Time, graft, sex, geographic location, and isokinetic speed influence the degree of quadriceps weakness after anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

PURPOSE: Although quadriceps weakness after ACL reconstruction (ACLR) is well documented, the magnitude of reported weakness varies considerably. Such variation raises the possibility that certain patients may be more susceptible to quadriceps weakness after ACLR. This meta-analysis identified factors explaining between-study variability in quadriceps weakness post-ACLR. METHODS: Studies between 2010 and 2020 were screened for the following criteria: human subjects, unilateral ACLR, and strength reported both for the ACLR leg and the uninjured or healthy-control leg. 122 studies met the criteria, resulting in 303 and 152 Cohen's d effect sizes (ESs) comparing ACLR legs to uninjured legs (a total of 4135 ACLR subjects) and to healthy controls (a total of 1,507 ACLR subjects vs. 1-193 healthy controls), respectively. Factors (time, graft, sex, activity, mass/height, geographic area, concomitant injury, and type of strength testing) that may affect study ES were examined. RESULTS: Meta-regressions indicated an association between time post-ACLR and study ESs (P < 0.001) and predicted full recovery (ES = 0) to occur at 54-59 months post-ACLR. When compared to uninjured legs, patients with patellar tendon autografts had greater deficits than studies using hamstring tendon autografts (P = 0.023). When compared to uninjured legs, studies including only males reported greater deficits than studies combining males and females (P = 0.045); whereas when compared to healthy controls, studies combining males and females reported greater deficits than studies with males (P = 0.013). When compared to controls, studies from USA reported greater deficits than studies from Europe (P = 0.003). Increased isokinetic-testing speed was associated with smaller deficits (P ≤ 0.025). Less than 25% of patients achieved a between-limb symmetry in quadriceps strength > 90% between 6 and 12 months post-ACLR. CONCLUSION: Time post-surgery, graft, sex, geographic location, and isokinetic speed influenced the magnitude of post-ACLR quadriceps weakness. Patients with patellar tendon autografts demonstrated greater between-limb asymmetry in quadriceps strength, while female strength deficits were underestimated to a greater extent. A slower isokinetic speed provided a more sensitive assessment of quadriceps strength post-ACLR. The overwhelming majority of patients were returning to sport with significantly impaired quadriceps strength. LEVEL OF EVIDENCE: III.

Voluntary and magnetically evoked muscle contraction protocol in males with Duchenne muscular dystrophy: Safety, feasibility, reliability, and validity.

INTRODUCTION/AIMS: Clinical trials addressing treatments for Duchenne muscular dystrophy (DMD) require reliable and valid measurement of muscle contractile function across all disease severity levels. In this work we aimed to evaluate a protocol combining voluntary and evoked contractions to measure strength and excitability of wrist extensor muscles for safety, feasibility, reliability, and discriminant validity between males with DMD and controls. METHODS: Wrist extensor muscle strength and excitability were assessed in males with DMD (N = 10; mean ± standard deviation: 15.4 ± 5.9 years of age), using the Brooke Upper Extremity Rating Scale (scored 1-6), and age-matched healthy male controls (N = 15; 15.5 ± 5.0 years of age). Torque and electromyographic (EMG) measurements were analyzed under maximum voluntary and stimulated conditions at two visits. RESULTS: A protocol of multiple maximal voluntary contractions (MVCs) and evoked twitch contractions was feasible and safe, with 96% of the participants completing the protocol and having a less than 7% strength decrement on either measure for both DMD patients and controls (P ≥ .074). Reliability was excellent for voluntary and evoked measurements of torque and EMG (intraclass correlation coefficient [ICC] over 0.90 and over 0.85 within and between visits, respectively). Torque, EMG, and timing of twitch-onset measurements discriminated between DMD and controls (P < .001). Twitch contraction time did not differ significantly between groups (P = .10). DISCUSSION: Findings from this study show that the protocol is a safe, feasible, reliable, and a valid method to measure strength and excitability of wrist extensors in males with DMD.

Downhill Running Impairs Activation and Strength of the Elbow Flexors.

