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• Heaviest treated patients in the real world with onasemnogene abeparvovec. • Liver impairment and only transitory improvement in functional outcomes. • Risk-benefit considerations is required in treating older and heavier SMA patients. Spinal muscular atrophy (SMA) is an autosomal recessive disorder with progressive muscle atrophy and weakness, caused by biallelic mutations in the survival motor neuron 1 (SNM1) gene. Onasemnogene abeparvovec (OA) is an approved gene replacement therapy for patients with SMA. We report on two patients with SMA type 1, weighing 20 kg, previously treated with Nusinersen, who received OA infusion at 7 years of age. To our knowledge, these two patients are the heaviest treated in the real-world and we describe their different courses after gene therapy, including liver impairment requiring long-term steroid treatment and additional immunosuppression, with only transitory improvement in functional outcomes. Our cases illustrate how careful risk-benefit consideration is required in treating older and heavier SMA patients with OA, especially in view of the multiple treatment choices available for older patients with SMA. [ABSTRACT FROM AUTHOR]

• Granulomatous myositis is a severe and difficult to treat disease in which distal motor deficit and clinical amyotrophy seem to be predictive factors for evolution towards severe disability. • A significant proportion of granulomatous myositis cases exhibit clinical or pathological features consistent with inclusion body myositis. • Granulomatous myositis with significant initial hypercalcemia typically show favorable progression with corticosteroid therapy. Granulomatous myositis is a clinical-pathological entity, which has been rarely reported, mostly described in sarcoidosis. Currently, no clear and simple prognostic factor has been identified to predict granulomatous myositis evolution. The clinical, anatomopathological, imaging, and biological characteristics of 26 patients with granulomatous myositis were retrospectively collected to describe clinical presentation and outcomes of this condition. Twenty-six patients with granulomatous myositis were included (14 males) with a median age of symptom onset of 65 years. 54 % of patients presented a severe form of the disease defined as a Rankin score ≥2 at last follow-up visit or a progressive form of the disease (no improvement under treatment). Etiology were sarcoidosis (n = 14), inclusion body myositis (n = 4), autoimmune disease (n = 1), hematological malignancy (n = 1), and idiopathic (n = 6). Distal deficit and amyotrophy were more frequent among those with a severe disease. Corticosteroids led to improvement in 75 % of cases, but 66 % of responders relapsed. Methotrexate appeared as a promising second line therapy with clinical improvement in 50 % of patients, and no relapse in responders. Granulomatous myositis is often a severe and difficult-to-treat disease in which patients frequently progress towards severe disability. The presence of muscle atrophy and distal weakness appears to be frequently associated with a severe form of the disease. [ABSTRACT FROM AUTHOR]

ZC4H2 -associated rare disorder (ZARD) is caused by pathogenic variations in the ZC4H2 gene on the X chromosome. This gene codes for a zinc finger protein involved in neural development. ZARD is characterized by highly variable symptoms, potentially influenced by the sex of the individual. The ZC4H2 -Associated Rare Disorder Natural History Study is a prospective natural history study conducted among individuals with ZARD that consists of standardized interviews, developmental assessments, and neurological examinations conducted every six months for two years. In this article, we present data from baseline visits with 40 participants, the largest ZARD cohort studied thus far, focusing on genotype-phenotype correlations and sex differences. Fisher exact, maximum likelihood χ 2, and Mann-Whitney tests were utilized. Males tended to have maternally inherited ZC4H2 pathogenic variations, whereas females tended to have de novo variations (P < 0.001). Female participants were more likely to have contractures at birth (P < 0.01), arthrogryposis multiplex congenita (P < 0.001), spasticity on examination (P < 0.1), and lower limb muscle atrophy (P < 0.05). Male participants were more likely to have seizures (P < 0.1), intermittent pain (P < 0.01), severe vision impairment (P < 0.05), dysphagia for solids (P < 0.01), and generalized muscle atrophy (P < 0.05). Our study suggests there is significant overlap in severity and range of symptoms between males and females, although several symptoms are more common in one sex than the other. Further analysis is needed to better understand how pathogenic variation type affects phenotype. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease caused by the degeneration of the α-motor neurons in the anterior horn of the spinal cord. SMA is clinically characterized by progressive and symmetrical muscle weakness and muscle atrophy and ends up with systemic multisystem abnormalities. Quantitative MRI (qMRI) has the advantages of non-invasiveness, objective sensitivity, and high reproducibility, and has important clinical value in evaluating the severity of neuromuscular diseases and monitoring the efficacy of treatment. This article summarizes the clinical use of muscular MRI and magnetic resonance neurography in assessing the progress of SMA. [ABSTRACT FROM AUTHOR]

Sarcopenia is characterized by loss of muscle strength and muscle mass with aging. The growing number of sarcopenia patients as a result of the aging population has no viable treatment. Exercise maintains muscle strength and mass by increasing peroxisome growth factor activating receptor γ-conjugating factor-1α (PGC-1α) and Akt signaling in skeletal muscle. The present study focused on the carbon monoxide (CO), endogenous activator of PGC-1α and Akt, and investigated the therapeutic potential of CO-loaded red blood cells (CO-RBCs), which is bioinspired from in vivo CO delivery system, as an exercise mimetic for the treatment of sarcopenia. Treatment of C2C12 myoblasts with the CO-donor increased the protein levels of PGC-1α which enhanced mitochondrial biogenesis and energy production. The CO-donor treatment also activated Akt, indicating that CO promotes muscle synthesis. CO levels were significantly elevated in the skeletal muscle of normal mice after intravenous administration of CO-RBCs. Furthermore, CO-RBCs restored the mRNA expression levels of PGC-1α in the skeletal muscle of two experimental sarcopenia mouse models, denervated (Den) and hindlimb unloading (HU) models. CO-RBCs also restored muscle mass in Den mice by activating Akt signaling and suppressing the muscle atrophy factors myostatin and atrogin-1, and oxidative stress. Treadmill tests further showed that the reduced running distance in HU mice was significantly restored by CO-RBC administration. These findings suggest that CO-RBCs have potential as an exercise mimetic for sarcopenia treatment. [Display omitted] • CO activates PGC-1α to promote mitochondrial biogenesis in skeletal muscle cells. • CO activates Akt signaling in vitro and in vivo. • CO-RBCs efficiently deliver CO to the skeletal muscles in vivo. • CO-RBCs restore muscle strength and mass in the two mouse models of sarcopenia. • CO-RBCs have potential as an excise mimetic for the treatment of sarcopenia. [ABSTRACT FROM AUTHOR]

Degenerative lumbar spondylolisthesis (DLS) is a prevalent spinal condition that can result in significant disability. DLS is thought to result from a combination of disc and facet joint degeneration, as well as various biological, biomechanical, and behavioral factors. One hypothesis is the progressive degeneration of segmental stabilizers, notably the paraspinal muscles, contributes to a vicious cycle of increasing slippage. To examine the correlation between paraspinal muscle status on MRI and severity of slippage in patients with symptomatic DLS. Retrospective cross-sectional study at an academic tertiary care center. Patients who underwent surgery for DLS at the L4/5 level between 2016–2018 were included. Those with multilevel DLS or insufficient imaging were excluded. The percentage of relative slippage (RS) at the L4/5 level evaluated on standing lateral radiographs. Muscle morphology measurements including functional cross-sectional area (fCSA), body height normalized functional cross-sectional area (HI) of Psoas, erector spinae (ES) and multifidus muscle (MF) and fatty infiltration (FI) of ES and MF were measured on axial MR. Disc degeneration and facet joint arthritis were classified according to Pfirrmann and Weishaupt, respectively. Descriptive and comparative statistics, univariable and multivariable linear regression models were utilized to examine the associations between RS and muscle parameters, adjusting for confounders sex, age, BMI, segmental degeneration, and back pain severity and symptom duration. The study analyzed 138 out of 183 patients screened for eligibility. The median age of all patients was 69.5 years (IQR 62 to 73), average BMI was 29.1 (SD±5.1) and average preoperative ODI was 46.4 (SD±16.3). Patients with Meyerding-Grade 2 (M2, N=25) exhibited higher Pfirrmann scores, lower MF fCSA and MF HI , and lower BMI, but significantly more fatty infiltration in the MF and ES muscles compared to those with Meyerding Grade 1 (M1). Univariable linear regression showed that each cm2 decrease in MF fCSA was associated with a 0.9%-point increase in RS (95% CI -1.4 to - 0.4, p<.001), and each cm2/m2 decrease in MF HI was associated with an increase in slippage by 2.2%-points (95% CI -3.7 to -0.7, p=.004). Each 1%-point rise in ES FI and MF FI corresponded to 0.17%- (95% CI 0.05–0.3, p=.01) and 0.20%-point (95% CI 0.1–0.3 p<.001) increases in relative slippage, respectively. Notably, after adjusting for confounders, each cm2 increase in Psoas fCSA and cm2/m2 in Psoas HI was associated with an increase in relative slippage by 0.3% (95% CI 0.1–0.6, p=.004) and 1.1%-points (95% CI 0.4–1.7, p=.001). While MF fCSA tended to be negatively associated with slippage, this did not reach statistical significance (p=.105). However, each 1%-point increase in MF FI and ES FI corresponded to increases of 0.15% points (95% CI 0.05–0.24, p=.002) and 0.14% points (95% CI 0.01–0.27, p=.03) in relative slippage, respectively. This study found a significant association between paraspinal muscle status and severity of slippage in DLS. Whereas higher degeneration of the ES and MF correlate with a higher degree of slippage, the opposite was found for the psoas. These findings suggest that progressive muscular imbalance between posterior and anterior paraspinal muscles could contribute to the progression of slippage in DLS. [ABSTRACT FROM AUTHOR]

