Muscle Weakness Research Articles

Effects of phrenic nerve magnetic stimulation on respiratory function in stroke patients: study protocol for a randomised controlled trial.

Respiratory dysfunction is a notable complication in stroke patients, in which the diaphragm, as the primary respiratory muscle, directly influences lung function. Repetitive peripheral magnetic stimulation (rPMS) is a new, non-invasive approach that is used to treat brain and nerve problems. Few studies have examined the effect of magnetic stimulation on the phrenic nerve, breathing and diaphragm in stroke patients. This study aims to assess the effect of magnetic phrenic nerve stimulation on respiratory muscle function and lung function in adults with stroke. The results of this study may provide a promising approach to managing respiratory dysfunction in stroke patients. This randomised controlled trial is designed to compare the effectiveness of bilateral magnetic phrenic nerve stimulation (rPMS) and conventional rehabilitation training in enhancing respiratory muscle strength, lung function indicators, diaphragmatic excursion and diaphragm thickness in patients with respiratory muscle weakness. Thirty patients admitted to the First Hospital of Fujian Medical University will be included in this study. Participants in the intervention group will undergo daily bilateral magnetic phrenic nerve stimulation for 2 weeks. Stimulation will be administered at a frequency of 25 Hz, with a pulse duration of 1.1 s and an inter-pulse interval of 5.9 s, for 5 days each week. Primary outcome measures will be assessed at baseline and after 2 weeks (end of the intervention) to evaluate the efficacy of rPMS compared with conventional rehabilitation techniques. Before commencing the study, all participants will receive a comprehensive explanation of the study procedures, including the assessments. They will also be provided informed consent forms for review, completion and signing. This study was approved by the Ethics Committee for Research at the First Affiliated Hospital of Fujian Medical University (No.: MRCTA, ECFAH of FMU [2021]641, dated 10 November 2023) (Appendix Ⅰ & Ⅱ). The trial protocol will strictly adhere to the Uniform Standards for Reporting of Trials (CONSORT) statement. The trial has been registered with the Chinese Clinical Trial Registry.Dissemination of individual findings for each participant will be available at the end of the study. The findings will be disseminated to different interest groups, participants or other patients with respiratory dysfunction through journal papers and/or conference presentations. The results of the primary trial will be submitted for publication in a peer-reviewed journal. ChiCTR2300075669, registered on 12 September 2023.

Dominant myosin storage myopathy mutations disrupt striated muscles in Drosophila and the myosin tail-tail interactome of human cardiac thick filaments.

Myosin storage myopathy (MSM) is a rare skeletal muscle disorder caused by mutations in the slow muscle/β-cardiac myosin heavy chain (MHC) gene. MSM missense mutations frequently disrupt the tail's stabilizing heptad repeat motif. Disease hallmarks include subsarcolemmal hyaline-like β-MHC aggregates, muscle weakness and, occasionally, cardiomyopathy. We generated transgenic, heterozygous Drosophila to examine the dominant physiological and structural effects of the L1793P, R1845W, and E1883K MHC MSM mutations on diverse muscles. The MHC variants reduced lifespan and flight and jump abilities. Moreover, confocal and electron microscopy revealed that they provoked indirect flight muscle breaks and myofibrillar disarray/degeneration with filamentous inclusions. Incorporation of GFP-myosin enabled in situ determination of thick filament lengths, which were significantly reduced in all mutants. Semi-automated heartbeat analysis uncovered aberrant cardiac function, which worsened with age. Thus, our fly models phenocopied traits observed among MSM patients. We additionally mapped the mutations onto a recently-determined, 6Å resolution, cryo-EM structure of the human cardiac thick filament. The R1845W mutation replaces a basic arginine with a polar-neutral, bulkier tryptophan, while E1883K reverses charge at critical filament loci. Both would be expected to disrupt the core and the outer shell of the backbone structure. Replacing L1793 with a proline, a potent breaker of alpha-helices, could disturb the coiled-coil of the myosin rod and alter the tail-tail interactome. Hence, all mutations likely destabilize and weaken the filament backbone. This may trigger disease in humans, while potentially analogous perturbations are likely to yield the observed thick filament and muscle disruption in our fly models.

