Reduced Muscle Force Research Articles

Abstract 4137264: Subclassification of Peripheral Artery Disease Based on Muscle Force: Leg Failure with Reduced Muscle Force and Leg Failure with Preserved Muscle Force

Introduction: All claudicating patients with peripheral artery disease (PAD) exhibit leg failure, as evidenced by distinct walking impairment. However, based on a detailed evaluation of leg biomechanics, some claudicating patients maintain preserved leg muscle strength, while others demonstrate reduced strength. In this study, we aim to compare the clinical and physiological characteristics of the two groups. Methods: Fifty-four claudicating patients were categorized into two groups: leg failure with preserved muscle force (LEF-PF) versus leg failure with reduced muscle force (LEF-RF), based on the peak torque (PT) from performing maximum isometric plantar flexion contractions on a Biodex system. All patients underwent history and physical exam, measurement of leg hemodynamics, walking performance and quality of life, and gastrocnemius biopsy to evaluate the histology and biochemistry of the affected leg muscles. We used independent samples T test and chi-square test to compare the two groups. Results: LEF-PF (N=19, PT 92±15 Nm) and LEF-RF (N=35, PT 49±13 Nm) had similar demographic and comorbidity profiles. While ankle-brachial index didn't differ between the two groups, during the reactive hyperemia test, ankle pressure of LEF-RF dropped more significantly (p=0.021) upon occlusion release and took longer to recover (p=0.023). Both groups performed similarly on the Gardner Treadmill test, but LEF-PF performed better in the 6-Minute Walking test (p=0.062). LEF-PF also trended towards higher scores on the modified falls efficacy scale (p=0.056). Histologically, gastrocnemius muscle from LEF-PF had larger myofibers, while biochemically, they exhibited lower mitochondrial respiratory activity dependent on complex-II compared to LEF-RF. Conclusion: Our study presents a novel approach to understanding the physiology of claudication, focusing on the strength of the ischemic muscles. Despite comparable demographics and hemodynamics at rest, notable differences separate the two groups during stress-induced hemodynamics, walking performance, myofiber histology, and mitochondrial biochemistry. Further investigations are necessary to elucidate the underlying mechanisms behind the differences in muscle strength among patients with claudication. Such insights may enhance our understanding of PAD physiology and potentially correlate with variations in mortality rates, progression to more advanced PAD stages, and responses to different therapeutic interventions.

A Gain-of-Function Mutation in the Ca2+ Channel ORAI1 Causes Stormorken Syndrome with Tubular Aggregates in Mice

Store-operated Ca2+ entry (SOCE) controls Ca2+ homeostasis and mediates multiple Ca2+-dependent signaling pathways and cellular processes. It relies on the concerted activity of the reticular Ca2+ sensor STIM1 and the plasma membrane Ca2+ channel ORAI1. STIM1 and ORAI1 gain-of-function (GoF) mutations induce SOCE overactivity and excessive Ca2+ influx, leading to tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two overlapping disorders characterized by muscle weakness and a variable occurrence of multi-systemic anomalies affecting spleen, skin, and platelets. To date, different STIM1 mouse models exist, but only a single ORAI1 mouse model with muscle-specific TAM/STRMK phenotype has been described, precluding a comparative analysis of the physiopathology in all affected tissues. Here, we generated and characterized mice harboring a prevalent ORAI1 TAM/STRMK mutation and we provide phenotypic, physiological, biochemical, and functional data. Examination of Orai1V109M/+ mice revealed smaller size, spleen enlargement, reduced muscle force, and decreased platelet numbers. Morphological analyses of muscle sections evidenced the presence of tubular aggregates, the histopathological hallmark on biopsies from TAM/STRMK patients absent in all reported STIM1 models. Overall, Orai1V109M/+ mice reliably recapitulate the human disorder and highlight the primary physiological defects caused by ORAI1 gain-of-function mutations. They also provide the possibility to investigate the formation of tubular aggregates and to develop a common therapy for different TAM/STRMK forms.

Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system

Huntington's Disease (HD) is a neurodegenerative disorder, part of the nine identified inherited polyglutamine (polyQ) diseases. Most commonly, HD pathophysiology manifests in middle-aged adults with symptoms including progressive loss of motor control, cognitive decline, and psychiatric disturbances. Associated with the pathophysiology of HD is the formation of insoluble fragments of the huntingtin protein (htt) that tend to aggregate in the nucleus and cytoplasm of neurons. To track both the intracellular progression of the aggregation phenotype as well as the physiological deficits associated with mutant htt, two constructs of human HTT were expressed in the Drosophila melanogaster nervous system with varying polyQ lengths, non-pathogenic-htt (NP-htt) and pathogenic-htt (P-htt), with an N-terminal RFP tag for in vivo visualization. P-htt aggregates accumulate in the ventral nerve cord cell bodies as early as 24 h post hatching and significant aggregates form in the segmental nerve branches at 48 h post hatching. Organelle trafficking up- and downstream of aggregates formed in motor neurons showed severe deficits in trafficking dynamics. To explore putative downstream deficits of htt aggregation, ultrastructural changes of presynaptic motor neurons and muscles were assessed, but no significant effects were observed. However, the force and kinetics of muscle contractions were severely affected in P-htt animals, reminiscent of human chorea. Reduced muscle force production translated to altered locomotory behavior. A novel HD aggregation model was established to track htt aggregation throughout adulthood in the wing, showing similar aggregation patterns with larvae. Expressing P-htt in the adult nervous system resulted in significantly reduced lifespan, which could be partially rescued by feeding flies the mTOR inhibitor rapamycin. These findings advance our understanding of htt aggregate progression as well the downstream physiological impacts on the nervous system and peripheral tissues.

Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system.

Huntington's Disease (HD) is a neurodegenerative disorder, part of the nine identified inherited polyglutamine (polyQ) diseases. Most commonly, HD pathophysiology manifests in middle-aged adults with symptoms including progressive loss of motor control, cognitive decline, and psychiatric disturbances. Associated with the pathophysiology of HD is the formation of insoluble fragments of the huntingtin protein (htt) that tend to aggregate in the nucleus and cytoplasm of neurons. To track both the intracellular progression of the aggregation phenotype as well as the physiological deficits associated with mutant htt, two constructs of human HTT were expressed with varying polyQ lengths, non-pathogenic-htt (Q15, NP-htt) and pathogenic-htt (Q138, P-htt), with an N-terminal RFP tag for in vivo visualization. P-htt aggregates accumulate in the ventral nerve cord cell bodies as early as 24 hours post hatching and significant aggregates form in the segmental nerve branches at 48 hours post hatching. Organelle trafficking up-and downstream of aggregates formed in motor neurons showed severe deficits in trafficking dynamics. To explore putative downstream deficits of htt aggregation, ultrastructural changes of presynaptic motor neurons and muscles were assessed, but no significant effects were observed. However, the force and kinetics of muscle contractions were severely affected in P-htt animals, reminiscent of human chorea. Reduced muscle force production translated to altered locomotory behavior. A novel HD aggregation model was established to track htt aggregation throughout adulthood in the wing, showing similar aggregation patterns with larvae. Expressing P-htt in the adult nervous system resulted in significantly reduced lifespan, which could be partially rescued by feeding flies the mTOR inhibitor rapamycin. These findings advance our understanding of htt aggregate progression as well the downstream physiological impacts on the nervous system and peripheral tissues.

Characterizing phenotypic data of Peromyscus leucopus compared to C57BL/6J Mus musculus and diversity outbred (DO) Mus musculus

Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.

Kinematics but not kinetics alterations to single-leg drop jump movements following a subject-tailored fatiguing protocol suggest an increased risk of ACL injury.