Sarcopenia, characterized by loss of muscle mass and decreased muscle strength, significantly affects adults but also influences pediatric health. However, definitions for low muscle mass, decreased strength, and sarcopenia in children are less established, impacting interventions for improving health outcomes. The objective of this scoping review is synthesize the existing literature on the diagnostic criteria, prevalence and clinical outcomes of sarcopenia. A scoping review, following the PRISMA extension for scoping reviews, examined pediatric sarcopenia literature until June 2023. The literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials with the last search conducted on June 30, 2023. Criteria included studies on aged 0–20 years, covering healthy subjects, acutely ill patients, and chronic disease cases excluding specific conditions like neuromuscular diseases or prematurity. Initial search found 503 studies, finally, we included 56 studies. Most studies diagnosed sarcopenia using skeletal muscle mass indicators like total psoas muscle area from Computed Tomography or Magnetic Resonance Imaging. Around half of the longitudinal studies highlighted sarcopenia as a risk factor for various clinical outcomes, predominantly in hospitalized patients. However, cutoff values for sarcopenia indicators lacked consistency, with studies employing diverse percentile-based measurements or z-scores. Pediatric sarcopenia diagnosis primarily relies on skeletal muscle mass, with identified links to future clinical outcomes in specific conditions. The lack of standardized cutoffs for sarcopenia indicators underscores the necessity for age, gender, and race-specific cutoff values derived from studies establishing reference values for muscle mass and strength across diverse pediatric populations. [ABSTRACT FROM AUTHOR]

• Guava leaf extract (GLE) enhanced muscle strength in muscle atrophy (MA) mice. • GLE normalized abnormal morphological changes in MA mice. • GLE attenuated muscle proteolysis via ubiquitin proteasome system in MA mice. • GLE reduced excessive autophagy and apoptosis, which triggers skeletal muscle damage in MA mice. Muscle atrophy is the waste or loss of muscle mass and is caused by physical inactivity, aging, or diseases such as diabetes, cancer, and heart failure. The number of patients suffering from musculoskeletal disorders is expected to increase in the future. However, intervention for muscle atrophy is limited, so research on treatment for muscle wasting is needed. This study hypothesized that guava leaf (Psidium guajava L. [GL]) would have ameliorative effects on muscle atrophy by regulation of protein degradation pathways in a dexamethasone (DEX)-induced muscle atrophy mice model. Muscle atrophy was induced by DEX injection for 28 days in 7 week-old-male ICR mice. Then, low-dose GL (LGL, 200 mg/kg) or high-dose GL (HGL, 500 mg/kg) extract (GLE) was supplemented by oral gavage for 21 days. Muscle strength, calf thickness, and body composition were analyzed. Histopathological changes in the gastrocnemius muscle were examined using hematoxylin and eosin staining, and molecular pathways related to muscle degradation were analyzed by western blots. GLE treatment regardless of dose increased muscle strength in mice with muscle atrophy accompanied by attenuating autophagy related pathway in the DEX-induced muscle atrophy mice. Moreover, a high dose of GLE treatment ameliorated ubiquitin proteasome system and apoptosis in the DEX-induced muscle atrophy mice. This study suggested that GLE could be helpful to improve muscle health and alleviate proteolysis by regulation of the ubiquitin–proteasome system, autophagy, and apoptosis, which are involved in muscle degradation. In conclusion, GLE could be a potential nutraceutical to prevent muscle atrophy. GLE contains many types of polyphenols such as gallic acid, epicatechin, quercetin, caffeic acid, and others. GLE supplementation attenuated muscle loss and enhanced muscle strength by inhibition of UPS-mediated muscle degradation, mTOR-related autophagy, and apoptosis pathway in DEX-induced muscle atrophy mice. Consequently, GLE might attenuate muscle dysfunction through multiple mechanisms expected to be used to prevent muscle atrophy. Abbreviations: CSA, cross-sectional area; DEX, dexamethasone; GL, guava leaf; GLE, GL extract; UPS, ubiquitin–proteasome system [Display omitted] [ABSTRACT FROM AUTHOR]

This study presents the findings of a newborn screening (NBS) pilot project for 5q-spinal muscular atrophy (5q-SMA) in multiple regions across Russia for during the year 2022. The aim was to assess the feasibility and reproducibility of NBS for SMA5q in diverse populations and estimate the real prevalence of 5q-SMA in Russia as well as the distribution of patients with different number of SMN2 copies. The pilot project of NBS here was based on data, involving the analysis of 202,908 newborns. SMA screening assay was performed using a commercially available real-time polymerase chain reaction kit, the Eonis SCID-SMA. In one year, 202,908 newborns were screened, identifying 26 infants with homozygous deletion of SMN1 exon 7, yielding an estimated 5q-SMA incidence of 1:7804 newborns. It was found that 38.46% had two SMN2 copies, 42.31% had three copies, 15.38% had four copies, and 3.85% had five copies of SMN2. Immediate treatment was proposed for patients with two or three SMN2 copies. Infants with four or more SMN2 copies warranted further investigation on management and treatment. Short-term monitoring after gene therapy showed motor function improvements. Delays in treatment initiation were observed, including the testing for adeno-associated virus 9 antibodies and nonmedical factors. The study emphasizes the need for a standardized algorithm for early diagnosis and management through NBS to benefit affected families. Overall, the NBS program for 5q-SMA in Russia demonstrated the potential to improve outcomes and transform SMA from a devastating disease to a chronic condition with evolving medical requirements. [ABSTRACT FROM AUTHOR]

Atrophy of the paraspinal musculature (PM) as well as generalized sarcopenia are increasingly reported as important parameters for clinical outcomes in the field of spine surgery. Despite growing awareness and potential similarities between both conditions, the relationship between "generalized" and "spine-specific" sarcopenia is unclear. To investigate the association between generalized and spine-specific sarcopenia. Retrospective cross-sectional study. Patients undergoing lumbar spinal fusion surgery for degenerative spinal pathologies. Generalized sarcopenia was evaluated with the short physical performance battery (SPPB), grip strength, and the psoas index, while spine-specific sarcopenia was evaluated by measuring fatty infiltration (FI) of the PM. We used custom software written in MATLAB® to calculate the FI of the PM. The correlation between FI of the PM and assessments of generalized sarcopenia was calculated using Spearman's rank correlation coefficient (rho). The strength of the correlation was evaluated according to established cut-offs: negligible: 0–0.3, low: 0.3–0.5, moderate: 0.5–0.7, high: 0.7–0.9, and very high≥0.9. In a Receiver Operating Characteristics (ROC) analysis, the Area Under the Curve (AUC) of sarcopenia assessments to predict severe multifidus atrophy (FI≥50%) was calculated. In a secondary analysis, factors associated with severe multifidus atrophy in nonsarcopenic patients were analyzed. A total of 125 (43% female) patients, with a median age of 63 (IQR 55–73) were included. The most common surgical indication was lumbar spinal stenosis (79.5%). The median FI of the multifidus was 45.5% (IQR 35.6–55.2). Grip strength demonstrated the highest correlation with FI of the multifidus and erector spinae (rho=-0.43 and -0.32, p<.001); the other correlations were significant (p<.05) but lower in strength. In the AUC analysis, the AUC was 0.61 for the SPPB, 0.71 for grip strength, and 0.72 for the psoas index. The latter two were worse in female patients, with an AUC of 0.48 and 0.49. Facet joint arthropathy (OR: 1.26, 95% CI: 1.11–1.47, p=.001) and foraminal stenosis (OR: 1.54, 95% CI: 1.10–2.23, p=.015) were independently associated with severe multifidus atrophy in our secondary analysis. Our study demonstrates a low correlation between generalized and spine-specific sarcopenia. These findings highlight the risk of misdiagnosis when relying on screening tools for general sarcopenia and suggest that general and spine-specific sarcopenia may have distinct etiologies. [ABSTRACT FROM AUTHOR]

Sarcopenia is associated with reduced quality of life and premature mortality. The sex disparities in the processes underlying sarcopenia pathogenesis, which include mitochondrial dysfunction, are ill-understood and can be decisive for the optimization of sarcopenia-related interventions. To improve the knowledge regarding the sex differences in skeletal muscle aging, the gastrocnemius muscle of young and old female and male rats was analyzed with a focus on mitochondrial remodeling through the proteome profiling of mitochondria-enriched fractions. To the best of our knowledge, this is the first study analyzing sex differences in skeletal muscle mitochondrial proteome remodeling. Data demonstrated that age induced skeletal muscle atrophy and fibrosis in both sexes. In females, however, this adverse skeletal muscle remodeling was more accentuated than in males and might be attributed to an age-related reduction of 17beta-estradiol signaling through its estrogen receptor alpha located in mitochondria. The females-specific mitochondrial remodeling encompassed increased abundance of proteins involved in fatty acid oxidation, decreased abundance of the complexes subunits, and enhanced proneness to oxidative posttranslational modifications. This conceivable accretion of damaged mitochondria in old females might be ascribed to low levels of Parkin, a key mediator of mitophagy. Despite skeletal muscle atrophy and fibrosis, males maintained their testosterone levels throughout aging, as well as their androgen receptor content, and the age-induced mitochondrial remodeling was limited to increased abundance of pyruvate dehydrogenase E1 component subunit beta and electron transfer flavoprotein subunit beta. Herein, for the first time, it was demonstrated that age affects more severely the skeletal muscle mitochondrial proteome of females, reinforcing the necessity of sex-personalized approaches towards sarcopenia management, and the inevitability of the assessment of mitochondrion-related therapeutics. [Display omitted] • Females' age-related muscle atrophy is linked to reduced 17beta-estradiol signaling. • Males' age-related muscle atrophy occurs independently of testosterone signaling. • Age affects more severely the skeletal muscle mitochondrial proteome of females. • Age rises fatty acid oxidation and impairs oxidative phosphorylation only in females. • Age increases the proneness of mitochondrial proteins to oxidation only in females. [ABSTRACT FROM AUTHOR]