ABSTRACT: Brandenberger, KJ, Warren, GL, Ingalls, CP, Otis, JS, and Doyle, JA. Downhill running impairs activation and strength of the elbow flexors. J Strength Cond Res 35(8): 2145-2150, 2021-The purpose of this study was to determine if knee extensor injury induced by 1 hour of downhill running attenuated force production in the elbow flexors. Subjects completed either downhill running for 1 hour (injured group; n = 6) or sedentary behavior (control group; n = 6). Strength and voluntary activation (%VA) were measured by isometric twitch interpolation of the elbow flexor and knee extensor muscles at the following time points in relation to the injury: before injury (Pre), after injury (Post), 24 hours after injury (24Post), and 48 hours after injury (48Post). Mean (±SE) knee extensor strength was significantly reduced (53.5 ± 9.9%) Post and remained reduced at 24Post and 48Post in the injury group. Knee extensor muscle twitch strength was reduced Post and 24Post after the downhill run (p < 0.022). Elbow flexor muscle strength was significantly reduced Post (13.2 ± 3.9%) and 24Post (17.3 ± 4.0%). Elbow flexor muscle twitch strength was not significantly different at any time point. Elbow flexor muscle %VA was not significantly reduced compared with Pre, at Post (16.2 ± 5.1%), 24Post (20.9 ± 6.7%), or 48Post (12.9 ± 4.5%). A 1-hour downhill run significantly injured the knee extensors. The elbow flexor muscles remained uninjured, but strength of these muscles was impaired by reduced %VA. These data suggest muscle injury can lead to prolonged strength deficits in muscles distant from the injury and should be accounted for when scheduling training that may lead to delayed-onset muscle soreness.

Acromion morphology and prevalence of rotator cuff tear: A systematic review and meta-analysis.

The causes of degenerative rotator cuff (RTC) tears are unclear but certain acromion morphology may contribute. This study's objective was to determine using a systematic review and meta-analysis the association of acromion type and acromial index with the prevalence of RTC tears. Six databases were searched electronically. Seventeen relevant studies between 1993 and 2017 were included in the meta-analyses determining the association of RTC tears with acromion type (n = 11) or acromial index (n = 10). Effect sizes were calculated as an odds ratio (OR) for the studies reporting acromion type and as raw mean difference (RMD) for the studies reporting acromial index. Meta-analysis was performed using a random-effects model. There was a significant small-to-medium effect found in the meta-analysis for acromion type (overall OR = 2.82, P = 0.000003), indicating an almost three times greater odds for a RTC tear in individuals with a type-III acromion as compared with those with a type-I or -II. A significant effect was also found for acromial index (RMD = 0.071, P < 0.0000001), indicating that a larger acromial index is associated with a greater likelihood of a RTC tear. Because of substantial heterogeneity in RMD for acromial index (Q-df = 92, P < 0.00001; I2 = 89%), subgroup analyses and meta-regressions were performed. Interestingly, the continent where the study was conducted (i.e., Europe vs. Asia) was the only moderator variable that could explain some of the acromial index heterogeneity. Overall, the findings from our analyses indicate that individuals with either a type-III acromion and/or a larger acromial index have a greater likelihood for non-traumatic RTC tears. Clin. Anat. 32:122-130, 2019. © 2018 Wiley Periodicals, Inc.

A moderate oestradiol level enhances neutrophil number and activity in muscle after traumatic injury but strength recovery is accelerated.

KEY POINTS: The female hormone oestrogen may protect muscle from injury by reducing inflammation but this is debatable. In this study, the inflammatory response of injured muscle from oestrogen-replete mice was comprehensively compared to that from oestrogen-deficient mice. We show that oestrogen markedly promotes movement of neutrophils, an inflammatory white blood cell type, into muscle over the first few days after injury but has only a minor effect on the movement of macrophages, another inflammatory cell type. Despite the enhancement of inflammation by oestrogen in injured muscle, we found strength in oestrogen-replete mice to recover faster and to a greater extent than it does in oestrogen-deficient mice. Our study and others indicate that lower doses of oestrogen, such as that used in our study, may affect muscle inflammation and injury differently from higher doses. ABSTRACT: Oestrogen has been shown to protect against skeletal muscle injury and a reduced inflammatory response has been suggested as a possible protective mechanism. There are, however, dissenting reports. Our objective was to conduct an unbiased, comprehensive study of the effect of oestradiol on the inflammatory response following muscle injury. Female C57BL6/J mice were ovariectomized and supplemented with and without oestradiol. Tibialis anterior muscles were freeze injured and studied primarily at 1-4 days post-injury. Oestradiol supplementation increased injured muscle gene expression of neutrophil chemoattractants (Cxcl1 and Cxcl5) and to a lesser extent that of monocyte/macrophage chemoattractants (Ccl2 and Spp1). Oestradiol markedly increased gene expression of the neutrophil cell surface marker (Ly6g) but had less consistent effects on the monocyte/macrophage cell surface markers (Cd68, Cd163 and Cd206). These results were confirmed at the protein level by immunoblot with oestradiol increasing LY6G/C content and having no significant effect on CD163 content. These findings were confirmed with fluorescence-activated cell sorting counts of neutrophils and macrophages in injured muscles; oestradiol increased the proportion of CD45+ cells that were neutrophils (LY6G+ ) but not the proportion that were macrophages (CD68+ or CD206+ ). Physiological impact of the oestradiol-enhanced neutrophil response was assessed by strength measurements. There was no significant difference in strength between oestradiol-supplemented and -unsupplemented mice until 2 weeks post-injury; strength was 13-24% greater in supplemented mice at 2-6 weeks post-injury. In conclusion, a moderate level of oestradiol supplementation enhances neutrophil infiltration in injured muscle and this is associated with a beneficial effect on strength recovery.

