Muscle Disorders Research Articles

Age-associated sleep spindle characteristics in Duchenne muscular dystrophy.

Brain oscillations of non-rapid eye movement sleep, including slow oscillations (SO, 0.5-1.5 Hz) and spindles (10-16 Hz), mirror underlying brain maturation across development and are associated with cognition. Hence, age-associated emergence and changes in the electrophysiological properties of these rhythms can lend insight into cortical development, specifically in comparisons between pediatric populations and typically developing peers. We previously evaluated age-associated changes in SOs in male patients with Duchenne muscular dystrophy (DMD), finding a significant age-related decline between 4 and 18 years. While primarily a muscle disorder, male patients with DMD can also have sleep, cognitive, and cortical abnormalities, thought to be driven by altered dystrophin expression in the brain. In this follow-up study, we characterized the age-associated changes in sleep spindles. We found that age-dependent spindle characteristics in patients with DMD, including density, frequency, amplitude, and duration, were consistent with age-associated trends reported in the literature for typically developing controls. Combined with our prior finding of age-associated decline in SOs, our results suggest that SOs, but not spindles, are a candidate intervention target to enhance sleep in patients with DMD.

Саркопения и саркопеническое ожирение

Sarcopenia is a progressive generalised skeletal muscle disorder that is associated with increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality. Sarcopenic obesity is a clinical and functional condition characterized by the coexistence of excess fat mass and sarcopenia. In 2018, the European Working Group on Sarcopenia in Older People presented updated data on sarcopenia (EWGSOP2). The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a definition and diagnostic criteria for sarcopenic obesity. This article contains the main provisions of the documents and a review of the literature on the mechanisms, diagnosis and clinical significance of sarcopenia and sarcopenic obesity.

Andersen-Tawil syndrome.

Andersen-Tawil syndrome (ATS) is one of the periodic paralyses, a set of skeletal muscle disorders that cause transient weakness of the arms and legs lasting minutes to many hours. Distinguishing features of ATS include facial and limb dysmorphisms, cardiac arrhythmia, difficulties with executive function, and association with dominant mutations in the potassium channel, KCNJ2. In this review, we discuss the key features of ATS, diagnostic testing, pathophysiology and treatment of ATS, and compare them with other periodic paralyses.

Molecular regulation of myocyte fusion.

Myocyte fusion is a pivotal process in the development and regeneration of skeletal muscle. Failure during fusion can lead to a range of developmental as well as pathological consequences. This review aims to comprehensively explore the intricate processes underlying myocyte fusion, from the molecular to tissue scale. We shed light on key players, such as the muscle-specific fusogens - Myomaker and Myomixer, in addition to some lesser studied molecules contributing to myocyte fusion. Conserved across vertebrates, Myomaker and Myomixer play a crucial role in driving the merger of plasma membranes of fusing myocytes, ensuring the formation of functional muscle syncytia. Our multiscale approach also delves into broader cell and tissue dynamics that orchestrate the timing and positioning of fusion events. In addition, we explore the relevance of muscle fusogens to human health and disease. Mutations in fusogen genes have been linked to congenital myopathies, providing unique insights into the molecular basis of muscle diseases. We conclude with a discussion on potential therapeutic avenues that may emerge from manipulating the myocyte fusion process to remediate skeletal muscle disorders.

Agricultural Risk Factor Petani Lansia pada Aktivitas Pertanian Padi

According to data from the Central Bureau of Statistics, the agricultural sector is the business field that absorbs the most elderly workers. However, elderly farmers actually become vulnerable to musculoskeletal disorders when doing agricultural work. This is because agriculture requires a lot of lifting activities, carrying heavy loads, working in bent and squatting positions, there is a risk of slipping and there is a risk of falling from the slippery paddy fields. This study aims to identify agricultural risks for elderly farmers. Data collection was carried out using Focus Group Discussions, to identify complaints with the Nordic Body Map (NBM) and risk assessment with the Agricultural Whole-Body Assessment (AWBA). Complaint data obtained, namely respondents stated that they had Gotrak complaints (muscle and skeletal disorders) on the waist and legs. Results questionnaire NBM, namely the level of complaints of pain in the highest part of the body that is felt, namely the waist. While the results of the AWBA risk assessment show that most of the work postures of elderly farmers are at high risk (high) with a percentage of 53% and a risk level of work duration of 73% of agricultural activities has a risk of 4 (very high).

Limb-girdle muscular dystrophies: An update

Limb-girdle muscular dystrophies (LGMDs) are a heterogenous group of genetically driven muscle disorders, which share the two common features of progressive, predominantly proximal girdle skeletal muscle involvement and dystrophic changes on pathology. This is a rapidly expanding landscape in neurology both in relation to diagnosis as well as evolving targeted treatment options. Thirty-one LGMD subtypes are described to date; five of autosomal dominant inheritance and 26 of autosomal recessive transmission. This article describes their pathogenesis, clinical presentation, diagnosis and recent therapeutic advances.

Herbal Medicine for Sarcopenia: A Systematic Review of Randomized Controlled Trials

Objectives: Sarcopenia is an age-associated skeletal muscle disorder that can profoundly impact the health of elderly people. However, the efficacy of herbal medicine in sarcopenia is uncertain. This review aims to investigate evidence of the effect of herbal medicine on sarcopenia.Methods: We systematically searched 12 electronic databases for relevant randomized controlled trials (RCTs). Only trials that met the inclusion criteria were selected, and the characteristics of the included studies were extracted and synthesized in a narrative manner. The quality of the included studies was assessed using Cochrane’s Risk of Bias (RoB) 2.0 tool.Results: 7 RCTs involving 672 participants with sarcopenia met the inclusion criteria. The intervention combining herbal medicine and conventional treatment (i.e., exercise, nutritional support) had a significant therapeutic effect compared with the conventional treatment, showing improvement in muscle strength (i.e., grip strength), muscle mass (i.e., appendicular skeletal muscle mass index), and physical function (i.e., gait speed, short physical performance battery, and timed up and go test). However, the methodological quality of the included RCTs was relatively low due to their high RoB, making it difficult to evaluate the efficacy of herbal medicine in sarcopenia. In terms of safety, several adverse events were reported.Conclusion: This review suggests that herbal medicine has a positive effect on muscle strength, muscle mass, and physical performance in elderly patients with sarcopenia, but there is a clear need for further research in this area.

