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Muscle dysfunction and muscle atrophy are common complications resulting from Chronic Obstructive Pulmonary Disease (COPD). The evaluation of the peripheral muscles can be carried out through the assessment of their structural components from ultrasound images or their functional components through isometric and isotonic strength tests. This evaluation, performed mainly on the quadriceps muscle, is not only of great interest for diagnosis, prognosis and monitoring of COPD, but also for the evaluation of the benefits of therapeutic interventions. In this work, bioimpedance spectroscopy technology is proposed as a low-cost and easy-to-use alternative for the evaluation of peripheral muscles, becoming a feasible alternative to ultrasound images and strength tests for their application in routine clinical practice. For this purpose, a laboratory prototype of a bioimpedance device has been adapted to perform segmental measurements in the quadriceps region. The validation results obtained in a pseudo-randomized study in patients with COPD in a controlled clinical environment which involved 33 volunteers confirm the correlation and correspondence of the bioimpedance parameters with respect to the structural and functional parameters of the quadriceps muscle, making it possible to propose a set of prediction equations. The main contribution of this manuscript is the discovery of a linear relationship between quadriceps muscle properties and the bioimpedance Cole model parameters, reaching a correlation of 0.69 and an average error of less than 0.2 cm regarding the thickness of the quadriceps estimations from ultrasound images, and a correlation of 0.77 and an average error of 3.9 kg regarding the isometric strength of the quadriceps muscle. [ABSTRACT FROM AUTHOR]

Sarcopenia refers to the progressive loss and atrophy of skeletal muscle function, often associated with aging or secondary to conditions involving systemic inflammation, oxidative stress, and mitochondrial dysfunction. Recent evidence indicates that skeletal muscle function is not only influenced by physical, environmental, and genetic factors but is also significantly impacted by nutritional deficiencies. Natural compounds with antioxidant properties, such as resveratrol and vitamin D, have shown promise in preventing mitochondrial dysfunction in skeletal muscle cells. These antioxidants can slow down muscle atrophy by regulating mitochondrial functions and neuromuscular junctions. This review provides an overview of the molecular mechanisms leading to skeletal muscle atrophy and summarizes recent advances in using resveratrol and vitamin D supplementation for its prevention and treatment. Understanding these molecular mechanisms and implementing combined interventions can optimize treatment outcomes, ensure muscle function recovery, and improve the quality of life for patients. [ABSTRACT FROM AUTHOR]

Abstract Background Glycative stress, characterized by the formation and accumulation of advanced glycation end products (AGEs) associated with protein glycation reactions, has been implicated in inducing a decline of muscle function. Although the inverse correlation between glycative stress and muscle mass and strength has been demonstrated, the underlying molecular mechanisms are not fully understood. This study aimed to elucidate how glycative stress affects the skeletal muscle, particularly the adaptive muscle response to hypertrophic stimuli and its molecular mechanism. Methods Male C57BL/6NCr mice were randomly divided into the following two groups: the bovine serum albumin (BSA)‐treated and AGE‐treated groups. Mice in the AGE‐treated group were intraperitoneally administered AGEs (0.5 mg/g) once daily, whereas those in the BSA‐treated group received an equal amount of BSA (0.5 mg/g) as the vehicle control. After 7 days of continuous administration, the right leg plantaris muscle of mice in each group underwent functional overload treatment by synergist ablation for 7 days to induce muscle hypertrophy. In in vitro studies, cultured C2C12 myocytes were treated with AGEs (1 mg/mL) to examine cell adhesion and cell membrane permeability. Results Continuous AGE administration increased the levels of fluorescent AGEs, Nε‐(carboxymethyl) lysine, and methylglyoxal‐derived hydroimidazolone‐1 in both plasma and skeletal muscle. Plantaris muscle weight, muscle fibre cross‐sectional area, protein synthesis rate, and the number of myonuclei increased with functional overload in both groups; however, the increase was significantly reduced by AGE treatment. Some muscles of AGE‐treated mice were destroyed by functional overload. Proteomic analysis was performed to explore the mechanisms of muscle hypertrophy suppression and myofibre destruction by AGEs. When principal component analysis was performed on 4659 data obtained by proteomic analysis, AGE treatment was observed to affect protein expression only in functionally overloaded muscles. Enrichment analysis of the 436 proteins extracted using the K‐means method further identified a group of proteins involved in cell adhesion. Consistent with this finding, dystrophin–glycoprotein complex proteins and cell adhesion‐related proteins were confirmed to increase with functional overload; however, this was attenuated by AGE treatment. Additionally, the treatment of C2C12 muscle cells with AGEs inhibited their ability to adhere and increased cell membrane permeability. Conclusions This study indicates that glycative stress may be a novel pathogenic factor in skeletal muscle dysfunctions by causing loss of membrane integrity and preventing muscle mass gain.

Abstract Objective Muscle dysfunction caused by repetitive work or strain in the neck region can interfere muscle responses. Muscle dysfunction can be an important factor in causing cervical spondylosis. However, there has been no research on how the biomechanical properties of the upper cervical spine change when the suboccipital muscle group experiences dysfunction. The objective of this study was to investigate the biomechanical evidence for cervical spondylosis by utilizing the finite element (FE) approach, thus and to provide guidance for clinicians performing acupoint therapy. Methods By varying the elastic modulus of the suboccipital muscle, the four FE models of C0-C3 motion segments were reconstructed under the conditions of normal muscle function and muscle dysfunction. For the two normal condition FE models, the elastic modulus for suboccipital muscles on both sides of the C0-C3 motion segments was equal and within the normal range In one muscle dysfunction FE model, the elastic modulus on both sides was equal and greater than 37 kPa, which represented muscle hypertonia; in the other, the elastic modulus of the left and right suboccipital muscles was different, indicating muscle imbalance. The biomechanical behavior of the lateral atlantoaxial joint (LAAJ), atlanto-odontoid joint (ADJ), and intervertebral disc (IVD) was analyzed by simulations, which were carried out under the six loadings of flexion, extension, left and right lateral bending, left and right axial rotation. Results Under flexion, the maximum stress in LAAJ with muscle imbalance was higher than that with normal muscle and hypertonia, while the maximum stress in IVD in the hypertonic model was higher than that in the normal and imbalance models. The maximum stress in ADJ was the largest under extension among all loadings for all models. Muscle imbalance and hypertonia did not cause overstress and stress distribution abnormalities in ADJ. Conclusion Muscle dysfunction increases the stress in LAAJ and in IVD, but it does not affect ADJ.

Objective: Muscle dysfunction caused by repetitive work or strain in the neck region can interfere muscle responses. Muscle dysfunction can be an important factor in causing cervical spondylosis. However, there has been no research on how the biomechanical properties of the upper cervical spine change when the suboccipital muscle group experiences dysfunction. The objective of this study was to investigate the biomechanical evidence for cervical spondylosis by utilizing the finite element (FE) approach, thus and to provide guidance for clinicians performing acupoint therapy. Methods: By varying the elastic modulus of the suboccipital muscle, the four FE models of C0-C3 motion segments were reconstructed under the conditions of normal muscle function and muscle dysfunction. For the two normal condition FE models, the elastic modulus for suboccipital muscles on both sides of the C0-C3 motion segments was equal and within the normal range In one muscle dysfunction FE model, the elastic modulus on both sides was equal and greater than 37 kPa, which represented muscle hypertonia; in the other, the elastic modulus of the left and right suboccipital muscles was different, indicating muscle imbalance. The biomechanical behavior of the lateral atlantoaxial joint (LAAJ), atlanto-odontoid joint (ADJ), and intervertebral disc (IVD) was analyzed by simulations, which were carried out under the six loadings of flexion, extension, left and right lateral bending, left and right axial rotation. Results: Under flexion, the maximum stress in LAAJ with muscle imbalance was higher than that with normal muscle and hypertonia, while the maximum stress in IVD in the hypertonic model was higher than that in the normal and imbalance models. The maximum stress in ADJ was the largest under extension among all loadings for all models. Muscle imbalance and hypertonia did not cause overstress and stress distribution abnormalities in ADJ. Conclusion: Muscle dysfunction increases the stress in LAAJ and in IVD, but it does not affect ADJ. [ABSTRACT FROM AUTHOR]