Neuromuscular fatigue causes a transient reduction of muscle force, and alters the mechanisms of motor control. Whether these alterations increase the risk of anterior cruciate ligament (ACL) injury is still debated. Here we compare the biomechanics of single-leg drop jumps before and after the execution of a fatiguing exercise, evaluating whether this exercise causes biomechanical alterations typically associated with an increased risk of ACL lesion. The intensity of the fatiguing protocol was tailored to the aerobic capacity of each participant, minimizing potential differential effects due to inter-individual variability in fitness. Twenty-four healthy male volunteers performed single leg drop jumps, before and after a single-set fatiguing session on a cycle ergometer until exhaustion (cadence: 65-70 revolutions per minute). For each participant, the intensity of the fatiguing exercise was set to 110% of the power achieved at their anaerobic threshold, previously identified by means of a cardiopulmonary exercise test. Joint angles and moments, as well as ground reaction forces (GRF) before and after the fatiguing exercise were compared for both the dominant and the non-dominant leg. Following the fatiguing exercise, the hip joint was more extended (landing: Δ=-2.17°, p = 0.005; propulsion: Δ=-1.83°, p = 0.032) and more abducted (landing: Δ=-0.72°, p = 0.01; propulsion: Δ=-1.12°, p = 0.009). Similarly, the knee joint was more extended at landing (non-dominant leg: Δ=-2.67°, p < 0.001; dominant: Δ=-1.4°, p = 0.023), and more abducted at propulsion (both legs: Δ=-0.99°, p < 0.001) and stabilization (both legs: Δ=-1.71°, p < 0.001) hence increasing knee valgus. Fatigue also caused a significant reduction of vertical GRF upon landing (Δ=-0.21 N/kg, p = 0.003), but not during propulsion. Fatigue did not affect joint moments significantly. The increased hip and knee extension, as well as the increased knee abduction we observed after the execution of the fatiguing exercise have been previously identified as risk factors for ACL injury. These results therefore suggest an increased risk of ACL injury after the execution of the participant-tailored fatiguing protocol proposed here. However, the reduced vertical GRF upon landing and the preservation of joint moments are intriguing, as they may suggest the adoption of protective strategies in the fatigued condition to be evaluated in future studied.

Abstract 3026: Genetic Deletion Of Skeletal Muscle Bag3 Exacerbates Ischemic Myopathy

Background: Bcl2-associated athanogene 3 (BAG3) is a multifunctional adaptor protein that regulates diverse cellular functions. Mutations in BAG3 are causally linked to myofibrillar myopathy and dilated cardiomyopathy in humans and now appear to be one of the most common to cause human disease. We previously identified a murine coding variant in Bag3 that contributes to hindlimb ischemia (HLI) pathology, however, no cell specific data on Bag3’s role in PAD pathology exists. Hypothesis: We hypothesized that muscle specific BAG3 is required for both the restoration of blood flow and muscle recovery following HLI. Methods: We generated a genetic model of lifelong muscle cell (mature fiber and progenitor) Bag3 deletion (Pax7-Cre; Bag3 -/- ) on a BL6 parental background. Male and Female mice (12-20 weeks; WT: n=45; KO: n=32) were evaluated at baseline and HLI d7 and d28 for blood flow via LDPI, isometric muscle force production, vascular density and muscle morphology. Bag3 deletion was validated by recombination, qRT-PCR and Western Blotting in whole tissue, isolated myofibers, and FACS muscle progenitor cells. Results: KO reduced muscle force production (n=18; 145.8mN Force ± 28.6 vs 56.9 ± 16.8 SEM; p=0.0208) and capillary perfusion (n=7; 0.17 CD31+/Lectin+ vessels ± 0.02 vs 0.09 ± 0.01 SEM p=0.0491) indicative of the multi-compartmental effect of BAG3 loss in skeletal muscle at HLI d7. Extended HLI (d28) revealed a KO phenotype characterized by reduced blood flow recovery (LDPI; n= 7; .68 ischemic/non limb ± 0.5 vs .38 ± 0.6 SEM p=0.0011) and sustained myopathy including reduced myofiber size ( n =7; 1585um 2 ± 161 vs 1093 ± 169 SEM; p =0.05) and increased tissue lesion size ( n =7; 2.5% muscle area ± 2.0 vs 48.3% ± 21.6; p =0.03). Conclusion: Loss of skeletal muscle Bag3 exacerbates myopathy and reduces capillary perfusion and blood flow recovery following HLI and demonstrate a requirement for BAG3 in recovery from limb ischemia.

