Improve Muscle Function Research Articles

Muscular Adaptations to Concurrent Resistance Training and High-Intensity Interval Training in Adults with Type 2 Diabetes: A Pilot Study.

This pilot study aimed to compare the effects of eight weeks of concurrent resistance training (RT) and high-intensity interval training (HIIT) vs. RT alone on muscle performance, mass and quality in adults with type 2 diabetes (T2DM). Twelve T2DM adults were randomly allocated to the RT + HIIT (n = 5) or RT (n = 7) group. Before and after training, maximal oxygen uptake (VO2max), muscle strength and power were evaluated by calorimetry, dynamometry and one-repetition maximum (1RM) test. Quadriceps muscle volume was determined by MRI, and muscle quality was estimated. After RT, VO2max (+12%), knee muscle power (+20%), quadriceps muscle volume (+5.9%) and quality (leg extension, +65.4%; leg step-up, +223%) and 1RM at leg extension (+66.4%), leg step-up (+267%), lat pulldown (+60.9%) and chest press (+61.2%) significantly increased. The RT + HIIT group improved on VO2max (+27%), muscle volume (+6%), muscle power (+9%) and 1RM at lat pulldown (+47%). No other differences were detected. Among groups, changes in muscle quality at leg step-up and leg extension and VO2max were significantly different. The combination of RT and HIIT effectively improves muscle function and size and increases cardiorespiratory fitness in adults with T2DM. However, HIIT combined with RT may interfere with the development of muscle quality.

Supervised Home-Based Exercise Prehabilitation in Unfit Patients Scheduled for Pancreatic Surgery: Protocol for a Multicenter Feasibility Study.

Morbidity rates in pancreatic surgery are high, and frail patients with low aerobic capacity are especially at risk of complications and require prophylactic interventions. Previous studies of small patient cohorts receiving intra-abdominal surgery have shown that an exercise prehabilitation program increases aerobic capacity, leading to better treatment outcomes. In this study, we aim to assess the feasibility of a home-based exercise prehabilitation program in unfit patients scheduled for pancreatic surgery on a larger scale. In this multicenter study, adult patients scheduled for elective pancreatic surgery with a preoperative oxygen uptake (VO2) at the ventilatory anaerobic threshold ≤13 mL/kg/min or a VO2 at peak exercise ≤18 mL/kg/min will be recruited. A total of 30 patients will be included in the 4-week, home-based, partly supervised exercise prehabilitation program. The program comprises 25-minute high-intensity interval training on an advanced cycle ergometer 3 times a week. Training intensity will be based on steep ramp test performance (ie, a short-term maximal exercise test on a cycle ergometer), aiming to improve aerobic capacity. Twice a week, patients will perform functional task exercises to improve muscle function and functional mobility. A steep ramp test will be repeated weekly, and training intensity will be adjusted accordingly. Next to assessing the feasibility (participation rate, reasons for nonparticipation, adherence, dropout rate, reasons for dropout, adverse events, and patient and therapist appreciation) of this program, individual patients' responses to prehabilitation on aerobic capacity, functional mobility, body composition, quality of life, and immune system factors will be evaluated. Recruitment for this study began in January 2022 and is expected to be completed in the summer of 2023. Results of this study will provide important clinical and scientific knowledge on the feasibility of a partly supervised home-based exercise prehabilitation program in a vulnerable patient population. This might ease the path to implementing prehabilitation programs in unfit patients undergoing complex abdominal surgery, such as pancreatic surgery. ClinicalTrials.gov NCT05496777; https://classic.clinicaltrials.gov/ct2/show/NCT05496777. DERR1-10.2196/46526.

Gpr18 agonist dampens inflammation, enhances myogenesis, and restores muscle function in models of Duchenne muscular dystrophy.