Pathological conditions characterized by systemic inflammation and oxidative stress can often impair the muscle cells efficiency. The gradual decline of muscle mass and tone drastically reduces the motor skills of the patient affecting the simplest daily activities. Muscle dysfunction, resulting in the deterioration of muscle tissue, can lead to a serious situation of muscle wasting that can evolve into sarcopenia. In addition, muscle dysfunction causing metabolic disorders impairs the quality of life. The function of skeletal muscle is deeply conditioned by environmental, nutritional, physical, and genetic factors. Proper nutrition with balanced protein and vitamins intake and an active lifestyle helps to strengthen tissues and counteract pathological conditions and generalized weakness. Vitamin D performs antioxidant actions, indispensable in skeletal muscle. Epidemiological data indicate that vitamin D deficiency is a widespread status in the world. Vitamin D deficiency induces mitochondrial failure, reduced production of adenosine triphosphate, oxidative injury, and compromised muscle function. Among the different types of antioxidants, vitamin D has been identified as the main compound that can improve the effectiveness of the treatment for muscle weakness and improve conditions related to sarcopenia. The purpose of this review is to analyze molecular processes used by vitamin D against oxidative stress and how it can affect muscle function in order to assess whether its use as a supplement in inflammatory pathologies and oxidative stress can be useful to prevent deterioration and improve/maintain muscle function.

Muscle dysfunction and muscle atrophy are common complications resulting from Chronic Obstructive Pulmonary Disease (COPD). The evaluation of the peripheral muscles can be carried out through the assessment of their structural components from ultrasound images or their functional components through isometric and isotonic strength tests. This evaluation, performed mainly on the quadriceps muscle, is not only of great interest for diagnosis, prognosis and monitoring of COPD, but also for the evaluation of the benefits of therapeutic interventions. In this work, bioimpedance spectroscopy technology is proposed as a low-cost and easy-to-use alternative for the evaluation of peripheral muscles, becoming a feasible alternative to ultrasound images and strength tests for their application in routine clinical practice. For this purpose, a laboratory prototype of a bioimpedance device has been adapted to perform segmental measurements in the quadriceps region. The validation results obtained in a pseudo-randomized study in patients with COPD in a controlled clinical environment which involved 33 volunteers confirm the correlation and correspondence of the bioimpedance parameters with respect to the structural and functional parameters of the quadriceps muscle, making it possible to propose a set of prediction equations. The main contribution of this manuscript is the discovery of a linear relationship between quadriceps muscle properties and the bioimpedance Cole model parameters, reaching a correlation of 0.69 and an average error of less than 0.2 cm regarding the thickness of the quadriceps estimations from ultrasound images, and a correlation of 0.77 and an average error of 3.9 kg regarding the isometric strength of the quadriceps muscle.

Background: The purpose was to investigate the content, construct, and criterion validity of muscle ultrasound in a mixed cohort of participants recovering from mild and critical COVID-19.Methods: A secondary analysis of a prospective cross-sectional study was conducted on data obtained from a battery of muscle and physical function assessments including a muscle biopsy and muscle ultrasonography (US). Rectus femoris (RF) muscle thickness (mT), quadricep complex (QC) mT, RF muscle cross-sectional area (CSA) using 2D freeform trace and estimated from Feret’s diameter, and RF echo intensity (EI) were assessed with US. Muscle fiber CSA, fiber type, protein content in muscle fibers, extracellular matrix content (ECM; wheat-germ agglutin), and percent area of collagen in ECM (picrosirius red) were examined from vastus lateralis muscle biopsies. Spearman rho correlations (r) were performed to assess validity of ultrasound parameters.Results: Thirty-three individuals participated including 11 patients surviving critical COVID-19, 15 individuals recovering from mild-COVID, and 7 controls. There were several significant correlations between RF mT, QC mT, RF CSA, and RF EI with age, comorbid burden, body-mass index, and measures of muscle strength, muscle power, and physical function (range r = 0.35–0.83). RF Feret’s CSA correlated to CSA of type II muscle fibers (r = 0.41, p = 0.022) and the average size of all muscle fibers (r = 0.39, p = 0.031). RF EI was correlated with collagen in muscle ECM (r = 0.53, p = 0.003) and protein content in muscle tissue (r = −0.52, p = 0.012).Conclusion: Muscle size and quality measured using US has moderate content and construct validity, and to lesser extent, fair to moderate criterion validity in a mixed cohort of individuals recovering from COVID. Muscle ultrasound quality (EI) appears to be sensitive at detecting muscle dysfunction as it is associated with strength, power, physical function, and collagen distribution in a mixed group of individuals recovering from COVID-19.

Changes in back muscle function and structure are highly prevalent in patients with chronic low back pain (CLBP). Since large heterogeneity in clinical presentation and back muscle dysfunctions exists within this population, the potential role of back muscle dysfunctions in the persistence of low back pain differs between individuals. Consequently, interventions should be tailored to the individual patient and be based on a thorough clinical examination taking into account the multidimensional nature of CLBP. Considering the complexity of this process, we will provide a state-of-the-art update on back muscle dysfunctions in patients with CLBP and their implications for treatment. To this end, we will first give an overview of (1) dysfunctions in back muscle structure and function, (2) the potential of exercise therapy to address these dysfunctions, and (3) the relationship between changes in back muscle dysfunctions and clinical parameters. In a second part, we will describe a framework for an individualised approach for back muscle training in patients with CLBP. [ABSTRACT FROM AUTHOR]