Taurine activates the AKT-mTOR axis to restore muscle mass and contractile strength in human 3D in vitro models of steroid myopathy.

Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.

Hip joint contact forces are lower in people with femoroacetabular impingement syndrome during squat tasks.

It remains unknown if hip joint forces during squat tasks are altered in people with femoroacetabular impingement syndrome (FAIS). The aim of this study is to compare hip joint forces between people with FAIS and healthy controls during double leg squat and single leg squat tasks and within limbs during a single leg squat task in people with FAIS. Kinematic and kinetic data were collected in eight people with FAIS and eight healthy matched controls using 3D motion capture and force plates. AnyBody Modeling System was used to perform musculoskeletal simulations to estimate hip joint angles, forces, and moments for all participants. Estimates were postprocessed with AnyPyTools and converted into normalized time series to be compared using a 1D statistical nonparametric mapping (SnPM) approach. SnPM with an independent samples t-test model was used to compare people with FAIS to controls, while a paired samples model was used to compare involved to uninvolved limb in people with FAIS. Patients demonstrated lower proximodistal force compared to controls (p < 0.01) and compared to the uninvolved side (p = 0.01) for single leg squat. The smaller joint contact forces in people with FAIS compared to controls could represent a strategy of reduced muscle forces to avoid pain and symptoms during this high demand task. These findings when combined with imaging data could help assess the severity of FAIS on hip related function during higher demand tasks.

Mid-Activity and At-Home Wearable Bioimpedance Elucidates an Interpretable Digital Biomarker of Muscle Fatigue.

Muscle health and decreased muscle performance (fatigue) quantification has proven to be an invaluable tool for both athletic performance assessment and injury prevention. However, existing methods estimating muscle fatigue are infeasible for everyday use. Wearable technologies are feasible for everyday use and can enable discovery of digital biomarkers of muscle fatigue. Unfortunately, the current state-of-the-art wearable systems for muscle fatigue tracking suffer from either low specificity or poor usability. We propose using dual-frequency bioimpedance analysis (DFBIA) to non-invasively assess intramuscular fluid dynamics and thereby muscle fatigue. A wearable DFBIA system was developed to measure leg muscle fatigue of 11 individuals during a 13-day protocol consisting of exercise and unsupervised at-home portions. We derived a digital biomarker of muscle fatigue, fatigue score, from the DFBIA signals that was able to estimate the percent reduction in muscle force during exercise with repeated-measures Pearson's r = 0.90 and mean absolute error (MAE) of 3.6%. This fatigue score also estimated delayed onset muscle soreness with repeated-measures Pearson's r = 0.83 and MAE = 0.83. Using at-home data, DFBIA was strongly associated with absolute muscle force of participants (n = 198, p < 0.001). These results demonstrate the utility of wearable DFBIA for non-invasively estimating muscle force and pain through the changes in intramuscular fluid dynamics. The presented approach may inform development of future wearable systems for quantifying muscle health and provide a novel framework for athletic performance optimization and injury prevention.

Does cross-education minimize the loss of muscle force and power and sEMG amplitude during short-term detraining in older women who are recreationally engaged in resistance training?

This study aimed to investigate whether 4 weeks of unilateral resistance training (RT) could attenuate the decline in muscle function in the contralateral limb of older women recreationally engaged in RT compared to control group (CTL). Twenty-four participants completed a 10-week RT before the cross-education (CR-Edu) phase and subsequent detraining. Afterward, participants were randomized into two groups: CTL (n = 8 women, n = 16 legs) who underwent 4 weeks of detraining without any training, and CR-Edu (n = 16 women, n = 16 legs) who performed 4 weeks of unilateral RT. Muscle force, power, and surface electromyography were measured unilaterally before and after the 4-week period, using five repetitions conducted at 40% and 60% of the 1RM. The results showed a reduction in muscle force at both 40% and 60% of 1RM, as well as a decrease in power at 60% of 1RM (P-time < 0.05) without significant differences between the two groups (P interaction > 0.05). There was a decline in power at 60% of 1RM (P-time < 0.05) but no significant change at 40% of 1RM (P-time > 0.05), and again, no significant differences were observed between the groups (P-interaction > 0.05). The surface electromyography of vastus lateralis decreased only in the CTL group (P-interaction < 0.05). Older women recreationally engaged in RT who perform in unilateral leg extension compared to a brief period of detraining seem not to retain muscle force and power, and sEMG amplitude of their homologous and contralateral limb.