Describe a new, safe, technique that uses titanium mesh to partially cover skull defects immediately after decompressive craniectomy (DC). This study is a retrospective review of 8 patients who underwent DC and placement of a titanium mesh. The mesh partially covered the defect and was placed between the temporalis muscle and the dura graft. The muscle was sutured to the mesh. All patients underwent cranioplasty at a later time. The study recorded and analyzed demographic information, time between surgeries, extra-axial fluid collections, postoperative infections, need for reoperation, cortical hemorrhages, and functional and aesthetic outcomes. After craniectomy, all patients underwent cranioplasty within an average of 112.5 days (30–240 days). One patient reported temporalis muscle atrophy, which was the only complication observed. During the cranioplasties, no adhesions were found between temporalis muscle, titanium mesh, and underlying dura. None of the patients showed complications in the follow-up computerized tomography scans. All patients had favorable aesthetic and functional results. Placing a titanium mesh as an extra step during DC could have antiadhesive and protective properties, facilitating subsequent cranioplasty by preventing adhesions and providing a clear surgical plane between the temporalis muscle and intracranial tissues. This technique also helps preserve the temporalis muscle and enhances functional and aesthetic outcomes postcranioplasty. Therefore, it represents a safe alternative to other synthetic anti-adhesive materials. Further studies are necessary to draw definitive conclusions and elucidate long-term outcomes, however, the results obtained hold great promise for the safety and efficacy of this technique. [ABSTRACT FROM AUTHOR]

• FSO protects against dexamethasone-induced skeletal muscle atrophy by preventing loss and rupture of muscle fiber architecture. • FSO ameliorates liver enzymes SGOT and SGPT. • FSO shows protective effects via ameliorating antioxidant makers like SOD, GSH & CAT. • FSO also shows a protective effect on serological lipid profiles (HDL, LDL, triglycerides & total cholesterol) in dexamethasone-induced skeletal muscle atrophy in rat. The production of omega-3 fatty acids in the lipids of muscle tissue was boosted by flaxseed oil (Linum usitatissimum), which is well-described in the Ayurvedic system of medicine. In skeletal muscle disorders, atrophy is a major problem which arises due to cachexia, sarcopenia and immobilization. Nevertheless, despite significant efforts, few FDA-approved medications are available in the market to treat skeletal muscle atrophy. The current project was conceptualized to investigate the protective effects of flaxseed oil against dexamethasone-induced muscular atrophy in adult Sprague Dawley Rats. Marketed preparation of dexamethasone was used to induce muscle atrophy and flaxseed oil was administered orally after disease induction of 7 days till 28 days. Body weight and behavioural studies were carried out to assess muscle mass and glucose. Due to its high antioxidant and fatty acid Omega-3 content, flaxseed oil promotes significant improvements in diseased animals. Rats administered with flaxseed oil demonstrated great weight gain and a decreased blood sugar level. After three weeks-blood sugar levels, muscle mass, momentary changes in rats and HDL levels were all significantly higher in the dexamethasone alone treated control group animals. Flaxseed oil protects against the biochemical and histopathological changes caused due to dexamethasone toxicity. The findings of this study reveals that, flaxseed oil protects against dexamethasone induced skeletal muscle atrophy and protective effect may be due to flaxseed oil's antioxidant properties. However, further research is essential to prove the protective effects of flaxseed oil in some more studies mainly revealing its actions at cellular and molecular level. [ABSTRACT FROM AUTHOR]

This study investigated the preventive effects of whey protein fermented with Lactobacillus gasseri IM13 (F-WP) against dexamethasone (DEX)-induced muscle atrophy. C2C12 muscle cells were treated with F-WP followed by DEX treatment. Dexamethasone treatment inhibited myotube formation and the expression of myogenic regulatory factors; however, pretreatment with F-WP attenuated DEX-induced damage. The F-WP significantly activated the phosphorylation of the IGF-1/PI3K/AKT pathway and improved muscle homeostasis suppressed by DEX. Moreover, F-WP alleviated the phosphorylation of mTOR, S6K1, and 4E-BP1 and enhanced muscle protein synthesis. Muscle-specific ubiquitin ligases and autophagy lysosomes, which were activated by the dephosphorylation of FOXO3a by DEX treatment, were significantly attenuated by F-WP pretreatment of myotubes. For peptidomic analysis, F-WP was fractionated using preparative HPLC (prep-HPLC), and the AA sequences of 11 peptides were identified using MALDI-TOF/MS/MS. In conclusion, fermentation of whey protein by the specific probiotic strain IM13 produced bioactive peptides with high antioxidant and anti-sarcopenic-sarcopenic effects, which markedly enhanced myogenesis and muscle protein synthesis while diminishing muscle protein degradation compared with intact whey protein. [Display omitted] [ABSTRACT FROM AUTHOR]

Ectodysplasin A2 receptor (EDA2R) upregulation in skeletal muscle is associated with aging, denervation, and disease states causing muscle wasting, such as cancer cachexia, muscular dystrophies, critical illness myopathy, and amyotrophic lateral sclerosis. EDA2R signaling, which involves the noncanonical NFκB pathway and NFκB-inducing kinase (NIK), promotes atrophy and insulin resistance in skeletal muscle. Depletion of EDA2R and NIK in mice ameliorates muscle loss linked to cancer cachexia, indicating that therapeutic targeting of this pathway can be beneficial in muscle wasting diseases. Inhibition of the EDA2R–NIK axis improves insulin sensitivity in muscle. Skeletal muscle is essential in generating mechanical force and regulating energy metabolism and body temperature. Pathologies associated with muscle tissue often lead to impaired physical activity and imbalanced metabolism. Recently, ectodysplasin A2 receptor (EDA2R) signaling has been shown to promote muscle loss and glucose intolerance. Upregulated EDA2R expression in muscle tissue was associated with aging, denervation, cancer cachexia, and muscular dystrophies. Here, we describe the roles of EDA2R signaling in muscle pathophysiology, including muscle atrophy, insulin resistance, and aging-related sarcopenia. We also discuss the EDA2R pathway, which involves EDA-A2 as the ligand and nuclear factor (NF)κB-inducing kinase (NIK) as a downstream mediator, and the therapeutic potential of targeting these proteins in the treatment of muscle wasting and metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Children with adolescent idiopathic scoliosis (AIS) may show asymmetrical paraspinal muscle characteristics. To summarize the evidence regarding: (1) the associations between various paraspinal muscle characteristics and spinal curvature; (2) whether paraspinal muscle properties significantly differed between children with and without AIS; and (3) whether baseline paraspinal muscle characteristics predicted curve progression. Systematic literature review. Five databases (CINAHL, Academic Search Premier, MEDLINE, Scopus, and PubMed) were searched from inception to May 2022. This protocol was registered in the PROSPERO database of systematic reviews CRD 42020171263. The Critical appraisal skills program, the Appraisal Tool for Cross-Sectional Studies and Quality In Prognosis Studies tool were used to evaluate the risk of bias of the included studies. The strength of evidence of each identified association was determined by the Grading of Recommendations Assessment, Development, and Evaluation System (GRADE). Of 1,530 identified citations, four cohort, 17 cross-sectional, and 23 case-control studies including 31 with low, nine with moderate and four with high risk of bias were included. Low to very low-strength evidence supported that the convex side of the curve had more type I muscle fibers, higher muscle volume and paraspinal muscle activity, while the concavity had more intramuscular fatty infiltration. Very low-strength evidence substantiated greater side-to-side surface electromyography signals during left trunk bending in prone lying, standing, and standing with perturbation between people with and without AIS. Also, low to very low-strength evidence supported that a larger side-to-side surface electromyography ratio at the lower end vertebra predicted curve progression. Our review highlights that paraspinal muscles on the concavity of the curve demonstrate consistent changes (ie, altered muscle-related gene expression, muscle atrophy, increased fatty infiltration, reduced type I fibers, and reduced muscle activity), which may be the cause or consequence. [ABSTRACT FROM AUTHOR]

Hirayama disease (HD) is a cervical compressive myelopathy. Anterior cervical discectomy and fusion (ACDF) is identified as the best surgical approach. We evaluated surgical outcomes and factors influencing ACDF in HD. Between 2015 and 2019, 126 patients with HD underwent ACDF. Contrast magnetic resonance imaging of the cervical spine in full flexion was performed. Clinical examination and preoperative/postoperative assessment of hand function using Fugl-Meyer assessment, Jebsen-Taylor hand function test, and handheld dynamometry were performed at 3-monthly intervals for 1 year. Surgical outcomes were assessed as per the Odom criteria and Hirayama outcome questionnaire. Age at onset and duration of illness were 12–31 years (mean, 18 ± 2.7) and 1–96 months (32.7 ± 24.4), respectively. All patients had progressive weakness and wasting of the affected limb. Cord atrophy was seen in 97.1%, with epidural detachment and engorgement of the posterior epidural venous plexus in all. All patients underwent ACDF. Of these patients, 54% had an excellent/good outcome and 39% had a satisfactory outcome as per the Odom scale at last follow-up (mean, 44.9 ± 16.5 months) after surgery. Handheld dynamometry showed improvement from preoperative values to 1 year follow-up. Duration of illness and age at onset had a negative correlation and the preoperative Fugl-Meyer score had a positive correlation with improvement. ACDF resulted in remarkable improvement or stabilization in neurologic deficits in many patients with HD. Because motor disability ensues over time, early surgical intervention during the progressive phase is advocated. [ABSTRACT FROM AUTHOR]