Early rehabilitation for volumetric muscle loss injury augments endogenous regenerative aspects of muscle strength and oxidative capacity.

BACKGROUND: Volumetric muscle loss (VML) injuries occur due to orthopaedic trauma or the surgical removal of skeletal muscle and result in debilitating long-term functional deficits. Current treatment strategies do not promote significant restoration of function; additionally appropriate evidenced-based practice physical therapy paradigms have yet to be established. The objective of this study was to develop and evaluate early rehabilitation paradigms of passive range of motion and electrical stimulation in isolation or combination to understand the genetic and functional response in the tissue remaining after a multi-muscle VML injury. METHODS: Adult male mice underwent an ~ 20% multi-muscle VML injury to the posterior compartment (gastrocnemius, soleus, and plantaris muscle) unilaterally and were randomized to rehabilitation paradigm twice per week beginning 2 days post-injury or no treatment. RESULTS: The most salient findings of this work are: 1) that the remaining muscle tissue after VML injury was adaptable in terms of improved muscle strength and mitigation of stiffness; but 2) not adaptable to improvements in metabolic capacity. Furthermore, biochemical (i.e., collagen content) and gene (i.e., gene arrays) assays suggest that functional adaptations may reflect changes in the biomechanical properties of the remaining tissue due to the cellular deposition of non-contractile tissue in the void left by the VML injury and/or differentiation of gene expression with early rehabilitation. CONCLUSIONS: Collectively this work provides evidence of genetic and functional plasticity in the remaining skeletal muscle with early rehabilitation approaches, which may facilitate future evidenced-based practice of early rehabilitation at the clinical level.

Increasing hip and knee flexion during a drop-jump task reduces tibiofemoral shear and compressive forces: implications for ACL injury prevention training.

Although most ACL injury prevention programmes encourage greater hip and knee flexion during landing, it remains unknown how this technique influences tibiofemoral joint forces. We examined whether a landing strategy utilising greater hip and knee flexion decreases tibiofemoral anterior shear and compression. Twelve healthy women (25.9 ± 3.5 years) performed a drop-jump task before and after a training session (10-15 min) that emphasised greater hip and knee flexion. Peak tibiofemoral anterior shear and compressive forces were calculated using an electromyography (EMG)-driven knee model that incorporated joint kinematics, EMG and participant-specific muscle volumes and patella tendon orientation measured using magnetic resonance imaging (MRI). Participants demonstrated a decrease in peak anterior tibial shear forces (11.1 ± 3.3 vs. 9.6 ± 2.7 N · kg-1; P = 0.008) and peak tibiofemoral compressive forces (68.4 ± 7.6 vs. 62.0 ± 5.5 N · kg-1; P = 0.015) post-training. The decreased peak anterior tibial shear was accompanied by a decrease in the quadriceps anterior shear force, while the decreased peak compressive force was accompanied by decreased ground reaction force and hamstring forces. Our data provide justification for injury prevention programmes that encourage greater hip and knee flexion during landing to reduce tibiofemoral joint loading.

Mitochondrial maintenance via autophagy contributes to functional skeletal muscle regeneration and remodeling.