Biomechanical effects of exercise fatigue on the lower limbs of men during the forward lunge.

Background: During competition and training, exercises involving the lungs may occur throughout the sport, and fatigue is a major injury risk factor in sport, before and after fatigue studies of changes in the lungs are relatively sparse. This study is to investigate into how fatigue affects the lower limb's biomechanics during a forward lunge. Methods: 15 healthy young men participate in this study before and after to exposed to a fatigue protocol then we tested the forward lunge to obtain kinematic, kinetic changing during the task, and to estimate the corresponding muscles' strength changes in the hip, knee, and ankle joints. The measurement data before and after the fatigue protocol were compared with paired samples t-test. Results: In the sagittal and horizontal planes of the hip and knee joints, in both, the peak angles and joint range of motion (ROM) increased, whereas the moments in the sagittal plane of the knee joint smaller. The ankle joint's maximum angle smaller after fatigue. Peak vertical ground reaction force (vGRF) and peak contact both significantly smaller after completing the fatigue protocol and the quadriceps mean and maximum muscular strength significantly increased. Conclusion: After completing a fatigue protocol during lunge the hip, knee, and ankle joints become less stable in both sagittal and horizontal planes, hip and knee range of motion becomes greater. The quadriceps muscles are more susceptible to fatigue and reduced muscle force. Trainers should focus more on the thigh muscle groups.

Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome

BackgroundMyalgic encephalomyelitis is an invalidating chronic disease often associated with exercise-induced alterations of muscle membrane excitability (M wave). No simultaneous measurements of maximal isometric force production and sarcolemma fatigue in the same muscle group have been previously reported. We hypothesized that M wave alterations could be partly responsible for the reduced muscle force present in this invalidating disease. MethodsThis retrospective study compared two groups of patients who presented (n = 30) or not (n = 28) alterations of M waves evoked by direct muscle stimulation during and after a cycling exercise bout. The maximal handgrip strength was measured before and after exercise, concomitantly with electromyogram recordings from flexor digitorum longus muscle. The patients also answered a questionnaire to identify eventual exacerbation of their clinical symptoms following the exercise test. FindingsThe M wave amplitude significantly decreased in muscles and the M wave duration significantly increased in the group of patients with M wave alterations after exercise. Resting values of handgrip were significantly lower in patients with exercise-induced M-wave alterations than in patients without M-wave abnormalities. In patients with exercise-induced M-wave alterations, handgrip significantly decreased after exercise and the changes in handgrip and M wave were positively correlated. The frequency of post-exertion malaise, increased fatigue, myalgia, headache and cognitive dysfunction was significantly higher in patients with M-wave alterations and variations in handgrip after exercise. InterpretationThese data suggest that post-exercise sarcolemma fatigue often measured in patients with myalgic encephalomyelitis could be the cause of muscle failure.

Linking histopathological changes in intervertebral disc with lumbar muscles strength.

Low back pain (LBP) is a painful condition affecting 80% of word population at some point in their life. Lumbar intervertebral disc degeneration and reduced muscle force is one the major cause of LBP. Sixty-two patients with LBP undergoing discectomy were recruited after receiving consent. Lumbar muscles strength and VAS (visual analogue scale) for lumbar pain were checked, MRI scan were analysed. Histological degenerative changes were analysed. The study revealed histological degeneration at intervertebral disc has direct effect on increase in pain at lumbar region, decrease in strength of lumbar flexor and extensors muscles and degenerative changes seen on MRI scan.