Protocol for a pilot study: Feasibility of a web-based platform to improve nutrition, mindfulness, and physical function in people living with Post COVID-19 condition (BLEND)

Individuals with Post COVID-19 condition (PCC), or long COVID, experience symptoms such as fatigue, muscle weakness, and psychological distress, including anxiety, depression, or sleep disorders that persist after recovery from COVID-19. These ongoing symptoms significantly compromise quality of life and diminish functional capacity and independence. Multimodal digital interventions targeting behavioural factors such as nutrition and mindfulness have shown promise in improving health outcomes of people with chronic health conditions and may be beneficial for those with PCC. The BLEND study (weB-based pLatform to improve nutrition, mindfulnEss, and physical function, in patients with loNg COVID) study is an 8-week pilot randomized controlled trial evaluating the feasibility of a digital wellness platform compared to usual care among individuals with PCC. The web-based wellness platform employed in this study, My Viva Plan (MVP)®, integrates a holistic, multicomponent approach to promote wellness. The intervention group receives access to the digital health platform for 8 weeks with encouragement for frequent interactions to improve dietary intake and mindfulness. The control group receives general content focusing on improvements in dietary intake and mindfulness. Assessments are conducted at baseline and week 8. The primary outcome is the feasibility of platform use. Secondary and exploratory outcomes include a between-group comparison of changes in body composition, nutritional status, quality of life, mindfulness, physical activity, and physical performance after 8 weeks. Findings of this study will inform the development of effective web-based wellness programs tailored for individuals with PCC to promote sustainable behavioural changes and improved health outcomes.

Contractile regulation of the glucocorticoid-sensitive transcriptome in young and aged skeletal muscle.

Elevated glucocorticoids alter the skeletal muscle transcriptome to induce a myopathy characterized by muscle atrophy, muscle weakness, and decreased metabolic function. These effects are more likely to occur and be more severe in aged muscles. Resistance exercise can blunt the development of glucocorticoid myopathy in young muscle, but the potential to oppose the signals initiating myopathy in aged muscle is unknown. To answer this, young (4-mo-old) and aged (24-to 25-mo-old) male C57BL/6 mice were randomized to receive either an intraperitoneal (IP) injection of dexamethasone (DEX; 2 mg/kg) or saline as a control. Two hours postinjections, the tibialis anterior (TA) muscles of mice were subjected to unilateral high-force contractions. Muscles were harvested 4 h later. The glucocorticoid- and contraction-sensitive genes were determined by RNA sequencing. The number of glucocorticoid-sensitive genes was similar between young and aged muscle. Contractions opposed changes to more glucocorticoid-sensitive genes in aged muscle, with this outcome primarily occurring when hormone levels were elevated. Glucocorticoid-sensitive gene programs opposed by contractions were primarily related to metabolism in young mice and muscle size regulation and inflammation in aged mice. In silico analysis implied peroxisome proliferator-activated receptor gamma-1 (PPARG) contributed to the contraction-induced opposition of glucocorticoid-sensitive genes in aged muscle. Increasing PPARG expression in the TA of aged mice using adeno-associated virus serotype 9 partially counteracted the glucocorticoid-induced reduction in runt-related transcription factor 1 (Runx1) mRNA content, recapitulating the effects observed by contractions. Overall, these data contribute to our understanding of the contractile regulation of the glucocorticoid transcriptome in aged skeletal muscle.NEW & NOTEWORTHY We establish the extent to which muscle contractions oppose changes to the glucocorticoid-sensitive transcriptome in both young and aged muscle. We also identify peroxisome proliferator-activated receptor gamma (PPARG) as a transcription factor likely contributing to contraction-induced opposition to the glucocorticoid transcriptome in aged muscle. Overall, these data contribute to our understanding of the contractile regulation of the glucocorticoid transcriptome.

Latent factors underlying the symptoms of adult-onset myotonic dystrophy type 1 during the clinical course

BackgroundMyotonic dystrophy type 1 (DM1) is a multisystem genetic disorder that classically presents with symptoms associated with myotonia, early onset cataracts, and muscular weakness, although the presentation and pattern of disease progression is quite varied. Presenting symptoms are well documented among adults with DM1. However, less is known about the co-occurrence of symptoms over time. We aimed to use factor analysis to explore the correlation pattern of signs and symptoms (S/S) that emerged during the clinical course.ResultsClinical records of 228 individuals with adult onset DM1 were abstracted using the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) from a six-site cohort in the United States during an eight-year study period. Factor analysis was used to group the correlated S/S into latent factors. Three factors were identified. Group 1: ‘Facial Weakness/Myotonia’ includes the two most common S/S, as indicated by its name. Group 2: ‘Skeletal Muscle Weakness’ includes eight muscular S/S and is more frequently reported by males and those with older age at onset. Group 3: ‘Gastrointestinal distress/Sleepiness’ includes four non-muscular S/S and hand stiffness. The abstracted medical records reported that over 63% of individuals had S/S from all three groups. Associations of covariates with factor scores were also examined using linear regression. CTG repeat length was significantly positively associated with higher factor scores for all three factors.ConclusionsThis study identified three latent factors of S/S which accumulated during the clinical course of adult onset DM1.