Background: Diabetic myopathy is characterized by the loss of skeletal muscle mass and function. NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis is a type of proinflammatory cell death, which can exacerbate significant muscle cell loss and adverse remodelling. The stimulator of interferon genes (STING) is an essential molecule involved in the regulation of inflammation and immune responses across various diseases. The regulatory mechanism by which STING affects muscle pyroptosis in diabetic myopathy remains unclear., Methods: STING-knockout and wild-type (WT) mice underwent intraperitoneal injection of streptozotocin (STZ). STING small interfering RNA (siRNA) was transfected into fully differentiated C2C12 myotubes prior to glucose treatment. Muscle function tests, body composition analysis, transmission electron microscopy, scanning electron microscopy, western blotting, immunofluorescence, immunohistochemistry, histology, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction were performed. Co-immunoprecipitation assays were employed to investigate the interaction between STING and NLRP3., Results: STING expression was elevated in the gastrocnemius muscle (GM) tissues of WT diabetic mice. STING-deficient diabetic mice exhibited pronounced hyperglycaemia accompanied by hypoinsulinaemia, with no significant difference compared with WT diabetic mice. However, STING-deficient diabetic mice demonstrated a significantly increased body weight and lean mass. A significant decrease in muscle weight, myofibrillar diameter and area, muscle function, and the expression of genes related to muscle atrophy (MuRF1, Atrogin1) were observed in WT diabetic mice, which was mitigated in STING-deficient diabetic mice. STING deficiency reduced the number of GSDMD-N formed pores and pyroptosis-related components (NLRP3, caspase-1, cle-caspase-1, GSDMD, and GSDMD-N) in the GM tissues and was associated with a reduction in inflammatory chemokines. Similar changes were observed in vitro with glucose-induced myotube atrophy and pyroptosis as seen in vivo. Activation of STING by the agonist diABZI exacerbated muscle atrophy and pyroptosis in C2C12 myotubes. Co-localization of STING and NLRP3 was observed, and the interaction between STING and NLRP3 was enhanced in GM tissues from WT diabetic mice. We also found that STING could activate NLRP3 dependent on its channel activity, which can be attenuated by treated with C53 (an inhibitor of STING's ion-channel function)., Conclusions: In conclusion, our results indicate that STING-induced activation of the NLRP3 inflammasome leads to pyroptosis, resulting in muscle atrophy and dysfunction. These findings not only elucidate the mechanism of STING-induced pyroptosis but also identify STING as a potential therapeutic target for diabetic myopathy., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Acute respiratory distress syndrome is associated with skeletal muscle compromise, which decreases survival and impairs functional capacity. A comparative analysis of peripheral and respiratory muscles' atrophy and dysfunction in acute lung injury (ALI) has not been performed. We aimed to evaluate diaphragmatic and peripheral muscle mass and contractility in an ALI animal model. ALI was induced in C57BL/6 mice by intratracheal lipopolysaccharides instillation. Muscle mass and in vitro contractility were evaluated at different time points in hindlimb soleus (slow‐twitch) and extensor digitorum longus (EDL, fast‐twitch), as well as in the main respiratory muscle diaphragm. Myogenic precursor satellite cell‐specific transcription factor Pax7 expression was determined by Western blot. Lung injury was associated with atrophy of the three studied muscles, although it was more pronounced and persistent in the diaphragm. Specific contractility was reduced during lung injury in EDL muscle but restored by the time lung injury has resolved. Specific force was not affected in soleus and diaphragm. A persistent increase in Pax7 expression was detected in diaphragm and EDL muscles after induction of ALI, but not in soleus muscle. Different peripheral and respiratory skeletal muscles are distinctly affected during the course of ALI. Each of the studied muscles presented a unique pattern in terms of atrophy development, contractile dysfunction and Pax7 expression. [ABSTRACT FROM AUTHOR]

Introduction: Quadriceps dysfunction is a common systemic manifestation of chronic obstructive pulmonary disease (COPD), for which treatment using resistance training is highly recommended. Even though training volume is suggested to be a key explanatory factor for intramuscular adaptation to resistance training in healthy older adults, knowledge is scarce on the role of progression of training volume for intramuscular adaptations in COPD. Methods: This study was a sub-analysis of a parallel-group randomized controlled trial. Thirteen patients with severe to very severe COPD (median 66 yrs, forced expiratory volume in 1 s 44% predicted) performed 8 weeks of low-load resistance training. In a post hoc analysis, they were divided into two groups according to their training volume progression. Those in whom training volume continued to increase after the first 4 weeks of training outlined the continued progression group (n = 9), while those with limited increase (<5%) or even reduction in training volume after the initial 4weeks composed the discontinued progression group (n = 4). Fiber-type distribution and oxidativemuscle protein levels, i.e., citrate synthase (CS), hydroxyacylcoenzyme A dehydrogenase (HADH), mitochondrial transcription factor A (TfAM) as well as quadriceps endurance measures (total work from elastic band and isokinetic knee extension tests), were assessed before and after the intervention period. Results: The continued progression group sustained their training volume progression during weeks 5-8 compared to weeks 1-4 (median +25%), while the discontinued progression group did not (median -2%) (p = 0.007 between groups). Compared with baseline values, significant between-group differences in fiber type distribution and TfAM muscle protein levels (range ± 17-62%, p < 0.05) and in individual responses to change in Type I and Type IIa fiber type proportion, CS, HADH, and TfAM muscle protein levels outcomes (median 89 vs. 50%, p = 0.001) were seen in favor of the continued progression group. Moreover, only the continued progression group had a significant increase in HADH muscle protein levels (+24%, p = 0.004), elastic band (+56%, p = 0.004) and isokinetic (+7%, p = 0.004) quadriceps endurance, but the between-group differences did not reach statistical significance (range 14-29%, p = 0.330-1.000). Discussion: The novel findings of the current study were that patients with COPD who had a continued progression of training volume across the 8-weeks intervention had an increased proportion of Type I fibers, and TfAM muscle protein levels and decreased proportion of Type II fibers compared to those that did not continue to progress their training volume after the initial weeks. Additionally, HADH muscle protein levels and quadriceps endurance measurements only improved in the continued progression group, although no significant between-group differences were seen. These findings highlight the importance of continued progression of training volume during resistive training to counteract quadriceps dysfunction within the COPD population. Still, considering the small sample size and the post hoc nature of our analyses, these results should be interpreted cautiously, and further research is necessary. [ABSTRACT FROM AUTHOR]

In recent years, the Diagnostic Criteria for Temporomandibular Pain Disorders (DC/TMD) has been questioned, mainly because of the dependence on the muscular pressure needed to be applied during the clinical examination. Therefore, it is necessary to establish improvements in diagnostic strategies for DC/TMD of axis I. The aim of this study was to determine the validity of the Isometric Contraction Test of the masticatory muscles (ICTest) to diagnose DC/TMD of axis I. Forty (n = 40) patients with muscular TMD (myalgia in any of its subtypes), as well as forty age and sex matched controls, participated. They were diagnosed according to DC/TMD of axis I and performed the ICTest in a single session. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and positive (LR+) and negative likelihood ratios (LR−) of the ICTest compared with the DC/TMD of axis I were calculated. The ICTest showed a specificity of 95% for the diagnosis of myalgia, and between 94.9% and 96.8% for all subtypes in relation to the DC/TMD of axis I. For sensitivity, lower values were obtained, that is, 90.0% for myalgia, and losing sensitivity depending on the type of myalgia. The LR+ was over 10 for all diagnoses, with the exception of myofascial pain with referral, which was lower. When addressing the LR−, the myofascial diagnosis was the only one below 0.2. According to the results, the ICTest could be considered a valid procedure to diagnose subjects with muscular TMD in a clinical setting. [ABSTRACT FROM AUTHOR]

Skeletal muscle symptoms strongly contribute to mortality of myotonic dystrophy type 1 (DM1) patients. DM1 is a neuromuscular genetic disease caused by CTG repeat expansions that, upon transcription, sequester the Muscleblind-like family of proteins and dysregulate alternative splicing of hundreds of genes. However, mis-splicing does not satisfactorily explain muscle atrophy and wasting, and several other contributing factors have been suggested, including hyperactivated autophagy leading to excessive catabolism. MicroRNA (miR)-7 has been demonstrated to be necessary and sufficient to repress the autophagy pathway in cell models of the disease, but the origin of its low levels in DM1 was unknown. We have found that the RNA-binding protein Musashi-2 (MSI2) is upregulated in patient-derived myoblasts and biopsy samples. Because it has been previously reported that MSI2 controls miR-7 biogenesis, we tested the hypothesis that excessive MSI2 was repressing miR-7 maturation. Using gene-silencing strategies (small interfering RNAs [siRNAs] and gapmers) and the small molecule MSI2-inhibitor Ro 08-2750, we demonstrate that reducing MSI2 levels or activity boosts miR-7 expression, represses excessive autophagy, and downregulates atrophy-related genes of the UPS system. We also detect a significant upregulation of MBNL1 upon MSI2 silencing. Taken together, we propose MSI2 as a new therapeutic target to treat muscle dysfunction in DM1.