To investigate muscle volume changes in all body regions after total hip arthroplasty (THA) with dual-energy X-ray absorptiometry (DEXA), and determine the positive effects of THA for systemic muscle atrophy in patients with hip osteoarthritis (HOA). In total, 116 patients with a mean age of 65.8 (45–84) years who had undergone THA for unilateral HOA were included in this study. DEXA scans were performed serially at 2 weeks, 3, 6, 12, 18, and 24 months after THA. The normalized height squared muscle volume (NMV) and the change ratio of NMV (ΔNMV) were calculated independently for operated lower extremity (LE), non-operated LE, both upper extremities (UEs), and trunk. Skeletal mass index, which is a sum of NMV of both LEs and UEs, was evaluated at 2 weeks and 24 months after THA to identify systemic muscle atrophy equivalent to the diagnostic criteria of sarcopenia. ΔNMVs in non-operated LE, both UEs, and trunk increased gradually up to 6, 12, and 24 months after THA, although that in operated LE did not increase during a 24-month period. The ΔNMVs in operated LE, non-operated LE, both UEs, and trunk at 24 months after THA were +0.6%, +7.1%, +4.0%, and +4.0%, respectively (P = 0.993, P < 0.001, P < 0.001, P = 0.012). The proportion of systemic muscle atrophy significantly decreased from 2 weeks (38%) to 24 months (23%) after THA (P = 0.022). THA can potentially have secondary positive effects for systemic muscle atrophy exception of operated LE. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nutritional support is an essential step to prevent muscle loss in aging process. • Fish oil and wheat oligopeptide had protective effects against sarcopenia in aging. • The combined intervention inhibits skeletal muscle atrophy by regulating protein expression. • The combined intervention promotes protein synthesis and skeletal muscle regeneration. • The combined intervention also reduces inflammation, oxidative stress and blood lipid. Nutritional support is potentially considered an essential step to prevent muscle loss and enhance physical function in older adults. This study aimed to assess the role of potential nutritional strategies, i.e., fish oil-derived ω-3 polyunsaturated fatty acids (PUFAs), wheat oligopeptide and their combined intervention, in preventing and reversing sarcopenia in aging process. One hundred 25-month-old Sprague-Dawley rats were randomly divided into 10 groups, and 10 newly purchased 6-month-old rats were included in young control group (n = 10). Fish oil (200, 400 or 800 mg/kg body weight), wheat oligopeptide (100, 200 or 400 mg/kg body weight), fish oil + wheat oligopeptide (800 + 100, 400 + 200 or 200 + 400 mg/kg body weight) or the equal volume of solvent were administered daily by gavage for 10 weeks. The effects of these interventions on natural aging rats were evaluated. All intervention groups had a significant increase in muscle mass and grip strength and reduction in perirenal fat weight when compared to the aged control group (P < 0.05). The results of biochemical parameters, magnetic resonance imaging, proteomics and western blot suggested that the combination of wheat oligopeptide and fish oil-derived ω-3 PUFA, especially group WFM 2 (400 + 200 mg/kg body weight fish oil + wheat oligopeptide), was found to be more effective against aging-associated muscle loss than single intervention. Additionally, the interventions ameliorated fatty infiltration, muscle atrophy, and congestion in the intercellular matrix, and inflammatory cell infiltration in muscle tissue. The interventions also improved oxidative stress, anabolism, hormone levels, and inflammatory levels of skeletal muscle. The combination of fish oil-derived ω-3 PUFA and wheat oligopeptide was found to be a promising nutritional support to prevent and reverse sarcopenia. The potential mechanism involved the promotion of protein synthesis and muscle regeneration, as well as the enhancement of muscle strength. [ABSTRACT FROM AUTHOR]

Oxidative stress has been implicated in the etiology of skeletal muscle weakness following joint injury. We investigated longitudinal patient muscle samples following knee injury (anterior cruciate ligament tear). Following injury, transcriptomic analysis revealed downregulation of mitochondrial metabolism-related gene networks, which were supported by reduced mitochondrial respiratory flux rates. Additionally, enrichment of reactive oxygen species (ROS)-related pathways were upregulated in muscle following knee injury, and further investigation unveiled marked oxidative damage in a progressive manner following injury and surgical reconstruction. We then investigated whether antioxidant protection is effective in preventing muscle atrophy and weakness after knee injury in mice that overexpress Mn-superoxide dismutase (MnSOD+/−). MnSOD+/− mice showed attenuated oxidative damage, atrophy, and muscle weakness compared to wild type littermate controls following ACL transection surgery. Taken together, our results indicate that ROS-related damage is a causative mechanism of muscle dysfunction after knee injury, and that mitochondrial antioxidant protection may hold promise as a therapeutic target to prevent weakness and development of disability. [Display omitted] • ACL injury and reconstruction reduce quadriceps muscle mitochondrial respiration. • Marked oxidative damage also occurs in muscle in a progressive manner in patients. • In a mouse ACL injury model, MnSOD overexpression prevents muscle oxidative damage. • MnSOD overexpression mitigates ACL injury-induced muscle atrophy and weakness. • Mitochondrial antioxidant protection may improve muscle function after ACL injury. [ABSTRACT FROM AUTHOR]

Downhill running has recently become a promising exercise modality for metabolic syndrome, but the effect and precise mechanism of downhill running training on insulin resistance (IR) induced skeletal muscle atrophy remains unclear. The current study aimed to explore the benefits of downhill running training accompanied by a low-fat diet on skeletal muscle atrophy in IR mice and its possible mechanisms. For in vivo study, high fat diet (HFD) -induced IR mice were submitted to the downhill running training or/and caloric restriction for 8 weeks. In vitro study was performed using co-cultured RAW264.7 macrophages and C2C12 myoblasts model. Glucose tolerance test (GTT), insulin tolerance test (ITT), immunofluorescence staining, Western blot analysis, hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), Cell counting kit-8 (CCK-8) assays and glucose uptake assays were employed to explore the benefits and possible mechanisms of downhill running training accompanied by a low-fat diet on IR mice. Our data revealed that HFD induces IR, which leading to skeletal muscle atrophy. Downhill running accompanied by caloric restriction mitigated HFD-induced IR and improve skeletal muscle atrophy. Further study suggested that descended TRIB3 mediated the favorable impact of downhill running on IR induced skeletal muscle atrophy by suppressing M1-like macrophages and promoting M2-like macrophages. Macrophages-specific knockdown of TRIB3 exerted similar effects on the macrophage polarization and IR related myogenesis to downhill running training accompanied by caloric restriction. In contrast, macrophages-specific overexpression of TRIB3 descended phosphorylation of AKT, further activated M1-like macrophages and aggravated IR related inhibition of myogenesis. This finding demonstrated the beneficial effects of downhill running training and caloric restriction on IR related skeletal muscle atrophy by promoting M2-like macrophages through TRIB3-AKT pathway. [Display omitted] This study has shown that. • The pro-inflammatory M1-like macrophages was significantly elevated in IR induced skeletal muscle atrophy mice. • The improvement of macrophages polarization via downhill running training and caloric restriction alleviate IR and skeletal muscle atrophy. • The important role of TRIB3-AKT pathway to mediate macrophages polarization and skeletal muscle regeneration. These novel findings collectively indicated macrophages polarization regulated by TRIB3-AKT pathway was an important potential mechanism for downhill running training and caloric restriction improving IR-induced skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by skeletal muscle atrophy and weakness. New treatments for SMA have been developed namely, the drugs nusinersen, onasemnogene abeparvovec, and risdiplam. However, there are limited reports on their effects on adult patients with SMA, particularly over long periods. Therefore, this study aimed to determine the efficacy of nusinersen treatment in adult patients with SMA. We retrospectively reviewed patients with SMA type 2 or 3 who received nusinersen treatment between January 2018 and January 2023. All patients were evaluated using the Hammersmith Functional Motor Scale-Expanded (HFMSE) before the commencement of nusinersen treatment, and the change with respect to the baseline HFMSE score was compared. A total of six patients, three patients each with SMA type 2 or 3, were treated with nusinersen. The median age of the patients before the commencement of nusinersen treatment was 51.5 years (range, 33–59 years), and the median treatment period was 50.5 months (range, 33–57 months). Three patients showed an increased tendency of improvement on the HFMSE at 15–26 months after nusinersen treatment, and the HFMSE score was maintained in two patients. Significant adverse events were observed in three patients: one subdural hematoma, one incidental bone fracture, and one cheek dermatofibrosarcoma. Nusinersen treatment showed later efficacy in adult patients with SMA type 2 or 3. The distinct efficacy of nusinersen requires further investigation using a large number of cases and a long follow-up period. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunctions predominantly cause encephalomyopathies with muscle atrophy and neurodegeneration. However, their impact on other tissues, particularly the gastrointestinal tract, requires further investigation. In a recent report in Nature , Moschandrea et al. used mice deficient in the mitochondrial aminoacyl-tRNA synthetase DARS2 to investigate the role of enterocytic mitochondria in dietary lipid processing and transport. Their work sheds light on the development of gastrointestinal disorders as a result of mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

• Safety issues in AAV-based gene therapies may result from different mechanisms specific to the serotype- the transgene or the underlying condition. • Specific risk management plan should be put in place to prevent and to manage serious adverse events. • Safety events observed in humans are not reproduced in animal models and therefore require a strong collaboration between sponsors, investigators, regulators and patients community to be better understood and managed. Adeno-associated virus (AAV) gene therapies are demonstrating much promise in the area of neuromuscular disorders. There are now therapies in clinical trials or real-world use for several disorders including spinal muscular atrophy and Duchenne muscular dystrophy. However, there have been several concerning reports of serious adverse events, including deaths. Reporting and monitoring of these is not consistent between trials. Therefore, a group of clinicians, investigators, industry and patient representatives met the weekend of 17th–19th June 2022 to discuss safety issues arising from the use of these therapies. The group shared information on safety events across a spectrum of AAV gene therapy products, both in clinical trials and commercial use. Patterns of serious adverse events were identified and the group discussed methods of identification and management of these as well as new ways of improving information sharing across industry in order to improve the safety of these promising treatments. [ABSTRACT FROM AUTHOR]

Exercise training during the acute phase of burns is difficult to implement but offers potential benefits. This multicenter trial explored the effects of an exercise program on muscular changes and quality of life during burn center stay. Fifty-seven adults with burns ranging between 10% and 70% TBSA were allocated to receive either standard of care (n = 29), or additionally exercise (n = 28), consisting of resistance and aerobic training, commenced as early as possible according to safety criteria. Muscle wasting (primary outcome), quantified by ultrasound-derived quadriceps muscle layer thickness (QMLT) and rectus femoris cross-sectional area (RF-CSA), muscle strength and quality of life (Burn Specific Health Scale-Brief (BSHS-B) and EQ-5D-5L) were assessed at baseline, four and eight weeks later, or hospital discharge. Mixed models were used to analyze between-group changes over time with covariates of interest added in stepwise forward modeling. The addition of exercise training to standard of care induced significant improvements in QMLT, RF-CSA, muscle strength and the BSHS-B subscale hand function (ß-coefficient. 0.055 cm/week of QMLT, p = 0.005). No added benefit was observed for other quality-of-life measures. Exercise training, administered during the acute phase of burns, reduced muscle wasting, and improved muscle strength throughout burn center stay. • There is a lack of evidence regarding the safety and efficacy of early exercise training in burn care. • Exercise training during the acute phase of burns increased muscle size and strength. • The short-term effects on quality-of-life parameters remain to be established. • Early exercise training is feasible and beneficial for adults with acute burns. [ABSTRACT FROM AUTHOR]