Sex-dependent interplay of phosphate and inflammation on muscle strength irrespective of muscle mass in middle-aged and older adults

BackgroundElevated circulatory phosphate levels are linked to age-related muscle dysfunction, yet the mechanisms remain unclear. This study investigated the hypothesis that inflammation plays a role in connecting elevated phosphate levels to muscular dysfunction in middle-aged and older individuals and explored potential sex-based differences in these associations. MethodsThe study, based on the I-Lan Longitudinal Aging Study Cohort, analyzed individuals' serum phosphate and hsCRP levels. Sex-specific analyses explored links between circulatory phosphate, inflammation, and muscle profiles (mass, handgrip strength, and walking speed). The study also examined potential mediation or synergistic effects of inflammation in the circulatory phosphate-muscle relationship. ResultsThe study included 2006 participants (mean age: 65.5 ± 6.5 years; 49.8 % men). Women exhibited higher circulatory phosphate levels than men. Linear analyses revealed that higher phosphate levels were significantly associated with weaker handgrip strength but not with reduced muscle mass in both men and women. In women, circulatory phosphate was not associated with inflammation (hsCRP levels), while in men, higher phosphate levels were significantly associated with higher hsCRP levels. In men, a synergistic effect was observed, where the combination of high hsCRP and elevated phosphate levels had a more pronounced impact on reducing handgrip strength than either factor alone. ConclusionsThis study highlights a sex-specific association of inflammation in the mechanisms of hyperphosphatemia-related muscle weakness. The findings emphasize the importance of managing both hyperphosphatemia and chronic inflammation to mitigate their collective impact on muscle function, particularly in older men. Addressing these factors is crucial for promoting muscle health in later life.

Sucla2 Knock-Out in Skeletal Muscle Yields Mouse Model of Mitochondrial Myopathy With Muscle Type-Specific Phenotypes.

Pathogenic variants in subunits of succinyl-CoA synthetase (SCS) are associated with mitochondrial encephalomyopathy in humans. SCS catalyses the conversion of succinyl-CoA to succinate coupled with substrate-level phosphorylation of either ADP or GDP in the TCA cycle. This report presents a muscle-specific conditional knock-out (KO) mouse model of Sucla2, the ADP-specific beta subunit of SCS, generating a novel invivo model of mitochondrial myopathy. The mouse model was generated using the Cre-Lox system, with the human skeletal actin (HSA) promoter driving Cre-recombination of a CRISPR-Cas9-generated Sucla2 floxed allele within skeletal muscle. Inactivation of Sucla2 was validated using RT-qPCR and western blot, and both enzyme activity and serum metabolites were quantified by mass spectrometry. To characterize the model invivo, whole-body phenotyping was conducted, with mice undergoing a panel of strength and locomotor behavioural assays. Additionally, exvivo contractility experiments were performed on the soleus (SOL) and extensor digitorum longus (EDL) muscles. SOL and EDL cryosections were also subject to imaging analyses to assess muscle fibre-specific phenotypes. Molecular validation confirmed 68% reduction of Sucla2 transcript within the mutant skeletal muscle (p < 0.001) and 95% functionally reduced SUCLA2 protein (p < 0.0001). By 3 weeks of age, Sucla2 KO mice were 44% the size of controls by body weight (p < 0.0001). Mutant mice also exhibited 34%-40% reduced grip strength (p < 0.01) and reduced spontaneous exercise, spending about 88% less cumulative time on a running wheel (p < 0.0001). Contractile function was also perturbed in a muscle-specific manner; although no genotype-specific deficiencies were seen in EDL function, SUCLA2-deficient SOL muscles generated 40% less specific tetanic force (p < 0.0001), alongside slower contraction and relaxation rates (p < 0.001). Similarly, a SOL-specific threefold increase in mitochondria (p < 0.0001) was observed, with qualitatively increased staining for both COX and SDH, and the proportion of Type 1 myosin heavy chain expressing fibres within the SOL was nearly doubled (95% increase, p < 0.0001) in the Sucla2 KO mice compared with that in controls. SUCLA2 loss within murine skeletal muscle yields a model of SCS-deficient mitochondrial myopathy with reduced body weight, muscle weakness and exercise intolerance. Physiological and morphological analyses of hindlimb muscles showed remarkable differences in exvivo function and cellular consequences between the EDL and SOL muscles, with SOL muscles significantly more impacted by Sucla2 inactivation. This novel model will provide an invaluable tool for investigations of muscle-specific and fibre type-specific pathogenic mechanisms to better understand SCS-deficient myopathy.