Abstract Acute respiratory distress syndrome is associated with skeletal muscle compromise, which decreases survival and impairs functional capacity. A comparative analysis of peripheral and respiratory muscles' atrophy and dysfunction in acute lung injury (ALI) has not been performed. We aimed to evaluate diaphragmatic and peripheral muscle mass and contractility in an ALI animal model. ALI was induced in C57BL/6 mice by intratracheal lipopolysaccharides instillation. Muscle mass and in vitro contractility were evaluated at different time points in hindlimb soleus (slow‐twitch) and extensor digitorum longus (EDL, fast‐twitch), as well as in the main respiratory muscle diaphragm. Myogenic precursor satellite cell‐specific transcription factor Pax7 expression was determined by Western blot. Lung injury was associated with atrophy of the three studied muscles, although it was more pronounced and persistent in the diaphragm. Specific contractility was reduced during lung injury in EDL muscle but restored by the time lung injury has resolved. Specific force was not affected in soleus and diaphragm. A persistent increase in Pax7 expression was detected in diaphragm and EDL muscles after induction of ALI, but not in soleus muscle. Different peripheral and respiratory skeletal muscles are distinctly affected during the course of ALI. Each of the studied muscles presented a unique pattern in terms of atrophy development, contractile dysfunction and Pax7 expression.

Introduction: Quadriceps dysfunction is a common systemic manifestation of chronic obstructive pulmonary disease (COPD), for which treatment using resistance training is highly recommended. Even though training volume is suggested to be a key explanatory factor for intramuscular adaptation to resistance training in healthy older adults, knowledge is scarce on the role of progression of training volume for intramuscular adaptations in COPD.Methods: This study was a sub-analysis of a parallel-group randomized controlled trial. Thirteen patients with severe to very severe COPD (median 66 yrs, forced expiratory volume in 1 s 44% predicted) performed 8 weeks of low-load resistance training. In a post hoc analysis, they were divided into two groups according to their training volume progression. Those in whom training volume continued to increase after the first 4 weeks of training outlined the continued progression group (n = 9), while those with limited increase (

Abstract Background Diabetic myopathy involves hyperglycaemia and inflammation that causes skeletal muscle dysfunction; however, the potential cellular mechanisms that occur between hyperglycaemia and inflammation, which induces sarcopenia, and muscle dysfunction remain unknown. In this study, we investigated hyperglycaemia‐induced inflammation mediating high‐mobility group box 1 activation, which is involved in a novel form of cell death, pyroptosis, diabetic sarcopenia, atrophy, and adverse muscle remodelling. Furthermore, we investigated the therapeutic potential of bone morphogenetic protein‐7 (BMP‐7), an osteoporosis drug, to treat pyroptosis, and diabetic muscle myopathy. Methods C57BL6 mice were treated with saline (control), streptozotocin (STZ), or STZ + BMP‐7 to generate diabetic muscle myopathy. Diabetes was established by determining the increased levels of glucose. Then, muscle function was examined, and animals were sacrificed. Gastrocnemius muscle or blood samples were analysed for inflammation, pyroptosis, weight loss, muscle atrophy, and adverse structural remodelling of gastrocnemius muscle using histology, enzyme‐linked immunosorbent assay, immunohistochemistry, western blotting, and reverse transcription polymerase chain reaction. Results A significant (P

Purpose Given the increased level of fatigue frequently reported by patients with Parkinson's disease (PD), this study investigated the interaction between central and peripheral components of neuromuscular fatigue (NF) in this population compared with healthy peers. Methods Changes in maximal voluntary activation (ΔVA, central fatigue) and potentiated twitch force (Δ Q tw,pot, peripheral fatigue) pre–post exercise were determined via the interpolated twitch technique in 10 patients with PD and 10 healthy controls (CTRL) matched for age, sex, and physical activity. Pulmonary gas exchange, femoral blood flow, and quadriceps EMG were measured during a fatiguing exercise (85% of peak power output [PPO]). For a specific comparison, on another day, CTRL repeat the fatiguing test matching the time to failure (TTF) and PPO of PD. Results At 85% of PPO (PD, 21 ± 7 W; CTRL, 37 ± 22 W), both groups have similar TTF (~5.9 min), pulmonary gas exchange, femoral blood flow, and EMG. After this exercise, the maximal voluntary contraction (MVC) force and Q twpot decreased equally in both groups (−16%, P = 0.483; −43%, P = 0.932), whereas VA decreased in PD compared with CTRL (−3.8% vs −1.1%, P = 0.040). At the same PPO and TTF of PD (21 W; 5.4 min), CTRL showed a constant drop in MVC, and Q twpot (−14%, P = 0.854; −39%, P = 0.540), instead VA decreased more in PD than in CTRL (−3.8% vs −0.7%, P = 0.028). Conclusions In PD, central NF seems exacerbated by the fatiguing task which, however, does not alter peripheral fatigue. This, besides the TTF like CTRL, suggests that physical activity may limit NF and counterbalance PD-induced degeneration through peripheral adaptations. [ABSTRACT FROM AUTHOR]

Atsushi Miyamoto, Kazuhisa Asai, Hideaki Kadotani, Naomi Maruyama, Hiroaki Kubo, Atsuko Okamoto, Kanako Sato, Kazuhiro Yamada, Naoki Ijiri, Tetsuya Watanabe, Tomoya Kawaguchi Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, JapanCorrespondence: Kazuhisa AsaiDepartment of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-Machi, Abeno-ku, Osaka-City, Osaka 545-8585, JapanTel +81-6-6645-3916Fax +81-6-6646-6160Email kazuasai@med.osaka-cu.ac.jpPurpose: Sarcopenia, the loss of skeletal muscle mass and strength, is a common systemic consequence of chronic obstructive pulmonary disease (COPD) and is correlated with higher mortality. Ninjin’yoeito (NYT) is a Japanese herbal medicine used to treat athrepsia and anorexia and is reported to ameliorate weight loss and muscular dysfunction. Recent studies have shown that its crude components upregulate the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-related pathway, which is involved in skeletal muscle functions. Here, we examined whether NYT improves skeletal muscle complications by upregulating PGC-1α in COPD model mice.Materials and Methods: Mice were divided into four groups: control, NYT, smoking, and smoking + NYT. The smoking and smoking + NYT groups were exposed to cigarette smoke for 60 min once daily. The mice in the NYT and smoking + NYT groups were fed an NYT-containing diet (3% w/w). We performed cellular analysis of bronchoalveolar lavage fluid, assessed pulmonary morphological changes, examined the expression of PGC-1α mRNA and protein in the gastrocnemius and soleus muscle, measured the hindlimb muscle volume with micro-computed tomography, and determined the myofiber proportion in soleus muscle after 12 weeks.Results: Cigarette smoke exposure resulted in reduced skeletal muscle volume and slow-twitch muscle fibers and development of pulmonary emphysema. NYT feeding induced partial recovery of the damaged alveolar wall; however, NYT did not ameliorate smoke-induced alveolar enlargement. These findings revealed that NYT did not have sufficient efficacy in suppressing pulmonary emphysema. On the other hand, PGC-1α expression in muscle tissue of the NYT-fed mice increased significantly, resulting in suppression of smoke-induced loss of muscle mass and alteration in the muscle fiber distribution.Conclusion: NYT increases PGC-1α expression in the muscle of COPD model mice and is involved in suppressing cigarette smoke-induced muscle complications. NYT may be a novel preventive and therapeutic medication for muscular dysfunctions in COPD.Keywords: chronic obstructive pulmonary disease, sarcopenia, peroxisome proliferator-activated receptor γ coactivator-1α, Ninjin’yoeito, muscle dysfunction

Parkinson's disease (PD) is currently diagnosed based on characteristic motor dysfunctions induced by the loss of dopaminergic neurons in the substantia nigra pars compacta [1,2]. The animal model most commonly used to reproduce PD-related motor deficits in rats is the massive degeneration of nigrostriatal neurons by using intracerebral infusion of 6-hydroxydopamine (6-OHDA) [3,4].This article presents data related to the research article “Quantifying muscle alterations in a Parkinson's disease animal model using electromyographic biomarkers” [5]. This study evaluated the effect of PD neurotoxic lesion model on muscle function of freely moving rats. The effects on muscle function considering the time post-lesion have never been described for this Parkinson's disease model. Electromyographic recordings were obtained from control and hemiparkinsonian rats walking in a circular treadmill. Chronic EMG electrodes were implanted subcutaneously in a hindlimb muscle - the biceps femoris muscle - for evaluating muscular activity during the gait. Five dataset of EMG recordings are presented in this article corresponding to control animals and four groups of lesioned animals at different time post-injury (three to six weeks after lesion). Stationarity of the EMG signals were established and the effective muscular contractions were detected by using signal processing methods described in [5]. Power spectrum density was characterized through the mean and median frequencies and signals probability distribution function analysis was also performed.These analyses have shown that PSD frequency contents progressively fall with time post-lesion suggesting muscle function changes along this enclosed time.This dataset could be reused to investigate muscular activation parameters under control and lesioned conditions in freely moving rats and for evaluating different signal processing methods for EMG patterns detection.

