics, recruitment rate, tolerability, and number of NMES sessions. Clinical outcomes included muscle strength, and ADL at six months. Overall, 1052 patients were identified, of whom 113 (11%) were eligible, and 29 (3%) were recruited (median Clinical Frailty Score 3, median Barthel ADL score 93/100). The recruitment rate was 0.45/week in phase 1 and 0.9/week in phase 2. Fifty-three percent achieved the target of 24 NMES sessions. However, 5/29 withdrew due to intolerance of NMES. Leg muscle strength improved in both treated and untreated legs, with marginally greater improvement observed in the tibialis anterior of treated legs. Although it would be feasible to evaluate the specific effect of NMES in fragility fracture patients in a multi-centre trial using home-based NMES, this would be possible only in a minority of mildly frail fragility fracture patients with little premorbid disability.

Transspinal stimulation downregulates flexion reflex pathways during walking in healthy humans.

The phase-dependent modulation pattern of the tibialis anterior (TA) flexion reflex was characterized during treadmill walking while transspinal stimulation was delivered at 15, 30, and 50 Hz above and below paresthesia in healthy participants. The flexion reflex was elicited following medial arch foot stimulation with a 30 ms (300 Hz) pulse train. During treadmill walking, the flexion reflex was evoked in the right leg every 3 to 5 steps, and stimuli were randomly dispersed across the step cycle that was divided into 16 equal bins. For each participant, condition and bin of the step cycle, the flexion reflex was measured as the area of the linear EMG envelope starting 20 ms after the end of the pulse train up to 200 ms and was normalized to the maximum locomotor TA EMG activity. The unconditioned flexion reflex was modulated in a phase-dependent manner. Transspinal stimulation, regardless frequency, or intensity produced pronounced flexion reflex depression during walking that coincided with an unchanged slope and intercept, computed from the linear relationship between the flexion reflex and background EMG activity. These findings suggest that transspinal stimulation above and below paresthesia intensities at 15, 30, and 50 Hz downregulates the flexion reflex. Based on our recently reported absent effects on the soleus H-reflex under similar conditions and our current findings we propose that transspinal stimulation downregulates flexion and not extension reflex pathways. More research is needed to delineate whether similar neuromodulation effects are present in flexion and extension reflexes after spinal cord injury in humans.

Postural control strategies in individuals with and without chronic ankle instability during the reach phase of the posteromedial direction of the star excursion balance test.

To compare center of mass (COM) and center of pressure (COP) displacement, joint angles, and muscle activity for the ankle, knee, and hip during the posteromedial (PM) reach direction of the Star Excursion Balance Test between individuals with chronic ankle instability (CAI) and healthy individuals. Cross-sectional Study. Biomechanics laboratory. Fifteen individuals with CAI (age: 20.0±1.2y) and 20 healthy individuals (age: 20.6±0.8y). The maximum reach distance (MRD). The COM and COP displacement, and ankle, knee, and hip joint angles of the stance limb during the PM reach task measured via a 3D motion analysis system. Electromyography (EMG) was also recorded during the task from the tibialis anterior (TA), soleus, peroneus longus, vastus medialis (VM), biceps femoris, and gluteus medius muscles. MRD of the CAI group was shorter than the healthy group (P=0.005). The CAI group showed higher COM positioning (P=0.007), less knee flexion (P=0.009), and lower muscle activity in TA (P=0.04), and VM (P=0.007) during performance of the PM reach as compared to the healthy group. These findings suggest that individuals with CAI demonstrate altered postural control strategies during PM reach performance, likely contributing to a shorter MRD.

Intramuscular pH monitoring before and during exercise in individuals with intermittent claudication compared to healthy controls: A feasibility study.