A Dual Diagnosis of Myasthenia Gravis and Sjogren’s Syndrome in a Hispanic Patient: A Case-based Discussion of Clinical Findings, Therapeutic Implications, and Culturally Competent Care

The co-occurrence of myasthenia gravis (MG) and Sjogren's syndrome (SS) in a young, Hispanic, female patient underscores the diagnostic and therapeutic complexities inherent in autoimmune disorders. MG, a rare neuromuscular disorder characterized by autoantibodies impairing neuromuscular transmission, leads to variable muscle weakness and fatigue, notably affecting ocular and bulbar muscles. SS, an autoimmune condition with systemic manifestations, primarily affects secretory glands, resulting in symptoms such as xerostomia and xerophthalmia. Both conditions have higher prevalence rates in females, with MG particularly affecting young women under 40. Herein we present a case report and case-based discussion on diagnostic and management challenges of these two autoimmune conditions while highlighting issues specific to the Hispanic and underrepresented populations. Our goal is to highlight the intricate interplay between these two autoimmune pathologies to allow for more rapid recognition and reduce delay in diagnosis.

Effect of early mobilization on functional recovery in ICU patients with post-COVID ARDS

Background. The COVID-19 pandemic has significantly increased the number of patients requiring intensive care unit (ICU) admissions due to severe complications such as acute respiratory distress syndrome (ARDS). Prolonged ICU stays, often associated with immobility, lead to muscle weakness, ICU-acquired weakness (ICU-AW), and reduced functional status, which impede recovery. Early mobilization in the ICU has been proposed as a beneficial intervention to mitigate these effects, but its impact on patients with post-COVID ARDS remains underexplored. Objective. This study aimed to evaluate the effect of early mobilization on functional recovery in ICU patients with post-COVID ARDS. Methods. A prospective, randomized controlled trial was conducted at Saveetha Medical College and Hospital, Chennai, from August 2021 to August 2024. Two hundred patients with post-COVID ARDS were randomly assigned to either an early mobilization or standard care group. The early mobilization group received structured physical therapy interventions within 48 hours of ICU admission. Functional status was measured using the ICU Mobility Scale (IMS) and Functional Status Scale ICU (FSS ICU) at baseline, weekly, and discharge. Secondary outcomes included the duration of ICU stay, mechanical ventilation, and incidence of ICU-AW. Results. Patients in the early mobilization group demonstrated significantly higher functional recovery, with a mean IMS score of 7.8 ± 1.2 compared to 4.3 ± 1.5 in the standard care group (p &lt; 0.001). The FSS ICU score was also significantly higher in the early mobilization group (90.6 ± 8.3) than in the standard care group (65.4 ± 10.7; p &lt; 0.001). Additionally, early mobilization reduced the mean ICU stay (14.5 ± 3.2 vs. 19.8 ± 4.1 days, p &lt; 0.001), shortened the duration of mechanical ventilation (10.1 ± 2.9 vs. 13.7 ± 3.6 days, p &lt; 0.001), and decreased the incidence of ICU-AW (20% vs. 45%, p = 0.002). Conclusion. Early mobilization significantly improves functional recovery, reduces ICU stay and mechanical ventilation duration, and lowers ICU-AW risk in post-COVID ARDS patients. These findings highlight the importance of integrating early mobility into standard ICU care to enhance patient outcomes.

Mortality and its predictors among patients with Guillain–Barré syndrome in the intensive care unit of a low-income country, Ethiopia: a multicenter retrospective cohort study