Muscle wasting is a currently incurable debilitating condition associated with multiple disease states, including cancer, kidney failure, and aging. Clinical trials involving drugs targeting the muscle loss in patients have yet to report improvements in both muscle mass and muscle strength. Studies on emerging pathways – such as growth differentiation factor 15 (GDF15), oncostatin M, and ectodysplasin A2 receptor (EDA2R)/nuclear factor κB (NFκB)-inducing kinase (NIK) – have presented new opportunities to target muscle wasting. Muscle wasting is a serious comorbidity associated with many disorders, including cancer, kidney disease, heart failure, and aging. Progressive loss of skeletal muscle mass negatively influences prognosis and survival, and is often accompanied by frailty and poor quality of life. Clinical trials testing therapeutics against muscle wasting have yielded limited success. Some therapies improved muscle mass in patients without appreciable differences in physical performance. This review article discusses emerging pathways that regulate muscle atrophy, including oncostatin M (OSM) and ectodysplasin A2 (EDA2) receptor (EDA2R) signaling, outcomes of recent clinical trials, and potential drug targets for future therapies. [ABSTRACT FROM AUTHOR]

The role of mitochondrial dysfunction in mediating skeletal muscle atrophy and therapeutic approaches. [Display omitted] • Skeletal muscle atrophy is characterized by a decrease in muscle strength and endurance, negatively affecting the quality of life. • Mitochondria in skeletal muscle atrophy play a critical role in several processes such as ATP production, metabolic processes, redox homeostasis, and regulation of apoptosis. • Mitochondrial signaling pathways to skeletal muscle atrophy in CVDs include ubiquitin–proteasome system, autophagy, mitophagy, mitochondrial fission–fusion and mitochondrial biogenesis. • Exercise, mitochondria-targeted antioxidants, and PGC-1 via in vivo transfection are some of the current therapeutic strategies for skeletal muscle atrophy. • Mitochondrial transplantation might be one of the possible therapeutic approaches for skeletal muscle atrophy. Skeletal muscle, which accounts for approximately 40% of total body weight, is one of the most dynamic and plastic tissues in the human body and plays a vital role in movement, posture and force production. More than just a component of the locomotor system, skeletal muscle functions as an endocrine organ capable of producing and secreting hundreds of bioactive molecules. Therefore, maintaining healthy skeletal muscles is crucial for supporting overall body health. Various pathological conditions, such as prolonged immobilization, cachexia, aging, drug-induced toxicity, and cardiovascular diseases (CVDs), can disrupt the balance between muscle protein synthesis and degradation, leading to skeletal muscle atrophy. Mitochondrial dysfunction is a major contributing mechanism to skeletal muscle atrophy, as it plays crucial roles in various biological processes, including energy production, metabolic flexibility, maintenance of redox homeostasis, and regulation of apoptosis. In this review, we critically examine recent knowledge regarding the causes of muscle atrophy (disuse, cachexia, aging, etc.) and its contribution to CVDs. Additionally, we highlight the mitochondrial signaling pathways involvement to skeletal muscle atrophy, such as the ubiquitin–proteasome system, autophagy and mitophagy, mitochondrial fission–fusion, and mitochondrial biogenesis. Furthermore, we discuss current strategies, including exercise, mitochondria-targeted antioxidants, in vivo transfection of PGC-1α, and the potential use of mitochondrial transplantation as a possible therapeutic approach. [ABSTRACT FROM AUTHOR]

• Symptoms of neuromuscular disease resulting from vitamin D deficiency. • Loss of ambulation and muscle atrophy presenting in nutritional rickets. • Avoiding anchoring bias in pediatric subspecialty care. Muscle atrophy, weakness, and loss of ambulation in the pediatric population are signs of progressive neuromuscular diseases. Rapid identification of such diseases is important to prevent further progression. In pediatric neurology, it is well understood to include neuromuscular disorders in the differential for such presentations. We report a case of severe nutritional rickets that mimicked the presentation of spinal muscular atrophy type III and discuss the importance of including rickets in the differential for muscle atrophy and loss of ambulation. A 33-month-old African American boy with several months of gait abnormality was referred to outpatient neurology. The initial diagnostic evaluation focused primarily on neuromuscular disorders, specifically SMA type III, given the absence of reflexes on examination and the history of prior ambulation. After an unfruitful genetic workup, it was elucidated that the child had very poor dietary intake and minimal sun exposure causing nutritional rickets that improved with intervention. [ABSTRACT FROM AUTHOR]

Heat stress (HS) markedly affects postabsorptive energetics and protein metabolism. Circulating urea nitrogen increases in multiple species during HS and it has been traditionally presumed to stem from increased skeletal muscle proteolysis; however, this has not been empirically established. We hypothesized HS would increase activation of the calpain and proteasome systems as well as increase degradation of autophagosomes in skeletal muscle. To test this hypothesis, lactating dairy cows (~139 d in milk; parity ~2.4) were exposed to thermal neutral (TN) or HS conditions for 7 d (8 cows/environment). To induce HS, cattle were fitted with electric blankets for the duration of the heating period and the semitendinosus was biopsied on d 7. Heat stress increased rectal temperature (1.3°C) and respiratory rate (38 breaths per minute) while it decreased dry matter intake (34%) and milk yield (32%). Plasma urea nitrogen (PUN) peaked following 3 d (46%) and milk urea nitrogen (MUN) peaked following 4 d of environmental treatment and while both decreased thereafter, PUN and MUN remained elevated compared with TN (PUN: 20%; MUN: 27%) on d 7 of HS. Contrary to expectations, calpain I and II abundance and activation and calpain activity were similar between groups. Likewise, relative protein abundance of E3 ligases, muscle atrophy F-box protein/atrogin-1 and muscle ring-finger protein-1, total ubiquitinated proteins, and proteasome activity were similar between environmental treatments. Finally, autophagosome degradation was also unaltered by HS. Counter to our hypothesis, these results suggest skeletal muscle proteolysis is not increased following 7 d of HS and call into question the presumed dogma that elevated skeletal muscle proteolysis, per se, drives increased AA mobilization. [ABSTRACT FROM AUTHOR]

[Display omitted] • Gradual decrease in total protein crotonylation level was observed during muscle differentiation. • Decreased crotonylation of AKT1 facilitated an increase in AKT1 phosphorylation. • Crotonylation of AKT1 weakened its binding with PDK1 and impaired its phosphorylation. • Increased expression of the crotonylation eraser HDAC3 decreased AKT1 crotonylation levels during myogenic differentiation, jointly promoting myogenic differentiation. • This is of great significance for exploring the pathophysiological process of muscle injury repair and sarcopenia. Myogenic differentiation plays an important role in pathophysiological processes including muscle injury and regeneration, as well as muscle atrophy. A novel type of posttranslational modification, crotonylation, has been reported to play a role in stem cell differentiation and disease. However, the role of crotonylation in myogenic differentiation has not been clarified. This study aims to find the role of crotonylation during myogenic differentiation and explore whether it is a potential target in myogenic dysfunction disease. C2C12 cell line and skeletal muscle mesenchymal progenitors of Mus musculus were used for myogenic process study in vitro, while muscle injury model of mice was used for in vivo muscle regeneration study. Mass spectrometry favored in discovery of potential target protein of crotonylation and its specific sites. We confirmed the gradual decrease in total protein crotonylation level during muscle differentiation and found decreased crotonylation of AKT1, which facilitated an increase in AKT1 phosphorylation. Then we verified that crotonylation of AKT1 at specific sites weakened its binding with PDK1 and impaired its phosphorylation. In addition, we found that increased expression of the crotonylation eraser HDAC3 decreased AKT1 crotonylation levels during myogenic differentiation, jointly promoting myogenic differentiation. Our study highlights the important role of decrotonylation of AKT1 in the process of muscle differentiation, where it aids the phosphorylation and activation of AKT1 and promotes myogenic differentiation. This is of great significance for exploring the pathophysiological process of muscle injury repair and sarcopenia. [ABSTRACT FROM AUTHOR]

A 63-year-old man diagnosed with mixed-type cervical spondylotic amyotrophy exhibited severe atrophy in the right biceps brachii, teres major, and intrinsic hand muscles, resulting in level 3 muscle weakness. Magnetic resonance imaging showed symmetrical high signal, also referred to as the snake eye sign. Previously, he was erroneously diagnosed with amyotrophic lateral sclerosis. He had undergone anterior cervical surgery 7 years prior. At present, his right upper limb muscles display minimal atrophy compared with the left, with muscle strength nearing level 4, which is considered normal. We believe that prompt surgical intervention on diagnosis of cervical spondylotic amyotrophy, along with comprehensive postsurgery rehabilitation, can halt further deterioration of the condition and accelerate recovery. [ABSTRACT FROM AUTHOR]

Hirayama disease or juvenile-onset monomelic amyotrophy is a clinical syndrome that disproportionately affects young males. Standard of care revolves around conservative management, but some patients experience disease progression that may benefit from surgical intervention. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of previous reports of surgical treatment for Hirayama disease was performed. Studies were included if they provided individual patient-level data, described the clinical presentation and surgical intervention, and reported neurological improvement at last follow-up. Comparison between those who improved and those with stable symptoms at last follow-up was performed. Decision-tree analysis was used to identify the best predictors of neurological improvement by last follow-up. Of 624 unique articles, 30 were included in the qualitative review and 23 in the meta-analysis. Among the 70 patients in the meta-analysis, mean age was 21.2 ± 6.3 years, 91% were male, and mean symptom duration at presentation was 43.3 ± 61.8 months. Fifty-nine patients (84.3%) had improvement in their neurological symptoms by last follow-up. Univariable analysis showed the only significant predictor of improvement in neurological symptoms by last follow-up was the use of stabilization-alone versus decompression with or without stabilization. Baseline clinical symptoms nor radiographic features predicted outcome. Decision-tree analysis showed surgical strategy (stabilization-alone vs. decompression ± stabilization), age (<20 vs. ≥20), and surgical approach (anterior-only vs. posterior-only or anterior-posterior) predicted a higher likelihood of neurological improvement by last follow-up. Nearly 85% of patients experienced improvement in neurological symptoms. Improvement was best for those who underwent stabilization-alone, and decision-tree analysis suggested that the likelihood of improvement was also superior for patients under 20 years of age and those treated with an anterior versus posterior or staged approach. [ABSTRACT FROM AUTHOR]