In this feasibility study, firstly, we aimed to assess whether intramuscular pH (IMpH) could be measured with a glass-tipped electrode. Secondly, we aimed to explore whether we could monitor changes in skeletal muscle pH before and throughout static (isometric) and after dynamic (treadmill) exercise, comparing individuals with intermittent claudication (IC) to a group of healthy controls. Forty participants with IC (mean age ± SD) 68 ± 8) and 40 healthy volunteers (63 ± 10) were recruited. Participants in the IC group had an ankle brachial pressure index of <0.7 (mean: 0.62 ± 0.13). The first 20 participants in each group underwent isometric ankle dorsiflexion for 120 s at 30% of maximum voluntary contraction and the remainder underwent treadmill exercise (3.6 km/h, 5° incline) to maximal walking distance. A sterilised reusable 1.5 mm shatterproof, heat strengthened glass tipped pH probe inserted using a peripheral venous cannula and in combination with a pH meter was used to measure IMpH of the tibialis anterior muscle prior to, during and continuously for 1 h after exercise. Resting IMpH was similar between the groups (median 6.8 (interquartile range (IQR) 6.7-6.9)) for IC individuals and 6.7 (6.6 to 6.8) for controls). Following isometric exercise, the magnitude of the decrease in IMpH was greatest in the IC group (median ΔpH max. in patients -0.2 (IQR: -0.2 to -0.1) versus -0.1 (IQR: -0.2 to -0.1) in the control group (p = 0.002). After treadmill exercise, the magnitude of the decrease in IMpH (ΔpH max) was greatest in individuals with IC (median ΔpH max. in patients -0.3 (IQR: -0.3 to -0.3) versus 0 (IQR: -0.2 to 0) in the control group, p = 0.04. IMpH monitoring with a flexible glass probe inserted into the tibialis anterior muscle is viable and changes in IMpH during static and dynamic exercises are detected.

Real-life experience with disease-modifying drugs in hereditary transthyretin amyloid polyneuropathy: A clinical and electrophysiological appraisal.

New treatments have dramatically improved the prognosis for Hereditary Transthyretin Amyloid Polyneuropathy (ATTRv-PN). However, there is a lack of routine follow-up studies outside of therapeutic trials. Our aim was to report the long-term clinical and electrophysiological evolution of a cohort of ATTRv-PN patients and to determine which biomarkers are most sensitive to change. We retrospectively collected neuropathy impairment scale (NIS), polyneuropathy disability scale (PND), overall neuropathy limitation scale (ONLS), rash built overall disability scale (RODS), electrodiagnostic data, motor unit number index (MUNIX), troponin and N-terminal pro-brain natriuretic peptide levels. Electrophysiological worsening was defined as a 20% decrease in previous values. Thirty-five patients, with a median age of 58 (interquartile ranges 42-71) years, were followed for a median of 36 (24-48) months. All patients received a transthyretin stabiliser, gene silencer or liver transplant. Overall assessment of the cohort showed clinical, biological and electrophysiological stability. However, on an individual basis, NIS worsened in 45% of patients (14/31), ONLS in 46% (13/28), PND in 28% (9/32) and RODS in 39% (11/28) at the last follow-up. Motor amplitude sum score decreased in 33% (11/33), amplitude recorded on tibialis anterior muscle in 44% (12/27), sensory amplitude sum score in 39% (11/28) and MUNIX sum score in 27% (7/26). Overall effectiveness of ATTRv-PN treatments in routine care is good. However, individual assessments show up to 40% deterioration over time. Electrophysiological measures are valuable monitoring tools but are not more sensitive to change than clinical scores. Results must be confirmed in larger cohorts.

Altered sphingolipid profile in response to skeletal muscle injury in a mouse model of type 1 diabetes mellitus.

A complication of type 1 diabetes mellitus (T1DM) is diabetic myopathy that includes reduced regenerative capacity of skeletal muscle. Sphingolipids are a diverse family of lipids with roles in skeletal muscle regeneration. Some studies have found changes in sphingolipid species levels in T1DM, however, the effect of T1DM on a sphingolipid panel in regenerating skeletal muscle has not been examined. Wild-type (WT) and diabetic Ins2Akita+/- (Akita) mice received cardiotoxin-induced muscle injury in their left quadriceps, gastrocnemius-plantaris-soleus, and tibialis anterior muscles with the contralateral muscles serving as uninjured controls. Muscles were collected at 1, 3, 5, or 7 days postinjury. In regenerating muscle from Akita mice, lipid staining with BODIPY 493/503 revealed increased intramyocellular and total lipids and perilipin-1-positive cell numbers as compared with WT. Liquid chromatography-mass spectrometry of quadriceps was used to identify sphingolipid levels in skeletal muscle. The C22:0 and C24:0 ceramides were significantly elevated in uninjured Akita, whereas ceramide C24:1 was decreased in injured Akita compared with WT. Ceramide-1-phosphate was increased in Akita compared with WT regardless of injury, whereas sphingosine-1-phosphate (S1P) was elevated with injury in WT but this response was muted in Akita mice. Western blotting of key enzymes involved in sphingolipid metabolism revealed S1P lyase, the enzyme that degrades S1P irreversibly, was significantly elevated in the injured muscle in Akita mice during regeneration, in accordance with lower S1P levels. This mouse model of T1DM demonstrates sphingolipidomic changes that may contribute to delayed muscle regeneration.NEW & NOTEWORTHY Muscle lipids become elevated, and the sphingolipid profile is altered by T1DM in skeletal muscle regeneration. A loss of S1P is accompanied by greater expression of sphingosine-1-phosphate lyase (SPL) in response to injury in Akita mice, suggesting a role for sphingolipids in the attenuated repair of skeletal muscle in T1DM rodent models. Although ceramide-1-phosphate (C1P) is increased with T1DM, there was no increase in ceramide kinase (CerK) suggesting an alternative route of ceramide phosphorylation in skeletal muscle.