BackgroundGuillain–Barré syndrome (GBS) is a rare autoimmune disease that affects the peripheral nervous system. It is characterized by the destruction of nerves involved in movement. This condition can lead to transient pain, changes in temperature and touch sensations, muscle weakness, loss of sensation in the legs and/or arms, and difficulty swallowing or breathing. Published data on the outcomes of critical care for patients with GBS are extremely scarce in Africa, particularly Ethiopia. Therefore, this study aimed to assess mortality and its predictors among patients with GBS in the intensive care unit (ICU) of specialized hospitals in Ethiopia, a low-income country.Materials and methodsThis retrospective cohort study was conducted at the Tibebe Ghion Specialized Hospital and the Felege Hiwot Comprehensive Specialized Hospital in Bahir Dar, Ethiopia, from 1 January 2019 to 30 December 2023. Data were collected in the medical record rooms. Cox regression analysis was performed to identify the predictors of mortality among GBS patients in the ICU. The crude and adjusted hazard ratios (AHRs) and 95% confidence intervals (CIs) were calculated using bivariable and multivariable Cox regression models. A p-value of &amp;lt;0.05 was considered statistically significant.ResultsOf 124 GBS patients admitted to the ICU, 120 were included in the final analysis. During the follow-up, there were 23 (19.17%) deaths. The overall incidence rate of death was 1.96 (95% CI: 1.30, 2.95) per 100 person-days of observation. Traditional medicine (AHR = 3.11, 95%: 1.12, 16.70), COVID-19 infection (AHR = 5.44, 95% CI: 1.45, 73.33), pre-ICU cardiac arrest (AHR = 6.44, 95% CI: 2.04, 84.50), and ICU readmission (AHR = 4.24, 95% CI: 1.03, 69.84) were identified as the independent predictors of mortality.ConclusionThe mortality rate among GBS patients admitted to the ICU was high. Traditional medicine, COVID-19 infection, pre-ICU cardiac arrest, and readmission to the ICU were the significant predictors of mortality. Conducting large-scale studies with a prospective design in the future would yield more robust evidence.

‘When nature breaks the rules’: Guillain-barré syndrome presenting with descending paralysis

Guillain-Barré Syndrome (GBS) typically presents with ascending paralysis, but we report an atypical case involving descending paralysis in a 36-year-old male. The patient experienced upper limb weakness and respiratory muscle involvement, progressing to respiratory distress. Initial cerebrospinal fluid (CSF) analysis and nerve conduction studies (NCS) were normal, delaying the diagnosis. Treatment with intravenous immunoglobulin (IVIG) led to partial recovery. This case highlights the diagnostic challenges of atypical GBS presentations and the importance of early intervention.

Whole-body-electro-myostimulation for the care of inclusion body myositis-A case report.

External muscle stimulation, possibly combined with active muscle contraction, could improve physical functioning and performance in inclusion body myositis. Inclusion body myositis (IBM) is a chronic, progressive inflammatory muscle disease with largely unknown causes. It typically affects men more than women, usually beginning in the latter half of life. IBM leads to muscle weakness and wasting, especially in the arms and legs, which significantly impairs daily functioning and complicates participation in exercise training. Few studies have examined the impact of physical training on fitness, inflammation markers, and quality of life in IBM patients. The patient, a Caucasian male (78.3 kg, 174.0 cm, born October 1948), was diagnosed with IBM in October 2011. From October 2017 to September 2019, he underwent exercise training focused on external muscle stimulation combined with active muscle contractions. Regular assessments included cardiopulmonary exercise testing, functional tests (6-min walking test, modified timed up and go test, modified chair rise test), lung function exams, blood parameters, body composition, and quality of life questionnaires. The decline in physical fitness may have been slowed during the intervention period, as indicated by some improvements like peak oxygen uptake and the functional test results while other parameters remained unchanged or declined like peak power output, fat-free mass or lung functioning. However, a recurrence of his prostate cancer after treatment with androgen deprivation therapy may have led to further declines and thus increased muscle wasting. The data may suggest that supportive exercise programs focusing on external muscle stimulation, possibly combined with active muscle contraction, might improve physical functioning, exercise performance, and quality of life in IBM management.

Prevalence of maxillofacial muscle weakness in post dental retainer patients

Prevalence of maxillofacial muscle weakness in post dental retainer patients

Cushing’s Myopathy in Dogs: Prevalence, Clinical Abnormalities, and Response to Treatment

A distinct myotonia is a muscle disorder that may occur secondary to excess corticosteroids (hyperadrenocorticism, HAC, or Cushing’s disease) and is associated with electrodiagnostic abnormalities on electromyography (EMG). Clinically these disorders cause muscle stiffness, weakness, atrophy, and/or contractures, which can severely limit the quality of life of those affected. To date, there are very few published data regarding the onset, development, and treatment of hyperadrenocorticism-associated myotonia/pseudomyotonia. This is a multi-institutional retrospective study describing the clinical signs, diagnosis, and treatment of HAC-associated myotonia/pseudomyotonia. We found that this disorder was and continues to be rare. It most commonly occurs in adult dogs with chronic steroid exposure secondary to pituitary-dependent HAC. No cases of adrenal dependent HAC were identified in this population. In addition to muscle stiffness, dermatologic disease and liver enzyme abnormalities were common. A wide variety of therapeutic strategies, including polypharmacy and physical rehabilitation, were implemented, with little success. Analgesics were the most frequently administered type of medication.