Plasma thymidine levels in rodents are higher than in other mammals including humans, possibly due to a different pattern and lower level of thymidine phosphorylase expression. Here, we generated a novel knock-in (KI) mouse line with high systemic expression of human thymidine phosphorylase to investigate this difference in nucleotide metabolism in rodents. The KI mice showed growth retardation around weaning and died by 4 weeks of age with a decrease in plasma thymidine level compared with the litter-control WT mice. These phenotypes were completely or partially rescued by administration of the thymidine phosphorylase inhibitor 5-chloro-6-(2-iminopyrrolidin-1-yl) methyl-2,4(1H,3H)-pyrimidinedione hydrochloride or thymidine, respectively. Interestingly, when thymidine phosphorylase inhibitor administration was discontinued in adult animals, KI mice showed deteriorated grip strength and locomotor activity, decreased bodyweight, and subsequent hind-limb paralysis. Upon histological analyses, we observed axonal degeneration in the spinal cord, muscular atrophy with morphologically abnormal mitochondria in quadriceps, retinal degeneration, and abnormality in the exocrine pancreas. Moreover, we detected mitochondrial DNA depletion in multiple tissues of KI mice. These results indicate that the KI mouse represents a new animal model for mitochondrial diseases and should be applicable for the study of differences in nucleotide metabolism between humans and mice. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the relationship between lumbar disc herniation and Goutallier classification (GC), lumbar indentation value, and subcutaneous adipose tissue thickness. 102 consecutive patients (59 female and 43 male) with lumbar back pain, numbness, tingling, or pain in the lower extremity indicating radiculopathy who had undergone lumbar magnetic resonance imaging (MRI) and had an intervertebral disc herniation in the L4-5 level, were included in the study. 102 patients who have undergone lumbar MRI in the same time period and have no disc herniation were chosen to be the control group and were selected so as to match the herniated group for sex and age. All these patients' scans were re-interpreted regarding paraspinal muscle atrophy (using the GC), lumbar indentation value, and subcutaneous adipose tissue thickness in the L4-5 level. The Goutallier score was higher in the herniated group, compared with the non-herniated group (p < 0.001). There was no statistical difference between herniated and non-herniated groups regarding lumbar indentation value (LIV) and subcutaneous adipose tissue thickness (SATT). A Goutallier score of 1.5 provided the highest sensitivity x specificity value to indicate the disc herniation according to the statistical results. The individuals with a Goutallier score of 2, 3, and 4 have 2.87 times more likely to have disc herniation in their MRIs than the ones with a score of 0 and 1. Paraspinal muscle atrophy seems to be related to the presence of disc herniations. The cut-off value of GC to indicate the disc herniation in this study might be useful to predict the risk for disc herniation regarding the Goutallier score. The LIV and SATT measured in magnetic resonance images were randomly distributed between individuals with herniated and non-herniated groups, and statistically, no relationship was observed between these groups regarding these parameters. The effect of the parameters studied in this research on disc herniations are expected to be an added value to the literature. The awareness of risk factors for intervertebral disc herniations might be used in preventive medicine to predict the risk and understand the tendency of an individual for disc herniations to occur in the future. Further investigations are needed to establish whether there is a causal relationship or correlation between these parameters and disc herniation. [ABSTRACT FROM AUTHOR]

Lespedeza bicolor (LB) is known to have antidiabetic activities; however, the underlying molecular mechanisms of LB in hyperglycemia-induced skeletal muscle damage is unclear. Inflammation and oxidative stress caused by type 2 diabetes mellitus (T2DM) not only contributes to insulin resistance, but also promotes muscle atrophy via decreased muscle protein synthesis and increased protein degradation, leading to frailty and sarcopenia. In this study, we hypothesized that LB extract (LBE) supplementatin has an ameliorative effect on hyperglycemia-induced skeletal muscle damage by activation of 5′ adenosine monophosphate-activated protein kinase (AMPK)/sirtuin (SIRT)/proliferator-activated receptor γ coactivator 1α (PGC1α)–associated energy metabolism in mice with T2DM. Diabetes was induced by a high-fat diet with a 2-time streptozotoxin injection (30 mg/kg body weight) in male C57BL/6J mice. After diabetes was induced (fasting blood glucose level ≥140 mg/dL), the mice were administered with LBE at a low dose (100 mg/kg/d) or high dose (250 mg/kg/d) by gavage for 12 weeks. LBE supplementation ameliorated glucose tolerance and hemoglobin A1c (%) in mice with T2DM. Moreover, LBE supplementation upregulated protein levels of insulin receptor subunit-1 and Akt accompanied by increased translocation of glucose transporter 4 in mice with T2DM. Furthermore, LBE increased mitochondrial biogenesis by activating SIRT1, SIRT3, SIRT4, and peroxisome PGC1α in diabetic skeletal muscle. Meanwhile, LBE supplementation reduced oxidative stress and inflammation in mice with T2DM. Taken together, the current study suggested that LBE could be a potential therapeutic to prevent skeletal muscle damage by regulation AMPK/SIRT/PGC1α–related energy metabolism in T2DM. Lespedeza bicolor (LB) contains many antioxidant compounds, including genistein, quercetin, daidzein, catechin, luteolin, and naringin. The natural compounds rich in LB extract (LBE) improved skeletal muscle energy metabolism with insulin signaling by regulation of 5′ adenosine monophosphate-activated protein kinase (AMPK)/sirtuin (SIRT)1/proliferator-activated receptor gamma coactivator-1 α (PGC1α) pathway in type 2 diabetes mellitus (T2DM) mice. Furthermore, LBE reduced oxidative stress and inflammation causing muscle protein degradation in T2DM mice. Consequently, LBE is expected to be a potential nutraceutical for alleviating hyperglycemia-induced skeletal muscle damage in T2DM. ROS, reactive oxygen species. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite the impact of muscle wasting after burn, tools to quantify muscle wasting are lacking. This multi-centre study examined the utility of ultrasound to measure muscle mass in acute burn patients comparing different methodologies. B-mode ultrasound was used by two raters to determine feasibility and inter-rater reliability in twenty burned adults following admission. Quadriceps muscle layer thickness (QMLT) and rectus femoris cross-sectional area (RF-CSA) were measured, comparing the use of i) a single versus average measurements, ii) a proximal versus distal location for QMLT, and iii) a maximum- versus no-compression technique for QMLT. Analysis of twenty burned adults (50 years [95%CI 42–57], 32%TBSA [95%CI 23–40]) yielded ICCs of> 0.97 for QMLT (for either location and compression technique) and> 0.95 for RF-CSA, using average measurements. Relative minimal detectable changes were smaller using no-compression than maximum-compression (6.5% vs. 15%). Using no-compression to measure QMLT was deemed feasible for both proximal and distal locations (94% and 96% of attempted measurements). In 9.5% of cases maximum-compression was not feasible. 95% of RF-CSA measurements were successfully completed. Ultrasound provides feasible and reliable values of quadriceps muscle architecture that can be adapted to clinical scenarios commonly encountered in acute burn settings. [Display omitted] • Ultrasound assessment of the quadriceps is feasible at burn centre admission • This study demonstrates high inter-rater reliability and sensitivity • Ultrasound can be carried out irrespective of wound status, thigh size, oedema • Ultrasound provides a means to monitor muscle wasting throughout hospital stay [ABSTRACT FROM AUTHOR]

Our primary aim was to demonstrate the effect of high protein on diaphragm muscle thickness, our secondary aim was to evaluate the correlation of diaphragm thickness fraction with rectus femoris muscle thickness in high protein patients. This study included 49 mechanically ventilated patients who were randomly divided into a standard protein (1.2 g/kg/d) group and high protein group (2.0 g/kg/d). Thickness of rectus femoris, thickness of peak inspiratory diaphragm, thickness of end expiratory diaphragm were measured by ultrasonography. Thickness fraction of diaphragm was calculated. In the high protein group, thickness of peak inspiratory diaphragm values were found to be statistically significantly higher on days 3rd, 5th, 7th, and 15th (P < 0.05). Thicknesses of end-expiratory diaphragm values were found to be statistically significantly higher on the 3rd, 5th and 7th days (P < 0.05). Thicknesses fraction of diaphragm values were found to be statistically significantly higher on days 3rd, 5th, 7th and 15th (P < 0.05) in the high protein group. Thicknesses of rectus femoris values were higher in the high protein group compared with standard protein group on the 5th, 7th, and 15th days (P < 0.005). In high protein group, statistically significant correlations were found between thickness of rectus femoris and thickness fraction of diaphragm at the 3rd day (rho = 0.429, P = 0.032). This study showed that diaphragmatic muscle thicknesses were higher in patients who received 2 g/kg/d protein supplement, These findings have shown that muscle atrophy can be prevented with high protein support in the intensive care unit. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterised by muscle weakness and muscle atrophy and classified into five known subtypes based on clinical features. The recent development of novel drugs to treat SMA has been encouraging, and nusinersen is the first drug approved to treat SMA. To explore cerebrospinal fluid (CSF) biomarkers of SMA and investigate their relationship with symptoms and the treatment response in pediatric patients. We analyzed the CSF levels of chitotriosidase 1 (CHIT1) and inflammatory cytokines (tumor necrosis factor [TNF]-α and interferon [INF]-γ) using enzyme-linked immunosorbent assays in pediatric SMA patients treated at Hiroshima University Hospital over 2 years. This study analyzed pediatric SMA patients. While the CSF inflammatory cytokines (TNF-α and INF-γ) in these SMA children were unchanged, the CHIT1 levels decreased significantly from year 1 to 2 of treatment. We also found a trend toward an inverse correlation between the motor function score (HINE-2 scores) and CHIT1 level from year 1 to 2 of treatment. CHIT1 may be a CSF biomarker of the treatment response in pediatric SMA. [ABSTRACT FROM AUTHOR]