Introduction: Muscle wasting in Duchenne Muscular Dystrophy is caused by myofiber fragility and poor regeneration that lead to chronic inflammation and muscle replacement by fibrofatty tissue. Our recent findings demonstrated that Resolvin-D2, a bioactive lipid derived from omega-3 fatty acids, has the capacity to dampen inflammation and stimulate muscle regeneration to alleviate disease progression. This therapeutic avenue has many advantages compared to glucocorticoids, the current gold-standard treatment for Duchenne Muscular Dystrophy. However, the use of bioactive lipids as therapeutic drugs also faces many technical challenges such as their instability and poor oral bioavailability. Methods: Here, we explored the potential of PSB-KD107, a synthetic agonist of the resolvin-D2 receptor Gpr18, as a therapeutic alternative for Duchenne Muscular Dystrophy. Results and discussion: We showed that PSB-KD107 can stimulate the myogenic capacity of patient iPSC-derived myoblasts in vitro. RNAseq analysis revealed an enrichment in biological processes related to fatty acid metabolism, lipid biosynthesis, small molecule biosynthesis, and steroid-related processes in PSB-KD107-treated mdx myoblasts, as well as signaling pathways such as Peroxisome proliferator-activated receptors, AMP-activated protein kinase, mammalian target of rapamycin, and sphingolipid signaling pathways. In vivo, the treatment of dystrophic mdx mice with PSB-KD107 resulted in reduced inflammation, enhanced myogenesis, and improved muscle function. The positive impact of PSB-KD107 on muscle function is similar to the one of Resolvin-D2. Overall, our findings provide a proof-of concept that synthetic analogs of bioactive lipid receptors hold therapeutic potential for the treatment of Duchenne Muscular Dystrophy.

Abstract P1153: ANT-Dependent MPTP Contributes To Necrotic Myofiber Death In Muscular Dystrophy

The Mitochondrial Permeability Transition Pore (MPTP) is a critical cell death mechanism that contributes to ischemia reperfusion injury in the heart and several degenerative diseases, including Muscular Dystrophy (MD). MD is a family of genetic disorders characterized by progressive muscle wasting, loss of muscle function, and premature death. We have recently demonstrated that the MPTP has two defined genetic components: one consisting of adenosine nucleotide translocase (ANT) family of proteins and a second, unidentified pore that requires the protein cyclophilin D (CypD) to activate. In this study we used MD as a model to test whether this new MPTP model could be applied to a physiological context of necrotic cell death in vivo . We observed that genetic deletion of ANT1 or CypD substantially reduced MD pathology in skeletal muscle, with reduced measures of muscle necrotic cell death, and improved muscle function compared to MD control animals. However, both ANT1KO and CypDKO MD mice still displayed elevated rates of cell death and MD pathology compared to healthy wildtype animals. MD mice lacking both ANT1 and CypD (ANT1KO-CypDKO) virtually eliminated features of skeletal muscle pathology in MD. We observed a near complete loss of MD histopathology, undetectable levels of tissue necrosis, and muscle function that was improved to non-MD levels in ANT1KO-CypDKO MD mice. This study demonstrates that inhibiting both the ANT-dependent and CypD-dependent components of MPTP together can prevent necrotic cell death in an in vivo model. This study also suggests that a therapy that inhibits both MPTP-components can effectively treat MD and may potentially reduce cardiac ischemia reperfusion injury.

Sensorimotor or Balance Training to Increase Knee-Extensor and Knee-Flexor Maximal Strength in Patients With Knee Osteoarthritis: A Critically Appraised Topic.