Water-soluble pristine C60 fullerenes attenuate isometric muscle force reduction in a rat acute inflammatory pain model

BackgroundBeing a scavenger of free radicals, C60 fullerenes can influence on the physiological processes in skeletal muscles, however, the effect of such carbon nanoparticles on muscle contractility under acute muscle inflammation remains unclear. Thus, the aim of the study was to reveal the effect of the C60 fullerene aqueous solution (C60FAS) on the muscle contractile properties under acute inflammatory pain.MethodsTo induce inflammation a 2.5% formalin solution was injected into the rat triceps surae (TS) muscle. High-frequency electrical stimulation has been used to induce tetanic muscle contraction. A linear motor under servo-control with embedded semi-conductor strain gauge resistors was used to measure the muscle tension.ResultsIn response to formalin administration, the strength of TS muscle contractions in untreated animals was recorded at 23% of control values, whereas the muscle tension in the C60FAS-treated rats reached 48%. Thus, the treated muscle could generate 2-fold more muscle strength than the muscle in untreated rats.ConclusionsThe attenuation of muscle contraction force reduction caused by preliminary injection of C60FAS is presumably associated with a decrease in the concentration of free radicals in the inflamed muscle tissue, which leads to a decrease in the intensity of nociceptive information transmission from the inflamed muscle to the CNS and thereby promotes the improvement of the functional state of the skeletal muscle.

Evaluation of split cord malformation between years 2006 and 2020: A case series study

BackgroundSplit spinal cord malformation (SCM) is a rare congenital disorder leading to the split of the spinal cord by a bony or fibrous septum. ObjectivesIn the current study, we aimed to evaluate the patients with SCM who underwent surgery between 2006 and 2020. MethodsIn this case series, thirty-five patients with SCM who underwent septal resection or spinal cord release surgery were enrolled and evaluated for type and site of the septum, accompanying some anomalies, such as neurological abnormalities, spinal deformities, and skin lesions. Also, the changes of neurological symptoms after surgery were securitized. ResultsThirty-five patients, including 27 females and 8 males, have been investigated. Scoliosis and Tethered cord syndrome were the most prevalent anomalies in 24 and 26 patients, respectively. The most common skin lesion was focal hirsutism in 14 patients, and the most common neurological disorder was the reduced muscle force observed in 5 patients, which was improved in two cases following surgeries. ConclusionSCM occurred more frequently in females in comparison with males (77.14% in females and 22.85% in males). Scoliosis and Tethered cord syndrome were two dominant accompanying disorders with SCM. Moreover, focal hirsutism and reduced muscle force were the most common skin lesion and neurological disorders, respectively in these patients, respectively.

Quadriceps Neuromuscular Function During and After Exercise-Induced Fatigue in Patients With Patellofemoral Pain.

Exercise-induced fatigue reduces muscle force production and motoneuron pool excitability. However, it is unclear if patients with patellofemoral pain (PFP) experience further loss in quadriceps neuromuscular function due to fatigue during exercise and postexercise. To observe how quadriceps maximal strength, activation, and force-generating capacity change during and after repetitive bouts of isokinetic knee-extension exercise in patients with PFP. Cross-sectional study. Laboratory. Twenty-two patients with PFP (visual analog scale mean pain severity = 4.2 of 10 cm, mean symptom duration = 38.6 months) and 19 healthy control individuals matched on age and body mass index. Quadriceps peak torque (PT), central activation ratio (CAR), and rate of torque development (RTD) were assessed at baseline and immediately after every 5 sets of knee-extension exercise (times 1-5). Participants continued knee-extension exercises until the baseline quadriceps PT dropped below 50% for 3 consecutive contractions. No group-by-time interaction was observed for quadriceps PT (F5,195 = 1.03, P = .40). However, group-by-time interactions were detected for quadriceps CAR (F5,195 = 2.63, P= .03) and RTD (F5,195 = 3.85, P = .002). Quadriceps CAR (-3.6%, P = .04, Cohen d = 0.53) and RTD (-18.9%, P = .0008, Cohen d = 1.02) decreased between baseline and time 1 in patients with PFP but not in their healthy counterparts (CAR -1.9%, P = .86; RTD -9.8%, P = .22). Quadriceps RTD also decreased between times 4 and 5 in patients with PFP (-24.9%, P = .002, Cohen d = 0.89) but not in the healthy group (-0.9%, P = .99). Patients with PFP appeared to experience an additional reduction in quadriceps activation, force-generating capacity, or both during the early and late stages of exercise compared with healthy individuals. Clinicians should be aware of such possible acute changes during exercise and postexercise and use fatigue-resistant rehabilitation programs for patients with PFP.