The anterior displacement of the articular disc is the most frequent cause of pathological alterations in the TMJ. Although it is an extremely common pathology, there is no certainty about the aetiopathogenesis of this disease. The main aim of the present report is to describe new anatomical findings that could help clarifying the aetiopathogenesis of this disease and determine a typology of treatment based on the cause of the disease. All the operative records of patients who underwent arthroscopic osteoplasty of the medial TMJ wall in our centre from January 2021 to September 2021 were reviewed and analysed to identify specific anatomical features observed in every procedure. Fifty-two joints were included for analysis in this study. Twenty-two joints were classified as Wilkes stages II-III and 30 as Wilkes stages IV-V. The most common complication observed in our sample was the dysaesthesias found in the temporal and preauricular regions. Other complications observed were frontal branch paresis (n = 2), intraoperative bleeding (n = 1), and postoperative malocclusion (n = 1). The compression of the superior head of pterygoid lateral muscle (SPLM) on the medial bony wall and the consequent muscle atrophy could be key for the aetiology of the anterior TMJ disc displacement. Therapeutic actions on the osseous and muscular component in this anatomical area could improve the outcomes of patients affected by TMJ internal derangement. A meticulous dissection of the fascia of the superior fascicle of the lateral pterygoid muscle allows a remodelling of the bone surfaces with minimal complications [ABSTRACT FROM AUTHOR]

Physical inactivity is the fourth leading global cause of death and is a major contributor to metabolic and endocrine diseases. In this review we provide a current update of the past 5 years in the field as it pertains to the most prevalent and deadly chronic diseases. Despite the prevalence of physical inactivity in modern society, it remains largely overlooked relative to other comparable risk factors such as obesity, and our molecular understanding of how physical inactivity impacts metabolism is still partially unknown. Therefore, we discuss current clinical inactivity models along with their most recent findings regarding health outcomes along with any discrepancies that are present in the field. Lastly, we discuss future directions and the need for translatable animal models of physical inactivity to discover novel molecular targets for the prevention of chronic disease. Physical inactivity and sedentary behavior are major contributors to endocrine and metabolic diseases. Recent clinical studies show bed rest induces insulin resistance, reduced VO 2max , increased blood pressure, etc. People that are classified as physically inactive are 1.4 times more likely to develop dementia, and insulin resistance is hypothesized to drive cognitive decline. The most physically inactive individuals are 1.75 times more likely to develop cardiovascular disease, as inactivity is one of the greatest single risk factors. Aging and declining physical activity levels lead to sarcopenia and muscle atrophy, which is associated with an increased risk of premature death. [ABSTRACT FROM AUTHOR]

Skeletal muscle in patients with heart failure (HF) exhibits altered structure, function and metabolism. Myocardial infarction (MI) is the most common cause of HF. Oxidative stress and cell apoptosis are involved in the pathophysiology of MI/HF-induced skeletal muscle atrophy. It is well recognized that aerobic exercise (AE) could prevent skeletal muscle atrophy after MI, but the underlying mechanism and molecular targets are still not fully clarified. In this study, Fndc5 −/− and Alcat1 −/− mice were used to establish the MI model and subjected to six weeks of moderate-intensity AE. C2C12 cells were treated with H 2 O 2 and recombinant human Irisin (rhIrisin), or transduced with a lentiviral vector to mediate the overexpression of ALCAT1 (LV- Alcat1). Results showed that MI reduced Irisin expression and antioxidant capacity of skeletal muscle, increased ALCAT1 expression, induced protein degradation and cell apoptosis, which were partly reversed by AE; Knockout of Fndc5 further aggravated MI-induced oxidative stress and cell apoptosis in skeletal muscle, and partly weakened the beneficial effects of AE. In contrast, knockout of Alcat1 reduced MI-induced oxidative stress and cell apoptosis and strengthened the beneficial effects of AE. rhIrisin and AICAR intervention inhibited ALCAT1 expression, oxidative stress and cell apoptosis, which induced by H 2 O 2 or LV- Alcat1 in C2C12 cells. These findings reveal that AE could alleviate the levels of oxidative stress and apoptosis in skeletal muscle following MI, partly via up-regulating Irisin and inhibiting ALCAT1 expression. [Display omitted] • Aerobic exercise (AE) regulated Irisin and ALCAT1 expression in skeletal muscle after myocardial infarction (MI). • Irisin participates in the AE-alleviated skeletal muscle atrophy following MI by inhibiting oxidative stress and apoptosis. • ALCAT1 is involved in MI-induced oxidative stress and cell apoptosis, which inhibited by AE. • Irisin inhibit ALCAT1 expression and apoptosis through PI3K/Akt signaling. [ABSTRACT FROM AUTHOR]

Exercise is beneficial for muscle atrophy. Peroxisome proliferator-activated receptor gamma (PPARγ) and microRNA-29b (miR-29b) have been reported to be responsible for angiotensinⅡ (AngⅡ)-induced muscle atrophy. However, it is unclear whether exercise can protect AngⅡ-induced muscle atrophy by targeting PPARγ/miR-29b. Skeletal muscle atrophy in both the control group and the run group was established by AngⅡ infusion; after 1 week of exercise training, the mice were sacrificed, and muscle weight was determined. Myofiber size was measured by hematoxylin-eosin and wheat-germ agglutinin staining. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression level of muscle atrogenes, including F-box only protein 32 (FBXO32, also called Atrogin-1) and muscle-specific RING-finger 1 (MuRF-1), the phosphorylation level of protein kinase B (PKB, also called AKT)/forkhead box O3A (FOXO3A)/mammalian target of rapamycin (mTOR) pathway proteins, the expression level of PPARγ and apoptosis-related proteins, including B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cysteine-aspartic acid protease 3 (caspase-3), and cleaved-caspase-3, were determined by western blot. The expression level of miR-29b was checked by reverse-transcription quantitative polymerase chain reaction. A PPARγ inhibitor (T0070907) or adeno-associated virus serotype-8 (AAV8)-mediated miR-29b overexpression was used to demonstrate whether PPARγ activation or miR-29b inhibition mediates the beneficial effects of exercise in AngⅡ-induced muscle atrophy. Exercise can significantly attenuate AngⅡ-induced muscle atrophy, which is demonstrated by increased skeletal muscle weight, cross-sectional area of myofiber, and activation of AKT/mTOR signaling and by decreased atrogenes expressions and apoptosis. In AngⅡ-induced muscle atrophy mice models, PPARγ was elevated whereas miR-29b was decreased by exercise. The protective effects of exercise in AngⅡ-induced muscle atrophy were inhibited by a PPARγ inhibitor (T0070907) or adeno-associated virus serotype-8 (AAV8)-mediated miR-29b overexpression. Exercise attenuates AngⅡ-induced muscle atrophy by activation of PPARγ and suppression of miR-29b. [Display omitted] [ABSTRACT FROM AUTHOR]

In addition to the diaphragm's role as the primary respiratory muscle, it also plays an under-recognized role in cardiac function. It serves as a pump facilitating venous and lymph return, modulating left ventricular afterload hemodynamics and pericardial pressures, as well as regulating autonomic tone. Heart failure (HF) is associated with diaphragmatic changes (ie, muscle fiber atrophy and weakness, increased ratio of type I to type II muscle fibers, and altered muscle metaboreflex) that lead to diaphragmatic dysfunction with subsequent symptomatic manifestations of HF. Herein, it is proposed that targeting the diaphragm in patients with HF via inspiratory muscle training or device-based stimulation can provide a novel treatment pathway for HF. Reviewed are several potential mechanisms through which therapies targeting the diaphragm can be beneficial in HF (ie, improving preload reserve, atrial and ventricular synchrony, and metaboreflex activity; reducing pericardial restraint; and restoring diaphragm strength). [ABSTRACT FROM AUTHOR]

• We identified a SCN4A mutation (p.L703P) in a Chinese family with non-dystrophic myotonias (NDM). • Characterization of mutant channel revealed both gain-of-function and loss-of-function changes in gating properties. • Literature search results in two independent case reports of NDM patients carrying L703P mutation in Nav1.4 channels. • The L703P is a recurrent mutation associated with NDM. The non-dystrophic myotonias are inherited skeletal muscle disorders characterized by skeletal muscle stiffness after voluntary contraction, without muscle atrophy. Based on their clinical features, non-dystrophic myotonias are classified into myotonia congenita, paramyotonia congenita, and sodium channel myotonia. Using whole-exome next-generation sequencing, we identified a L703P mutation (c.2108T>C, p.L703P) in SCN4A in a Chinese family diagnosed with non-dystrophic myotonias. The clinical findings of patients in this family included muscle stiffness and hypertrophy. The biophysical properties of wildtype and mutant channels were investigated using whole-cell patch clamp. L703P causes both gain-of-function and loss-of-function changes in Nav1.4 properties, including decreased current density, impaired recovery, enhanced activation and slow inactivation. Our study demonstrates that L703P is a pathogenic variant for myotonia, and provides additional electrophysiological information for understanding the pathogenic mechanism of SCN4A -associated channelopathies. [ABSTRACT FROM AUTHOR]

It has been reported that in patients with spinal muscular atrophy (SMA), lower levels of motor function are associated with hyperleptinemia. Additionally, hyperleptinemia has been found to be more frequent in underweight SMA patients. Therefore, we aimed to analyze serum leptin levels in patients with SMA. This was a cross-sectional study of pediatric patients (2–19 years old) with SMA types 2 and 3. The investigations included anthropometric measurements, assessment of pubertal status, motor function evaluation using the Hammersmith Functional Motor Scale – Expanded (HFMSE), and serum leptin levels. In total, 37 patients (22 with type 2 and 15 with type 3 SMA) were included in the study. The male-to-female ratio was 1:1.3 and 62.2% of patients were prepubertal. No statistically significant correlation was found between the HFMSE score and leptin levels, r s (35) = 0.24, p = 0.15. There was, however, a strong positive relationship between the body mass index (BMI) z-score and leptin levels, r s (35) = 0.87, p < 0.001. Serum leptin levels do not seem to be a useful marker of disease severity in children and adolescents with types 2 and 3 SMA. As in the general pediatric population, leptin levels are strongly correlated with BMI, which is a surrogate measure of body fat. [ABSTRACT FROM AUTHOR]