Knee osteoarthritis (KOA) is a complex progressive synovial joint disease that results in impaired muscle function, including a considerable loss of maximal strength and power. Exercise therapies, such as sensorimotor or balance training and resistance training, are frequently used to improve muscle function, mobility, and quality of life, but their impact on maximal muscle strength in patients with KOA is not well understood. Does sensorimotor or balance training improve knee-extensor and knee-flexor maximal muscle strength compared with strength training or no intervention in patients with KOA? Results from 4 fair- to good-quality randomized controlled/clinical trials (level 1b) revealed inconsistent grade B evidence regarding the effect of sensorimotor or balance training to improve knee-extensor and knee-flexor maximal muscle strength in patients with KOA. Two studies, one good-quality study and one fair-quality study, showed significant strength improvements, and 2 good-quality studies demonstrated no significant strength enhancements. Sensorimotor or balance training may be useful to improve maximal strength of quadriceps and hamstring muscle groups in patients with KOA; however, it seems that this depends on a training duration of at least 8weeks and the use of unstable devices to induce destabilization of patients' balance, initiating neuromuscular adaptations. Due to inconsistent evidence (grade B), the true effect of sensorimotor or balance training to improve knee-extensor and knee-flexor maximal muscle strength in patients with KOA remains unclear and needs to be further investigated.

Tetrahedral Framework Nucleic Acids Inhibit Muscular Mitochondria-Mediated Apoptosis and Ameliorate Muscle Atrophy in Sarcopenia.

Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance. To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems. In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro. Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis. Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.

Effects of 12 Weeks of Resistance Training on Body Composition, Muscle Hypertrophy and Function, Blood Lipid Level, and Hemorheological Properties in Middle-Aged Obese Women.

This study investigated the effects of 12-week resistance training on body composition, blood pressure, blood lipid levels, muscle cross-sectional area (CSA), isokinetic muscle function, and hemorheological properties in middle-aged obese women. Twenty-eight obese women with a mean age of 50.79 5.80 years were randomly assigned to the control (CON, n = 13) or experimental (EXP, n = 15) group. The EXP group underwent a resistance training program composed of warm-up, main resistance exercise (deadlift, barbell squat, seated leg extension, and lying leg curl, bench press, preacher bench biceps curl, barbell rowing, and dumbbell shoulder press), and cool-down. The resistance exercise consisted of three sets of 8-10 repetitions (reps) performed with 70-80% of 1-rep maximum, and reps and sets were increased every 3 weeks. The training frequency was 80 min, 3 days per week for 12 weeks. The CON group maintained their daily lifestyle without training. All participants underwent measurements of body composition (weight, body mass index, lean body mass, fat mass, and % body fat), blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure), blood lipid levels (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), CSA of the muscles (quadriceps, hamstring, and total thigh muscle), isokinetic muscle function (peak torque [PT], relative PT, mean power, and total work [TW]), and hemorheological properties (erythrocyte deformability and aggregation) before and after 12 weeks of training. The EXP group showed a significant improved muscle function, including PT (p 0.001), relative PT (p 0.001) in extension 60°/s, TW (p 0.001) in extension 180°/s, and TW (p = 0.018) in flexion 180°/s. Regarding hemorheological properties, the EXP group showed significant improvement in erythrocyte aggregation (p 0.001) and deformability (p 0.001). The present study verified that our resistance training program resulted in greater muscle function, decreased fat mass, and improved hemorheological properties. This study was registered with cris.nih.go.kr (No. KCT0007412).

Establishment of regression-based normative isometric strength values for major lower limb muscle groups in persons with multiple sclerosis