Effects of intramuscular administration of Platelet-Rich Plasma on denervated muscle after peripheral nerve injury

ABSTRACT Purpose After peripheral nerve injury (PNI), prolonged denervation of the target muscle prevents adequate reinnervation even if the nerve is repaired. The aim of this work is to analyze the effect of intramuscular Platelet-Rich Plasma (PRP) in a denervated muscle due to PNI.Materials and Methods An irreversible PNI was generated in the common peroneal nerve of 80 Wistar rats by nerve resection. Animals were divided into groups: non-treatment (NT), saline (S) and PRP (PRP). 200 uL of saline (S group) and PRP (PRP group) were infiltrated intramuscularly into the tibialis anterior muscle on a weekly basis, from surgery to sacrifice (at 2, 4 and 7 weeks). Muscles were histologically processed for immunofluorescence and Western blotting. Effects on nicotinic acetylcholine receptor (nAChR), satellite cells (SC) and myogenin expression were analyzed. Comparisons were performed by two-way analysis of variance (ANOVA). Results PRP had a platelet concentration 1.5-fold higher than blood, without erythrocytes and leukocytes. The PRP group had a higher percentage weight than the S and NT groups (p < 0.05). The levels of nAChRα1 and nAChRε subunit were lower in the PRP group relative to the NT and S (p < 0.05), while the nAChRγ subunit showed an increase in the PRP group (p < 0.05). The activation of SCs was higher in the PRP group compared to NT and S groups (p < 0.05). Conclusion PRP treatment can modulate NMJ configuration as well as key myogenic regulatory factors in denervated muscle, enhancing SC activation while mitigating muscle atrophy.

Comparing virtual reality and balance training effects on postural strategies during ball kicking in soccer players with chronic ankle instability

The study aimed to determine if virtual reality (VR) games could enhance neuromuscular control and improve anticipatory and compensatory strategies in ball-kicking for soccer players. It was a single-blind randomized clinical trial involving 32 male soccer players with chronic ankle instability. Participants were divided into two groups: VR games and balance training. The primary outcomes measured were the amplitude and onset time of muscle activities in the peroneus longus (PL), tibialis anterior (TA), soleus (SOL), rectus femoris (RF), biceps femoris (BF), and gluteus medius (GM) in three phases: anticipatory (APA), compensatory 1 (CPA1), and compensatory 2 (CPA2). Secondary outcomes included the Y-balance test and perceived ankle instability. Evaluations were done before and after treatment. Both groups underwent 12 sessions, three times a week, each lasting 60 min. In the VR games group, there was a significant decrease in SOL muscle activity amplitude during CPA2 after treatment (P = 0.033), and the BF muscle activated earlier (P = 0.043). The balance training group showed a significant increase in GM muscle activity amplitude during APA (P = 0.037) and earlier activation of the GM muscle post-treatment (P = 0.050). Additionally, this group demonstrated significant decreases in RF activity during CPA1 and PL activity in CPA1 and CPA2 (P = 0.048, P = 0.030, and P = 0.050, respectively). Between-group comparisons indicated a significant increase in GM muscle activity amplitude during APA and a reduction during CPA1 for the balance training group compared to the VR games group (P = 0.050 and P = 0.012, respectively). Both groups showed significant reductions in perceived ankle instability (VR group: P = 0.002, balance training group: P < 0.001) and improvements on the Y-balance test (VR group: P < 0.021, balance training group: P < 0.033), although neither group showed significant improvement in the anterior direction. Overall, both VR games and balance training effectively enhanced perceived ankle stability and dynamic postural control, with neither approach showing clear superiority. Both groups exhibited improvements in muscle activation timing, though neither outperformed the other. While both interventions led to increased muscle activity amplitude during the anticipatory and compensatory phases, the balance training group achieved somewhat greater improvements. These results suggest that both VR games and balance training are effective rehabilitation approaches for chronic ankle instability, providing comparable benefits for enhancing ankle stability and neuromuscular control, without a distinct advantage of one over the other.RCT Registration: On the Iranian Registry of Clinical Trials (IRCT20230124057197N1). Registration date: 30/06/2023