The influence of induced gait asymmetry on joint reaction forces

Chronic injury- or disease-induced joint impairments result in asymmetric gait deviations that may precipitate changes in joint loading associated with pain and osteoarthritis. Understanding the impact of gait deviations on joint reaction forces (JRFs) is challenging because of concurrent neurological and/or anatomical changes and because measuring JRFs requires medically invasive instrumented implants. Instead, we investigated the impact of joint motion limitations and induced asymmetry on JRFs by simulating data recorded as 8 unimpaired participants walked with bracing to unilaterally and bilaterally restrict ankle, knee, and simultaneous ankle + knee motion. Personalized models, calculated kinematics, and ground reaction forces (GRFs) were input into a computed muscle control tool to determine lower limb JRFs and simulated muscle activations guided by electromyography-driven timing constraints. Unilateral knee restriction increased GRF peak and loading rate ipsilaterally but peak values decreased contralaterally when compared to walking without joint restriction. GRF peak and loading rate increased with bilateral restriction compared to the contralateral limb of unilaterally restricted conditions. Despite changes in GRFs, JRFs were relatively unchanged due to reduced muscle forces during loading response. Thus, while joint restriction results in increased limb loading, reductions in muscle forces counteract changes in limb loading such that JRFs were relatively unchanged.

Large Maf transcription factor family is a major regulator of fast type IIb myofiber determination

Myofibers are broadly characterized as fatigue-resistant slow-twitch (type I) fibers and rapidly fatiguing fast-twitch (type IIa/IIx/IIb) fibers. However, the molecular regulation of myofiber type is not entirely understood; particularly, information on regulators of fast-twitch muscle is scarce. Here, we demonstrate that the large Maf transcription factor family dictates fast type IIb myofiber specification in mice. Remarkably, the ablation of three large Mafs leads to the drastic loss of type IIb myofibers, resulting in enhanced endurance capacity and the reduction of muscle force. Conversely, the overexpression of each large Maf in the type I soleus muscle induces type IIb myofibers. Mechanistically, a large Maf directly binds to the Maf recognition element on the promoter of myosin heavy chain 4, which encodes the type IIb myosin heavy chain, driving its expression. This work identifies the large Maf transcription factor family as a major regulator for fast type IIb muscle determination.

Endogenous and Exogenous Antioxidants in Skeletal Muscle Fatigue Development during Exercise

Muscle fatigue is defined as a decrease in maximal force or power generated in response to contractile activity, and it is a risk factor for the development of musculoskeletal injuries. One of the many stressors imposed on skeletal muscle through exercise is the increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which intensifies as a function of exercise intensity and duration. Exposure to ROS/RNS can affect Na+/K+-ATPase activity, intramyofibrillar calcium turnover and sensitivity, and actin-myosin kinetics to reduce muscle force production. On the other hand, low ROS/RNS concentrations can likely upregulate an array of cellular adaptative responses related to mitochondrial biogenesis, glucose transport and muscle hypertrophy. Consequently, growing evidence suggests that exogenous antioxidant supplementation might hamper exercise-engendering upregulation in the signaling pathways of mitogen-activated protein kinases (MAPKs), peroxisome-proliferator activated co-activator 1α (PGC-1α), or mammalian target of rapamycin (mTOR). Ultimately, both high (exercise-induced) and low (antioxidant intervention) ROS concentrations can trigger beneficial responses as long as they do not override the threshold range for redox balance. The mechanisms underlying the two faces of ROS/RNS in exercise, as well as the role of antioxidants in muscle fatigue, are presented in detail in this review.