Limb weakness is a major impairment that affects mobility in persons with multiple sclerosis (PwMS). Specifically, lower limb (LL) weakness can greatly affect gait and balance, while increasing fall risk and decreasing quality of life. Numerous studies have compared LL strength of PwMS to healthy controls, however none have objectively measured strength in all major LL joints (hip, knee, and ankle) in a large number of PwMS. Additionally, while discrete normative values exist for knee extensors in PwMS, there has yet to be regression-based normative isometric strength values for all major LL muscle groups. Therefore, this study aimed to develop gender-specific regression-based normative prediction equations, with 95% confidence intervals, for maximal isometric peak torque of major LL muscles in PwMS. A secondary aim was to characterize the prevalence of LL weakness in PwMS, defined as ≥ 2 SD below values reported for healthy individuals. A convenience sample of 175 (women: n=135) PwMS participated in a prospective, cross-sectional study where isometric peak torque of hip flexors, extensors, and abductors, knee flexors and extensors, and ankle plantarflexors and dorsiflexors were measured using the Biodex System 4 Pro-Dynamometer®. Demographics (age, height, and weight) and disease characteristics (disease duration and disability) were collected. Performances were separated for each muscle group into strongest limb and weakest limb. For each gender, regression-based equations were generated for the LL muscle groups by limb with age, height, weight, disability, and disease duration as the covariates. Descriptive statistics were used to examine the frequency of LL weakness by gender and disability level. For comparison purposes, age-stratified (<30, 30-39, 40-49, 50-59, 60-69, >70 years) and disability-stratified (mild, moderate, and severe ambulant) discrete peak torque values were also generated for each gender. Regression-based normative data are presented for men and women, accounting for age, height, weight, disability, and disease duration. Men were significantly stronger (P < 0.001) than women for all LL, with the men's models accounting for a greater percent of muscle strength variation than women's models for all muscle groups, except for hip extension. Disability was inversely related to strength in all of the models. LL weakness was prevalent in hip flexion (m: 47.5%; w: 63.0%) and extension (m: 92.5%; w: 88.1%), knee extension (m: 30.0%; w: 33.3%) and flexion (m: 25.0%; w: 34.8%), and ankle plantarflexion (m: 15.0%; w: 10.4%) and dorsiflexion (m: 100.0%; w: 96.3%). PwMS with mild disability had a high prevalence of ankle dorsiflexion (94.9-100.0%) and hip extension (81.4-90.0%) weakness. This study is the first to provide regression-based normative data of bilateral strength in all major LL muscle groups and clinically useful prevalence data on the occurrence of weakness in these muscles. Of note, PwMS had a high prevalence of ankle dorsiflexion and hip extension weakness even when they were only mildly disabled. These findings can help guide the direction of future interventions and treatments to improve muscle function in PwMS.

A randomized controlled pilot trial to assess the effectiveness of a specially formulated food supplement and pelvic floor muscle training in women with stress-predominant urinary incontinence

BackgroundPelvic floor muscle training (PFMT) is the first-line treatment approach for stress urinary incontinence. Creatine and leucine have been shown to improve muscle function. Our aim was to assess the effectiveness of a food supplement and PFMT in women with stress-predominant urinary incontinence.MethodsWomen with stress-predominant urinary incontinence were randomized in 1:1 ratio to receive daily oral supplementation for six weeks with either a food supplement (treatment group) or placebo (control group). Both groups were instructed to perform standardized daily PFMT. The primary outcome was the Urogenital Distress Inventory Short Form (UDI-6) score. Secondary outcomes were the Incontinence Impact Questionnaire (IIQ-7) score, Patient’s Global Impression of Severity (PGI‐S), and Biomechanical Integrity score (BI-score) measured by Vaginal Tactile Imager. To have a power of 80% and a significance level of 5% to detect a decrease of 16 points in the UDI-6 score, a sample size of 32 was needed, with 16 patients in each arm of our trial.ResultsSixteen women in the control group and sixteen in the treatment group completed the trial. Between-group analysis revealed no significant differences between the control and treatment group except for mean change (delta) in vaginal squeeze pressure [(cmH2O, mean ± SD), 5 ± 12 vs. 15 ± 15, P = 0.04] and mean change (delta) in PGI-S score [(mean ± SD), -0.2 ± 0.9 vs. -0.8 ± 0.8, P = 0.04]. Within-group analysis showed that UDI-6 and IIQ-7 scores improved significantly from baseline to six weeks in the treatment group but not in the control group [UDI-6 score (mean ± SD) 45 ± 21 vs. 29 ± 21, P = 0.02; 43 ± 18 vs. 33 ± 26, P = 0.22] [IIQ-7 score (mean ± SD) 50 ± 30 vs. 30 ± 21, P = 0.01; 48 ± 23 vs.40 ± 28, P = 0.36]. PGI-S scores only improved in the treatment group from baseline to six weeks after treatment [PGI-S score (mean ± SD) 3.1 ± 0.8 vs. 2.3 ± 0.8, P = 0.0001]. BI-score, on average, improved significantly in the treatment and control group as well [SD unit, mean, from − 1.06 to -0.58, P = 0.001; from − 0.66 to -0.42, P = 0.04].ConclusionsWomen with stress-predominant urinary incontinence receiving a specially formulated supplement in addition to daily PFMT for six weeks had significantly improved urinary symptoms (decrease in UDI-6 score and IIQ-7) and BI-score compared to their baseline.Trial registrationClinicalTrials.gov Identifier: NCT05358769. 27/04/2022.