Critical illnesses, including sepsis, cancer cachexia, and burn injury, invoke a milieu of systemic metabolic and inflammatory derangements that ultimately results in increased energy expenditure leading to fat and lean mass catabolism. Burn injuries present a unique clinical challenge given the magnitude and duration of the hypermetabolic response compared with other forms of critical illness, which drastically increase the risk of morbidity and mortality. Skeletal muscle metabolism is particularly altered as a consequence of burn-induced hypermetabolism, as it primarily provides a main source of fuel in support of wound healing. Interestingly, muscle catabolism is sustained long after the wound has healed, indicating that additional mechanisms beyond wound healing are involved. In this review, we discuss the distinctive pathophysiological response to burn injury with a focus on skeletal muscle function and metabolism. We first examine the diverse consequences on skeletal muscle dysfunction between thermal, electrical, and chemical burns. We then provide a comprehensive overview of the known mechanisms underlying skeletal muscle dysfunction that may be attributed to hypermetabolism. Finally, we review the most promising current treatment options to mitigate muscle catabolism, and by extension improve morbidity and mortality, and end with future directions that have the potential to significantly improve patient care. [ABSTRACT FROM AUTHOR]

The aim of the paper is to assess the change in the mitochondrial respirometric function under conditions of various pathologies.Materials and methods. The study was performed on male Wistar rats. Experimental focal cerebral ischemia, traumatic brain injury, coronary occlusive myocardial infarction and muscle dysfunction were used as pathological models. Focal ischemia was reproduced by the method of irreversible thermocoagulation of the middle cerebral artery. Traumatic brain injury was modeled by the method of free fall of the load. Experimental myocardial infarction was reproduced by ligating the descending branch of the left coronary artery. Muscle dysfunction was modeled by the method of «forced swimming with a 20% burden». The respiratory function of mitochondria was assessed by the method of respirometry by the change in oxygen consumption when introducing mitochondrial respiration into the medium: Oligomycin, Rotenone and FCCP. Additionally, we evaluated the intensity of the glycolysis process and the activity of respiratory complexes I, II, IV and V. In order to comprehensively assess the respiratory function, an ELISA study was conducted to determine the concentration of ATP, mitochondrial ATP synthetase, cytochrome C oxidase and NADP-Oxidase 4.Results. In the course of the study it was established that under conditions of experimental cerebral ischemia, traumatic brain injury, myocardial infarction and muscle dysfunction, the ATP-generating ability of mitochondria the maximum breathing and respiratory capacity deteriorated, herby the decrease in overall respiratory function was accompanied by an increase in glycolysis, which was uncompensated, as well as dysfunction of mitochondrial complexes I, II, IV and V, confirmed by an increase in NADPH oxidase 4 activity and a decrease in cytochrome C oxidases and ATP synthetase. As a result, the observed changes in mitochondrial respiration function contributed to a decrease in ATP concentration under conditions of cerebral ischemia - by 3.2 times (p

In recent years, the Diagnostic Criteria for Temporomandibular Pain Disorders (DC/TMD) has been questioned, mainly because of the dependence on the muscular pressure needed to be applied during the clinical examination. Therefore, it is necessary to establish improvements in diagnostic strategies for DC/TMD of axis I. The aim of this study was to determine the validity of the Isometric Contraction Test of the masticatory muscles (ICTest) to diagnose DC/TMD of axis I. Forty (n = 40) patients with muscular TMD (myalgia in any of its subtypes), as well as forty age and sex matched controls, participated. They were diagnosed according to DC/TMD of axis I and performed the ICTest in a single session. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and positive (LR+) and negative likelihood ratios (LR−) of the ICTest compared with the DC/TMD of axis I were calculated. The ICTest showed a specificity of 95% for the diagnosis of myalgia, and between 94.9% and 96.8% for all subtypes in relation to the DC/TMD of axis I. For sensitivity, lower values were obtained, that is, 90.0% for myalgia, and losing sensitivity depending on the type of myalgia. The LR+ was over 10 for all diagnoses, with the exception of myofascial pain with referral, which was lower. When addressing the LR−, the myofascial diagnosis was the only one below 0.2. According to the results, the ICTest could be considered a valid procedure to diagnose subjects with muscular TMD in a clinical setting.

Background: Diabetic myopathy involves hyperglycaemia and inflammation that causes skeletal muscle dysfunction; however, the potential cellular mechanisms that occur between hyperglycaemia and inflammation, which induces sarcopenia, and muscle dysfunction remain unknown. In this study, we investigated hyperglycaemia‐induced inflammation mediating high‐mobility group box 1 activation, which is involved in a novel form of cell death, pyroptosis, diabetic sarcopenia, atrophy, and adverse muscle remodelling. Furthermore, we investigated the therapeutic potential of bone morphogenetic protein‐7 (BMP‐7), an osteoporosis drug, to treat pyroptosis, and diabetic muscle myopathy. Methods: C57BL6 mice were treated with saline (control), streptozotocin (STZ), or STZ + BMP‐7 to generate diabetic muscle myopathy. Diabetes was established by determining the increased levels of glucose. Then, muscle function was examined, and animals were sacrificed. Gastrocnemius muscle or blood samples were analysed for inflammation, pyroptosis, weight loss, muscle atrophy, and adverse structural remodelling of gastrocnemius muscle using histology, enzyme‐linked immunosorbent assay, immunohistochemistry, western blotting, and reverse transcription polymerase chain reaction. Results: A significant (P < 0.05) increase in hyperglycaemia leads to an increase in inflammasome (high‐mobility group box 1, toll‐like receptor‐4, and nucleotide‐binding oligomerization domain, leucine‐rich repeat and pyrin domain containing protein 3) formation in diabetic muscle cells. Further analysis showed an up‐regulation of the downstream pyroptotic pathway with significant (P < 0.05) number of positive muscle cells expressing pyroptosis‐specific markers [caspase‐1, interleukin (IL)‐1β, IL‐18, and gasdermin‐D]. Pyroptotic cell death is involved in further increasing inflammation by releasing pro‐inflammatory cytokine IL‐6. Structural analysis showed the loss of muscle weight, decreased myofibrillar area, and increased fibrosis leading to muscle dysfunction. Consistent with this finding, BMP‐7 attenuated hyperglycaemia (~50%), pyroptosis, inflammation, and diabetic adverse structural modifications as well as improved muscle function. Conclusions: In conclusion, we report for the first time that increased hyperglycaemia and inflammation involve cellular pyroptosis that induces significant muscle cell loss and adverse remodelling in diabetic myopathy. We also report that targeting pyroptosis with BMP‐7 improves diabetic muscle pathophysiology and muscle function. These findings suggest that BMP‐7 could be a potential therapeutic option to treat diabetic myopathy. [ABSTRACT FROM AUTHOR]