Efficacy of Nusinersen Treatment in Type 1, 2, and 3 Spinal Muscular Atrophy: Real-World Data from a Single-Center Study

Background: Spinal muscular atrophy (SMA) is an inherited neuromuscular disease characterized by progressive muscle weakness and atrophy due to the absence of the survival motor neuron 1 (SMN1) gene. SMA is classified into types 0 through 4 based on the age of symptom onset and the severity of motor function decline. Recent advances in SMA treatment, including nusinersen, onasemnogene abeparvovec, and risdiplam, have significantly improved the prognosis of SMA patients. This study evaluated the safety and efficacy of nusinersen in pediatric patients with SMA types 1, 2, and 3 in a real-world clinical setting. Methods: This prospective observational single-center study assessed the treatment effects of nusinersen in 23 pediatric patients with genetically confirmed SMA over a 22-month observation period. All the participants received intrathecal loading doses of 12 mg of nusinersen on days 1, 14, 28, and 63, followed by maintenance doses every four months. Functional assessments were conducted using the CHOP-INTEND scale. Data were collected during routine patient visits, including clinical laboratory tests and vital sign parameters, and adverse events were recorded. The inclusion criteria were defined by the national reimbursement program for nusinersen treatment in Poland. Results: Initially, 37 patients ranging from 1 month old to 18 years old were included, but 23 were ultimately observed due to changes in treatment regimens or assessment scales. The patients showed significantly improved CHOP-INTEND scores over the 22-month period. At 6 months, the average increase was 4.2 points, continuing to 17.8 points at 22 months. By the end of the study, 100% of patients showed either stabilization or improvement, with significant clinical improvements observed in several patients. Nusinersen was generally well-tolerated, with post-lumbar puncture headache and lower back pain being the most common adverse events. Conclusions: Nusinersen treatment significantly enhances motor function in pediatric patients with SMA types 1, 2, and 3. This study demonstrates the importance of early and sustained treatment, with most patients showing the continuous improvement or stabilization of motor function. These findings support the use of nusinersen as an effective therapy for SMA; however, further research is needed to understand the long-term outcomes and optimize treatment strategies.

Effect of hip abductors training on pelvic drop and knee valgus in runners with medial tibial stress syndrome: a randomized controlled trial

BackgroundMedial tibial stress syndrome (MTSS) is a prevalent running-related injury that could impact athletic performance and quality of life. The purpose of the study was to investigate the effectiveness of functional hip abductor strength training on reducing contralateral pelvic drop angle (hip frontal plane projection angle), and dynamic knee valgus (knee frontal plane projection angle) in runners with medial tibial stress syndrome (MTSS).MethodsForty male and female recreational runners were diagnosed with MTSS for at least one month. The age ranged from 25 to 35 years old, and the body mass index (BMI) ranged between (18.5 and 25 kg/m2) participated in this study. This was a single-blind, randomized controlled trial. Participants were randomized into two groups: a control group (Group A, n = 20) received a selected physical therapy exercise program, and an experimental group (Group B, n = 20) received the same program plus functional hip abductor strength training. Dynamic knee valgus (frontal plane projection angle) and contralateral pelvic drop angle were measured using 2D video and analyzed by Kinovea software at baseline and after 8 weeks. Mixed-effect multifactor analysis of variance (MANOVA) was conducted to compare within and between groups effects on FPPA and pelvic drop angle.ResultsAfter 8 weeks, Group B exhibited a significantly decreased frontal plane projection and pelvic drop angles compared to Group A (p < 0.05). Group A also demonstrated a reduced pelvic drop angle, but to a lesser extent, and their frontal plane projection angle increased.ConclusionsThis study demonstrates that 8 weeks of functional hip abductor strength training, combined with traditional physical therapy, effectively improves lower extremity kinematics in runners with MTSS by reducing dynamic knee valgus and contralateral pelvic drop. This targeted approach likely addresses underlying muscle weakness and movement dysfunction, offering hope for potentially reducing MTSS recurrence.Trial registration: clinicaltrials.gov. NO: NCT05637476. Date: December 1, 2022.

Understanding the Role of Type I Interferons in Cutaneous Lupus and Dermatomyositis: Toward Better Therapeutics.