The primary objective of this study was to determine whether alterations in mitochondria affect recovery of skeletal muscle strength and mitochondrial enzyme activity following myotoxic injury. 3-Methyladenine (3-MA) was administered daily (15 mg/kg) to blunt autophagy, and the creatine analog guanidionpropionic acid (ß-GPA) was administered daily (1% in chow) to enhance oxidative capacity. Male C57BL/6 mice were randomly assigned to nontreatment (Con, n = 6), 3-MA-treated (n = 6), and ß-GPA-treated (n = 8) groups for 10 wk. Mice were euthanized at 14 days after myotoxic injury for assessment of mitochondrial remodeling during regeneration and its association with the recovery of muscle strength. Expression of several autophagy-related proteins, e.g., phosphorylated Ulk1 (∼2- to 4-fold, P < 0.049) was greater in injured than uninjured muscles, indicating a relationship between muscle regeneration/remodeling and autophagy. By 14 days postinjury, recovery of muscle strength (18% less, P = 0.03) and mitochondrial enzyme (e.g., citrate synthase) activity (22% less, P = 0.049) were significantly lower in 3-MA-treated than Con mice, suggesting that the autophagy process plays an important role during muscle regeneration. In contrast, muscle regeneration was nearly complete in ß-GPA-treated mice, i.e., muscle strength recovered to 93% of baseline vs. 78% for Con mice. Remarkably, 14 days allowed sufficient time for a near-complete recovery of mitochondrial function in ß-GPA-treated mice (e.g., no difference in citrate synthase activity between injured and uninjured, P = 0.49), indicating a robust mitochondrial remodeling process during muscle regeneration. In conclusion, autophagy is likely activated following muscle injury and appears to play an important role in functional muscle regeneration.

Aging and the muscle-bone relationship.

Aging-induced declines in muscle size and quality are thought to contribute to catabolic alterations in bone, but changes in bone with age also profoundly alter its response to muscle-derived stimuli. This review provides an overview of some of the alterations that occur in muscle and bone with aging, and discusses the cellular and molecular mechanisms that may impact these age-associated changes.

Guidelines for Models of Skeletal Muscle Injury and Therapeutic Assessment.

Volumetric muscle loss (VML) injuries present a large clinical challenge with a significant need for new interventions. While there have been numerous reviews on muscle injury models, few have critically evaluated VML models. The objective of this review is to discuss current preclinical models of VML in terms of models, analytical outcomes, and therapeutic interventions, and to provide guidelines for the future use of preclinical VML models. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel.

Small Beneficial Effect of Caffeinated Energy Drink Ingestion on Strength.

Collier, NB, Hardy, MA, Millard-Stafford, ML, and Warren, GL. Small beneficial effect of caffeinated energy drink ingestion on strength. J Strength Cond Res 30(7): 1862-1870, 2016-Because caffeine ingestion has been found to increase muscle strength, our aim was to determine whether caffeine when combined with other potential ergogenic ingredients, such as those in commercial energy drinks, would have a similar effect. Fifteen young healthy subjects were used in a double-blind, repeated-measures experimental design. Each subject performed 3 trials, ingesting either a caffeinated energy drink, an uncaffeinated version of the drink, or a placebo drink. The interpolated twitch procedure was used to assess maximum voluntary isometric contraction (MVIC) strength, electrically evoked strength, and percent muscle activation during MVIC of the knee extensors both before and after drink ingestion, and after a fatiguing bout of contractions; electromyographic (EMG) amplitude of the knee extensors during MVIC was also assessed. The mean (±SE) change in MVIC strength from before to after drink ingestion was significantly greater for the caffeinated energy drink compared with placebo [+5.0 (±1.7) vs. -0.5 (±1.5)%] and the difference between the drinks remained after fatigue (p = 0.015); the strength changes for the uncaffeinated energy drink were not significantly different from those of the other 2 drinks at any time. There was no significant effect of drink type on the changes in electrically evoked strength, percent muscle activation, and EMG from before to after drink ingestion. This study indicates that a caffeinated energy drink can increase MVIC strength but the effect is modest and the strength increase cannot be attributed to increased muscle activation. Whether the efficacy of energy drinks can be attributed solely to caffeine remains unclear.

CCR2 elimination in mice results in larger and stronger tibial bones but bone loss is not attenuated following ovariectomy or muscle denervation.