Non-dioxin like polychlorinated biphenyls (NDL-PCBs) are legacy environmental contaminants with contemporary unintentional sources. NDL-PCBs interact with ryanodine receptors (RyRs), Ca(2+) channels of sarcoplasmic/endoplasmic reticulum (SR/ER) that regulate excitation-contraction coupling (ECC) and Ca(2+)-dependent cell signaling in muscle. Activities of 4 chiral congeners PCB91, 95, 132, and 149 and their respective 4- and 5-hydroxy (-OH) derivatives toward rabbit skeletal muscle ryanodine receptor (RyR1) are investigated using [(3)H]ryanodine binding and SR Ca(2+) flux analyses. Although 5-OH metabolites have comparable activity to their respective parent in both assays, 4-OH derivatives are unable to trigger Ca(2+) release from SR microsomes in the presence of Ca(2+)-ATPase activity. PCB95 and derivatives are investigated using single channel voltage-clamp and primary murine embryonic muscle cells (myotubes). Like PCB95, 5-OH-PCB95 quickly and persistently increases channel open probability (p o > .9) by stabilizing the full-open channel state, whereas 4-OH-PCB95 transiently enhances p o. Ca(2+) imaging of myotubes loaded with Fluo-4 show that acute exposure to PCB95 (5 µM) potentiates ECC and caffeine responses and partially depletes SR Ca(2+) stores. Exposure to 5-OH-PCB95 (5 µM) increases cytoplasmic Ca(2+), leading to rapid ECC failure in 50% of myotubes with the remainder retaining negligible responses. 4-OH-PCB95 neither increases baseline Ca(2+) nor causes ECC failure but depresses ECC and caffeine responses by 50%. With longer (3h) exposure to 300 nM PCB95, 5-OH-PCB95, or 4-OH-PCB95 decreases the number of ECC responsive myotubes by 22%, 81%, and 51% compared with control by depleting SR Ca(2+) and/or uncoupling ECC. NDL-PCBs and their 5-OH and 4-OH metabolites differentially influence RyR1 channel activity and ECC in embryonic skeletal muscle.

Background: Glycative stress, characterized by the formation and accumulation of advanced glycation end products (AGEs) associated with protein glycation reactions, has been implicated in inducing a decline of muscle function. Although the inverse correlation between glycative stress and muscle mass and strength has been demonstrated, the underlying molecular mechanisms are not fully understood. This study aimed to elucidate how glycative stress affects the skeletal muscle, particularly the adaptive muscle response to hypertrophic stimuli and its molecular mechanism., Methods: Male C57BL/6NCr mice were randomly divided into the following two groups: the bovine serum albumin (BSA)-treated and AGE-treated groups. Mice in the AGE-treated group were intraperitoneally administered AGEs (0.5 mg/g) once daily, whereas those in the BSA-treated group received an equal amount of BSA (0.5 mg/g) as the vehicle control. After 7 days of continuous administration, the right leg plantaris muscle of mice in each group underwent functional overload treatment by synergist ablation for 7 days to induce muscle hypertrophy. In in vitro studies, cultured C2C12 myocytes were treated with AGEs (1 mg/mL) to examine cell adhesion and cell membrane permeability., Results: Continuous AGE administration increased the levels of fluorescent AGEs, Nε-(carboxymethyl) lysine, and methylglyoxal-derived hydroimidazolone-1 in both plasma and skeletal muscle. Plantaris muscle weight, muscle fibre cross-sectional area, protein synthesis rate, and the number of myonuclei increased with functional overload in both groups; however, the increase was significantly reduced by AGE treatment. Some muscles of AGE-treated mice were destroyed by functional overload. Proteomic analysis was performed to explore the mechanisms of muscle hypertrophy suppression and myofibre destruction by AGEs. When principal component analysis was performed on 4659 data obtained by proteomic analysis, AGE treatment was observed to affect protein expression only in functionally overloaded muscles. Enrichment analysis of the 436 proteins extracted using the K-means method further identified a group of proteins involved in cell adhesion. Consistent with this finding, dystrophin-glycoprotein complex proteins and cell adhesion-related proteins were confirmed to increase with functional overload; however, this was attenuated by AGE treatment. Additionally, the treatment of C2C12 muscle cells with AGEs inhibited their ability to adhere and increased cell membrane permeability., Conclusions: This study indicates that glycative stress may be a novel pathogenic factor in skeletal muscle dysfunctions by causing loss of membrane integrity and preventing muscle mass gain., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Patients with chronic pulmonary conditions such as chronic obstructive pulmonary disease (COPD) often develop skeletal muscle dysfunction, which is strongly and independently associated with poor outcomes including higher mortality. Some of these patients also develop chronic CO2 retention, or hypercapnia, which is also associated with worse prognosis. While muscle dysfunction in these settings involve reduction of muscle mass and disrupted fibers’ metabolism leading to suboptimal muscle work, mechanistic research in the field has been limited by the lack of adequate animal models. Over the last years, we have established a rodent model of COPD-induced skeletal muscle dysfunction that allowed a disaggregated interrogation of the cellular and physiological effects driven by COPD from the ones unique to hypercapnia. We found that while COPD and hypercapnia synergistically contribute to muscle atrophy, they are antagonistic processes regarding fibers respiratory capacity. We propose that AMP-activated protein kinase (AMPK) is a crucial regulator of CO2 signaling in hypercapnic muscles, which leads to both net protein catabolism and improved mitochondrial respiration to support a transition into a substrate-rich, fuel-efficient metabolic mode that allows muscle cells cope with the CO2 toxicity.

Previous research has shown that resistance training (RT) before doxorubicin (DOX) treatment attenuates the decline in muscle dysfunction; however, the effect of RT during DOX treatment is less known. Purpose: Investigate the effects of RT before and during a 4-wk course of incremental DOX treatment on skeletal muscle function. Methods: Male, Sprague-Dawley rats (N = 36) were randomly assigned to the following groups: sedentary+saline (SED + SAL), sedentary+DOX (SED + DOX), RT + SAL, or RT + DOX. The RT protocol utilized a raised cage model, which provided progressive hindlimb loading throughout the 14-wk study, whereas SED animals were kept in normal housing. Starting at week 10, DOX-treated animals received 3 mg·kg−1 DOX weekly for 4 wk (12 mg·kg−1 cumulative); whereas SAL-treated groups received 0.9% NaCl as a placebo. Grip strength was recorded at 0, 10, 12, and 14 wk. Ex vivo muscle function was performed on excised soleus (SOL) and extensor digitorum longus (EDL) from the right hind limb 5 d after the last injection and were analyzed for expression of creatine kinase (CK) and creatine transporters. Results: SED + DOX – treated animals had significantly lower EDL mass compared with SED + SAL – and RT + DOX – treated animals. Grip strength, EDL maximal force, and EDL force development were significantly lower in SED + DOX – treated animals compared with RT + SAL and SED + SAL. No significant differences in EDL function were found between RT + DOX and RT + SAL animals. DOX treatment reduced expression of CK in the SOL, which abated with RT. Conclusions: Low-intensity RT may attenuate the decline in skeletal muscle function during incremental DOX treatment. [ABSTRACT FROM AUTHOR]