A 29-year-old female presented to a rheumatology-dermatology clinic with a pruritic rash that began 6 months prior, after a viral illness. She had previously been diagnosed with eczema and treated with antihistamines and topical steroids without improvement. She also noted fatigue, hair loss, and severe scalp pruritus. Physical examination was notable for violaceous periorbital edema, scaly erythematous papules on the metacarpophalangeal joints of bilateral hands, dilated capillaries of the proximal nail folds, scaly plaques on bilateral elbows, and excoriated erythematous plaques on upper chest, back and hips. The patient reported no muscle weakness, and strength testing and creatinine phosphokinase were normal. Magnetic resonance imaging of the thigh showed no evidence of inflammation or edema. Antibody testing was negative. A diagnosis of clinically amyopathic dermatomyositis was made. Computed tomography scans of the chest, abdomen and pelvis, colonoscopy, and mammogram showed no evidence of cancer. The patient was initiated on methotrexate. Her cutaneous manifestations persisted with debilitating intractable pruritus, and thus, she was transitioned to mycophenolate mofetil, again with minimal improvement. Intravenous immunoglobulin was not approved by insurance given the lack of muscle involvement in her disease. This patient's case highlights a common clinical scenario in rheumatology and dermatology and raises several important issues related to the immunologic underpinnings of cutaneous lupus erythematosus (CLE) and dermatomyositis (DM): What is the role of type I interferon (IFN) in triggering skin disease in CLE and DM? What is the role of IFN in the pathogenesis of skin inflammation in CLE and DM? Can we apply what we know about IFN-targeted therapeutics in CLE and DM to develop better treatments for skin disease?

Association of 5-times sit-to-stand test with muscle weakness and prognosis in older patients with cardiovascular disease

Abstract Background/Introduction In the elderly with cardiovascular disease (CVD), maintaining muscle strength and physical function is essential for preventing adverse outcomes like falls and hospitalizations. The decline in lower limb strength signals increased morbidity and mortality risks. The 5-times sit-to-stand test (5STS) is a practical method for assessing lower limb strength, yet its predictive value for muscle weakness and prognosis in older CVD patients is underexplored. Purpose This study aims to elucidate the 5STS's role in identifying muscle weakness and its impact on the prognosis of older patients with CVD, offering insights for targeted interventions. Methods We included 3585 patients aged ≥ 65 years with CVD (mean age, 75.8 ± 6.6 years, 64.5% male) who underwent assessment of the 5STS before discharge. Maximal quadriceps isometric strength (QIS) was evaluated as a marker of lower limb strength and expressed relative to body weight (% body weight: BW). The primary outcome was all-cause mortality. We used the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for each sex to calculate the cut-off values of the 5STS for low QIS (male &amp;lt; 45%BW, female &amp;lt; 35%BW), which have been reported to be associated with prognosis. In addition, we performed Kaplan-Meier curves and Cox regression analyses in five groups defined by 5STS time quartile and 5STS inability to assess the prognostic significance of 5STS. Cox regression analysis was performed as a multivariate model including the following variables; age, sex, body mass index, acute coronary syndrome, heart failure, hypertension, diabetes, dyslipidemia, current smoker, prior myocardial infarction, prior heart failure, prior chronic obstructive pulmonary disease, prior dementia, albumin, hemoglobin, estimated glomerular filtration rate, C-reactive protein. Result Over a median follow-up of 2.23 years (interquartile range 0.87-4.52 years), 657 (18.3%) patients died. Kaplan-Meier analysis indicated that both slow 5STS performance and inability to execute the 5STS were significantly linked with poorer prognosis (log-rank p &amp;lt; 0.001, Figure 1). After comprehensive adjustment, the slowest quartile and inability to perform the 5STS were associated with significantly higher mortality rates compared to the fastest quartile (HR 1.34; 95% CI: 1.05-1.72; p = 0.021; HR: 2.28; 95% CI: 1.60-3.24; p &amp;lt; 0.001, Figure 2). The ROC AUC for 5STS in identifying low QIS was 0.75 (95% CI: 0.73-0.77) for males and 0.75 (95% CI: 0.72-0.77) for females, with cut-off times established at 9.71s for males and 9.48s for females. Conclusion The 5STS, assessable in diverse settings without specialized equipment and reflecting key clinical outcomes, could serve as a standard tool for evaluating lower limb function.