Transjugular intrahepatic portosystemic shunt insertion improves muscle mass but not muscle function or frailty measures.

Sarcopenia in cirrhosis is associated with poor outcomes. While transjugular intrahepatic portosystemic shunt (TIPS) insertion improves radiological measures of muscle mass, its impact on muscle function, performance and frailty has not been evaluated. Patients with cirrhosis referred for TIPS were prospectively recruited and followed for 6 months. L3 CT scans were used to calculate skeletal muscle and adipose tissue parameters. Handgrip strength, Liver Frailty Index and short physical performance battery were serially monitored. Dietary intake, insulin resistance, insulin-like growth factor (IGF)-1, and immune function using QuantiFERON Monitor (QFM) were measured. Twelve patients completed the study with a mean age of 58 ± 9 years and model for end-stage liver disease score of 16 ± 5. At 6 months post-TIPS, skeletal muscle area increased from 139.33 cm 2 ± 22.72 to 154.64 ± 27.42 ( P = 0.012). Significant increases were observed in the subcutaneous fat area ( P = 0.0076) and intermuscular adipose tissue ( P = 0.041), but not muscle attenuation or visceral fat. Despite marked changes in muscle mass, no improvements were observed in handgrip strength, frailty, or physical performance. At 6 months post-TIPS, IGF-1 ( P = 0.0076) and QFM ( P = 0.006) increased compared to baseline. Nutritional intake, hepatic encephalopathy measures, insulin resistance and liver biochemistry were not significantly impacted. Muscle mass increased following TIPS insertion as did IGF-1, a known driver of muscle anabolism. The lack of improvement in muscle function was unexpected and may relate to impairment in muscle quality and the effects of hyperammonaemia on muscle contractile function. Improvements in QFM, a marker of immune function, may suggest a reduction in infection susceptibility in this at-risk population and requires further evaluation.

The problem of vitamin D deficiency among the population and the efficacy of drugs in increasing its level

A review of the literature shows that cholecalciferol, ergocalciferol and calcifediol are currently used in foreign and domestic practice to increase vitamin D levels, while there is no consensus on the effectiveness, necessity and possibility of using one or another type of vitamin D supplements. In this regard, we conducted statistical studies of the effectiveness of increasing the level of vitamin D in the patient's blood serum, and also made an analysis of literary sources on the biological activity and safety of the use of cholecalciferol, ergocalciferol and calcifediol. Research has shown that cholecalciferol is currently the most commonly used vitamin D supplement, with calcifediol gaining popularity, which is an order of magnitude superior to cholecalciferol in terms of dose-time-effectiveness. Clinical studies by foreign authors have shown that the use of calcifediol in some cases is accompanied by an improvement in muscle function, a decrease in systolic blood pressure, restoration of acceptable levels of parathyroid hormone and other positive biological effects. Also, there is no doubt about the safety and absence of toxic effects of calcifediol as a therapeutic agent. Most foreign experts studying the applicability of calcifediol for the treatment of patients indicate its increased hydrophilicity, which provides it with the greatest advantages in the treatment of diseases associated with a decrease in absorption in the intestine. It is clear that large-scale laboratory and clinical studies are needed to obtain final conclusions about the therapeutic usefulness, scope, dosage and duration of use of calcifediol, however, the prospect of widespread use of this drug as a therapeutic agent is also beyond doubt.