Patients with chronic pulmonary conditions such as chronic obstructive pulmonary disease (COPD) often develop skeletal muscle dysfunction, which is strongly and independently associated with poor outcomes including higher mortality. Some of these patients also develop chronic CO2 retention, or hypercapnia, which is also associated with worse prognosis. While muscle dysfunction in these settings involve reduction of muscle mass and disrupted fibers' metabolism leading to suboptimal muscle work, mechanistic research in the field has been limited by the lack of adequate animal models. Over the last years, we have established a rodent model of COPD-induced skeletal muscle dysfunction that allowed a disaggregated interrogation of the cellular and physiological effects driven by COPD from the ones unique to hypercapnia. We found that while COPD and hypercapnia synergistically contribute to muscle atrophy, they are antagonistic processes regarding fibers respiratory capacity. We propose that AMP-activated protein kinase (AMPK) is a crucial regulator of CO2 signaling in hypercapnic muscles, which leads to both net protein catabolism and improved mitochondrial respiration to support a transition into a substrate-rich, fuel-efficient metabolic mode that allows muscle cells cope with the CO2 toxicity. [ABSTRACT FROM AUTHOR]

Patients with chronic obstructive pulmonary disease (COPD) usually develop skeletal muscle dysfunction, which represents a major comorbidity in these patients and is strongly associated with mortality and other poor outcomes. Although clinical data indicates that accelerated protein degradation and metabolic disruption are common associations of muscle dysfunction in COPD, there is very limited data on the mechanisms regulating the process, in part, due to the lack of research performed on a validated animal model of pulmonary emphysema. This model deficiency complicates the translational value of data generated with highly reductionist settings. Here, we use an established transgenic animal model of COPD based on inducible IL-13-driven pulmonary emphysema (IL-13TG) to interrogate the mechanisms of skeletal muscle dysfunction. Skeletal muscles from these emphysematous mice develop most features present in COPD patients, including atrophy, decreased oxygen consumption, and reduced force-generation capacity. Analysis of muscle proteome indicates downregulation of succinate dehydrogenase C (SDH-C), which correlates with reduced enzymatic activity, also consistent with previous clinical observations. Ontology terms identified with human data, such as ATP binding/bioenergetics are also downregulated in this animal's skeletal muscles. Moreover, chronic exercise can partially restore muscle mass, metabolic and force-generation capacity, and SDH activity in COPD mice. We conclude that this animal model of COPD/emphysema is an adequate platform to further investigate mechanisms of muscle dysfunction in this setting and demonstrates multiple approaches that can be used to address specific mechanisms regulating this process. [ABSTRACT FROM AUTHOR]

Paediatric cancer treatment has advanced significantly over the last half century to a point where >80% of all childhood cancer cases survive >5 years from diagnosis. However, childhood cancer treatments cause a wide range of long-term adverse effects including endocrine dysfunctions, impaired physical function, and a markedly increased risk of developing metabolic and cardiovascular complications. Emerging evidence suggests that treatment-related muscle toxicities may play a key role in the development of such late effects, but limited research has been performed towards elucidating this phenomenon and therapeutic countermeasures are scarcely available in clinical practice. Here, we review the current literature describing the physiological manifestations of treatment-induced muscular toxicities in paediatric oncology and discuss the use of structured exercise as a targeted countermeasure.

Background: The 6-min walking test (6MWT) is one of the most commonly used tests to assess exercise capacity during chronic obstructive pulmonary disease (COPD). However, it is a relatively time-consuming test. Many authors assessed the usefulness of simpler methods, as the sit-to-stand test (STST), to estimate exercise capacity. Purpose: To demonstrate the feasibility of STST, in comparison to 6MWT, for the evaluation of functional status in Tunisian COPD patients and evaluate its correlation to the severity of the disease. Methods: We studied patients with COPD (Global Initiative for Chronic Obstructive Lung Disease A-D). All patients had plethysmography and manual quadriceps femoris muscle strength evaluation. Each patient completed a 6MWT and a STST. During the tests, dyspnea severity (Borg scale), heart rate, pulsed oxygen saturation, and blood pressure were measured. Results: In 49 patients with stable COPD (mean age 67.06 ± 8.4 years, mean forced expiratory volume in the first second 46.25% ± 19.64%), 6MWT and STST were correlated with each other (r = 0.47, P = 0.001). During 6MWT and STST, the rise in heart rate, systolic blood pressure, and severity of dyspnea were statistically significant compared to baseline (P < 0.05). However, cardiorespiratory stress was lower after STST than after 6MWT (P < 0.05). A statistically significant positive correlation was noted between the 6MWT distance and forced vital capacity (r = 0.357, P < 0.05). The 6MWT was negatively correlated with dyspnea severity at baseline (r = −0.289, P < 0.05) and with BODE index (r = −0.672, P < 0.01). STST was correlated only with age (r = 0.377, P < 0.01). No correlation was found between both tests and quadriceps femoris strength. Conclusion: As like as 6MWT, STST can determine functional status during COPD. In addition, it is less time consuming and produces less hemodynamical stress compared to 6MWT. STST can be used as an alternative for 6MWT in patients with COPD.

Background: The purpose was to investigate the content, construct, and criterion validity of muscle ultrasound in a mixed cohort of participants recovering from mild and critical COVID-19. Methods: A secondary analysis of a prospective cross-sectional study was conducted on data obtained from a battery of muscle and physical function assessments including a muscle biopsy and muscle ultrasonography (US). Rectus femoris (RF) muscle thickness (mT), quadricep complex (QC) mT, RF muscle cross-sectional area (CSA) using 2D freeform trace and estimated from Feret's diameter, and RF echo intensity (EI) were assessed with US. Muscle fiber CSA, fiber type, protein content in muscle fibers, extracellular matrix content (ECM; wheat-germ agglutin), and percent area of collagen in ECM (picrosirius red) were examined from vastus lateralis muscle biopsies. Spearman rho correlations (r) were performed to assess validity of ultrasound parameters. Results: Thirty-three individuals participated including 11 patients surviving critical COVID-19, 15 individuals recovering from mild-COVID, and 7 controls. There were several significant correlations between RF mT, QC mT, RF CSA, and RF EI with age, comorbid burden, body-mass index, and measures of muscle strength, muscle power, and physical function (range r = 0.35-0.83). RF Feret's CSA correlated to CSA of type II muscle fibers (r = 0.41, p = 0.022) and the average size of all muscle fibers (r = 0.39, p = 0.031). RF EI was correlated with collagen in muscle ECM (r = 0.53, p = 0.003) and protein content in muscle tissue (r = -0.52, p = 0.012). Conclusion: Muscle size and quality measured using US has moderate content and construct validity, and to lesser extent, fair to moderate criterion validity in a mixed cohort of individuals recovering from COVID. Muscle ultrasound quality (EI) appears to be sensitive at detecting muscle dysfunction as it is associated with strength, power, physical function, and collagen distribution in a mixed group of individuals recovering from COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mayer, Kosmac, Wen, Parry, Dhar, Foster, Starck, Montgomery-Yates, Dupont-Versteegden and Kalema.)