Bone loss due to age and disuse contributes to osteoporosis and increases fracture risk. It has been hypothesized that such bone loss can be attenuated by modulation of the C-C chemokine receptor 2 (CCR2) and/or its ligands. The objectives of this study were to examine the effects of genetic elimination of CCR2 on cortical and trabecular bones in the mouse tibia and how bone loss was impacted following disuse and estrogen loss. Female CCR2 knockout (CCR2(-/-)) and wildtype mice underwent ovariectomy (OVX) or denervation of musculature adjacent to the tibia (DEN) to induce bone loss. Cortical and trabecular structural properties as well as mechanical properties (i.e., strength) of tibial bones were measured. Compared to wildtype mice, CCR2(-/-) mice had tibiae that were up to 9% larger and stronger; these differences could be explained mainly by the 17% greater body mass (P < 0.001) of CCR2(-/-) mice. The majority of the tibia's structural and functional responses to OVX and DEN were similar regardless of the lack or presence of CCR2, indicating that CCR2 is not protective against bone loss per se. These findings indicate that while CCR2(-/-) mice do have larger and stronger bones than do wildtype mice, there is minimal evidence that CCR2 elimination provides protection against bone loss during disuse and estrogen loss.

Effectiveness of constraint-induced movement therapy on upper-extremity function in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To systematically examine the research literature on the effectiveness of constraint-induced movement therapy on improving arm function in children with cerebral palsy, and to assess the association between the study effect size and the characteristics of the patients and intervention protocol. DATA SOURCES: A systematic literature search was conducted in PubMed, PsycINFO, Cochrane, CINAHL, Web of Science, and TRIP Database up to May 2014. REVIEW METHODS: Studies employing randomized controlled trial design, children with cerebral palsy, comparing constraint-induced movement therapy with another intervention with a focus on arm function, and upper-extremity measures were included in this review. Methodological quality was evaluated using the Physiotherapy Evidence-based Database (PEDro) scale. RESULTS: The literature search resulted in 27 randomized controlled trial studies with good methodological quality that compared constraint-induced movement therapy with other intervention therapy. Overall, constraint-induced movement therapy provided a medium beneficial effect (d = 0.546; p < 0.001) when compared with conventional therapy. For the subgroup analyses, presence of a dose-equivalent comparison group, intervention location, and time of follow-up were significant factors. Studies examining constraint-induced movement therapy effect without a dose-equivalent comparison group showed a large effect in children with cerebral palsy, but studies with a dose-equivalent group only showed a small effect. Children who received home-based constraint-induced movement therapy had a better improvement in arm function than those who received constraint-induced movement therapy elsewhere. CONCLUSION: The research literature supports constraint-induced movement therapy as an effective intervention to improve arm function in children with cerebral palsy.

Persistent altered knee loading in patients with meniscectomy: A systematic review and meta-analysis.

OBJECTIVES: To determine the changes in knee flexion moment (KFM) and knee adduction moment (KAM) during weight-bearing activities following meniscectomy. DESIGN: Meta-Analysis. SETTING: Laboratory. PARTICIPANTS: 332 meniscectomy patients and 137 healthy controls (from 13 qualified studies) MAIN OUTCOME MEASURES: Cohen's d effect sizes (ESs) were calculated to compare KAM and KFM values of the surgical legs to the non-surgical and to healthy control legs. RESULTS: When compared to healthy controls, meniscectomy patients' surgical legs demonstrated a significantly greater KAM (ES = 0.310; P = 0.002) but no significant difference in KFM (ES = -0.182; P = 0.051). When compared to the patients' non-surgical legs, however, the surgical legs showed no difference in KAM (ES = -0.024; P = 0.716) but a significantly lower KFM (ES = -0.422; P < 0.001). High heterogeneity among study ESs was observed in patients' between-limb comparison for KAM (Q-value = 20.08, P = 0.005; I2 = 65.1%) and KFM (Q-value = 43.96, P < 0.001; I2 = 79.5%). However, no significant differences in study ESs (all P > 0.102) of KFM and KAM were identified when comparing studies with various times post-surgery, weight-bearing tasks, walking speeds, or patient demographics. CONCLUSION: Elevated KAM and reduced/asymmetrical KFM observed in meniscectomy patients may contribute to the increased risk of knee OA. Rehabilitation should focus on movement education to restore between-limb KFM symmetry and reduce KAM bilaterally post-meniscectomy.

Tibial bone strength is negatively affected by volumetric muscle loss injury to the adjacent muscle in male mice.