Intrinsic Muscle Stem Cell Dysfunction Contributes to Impaired Regeneration in the mdx Mouse.

Duchenne muscular dystrophy (DMD) is a devastating disease characterized by progressive muscle wasting that leads to diminished lifespan. In addition to the inherent weakness of dystrophin-deficient muscle, the dysfunction of resident muscle stem cells (MuSC) significantly contributes to disease progression. Using the mdx mouse model of DMD, we performed an in-depth characterization of disease progression and MuSC function in dystrophin-deficient skeletal muscle using immunohistology, isometric force measurements, transcriptomic analysis and transplantation assays. We examined the architectural and functional changes in mdx skeletal muscle from 13 and 52 weeks of age and following acute cardiotoxin (CTX) injury. We also studied MuSC dynamics and function under homeostatic conditions, during regeneration post-acute injury, and following engraftment using a combination of histological and transcriptomic analyses. Dystrophin-deficient skeletal muscle undergoes progressive changes with age and delayed regeneration in response to acute injury. Muscle hypertrophy, deposition of collagen and an increase in small myofibres occur with age in the tibialis anterior (TA) and diaphragm muscles in mdx mice. Dystrophic mdx mouse TA muscles become hypertrophic with age, whereas diaphragm atrophy is evident in 1-year-old mdx mice. Maximum tetanic force is comparable between genotypes in the TA, but maximum specific force is reduced by up to 38% between 13 and 52 weeks in the mdx mouse. Following acute injury, myofibre hyperplasia and hypotrophy and delayed recovery of maximum tetanic force occur in the mdx TA. We also find defective MuSC polarity and reduced numbers of myocytes in mdx muscle following acute injury. We observed a 50% and 30% decrease in PAX7+ and MYOG+ cells, respectively, at 5 days post CTX injury (5 dpi) in the mdx TA. A similar decrease in mdx progenitor cell proportion is observed by single cell RNA sequencing of myogenic cells at 5 dpi. The global expression of commitment-related genes is also reduced at 5 dpi. We find a 46% reduction in polarized PARD3 in mdx MuSCs. Finally, mdx MuSCs exhibit elevated PAX7+ cell engraftment with significantly fewer donor-derived myonuclei in regenerated myofibres. Our study provides evidence that dystrophin deficiency in MuSCs and myofibres together contributes to progression of DMD. Ongoing muscle damage stimulates MuSC activation; however, aberrant intrinsic MuSC polarity and stem cell commitment deficits due to the loss of dystrophin impair muscle regeneration. Our study provides invivo validation that dystrophin-deficient MuSCs undergo fewer asymmetric cell divisions, instead favouring symmetric expansion.

Trunk fatigue effect on lower limb kinematic and electromyographic patterns during the single-leg drop-landing test in female novice runners

Trunk muscle fatigue could influence the dynamic control of the lower limbs in runners, and the single-leg drop-landing (SLDL) test could simulate the landing and reveal those changes. This study compared the effect of trunk muscle fatigue on the kinematic and electromyographic patterns of the lower limb during SLDL in female novice runners. The kinematics of the main joints and electromyographic (EMG) of the main muscles of the lower limb during SLDL pre- and post-fatigue muscle trunk were registered in 18 female novice runners. The integrated EMG (iEMG) was calculated into 3 phases (F1, before movement starts; F2, eccentric; and F3, concentric). There was an increase in the tibialis anterior and soleus mean iEMG in F1, a reduction in tibialis anterior (TA) and gastrocnemius medialis (GM) maximum iEMG in F2, and an increase in the biceps femoris (BF) minimal iEMG in F2. Also, we found a reduced ankle angle, increased hip angle in the sagittal plane, and a reduced knee angle in the frontal plane post-intervention. The induction of trunk muscle fatigue in female novice runners influenced the TA, SO, GM, and BF EMG changes, the kinematic pattern of the ankle and hip in the sagittal plane, and the knee in the frontal plane during the SDLD.