IPSCs ameliorate hypoxia-induced autophagy and atrophy in C2C12 myotubes via the AMPK/ULK1 pathway

BackgroundDuchenne muscular dystrophy (DMD) is an X-linked lethal genetic disorder for which there is no effective treatment. Previous studies have shown that stem cell transplantation into mdx mice can promote muscle regeneration and improve muscle function, however, the specific molecular mechanisms remain unclear. DMD suffers varying degrees of hypoxic damage during disease progression. This study aimed to investigate whether induced pluripotent stem cells (iPSCs) have protective effects against hypoxia-induced skeletal muscle injury.ResultsIn this study, we co-cultured iPSCs with C2C12 myoblasts using a Transwell nested system and placed them in a DG250 anaerobic workstation for oxygen deprivation for 24 h. We found that iPSCs reduced the levels of lactate dehydrogenase and reactive oxygen species and downregulated the mRNA and protein levels of BAX/BCL2 and LC3II/LC3I in hypoxia-induced C2C12 myoblasts. Meanwhile, iPSCs decreased the mRNA and protein levels of atrogin-1 and MuRF-1 and increased myotube width. Furthermore, iPSCs downregulated the phosphorylation of AMPKα and ULK1 in C2C12 myotubes exposed to hypoxic damage.ConclusionsOur study showed that iPSCs enhanced the resistance of C2C12 myoblasts to hypoxia and inhibited apoptosis and autophagy in the presence of oxidative stress. Further, iPSCs improved hypoxia-induced autophagy and atrophy of C2C12 myotubes through the AMPK/ULK1 pathway. This study may provide a new theoretical basis for the treatment of muscular dystrophy in stem cells.

SAT-543 - Continuous terlipressin infusion improves muscle function but not muscle mass in patients with cirrhosis and portal hypertension

SAT-543 - Continuous terlipressin infusion improves muscle function but not muscle mass in patients with cirrhosis and portal hypertension

Localization of the gracilis muscle motor points - key considerations for botulinum neurotoxin injection and electrical stimulation.

Muscle motor points are considered the best sites for electrode positioning in electrical stimulation and, by some researchers, for botulinum neurotoxin injections. The aim of this study is to locate the motor points in the gracilis muscle to improve muscle function maintenance and treatment of spasticity. Ninety-three gracilis muscles (49 right, 44 left), fixed in 10% formalin solution, were subjected to the research. All nerve branches running towards the muscle were precisely traced to each motor point. Specific measurements were collected. The gracilis muscle presents multiple motor points (median of 12), all of which were localized on the deep (lateral) side of the muscle belly. Generally, motor points of this muscle were spread between 15% - 40% of the reference line length. Our findings may help clinicians identify appropriate locations for electrode placement during electrical stimulation of the gracilis muscle; they also deepen our understanding of the correlation between motor points and motor end plates and improve the application of botulinum neurotoxin injections.

Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65–79 y old men and women

We have previously demonstrated that acute ingestion of inorganic nitrate (NO3−)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO3− → nitrite (NO2−) → NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g., nitroglycerin. Using a double-blind, placebo-controlled, crossover design, we therefore studied 16 community-dwelling older (age 71 ± 5 y) individuals after both acute and short-term (i.e., daily for 2 wk) BRJ supplementation. Blood samples were drawn and blood pressure was measured periodically during each ∼3 h experiment, with muscle function determined using isokinetic dynamometry. Acute ingestion of BRJ containing 18.2 ± 6.2 mmol of NO3− increased plasma NO3− and NO2− concentrations 23 ± 11 and 2.7 ± 2.1-fold over placebo, respectively. This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively. After daily supplementation for 2 wk, BRJ ingestion elevated NO3− and NO2− levels 24 ± 12 and 3.3 ± 4.0-fold, respectively, whereas Vmax and Pmax were 7 ± 9% and 9 ± 11% higher than baseline. No changes were observed in blood pressure or in plasma markers of oxidative stress with either acute or short-term NO3− supplementation. We conclude that both acute and short-term dietary NO3− supplementation result in similar improvements in muscle function in older individuals. The magnitudes of these improvements are sufficient to offset the decline resulting from a decade or more of aging and are therefore likely to be clinically significant.