This study's objective was to investigate how contractile strength loss associated with a volumetric muscle loss (VML) injury affects the adjacent tibial bone structural and functional properties in male C57BL/6J mice. Mice were randomized into one of two experimental groups: VML-injured mice that were injured at age 12 weeks and aged to 20 weeks (8 weeks postinjury, VML) and 20-week-old age-matched uninjured mice (Uninjured-20). Tibial bone strength, mid-diaphysis cortical geometry, intrinsic material properties, and metaphyseal trabecular bone structure were assessed by three-point bending and microcomputed tomography (µCT). The plantar flexor muscle group (gastrocnemius, soleus, plantaris) was analyzed for its functional capacities, that is, peak-isometric torque and peak-isokinetic power. VML-injured limbs had 25% less peak-isometric torque and 31% less peak-isokinetic power compared to those of Uninjured-20 mice (p < 0.001). Ultimate load, but not stiffness, was significantly less (10%) in tibias of VML-injured limbs compared to those from Uninjured-20 (p = 0.014). µCT analyses showed cortical bone thickness was 6% less in tibias of VML-injured limbs compared to Uninjured-20 (p = 0.001). Importantly, tibial bone cross-section moment of inertia, the primary determinant of bone ultimate load, was 16% smaller in bones of VML-injured limbs compared to bones from Uninjured-20 (p = 0.046). Metaphyseal trabecular bone structure was also altered up to 23% in tibias of VML-injured limbs (p < 0.010). These changes in tibial bone structure and function after a VML injury occur during a natural maturation phase between the age of 12 and 20 weeks, as evidenced by Uninjured-20 mice having greater tibial bone size and strength compared to uninjured-aged 12-week mice.

The Influence of COVID-19 on Patient Mobilization and Injury Attributes in the ICU: A Retrospective Analysis of a Level II Trauma Center.

The objectives of this study were to determine the effect of COVID-19 on physical therapy (PT) mobilization of trauma patients and to determine if mobilization affected patient course in the ICU. This retrospective study included patients who were admitted to the ICU of a level II trauma center. The patients were divided into two groups, i.e., those admitted before (n = 378) and after (n = 499) 1 April 2020 when Georgia's COVID-19 shelter-in-place order was mandated. The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. A secondary analysis focused specifically on the after-COVID patients examined the extent to which mobilization (n = 328) or lack of mobilization (n = 171) influenced ICU outcomes (e.g., mortality, readmission). The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. The after-COVID patients had higher injury severity as a greater proportion was classified as severely injured (i.e., >15 on Injury Severity Score) compared to the before-COVID patients. After-COVID patients also had a greater cumulative number of comorbidities and experienced greater complications in the ICU. Despite this, there was no difference between patients in receiving a PT consultation or days to mobilization. Within the after-COVID cohort, those who were mobilized were older, had greater Glasgow Coma Scale scores, had longer total hospital days, and had a lesser mortality rate, and a higher proportion were female. Despite shifting patient injury attributes post-COVID-19, a communicable disease, mobilization care remained consistent and effective.

Acute failure of action potential conduction in mdx muscle reveals new mechanism of contraction-induced force loss.

A primary feature of skeletal muscle lacking the protein dystrophin, as occurring in Duchenne muscular dystrophy, is a hypersensitivity to contraction-induced strength loss. We tested the hypothesis that the extensive strength loss results from an impairment in the electrophysiological function of the plasmalemma specifically impaired action potential development. Anterior crural muscles from mdx and wildtype mice performed a single bout of 100 electrically stimulated eccentric contractions in vivo. Electromyography, specifically the M-wave, was analysed during muscle contraction to assess the ability of the tibialis anterior muscle plasmalemma to generate and conduct action potentials. During eccentric contractions, wildtype mice exhibited a 36% loss in torque about the ankle but mdx mice exhibited a greater torque loss of 73% (P < 0.001). Despite the loss of torque, there was no reduction in M-wave root mean square (RMS) for wildtype mice, which was in stark contrast to mdx mice that had a 55% reduction in M-wave RMS (P < 0.001). This impairment resolved within 24 h and coincided with a significant improvement in strength and membrane integrity. Intracellular measurements of resting membrane potential (RMP) in uninjured and injured extensor digitorum longus muscles were made to determine if a chronic depolarization had occurred, which could lead to impaired fibre excitability and/or altered action potential conduction properties. The distributions of RMP were not different between wildtype uninjured and injured muscle cells (median: -73.2 mV vs. -72.7 mV, P = 0.46) whereas there was a significant difference between mdx uninjured and injured cells (median: -71.5 mV vs. -56.6 mV, P < 0.001). These data show that mdx muscle fibres are depolarized after an injurious bout of eccentric contractions. These findings (i) suggest a major plasmalemma-based mechanism of strength loss underlying contraction-induced injury in Duchenne muscular dystrophy distinctly different from that for healthy muscle, and (ii) demonstrate dystrophin is critical for maintaining action potential generation and conduction after eccentric contractions.