Supplemental digital content is available in the text. Purpose: Lower muscle strength and endurance have been reported in severe obstructive sleep apnea (OSA). Increased intracortical inhibition previously reported at rest in OSA suggests central neuromuscular impairments in these patients. We hypothesized that (i) OSA patients demonstrate reduced knee extensor strength and endurance due to central impairments and (ii) continuous positive airway pressure (CPAP) treatment improves neuromuscular function in these patients. Methods: Twelve OSA patients and 11 healthy controls performed intermittent knee extensions until task failure before and after 8 wk of CPAP treatment or control period. Maximal voluntary contraction, voluntary activation and corticospinal excitability and inhibition assessed by single- and paired-pulse transcranial magnetic stimulation were measured before and during the fatiguing task. Results: Time to exhaustion was lower in OSA (before CPAP treatment: 1008 ± 549 s; after CPAP treatment: 975 ± 378 s) compared with controls (before control period: 1476 ± 633 s; after control period: 1274 ± 506 s; P = 0.017). Obstructive sleep apnea patients had reduced maximal voluntary contraction and VATMS compared with controls throughout the fatiguing task as well as increased intracortical inhibition (all P < 0.05). Continuous positive airway pressure treatment did not induce any changes in neuromuscular function ( P > 0.05 for all parameters). Conclusions: This study demonstrates that severe OSA patients have cortical impairments which are likely contributing to their reduced knee extensors strength and endurance. Both cortical impairments and neuromuscular function are not improved after 8 wk of CPAP treatment. [ABSTRACT FROM AUTHOR]

Patients with chronic obstructive pulmonary disease (COPD) exhibit an altered skeletal muscle mitochondrial phenotype, which often includes reduced mitochondrial density, altered respiratory function, and elevated oxidative stress. As this phenotype may be explained by the sedentary lifestyle that commonly accompanies this disease, the aim of this study was to determine whether such alterations are still evident when patients with COPD are compared to control subjects matched for objectively measured physical activity (PA; accelerometry). Indexes of mitochondrial density [citrate synthase (CS) activity], respiratory function (respirometry in permeabilized fibers), and muscle oxidative stress [4-hydroxynonenal (4-HNE) content] were assessed in muscle fibers biopsied from the vastus lateralis of nine patients with COPD and nine PA-matched control subjects (CON). Despite performing similar levels of PA (CON: 18 ± 3, COPD: 20 ± 7 daily minutes moderate-to-vigorous PA; CON: 4,596 ± 683, COPD: 4,219 ± 763 steps per day, P > 0.70), patients with COPD still exhibited several alterations in their mitochondrial phenotype, including attenuated skeletal muscle mitochondrial density (CS activity; CON 70.6 ± 3.8, COPD 52.7 ± 6.5 U/mg, P < 0.05), altered mitochondrial respiration [e.g., ratio of complex I-driven state 3 to complex II-driven state 3 (CI/CII); CON: 1.20 ± 0.11, COPD: 0.90 ± 0.05, P < 0.05), and oxidative stress (4-HNE; CON: 1.35 ± 0.19, COPD: 2.26 ± 0.25 relative to β-actin, P < 0.05). Furthermore, CS activity (r = 0.55), CI/CII (r = 0.60), and 4-HNE (r = 0.49) were all correlated with pulmonary function, assessed as forced expiratory volume in 1 s (P < 0.05), but not PA (P > 0.05). In conclusion, the altered mitochondrial phenotype in COPD is present even in the absence of differing levels of PA and appears to be related to the disease itself. NEW & NOTEWORTHY Chronic obstructive pulmonary disease (COPD) is associated with debilitating alterations in the function of skeletal muscle mitochondria. By comparing the mitochondrial phenotype of patients with COPD to that of healthy control subjects who perform the same amount of physical activity each day, this study provides evidence that many aspects of the dysfunctional mitochondrial phenotype observed in COPD are not merely due to reduced physical activity but are likely related to the disease itself. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a complex disorder with extrapulmonary manifestations. Even though there is some knowledge regarding sex differences in the lung disease, little is known about extrapulmonary manifestations. Our aim was to analyze the specific profile of muscle dysfunction, structure, and biology in COPD women. Twenty-one women and 19 men with stable COPD as well as 15 controls were included. Nutritional status, physical activity, lung and muscle function, exercise capacity, and quality of life were assessed. In addition, blood, breath condensate, and quadriceps muscle samples were tested for inflammatory markers. Moreover, fiber phenotype, signs of damage–regeneration, and the expression of key genes linked to myogenesis and inflammation were assessed in the muscle. Inflammatory markers were increased in all body compartments but no correlation was found among them. Muscle dysfunction was present in both COPD groups but was more marked in women. The opposite occurred with the increase in the percentage of type II fibers that was lower in women despite a similar level of airway obstruction as in men. Female COPD also showed higher signs of muscle damage than COPD men who, in contrast, exhibited slightly higher signs of regeneration. We conclude that sex influences muscle phenotype and function in COPD. [ABSTRACT FROM AUTHOR]

Eccentric ergometer training (EET) is increasingly being proposed as a therapeutic strategy to improve skeletal muscle strength in various cardiorespiratory diseases, due to the principle that lengthening muscle actions lead to high force-generating capacity at low cardiopulmonary load. One clinical population that may particularly benefit from this strategy is chronic obstructive pulmonary disease (COPD), as ventilatory constraints and locomotor muscle dysfunction often limit efficacy of conventional exercise rehabilitation in patients with severe disease. While the feasibility of EET for COPD has been established, the nature and extent of adaptation within COPD muscle is unknown. The aim of this study was therefore to characterize the locomotor muscle adaptations to EET in patients with severe COPD, and compare them with adaptations gained through conventional concentric ergometer training (CET). Male patients were randomized to either EET (n = 8) or CET (n = 7) for 10 weeks and matched for heart rate intensity. EET patients trained on average at a workload that was three times that of CET, at a lower perception of leg fatigue and dyspnea. EET led to increases in isometric peak strength and relative thigh mass (p < 0.01) whereas CET had no such effect. However, EET did not result in fiber hypertrophy, as morphometric analysis of muscle biopsies showed no increase in mean fiber cross-sectional area (p = 0.82), with variability in the direction and magnitude of fiber-type responses (20% increase in Type 1, p = 0.18; 4% decrease in Type 2a, p = 0.37) compared to CET (26% increase in Type 1, p = 0.04; 15% increase in Type 2a, p = 0.09). EET had no impact onmitochondrial adaptation, as revealed by lack of change in markers of mitochondrial biogenesis, content and respiration, which contrasted to improvements (p < 0.05) within CET muscle. While future study is needed to more definitively determine the effects of EET on fiber hypertrophy and associated underlying molecular signaling pathways in COPD locomotor muscle, our findings promote the implementation of this strategy to improve muscle strength. Furthermore, contrasting mitochondrial adaptations suggest evaluation of a sequential paradigm of eccentric followed by concentric cycling as a means of augmenting the training response and attenuating skeletal muscle dysfunction in patients with advanced COPD. [ABSTRACT FROM AUTHOR]

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 (VO 2max ), 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, VO 2max (+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 VO 2max (+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 VO 2max 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.

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by a CTG repeat expansion in the DMPK gene that generates toxic RNA with a myriad of downstream alterations in RNA metabolism. A key consequence is the sequestration of alternative splicing regulatory proteins MBNL1/2 by expanded transcripts in the affected tissues. MBNL1/2 depletion interferes with a developmental alternative splicing switch that causes the expression of fetal isoforms in adults. Boosting the endogenous expression of MBNL proteins by inhibiting the natural translational repressors miR-23b and miR-218 has previously been shown to be a promising therapeutic approach. We designed antimiRs against both miRNAs with a phosphorodiamidate morpholino oligonucleotide (PMO) chemistry conjugated to cell-penetrating peptides (CPPs) to improve delivery to affected tissues. In DM1 cells, CPP-PMOs significantly increased MBNL1 levels. In some candidates, this was achieved using concentrations less than two orders of magnitude below the median toxic concentration, with up to 5.38-fold better therapeutic window than previous antagomiRs. In HSA LR mice, intravenous injections of CPP-PMOs improve molecular, histopathological, and functional phenotypes, without signs of toxicity. Our findings place CPP-PMOs as promising antimiR candidates to overcome the treatment delivery challenge in DM1 therapy., Competing Interests: B.L. and R.A. are founders, and CEO and scientific consultant of Arthex Biotech, respectively. Arthex Biotech is developing antimiRs for use in the treatment of DM1., (© 2023 The Authors.)

Chronic obstructive pulmonary disease is a preventable and treatable disease. It is characterized by persistent airflow limitation that is usually progressive and associated with enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Although COPD affects the lungs, it also results in significant systemic disorders and exacerbates comorbidities [1].