Sleep duration affects the sequential change of body mass index and muscle strength: a contribution to dynapenic obesity

BackgroundWith aging, body mass index (BMI) increases and muscle strength declines, resulting in dynapenic obesity. It remains unknown whether and how sleep duration contributes to the sequence of BMI and muscle strength change in the progression of dynapenic obesity.MethodsData were derived from the first two waves of China Health and Retirement Longitudinal Study. Sleep duration was self-reported. BMI was calculated and grip strength (GS) was measured to reflect muscle strength. The effect of baseline sleep duration on the sequential change of BMI and GS was assessed using two mediation models considering the nonlinear associations between them. The moderating effect of metabolic disorder was also tested.ResultsTotally 4986 participants aged ≥ 50 years (50.8% females) with complete information on variables were included. Baseline BMI fully mediated the nonlinear association between sleep duration and follow-up GS change, but baseline GS did not mediate between sleep duration and follow-up BMI change for older men and women. Short sleep duration positively affected BMI-induced GS change (β = 0.038; 95%CI, 0.015–0.074), while this favorable effect became nonsignificant for moderate sleep duration (β = 0.008; 95% CI, -0.003–0.024) and turned negative with prolonged sleep duration (β = − 0.022; 95%CI, − 0.051 to − 0.003). This nonlinear mediation effect was more pronounced in older women who are relatively metabolically healthy at baseline.ConclusionFor older adults in China, the influence of sleep duration on BMI-induced GS change but not the GS-induced BMI change suggested the contribution of sleep duration to the sequential course in the progression of dynapenic obesity. Sleep duration deviated either above or below normal range may confer adverse impact on GS through BMI. Strategies addressing sleep and obesity jointly to improve muscle function and delay the progression of dynapenic obesity are required.

Electrically stimulated eccentric contraction training enhances muscle mass, function, and size following volumetric muscle loss.

Volumetric muscle loss (VML) overwhelms muscle's innate capacity for repair and can lead to permanent disability. The standard of care for VML injuries includes physical therapy, which can improve muscle function. The objective of this study was to develop and evaluate a rehabilitative therapy using electrically stimulated eccentric contraction training (EST) and determine the structural, biomolecular, and functional response of the VML-injured muscle. This study implemented EST using three different frequencies (50, 100, and 150 Hz) in VML-injured rats starting at 2 weeks postinjury. Four weeks of EST at 150 Hz showed a progressive increase in eccentric torque with an improvement in muscle mass (~39%), myofiber cross-sectional area, and peak isometric torque (~37.5%) relative to the untrained VML-injured sham group. EST at 150 Hz group also increased the number of large type 2B fibers (>5000 µm2 ). Elevated gene expression of markers associated with angiogenesis, myogenesis, neurogenesis, and an anti-inflammatory response was also observed. These results suggest that VML-injured muscles can respond and adapt to eccentric loading. The results of this study may aid in developing physical therapy regimens for traumatized muscles.

Vemurafenib improves muscle histopathology in a mouse model of LAMA2-related congenital muscular dystrophy.

Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a neuromuscular disease affecting around 1-9 in 1,000,000 children. LAMA2-CMD is caused by mutations in the LAMA2 gene resulting in the loss of laminin-211/221 heterotrimers in skeletal muscle. LAMA2-CMD patients exhibit severe hypotonia and progressive muscle weakness. Currently, there is no effective treatment for LAMA2-CMD and patients die prematurely. The loss of laminin-α2 results in muscle degeneration, defective muscle repair and dysregulation of multiple signaling pathways. Signaling pathways that regulate muscle metabolism, survival and fibrosis have been shown to be dysregulated in LAMA2-CMD. As vemurafenib is a US Food and Drug Administration (FDA)-approved serine/threonine kinase inhibitor, we investigated whether vemurafenib could restore some of the serine/threonine kinase-related signaling pathways and prevent disease progression in the dyW-/- mouse model of LAMA2-CMD. Our results show that vemurafenib reduced muscle fibrosis, increased myofiber size and reduced the percentage of fibers with centrally located nuclei in dyW-/- mouse hindlimbs. These studies show that treatment with vemurafenib restored the TGF-β/SMAD3 and mTORC1/p70S6K signaling pathways in skeletal muscle. Together, our results indicate that vemurafenib partially improves histopathology but does not improve muscle function in a mouse model of LAMA2-CMD.

The exercise-mediated metabokine Beta-aminoisobutyric acid is an exercise mimetic driving skeletal muscle metabolic and functional adaptation

Skeletal muscle integrates many of the systemic signals, which contribute to the adaptive remodeling, and beneficial effects of exercise. One mechanism through which muscle mediates the systemic effects of exercise is through muscle-derived hormones known as myokines. We identified the metabolite β-aminoisobutyric acid (BAIBA) as an exercise-mediated small molecule myokine. BAIBA is secreted from muscle in response to increased expression of the transcriptional co-regulator PGC-1α, a master regulator of the muscle adaptive response to exercise. However, how BAIBA functions to regulate the adaptive responses of skeletal muscle to exercise remains poorly understood. We show that BAIBA improves muscle metabolism, exercise efficiency and performance in mice. Oxygen consumption (VO2) and energy expenditure are increased in BAIBA-treated mice. Furthermore, BAIBA increased soleus in situ muscle contractile force, fatigue resistance, mitochondrial number and function. We found that BAIBA drives muscle fiber-type switching to an oxidative phenotype in vivo. BAIBA regulates specific fiber-type gene expression in human myocytes through PPARΔ. Our findings demonstrate that BAIBA is a key paracrine myokine, which, in part, regulates the effects of exercise to improve muscle function with resultant effects on exercise performance. H.N.D. acknowledges the support of the Biotechnology and Biological Sciences Research Council (BB/T004231/1). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effect of perturbation training with and without applying the dry needling on leg muscles in patients with chronic ankle sprain

IntroductionAnkle sprain is a common musculoskeletal injury that leads to recurrent instability. Repeated ankle sprain can be a mechanism for creating trigger point. Proper treatment of trigger points, in addition to preventing recurrence of sprains, may reduce pain and improve muscle function. This improvement can be the result of preserving the surrounding tissues from excessive pressure. ObjectiveInvestigate the added value of dry needling into perturbation training protocol for chronic ankle sprain. DesignRandomized clinical trial; assessor-blind; before and after comparison. SettingTreatment of patients referred to the institutional rehabilitation clinics. Main outcome measure(s)Functional assessment with FAAM questionnaire score, Pain with NPRS scale, ankle instability severity with Cumberland tool. MethodsTwenty-four patients with chronic ankle instability participated in this clinical trial and were randomly divided into two groups. Intervention was 12 sessions in which one group received only perturbation training and the other group received perturbation training along with dry needling. Repeated measures ANOVA was used to investigate the effect of treatment. ResultsData Analysis showed significant difference in NPRS and FAAM and Cumberland score before and after treatment in each group (P < 0.001). Comparison of the results between the groups did not show any significant difference (P > 0.05). ConclusionThe findings showed that adding dry needling technique to the perturbation training does not have greater effects on the pain and function of patients with chronic ankle instability.