Efficacy of cold and cryo-preserved nerve allografts with low-dose FK506 for motor nerve regeneration: a preclinical study

BackgroundDespite their ability to regenerate as well as autografts, the use of nerve allografts is limited by the need for immunosuppression and the risk of disease transmission. Further, decellularized allografts lacking Schwann cells limit axonal regeneration in long nerve defects. This study evaluated sciatic nerve regeneration in rats implanted with cold- or cryopreserved allografts, and examined the effects of FK506, an immunosuppressant that targets calcineurin function, on motor recovery.MethodsSixty-five male Lewis rats were divided into five groups of 13, each with a 10-mm sciatic nerve gap. Group I received an autograft, whereas Groups II and III received allografts pretreated with cryopreservation and cold preservation, respectively. Groups IV and V were also implanted with cryo- and cold-preserved allografts, but were treated with a low dose of FK506. Motor regeneration was assessed at 20 weeks by the measurement of ankle contracture, compound muscle action potential, maximal isometric tetanic force, wet muscle weight of the tibialis anterior, peroneal nerve histomorphometry, and immunohistochemistry of the reconstructed sciatic nerve.ResultsSimilar motor recovery was observed between the autografts and both types of allografts. The groups treated with FK506 showed improved recovery, particularly in terms of ankle angle and tibialis anterior muscle weight. Histomorphometry revealed a superior myelinated fiber area and nerve ratio in the cold-preserved allograft group, while Group II displayed a less well-organized morphology.ConclusionThis study demonstrates that cold- or cryopreserved nerve allografts represent effective alternatives to autografts for peripheral nerve reconstruction, with low-dose FK506 enhancing motor recovery without necessitating immunosuppression.Level of Evidence IBasic Science Level I.

Postural adjustment and muscle activity during each phase of gait initiation in chronic ankle instability: an observational study

BackgroundGait initiation (GI) can be divided into three sections according to the center of pressure (COP) trace (S1, S2, and S3). Almost all studies do not separate each phase of the GI profile in postural control assessment and muscular investigation, whereas differences in the COP and muscles are found in each phase of the GI profile in people with gait problems.MethodsTwenty individuals with CAI and twenty healthy controls were included in the present study. A force plate synchronized with Qualisys motion analysis, MEGAWIN electromyography, and a pair of auditory cues were used for data capture. The participants carried out five trials of GI with the affected leg (dominant leg). The peak and mean COP excursions; the mean and maximum velocities of COP excursion during S1, S2,, S3, and the total phases in the mediolateral (ML) and anterior‒posterior (AP) directions; the root mean square (RMS); and the onset activity of the Tibialis Anterior (TA) and Soleus (SOL) muscles for both legs were used for statistical analysis. Independent t tests and Mann‒Whitney U tests were used for statistical analysis on the basis of a significance level of ≤ 0.05.ResultsCompared with those of healthy controls, independent t tests revealed a significant decrease in the peak COP excursion in the AP direction during S2 (P = 0.021) and in the mean velocity of COP excursion in the AP direction during S1 (P = 0.044) in the CAI group. Additionally, there was a significant increase in the duration of S1 in the GI profile (P = 0.045) in the CAI group compared with the healthy control group. There was no significant difference in the other COP variables, TA or SOL RMS or onset activity for either leg during S1, S2, or S3 between the two groups (P > 0.065).ConclusionIndividuals with CAI exhibit increased stiffness in the AP direction in the injured ankle. This leads to a reduction in the velocity and peak of COP excursion, as well as an increase in the time required for postural control adjustment. These findings highlight the challenges individuals with CAI may face in meeting postural demands when trying to unload the affected foot.Ethical codeIR.SBMU.RETECH.REC.1402.095, 2023–5-28.