In vivo potentiation of muscle torque is enhanced in female mice through estradiol-estrogen receptor signaling.

Estradiol affects several properties of skeletal muscle in females including strength. Here, we developed an approach to measure in vivo posttetanic twitch potentiation (PTP) of the anterior crural muscles of anesthetized mice and tested the hypothesis that 17ß-estradiol (E2) enhances PTP through estrogen receptor (ER) signaling. Peak torques of potentiated twitches were ∼40%-60% greater than those of unpotentiated twitches and such PTP was greater in ovary-intact mice, or ovariectomized (Ovx) mice treated with E2, compared with Ovx mice (P ≤ 0.047). PTP did not differ between mice with and without ERα ablated in skeletal muscle fibers (P = 0.347). Treatment of ovary-intact and Ovx mice with ERß antagonist and agonist (PHTPP and DPN, respectively) did not affect PTP (P ≥ 0.258). Treatment with G1, an agonist of the G protein-coupled estrogen receptor (GPER), significantly increased PTP in Ovx mice from 41 ± 10% to 66 ± 21% (means ± SD; P = 0.034). Collectively, these data indicate that E2 signals through GPER, and not ERα or ERß, in skeletal muscles of female mice to augment an in vivo parameter of strength, namely, PTP.NEW & NOTEWORTHY A novel in vivo approach was developed to measure potentiation of skeletal muscle torque in female mice and highlight another parameter of strength that is impacted by estradiol. The enhancement of PTP by estradiol is mediated distinctively through the G-protein estrogen receptor, GPER.

Can exercise interventions reduce external knee adduction moment during gait? A systematic review and meta-analysis.

BACKGROUND: An increased external knee adduction moment has been identified as a factor contributing to the progression of medial knee osteoarthritis. Interventions that reduce knee adduction moment may help prevent knee osteoarthritis onset and progression. While exercise interventions have been commonly used to treat knee osteoarthritis, whether exercises can modulate knee adduction moment in knee osteoarthritis patients remains unknown. This systematic review and meta-analysis aimed to determine if exercise interventions are effective in reducing knee adduction moment during gait. METHODS: Study reports published through May 2023 were screened for pre-specified inclusion/exclusion criteria. Nine studies met the eligibility criteria and yielded 24 effect sizes comparing the reduction in knee adduction moment of the exercise intervention groups to the control groups. Moderator/experimental variables concerning characteristics of the exercise interventions and included subjects (e.g., sex, BMI, type of exercise, muscle group targeted, training volume, physical therapist supervision) that may contribute to variation among studies were explored through subgroup analysis and meta-regression. FINDINGS: The effect of exercise intervention on modulating knee adduction moment during gait was no better than control (ES = -0.004, P = 0.946). Sub-group analysis revealed that the effect sizes of studies containing only females (positive exercise effect) were significantly greater than studies containing both males and females. INTERPRETATION: Exercise may not be effective in reducing knee adduction moment during gait. Clinicians aiming to decrease knee adduction moment in patients with medial knee osteoarthritis should consider alternative treatment options. Exploring the underlying mechanism(s) regarding a more positive response to exercises in females may help design more effective exercise interventions.

Toll-like and adenosine receptor expression in injured skeletal muscle.

INTRODUCTION: Many aspects of skeletal muscle regeneration are now considered to be controlled by the innate immune system, specifically macrophages, but the mechanisms for activation and modulation of the innate immune system during injury are not well understood. METHODS: We analyzed the expression of toll-like receptors (TLRs) and adenosine receptors during traumatic skeletal muscle injury. mRNA expression and immunostaining of these receptors were evaluated in mouse skeletal muscle injured by freezing. RESULTS: Expression of nearly all mammalian TLRs was induced at 1 and/or 3 days postinjury with a common trend for higher expression at day 3. Injury also elicited a dramatic increase in the expression of adenosine receptors A(2B) and A(3) but not A(1) and A(2A) . CONCLUSIONS: Both receptor types may be potential targets for stimulation of skeletal muscle tissue regeneration and functional restoration after injury.