Skeletal and respiratory muscle weakness contributes to decreased exercise capacity in hypertrophic cardiomyopathy

Abstract Background and Aims Although decreased exercise capacity (due to dyspnea or angina-like symptoms) constitutes the fundamental characteristics of hypertrophic cardiomyopathy (HCM), the pathophysiology of these symptoms remains only partly understood. We investigated clinical and functional determinants of decreased exercise capacity in a broad range of HCM patients irrespective of primary disease aetiology (either genetic disorder or e.g. infiltrative phenocopies in the course of cardiac amyloidosis), overt heart failure (HF) and the presence of haemodynamically significant left ventricular outflow tract obstruction (LVOTO). Further, we deterimined the contribution of skeletal and respiratory muscle weakness to decresed exercise capacity. Methods We analyzed clinical data and functional assessments (skeletal and respiratory muscle strength, physical fitness) in relation to symptomatology and sub-maximal exercise capacity in 82 clinically stable patients with HCM (females: 32 %; age: 62±16 years; left ventricular ejection fraction [LVEF] 59±7%; intraventricular septum wall thickness [IVS] 19±4 mm; median plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 818 pg/mL [lower and upper quartile: 208-1917]; New York Heart Association [NYHA] class 0/I/II/III: 38/18/33/11 % [0 indicates no HF]; significant LVOTO: 29%). Results HCM patients with more severe symptomatology (NYHA class II-III vs 0-I) were older, had more frequently significant LVOTO and greater comorbidity burden, and had higher NT-proBNP and worse estimated renal function (all p≤0.03). Gender distribution, percentage of beta-blocker therapy and implanted device, body mass index, major echocardiography parameters (including LVEF, left ventricular end-diastolic diameter and IVS), high-sensitive (hs) cardiac troponin type I and hs-C-reactive protein were comparable in these 2 groups of subjects (all p&amp;gt;0.05). In multivariable linear regression models more advanced age, higher circulating natriuretic peptides (NT-proBNP) and previous coronary revascularization were independent predictors of more advanced NYHA class (standardized β-coefficient=0.30, p&amp;lt;0.01; β=0.27, p&amp;lt;0.01; and β=0.22, p&amp;lt;0.05; respectively). Similarly, more advanced age, female sex and higher NT-proBNP were independent correlates of shorter distance in 6-minute walking test (6MWT) (β=-0.46, p&amp;lt;0.001; β=-0.26, p&amp;lt;0.001; and β=-0.36, p&amp;lt;0.001; respectively). All analyzed muscle parameters (including respiratory muscle strength parameters) and objective measures of physical fitness (Functional Fitness Test for older adults) remained independently associated with 6MWT distance (all p&amp;lt;0.001) when adjusted for aforementioned clinical and laboratory correlates of 6MWT. Conclusions Muscle weakness and low physical fitness are related to decreased exercise capacity in HCM and may be potential therapeutic targets to alleviate disease symptoms also in non-obstructive HCM phenotype.

Compound heterozygous RYR1-RM mouse model reveals disease pathomechanisms and muscle adaptations to promote postnatal survival.

Pathogenic variants in the type I ryanodine receptor (RYR1) result in a wide range of muscle disorders referred to as RYR1-related myopathies (RYR1-RM). We developed the first RYR1-RM mouse model resulting from co-inheritance of two different RYR1 missense alleles (Ryr1TM/SC-ΔL mice). Ryr1TM/SC-ΔL mice exhibit a severe, early onset myopathy characterized by decreased body/muscle mass, muscle weakness, hypotrophy, reduced RYR1 expression, and unexpectedly, incomplete postnatal lethality with a plateau survival of ~50% at 12 weeks of age. Ryr1TM/SC-ΔL mice display reduced respiratory function, locomotor activity, and invivo muscle strength. Extensor digitorum longus muscles from Ryr1TM/SC-ΔL mice exhibit decreased cross-sectional area of type IIb and type IIx fibers, as well as a reduction in number of type IIb fibers. Exvivo functional analyses revealed reduced Ca2+ release and specific force production during electrically-evoked twitch stimulation. In spite of a ~threefold reduction in RYR1 expression in single muscle fibers from Ryr1TM/SC-ΔL mice at 4 weeks and 12 weeks of age, RYR1 Ca2+ leak was not different from that of fibers from control mice at either age. Proteomic analyses revealed alterations in protein synthesis, folding, and degradation pathways in the muscle of 4- and 12-week-old Ryr1TM/SC-ΔL mice, while proteins involved in the extracellular matrix, dystrophin-associated glycoprotein complex, and fatty acid metabolism were upregulated in Ryr1TM/SC-ΔL mice that survive to 12 weeks of age. These findings suggest that adaptations that optimize RYR1 expression/Ca2+ leak balance, sarcolemmal stability, and fatty acid biosynthesis provide Ryr1TM/SC-ΔL mice with an increased survival advantage during postnatal development.