The mitochondria are double-membrane organelles integral for energy metabolism. Mitochondrial dynamics is regulated by inner and outer mitochondrial membrane (IMM and OMM) proteins, which promote fission and fusion. Optic atrophy 1 (OPA1) regulates IMM fusion, prevents apoptosis, and is a key regulator of morphological change in skeletal and cardiac muscle physiology and pathophysiology. OPA1 fuses the inner membranes of adjacent mitochondria, allowing for an increase in oxidative phosphorylation (OXPHOS). Considering the importance of energy metabolism in whole-body physiology, OPA1 and its regulators have been proposed as novel targets for the treatment of skeletal muscle atrophy and heart failure. Here, we review the role and regulation of OPA1 in skeletal muscle and cardiac pathophysiology, epitomizing its critical role in the cell. Mitochondria are known for their role in energy metabolism and play important roles in regulating apoptosis, calcium storage, and signaling. Optic atrophy 1 (OPA1) mediates inner mitochondrial membranes of adjacent mitochondria and is therefore crucial in increasing mitochondrial membrane cross-sectional area and thus oxidative phosphorylation. A reduction in OPA1 expression leads to mitochondrial fragmentation, resulting in skeletal muscle atrophy, and has been linked to the onset of metabolic disease such as type 2 diabetes. Altered OPA1 function has been proposed to contribute to the pathogenesis of heart failure. Chronic/acute exercise training results in more fused, tubular skeletal muscle mitochondrial networks, which is reflected by an increase in skeletal muscle OPA1 expression. [ABSTRACT FROM AUTHOR]

• Establishing a method for determination of CaHMB in special medical formula food and sports nutrition food by HPLC. • SPE purification method was firstly introduced to analyze real samples. • Good purification effect, high separation specificity, good repeatability and accuracy. Calcium β‑hydroxy-β-methylbutyrate (CaHMB) can promote muscle growth, prevent muscle atrophy, and enhance immunity, therefore, it is widely used as a nutritional supplement in special medical formula food and sports nutrition food. Many methods for the detection of CaHMB have been reported, but the pretreatment method for these reported literatures directly involves extraction using hydrochloric acid solution, without any purification steps. A method for accurately determining CaHMB in special medical formula food and sports nutrition food was established for the first time using solid-phase extraction (SPE) purification and high-performance liquid chromatography method (HPLC). The samples were extracted and precipitated protein using methanol-water solution, purified using SPE method and analyzed by HPLC on diode array detector (DAD) mode under external standard method. The method obtained excellent calibration linearity (r2>0.9993) and a satisfactory analysis of the targeted compound, which were evaluated with calibration standards over the range of 0.020–2.00 mg/mL. The limit of quantifications (LOQs), which defined as the lowest spiking level, were set at 0.4 g/100 g (special medical formula food) and 1.0 g/100 g (sports nutrition food). The average recoveries were within 92.9–104% for the analytes, and the relative standard deviations (RSDs) were below 3.93%, measured at low, medium, and high concentrations. Moreover, the positive sample analysis results indicated that CaHMB was detected on 10 real special medical formula food and sports nutrition food products, the contents of which were generally consistent with their labeled values, with measured values ranging from 97.1 % to 119 % of the labeled values. These results suggested that the developed highly sensitive and specific method is highly feasible for monitoring of the target analyte in special medical formula food and sports nutrition food. [ABSTRACT FROM AUTHOR]

Obesity-induced muscle atrophy leads to physical impairment and metabolic dysfunction, which are risky for older adults. The activity of pyruvate dehydrogenase (PDH), a critical regulator of glucose metabolism, is reduced in obesity. Additionally, PDH activator dichloroacetate (DCA) improves metabolic dysfunction. However, the effects of PDH activation on skeletal muscles in obesity remain unclear. Thus, this study aimed to evaluate the effects of PDH activation by DCA treatment on obesity-induced muscle atrophy in vitro and in vivo and elucidate the possible underlying mechanisms. Results showed that PDH activation by DCA treatment ameliorated muscle loss, decreased the cross-sectional area, and reduced grip strength in C57BL/6 mice fed a high-fat diet (HFD). Elevation of muscle atrophic factors atrogin-1 and muscle RING-finger protein-1 (MuRF-1) and autophagy factors LC3BII and p62 were abrogated by DCA treatment in palmitate-treated C2C12 myotubes and in the skeletal muscles of HFD-fed mice. Moreover, p-Akt, p-FoxO1, and p-FoxO3 protein levels were reduced and p-NF-κB p65 and p-p38 MAPK protein levels were elevated in palmitate-treated C2C12 myotubes, which were restored by DCA treatment. However, the protective effects of DCA treatment against myotube atrophy were reversed by treatment with Akt inhibitor MK2206. Taken together, our study demonstrated that PDH activation by DCA treatment can alleviate obesity-induced muscle atrophy. It may serve as a basis for developing novel strategies to prevent obesity-associated muscle loss. [ABSTRACT FROM AUTHOR]

Degenerative lumbar spondylolisthesis (DLS) is a prevalent spinal condition that can result in significant disability. DLS is thought to result from a combination of disc and facet joint degeneration, as well as various biological, biomechanical, and behavioral factors. One hypothesis is the progressive degeneration of segmental stabilizers, notably the paraspinal muscles, contributes to a vicious cycle of increasing slippage. To examine the correlation between paraspinal muscle status on MRI and severity of slippage in patients with symptomatic DLS. To examine the correlation between paraspinal muscle status on MRI and severity of slippage in patients with symptomatic DLS. Patients who underwent surgery for DLS at the L4/5 level between 2016-2018 were included. Those with multilevel DLS or insufficient imaging were excluded. The percentage of relative slippage (RS) at the L4/5 level evaluated on standing lateral radiographs. Muscle morphology measurements including functional cross-sectional area (fCSA), body height normalized functional cross-sectional area (HI) of Psoas, erector spinae (ES) and multifidus muscle (MF) and fatty infiltration (FI) of ES and MF were measured on axial MR. Disc degeneration and facet joint arthritis were classified according to Pfirrmann and Weishaupt, respectively. Descriptive and comparative statistics, univariable and multivariable linear regression models were utilized to examine the associations between RS and muscle parameters, adjusting for confounders sex, age, BMI, segmental degeneration, and back pain severity. The study analyzed 138 out of 183 patients screened for eligibility. The median age of all patients was 69.5 years (IQR 62 to 73), average BMI was 29.1 (SD ± 5.1) and average preoperative ODI was 46.4 (SD ± 16.3). Patients with Meyerding-Grade 2 (M2, N=25) exhibited higher Pfirrmann scores, lower MF fCSA and MF HI , and lower BMI, but significantly more fatty infiltration in the MF and ES muscles compared to those with Meyerding Grade 1 (M1). Univariable linear regression showed that each cm2 decrease in MF fCSA was associated with a 0.9%-point increase in RS (95%CI -1.4 to - 0.4, p<0.001), and each cm2/m2 decrease in MF HI was associated with an increase in slippage by 2.2%-points (95%CI -3.7 to -0.7, p=0.004). Each 1%-point rise in ES FI and MF FI corresponded to 0.17%- (95%CI 0.05 - 0.3, p=0.01) and 0.20%-point (95%CI 0.1 – 0.3 p<0.001) increases in relative slippage, respectively. Notably, after adjusting for confounders, each cm2 increase in Psoas fCSA and cm2/m2 in Psoas HI was associated with an increase in relative slippage by 0.3% (95%CI 0.1 - 0.6, p = 0.004) and 1.1%-points (95%CI 0.4 -1.7, p= 0.001). While MF fCSA tended to be negatively associated with slippage, this did not reach statistical significance (p = 0.086). However, each 1%-point increase in MF FI and ES FI corresponded to increases of 0.15% points (95%CI 0.05 – 0.24, p= 0.003) and 0.14% points (95%CI 0.01 - 0.27, p= 0.03) in relative slippage, respectively. This study found a significant association between paraspinal muscle status and severity of slippage in DLS. Whereas, higher degeneration of the ES and MF correlate with a higher degree of slippage, the opposite was found for the psoas. These findings suggest that progressive muscular imbalance between posterior and anterior paraspinal muscles could contribute to the progression of slippage in DLS. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

This study investigated the anti-sarcopenic effect of fermented Tenebrio molitor larvae (mealworms) extract (FME) in both dexamethasone (DEX)-treated C2C12 cells and mice. FME (100 µg/mL) increased the diameter of myotubes and inhibited the gene and protein expression of atrogin-1 compared to DEX- or non-fermented mealworms extract (ME)-treated C2C12 cells. Male C57BL/6N mice were divided into five groups: Normal Control (NC), DEX (10 mg/kg, intraperitoneal), and three groups of DEX+FME (100, 200, or 500 mg FME/kg/day, oral) for two weeks. FME at doses of 200 and 500 mg/kg effectively improved grip strength when compared to the DEX group. Histological analysis of the quadriceps muscle showed a larger muscle fiber size in the DEX+FME groups compared to DEX group. FME (200 and 500 mg/kg) significantly increased cross-sectional area of the muscle fiber compared to DEX group. FME (500 mg/kg) significantly decreased the ubiquitin, atrogin-1 and MuRF-1 protein levels, and increased levels of MHC and MyoG in DEX-treated mice. The puromycin labeling assay revealed that FME increased protein synthesis in DEX-induced muscle atrophy. The FME treatment demonstrated significant upregulation in phosphorylation levels, including mTOR, FoxO3α, Akt, and PI3K compared to DEX group. In conclusion, FME inhibited the increase in proteins associated with muscle atrophy, including, atrogin-1 and MuRF-1, by regulating the PI3K-Akt-FoxO3α pathway. FME improved the PI3K-Akt-mTOR signaling pathway, which was reduced by DEX. This study suggests that FME has the potential for use in sarcopenia therapy, possibly serving as a natural agent that counteracts the negative effects of DEX on muscle tissue. [Display omitted] • Fermented mealworm extract improved muscle function in mice with muscle atrophy. • Fermented mealworm extract inhibited protein degradation in mice with muscle atrophy. • Fermented mealworm extract stimulated protein synthesis in mice with muscle atrophy. [ABSTRACT FROM AUTHOR]