Regulation of Satellite Cells Functions during Skeletal Muscle Regeneration: A Critical Step in Physiological and Pathological Conditions.

Skeletal muscle regeneration is a complex process involving the generation of new myofibers after trauma, competitive physical activity, or disease. In this context, adult skeletal muscle stem cells, also known as satellite cells (SCs), play a crucial role in regulating muscle tissue homeostasis and activating regeneration. Alterations in their number or function have been associated with various pathological conditions. The main factors involved in the dysregulation of SCs' activity are inflammation, oxidative stress, and fibrosis. This review critically summarizes the current knowledge on the role of SCs in skeletal muscle regeneration. It examines the changes in the activity of SCs in three of the most common and severe muscle disorders: sarcopenia, muscular dystrophy, and cancer cachexia. Understanding the molecular mechanisms involved in their dysregulations is essential for improving current treatments, such as exercise, and developing personalized approaches to reactivate SCs.

Zastosowanie toksyny botulinowej w okuloplastyce

Botulinum toxin is one of the strongest functional organic toxins. Throughout history, detailed research has contributed to changing the perception of this substancefrom a toxin to a widely used medication. Botulinum toxin has found therapeutic use in many fields of medicine, and indications for its use are constantly widening in a variety of diseases that all characterize muscular hyperactivity. Intramuscular injection causes a transient paralysis, by acting on the motorend-plate of the neural axon and blocking a release of acetylcholine. In oculoplasty, it is used in treating localized dystonia such as :eyelid droop and facial hemiparesis, lower eyelid curl, eyelid retraction in cases of thyroid ophthalmopathy, treatment of non-healing corneal ulcers such as post-paresis upper eyelid insufficiency and dry-eye syndrome. In the general field of ophthalmology, the use of botulinum toxin successfully treats strabismus as well as otherextraocular muscle disorders that are present in nystagmus as well as Grave’s disease. The aim of this scientific study is to analyze the possibilities of botulinum toxin injections in various ophthalmic disorders, considering their potential as an alternativeto traditional surgeries, and discussing their benefits and risks. The research methodology relies on a systematic review of literature available in medical databases, analyzing publications and clinical studies related to botulinum toxin injections in ophthalmology. Since its discovery, botulinum toxin has undergone a remarkable transformation, from a deadly poison to a medicine used in various fields of medicine. When administered in appropriate doses, at proper intervals, and by qualified personnel, it becomes a safe form of the rapyfor numerous medical conditions characterized by excessive muscle activity.

Safety Education through Risk Analysis in the Printing Informal Sector

The printing industry is one of the most informal industries in university environments, such as in Universitas Negeri Semarang which has many printers, ranging from printing books to banners. The printing industry is not free from risks of danger, even though it is only in a small sector, but all workplaces have their own risks of danger. The method used in this research was descriptive research. Analysis was carried out by collecting data through field observations and analysis using JSA. The population and sample in this study were 10 workers in three printing houses in the Universitas Negeri Semarang area. There are a total of 6 routine work processes carried out by workers in the printing industry with 38 hazards identified. The highest intensity risks were found in muscle, bone and skeletal disorders as well as skin irritation and respiratory problems. This was because when working the position of the worker was not ergonomic and the work involved chemicals in the form of ink. The recommended improvement for printing owners is the use of APB to minimize risks arising from identified hazards such as wearing masks to reduce exposure to chemical vapours.

Clinical and Instrumental Temporomandibular Joint Evaluation in Children and Adolescents with Juvenile Idiopathic Arthritis: A Medium-Term Follow-Up

(1) Background: The aim of the study was to assess the potential effectiveness of clinical diagnostic examinations, such as muscle palpation, and instrumental examinations, such as electromyography, in the early detection of TMJ involvement in patients with juvenile idiopathic arthritis (JIA), as early diagnosis of these disorders can reduce the risk of developing facial growth anomalies and dento-skeletal malocclusions. (2) Methods: Evaluations were conducted on a cohort of 15 people with juvenile idiopathic arthritis (JIA) and a comparison group of 15 healthy participants at the start of the trial (T0) and after 18 ± 6 months (T1). Data were obtained through clinical examination, involving muscle palpation of the anterior temporalis, masseters, and sternocleidomastoids, and by instrumental analysis using electromyography. The parametric student’s t-test was used to evaluate group comparisons for data that were normally distributed, whereas the nonparametric Mann–Whitney U test was employed for parameters that did not follow a normal distribution. (3) Results: In the JIA group, higher levels of pain were recorded in the sternocleidomastoid muscles on both sides as compared to the control group (p < 0.05) at both T0 and T1. Electromyography revealed no statistically significant variances both in the JIA group and in the control group, except for the IMP index, characterized by a significant improvement over time for the JIA group. (4) Conclusions: According to the methodology employed in this study, all JIA patients had TMD symptoms, mainly muscle disorders. The existence of statistically significant parameters suggests the potential to regard muscle palpation and electromyography as predictive indicators of TMJ involvement in JIA subjects. Additional research is required to validate their reliability.

Network pharmacology combined with an animal model to reveal the material basis and mechanism of Amomum villosum in alleviating constipation in mice

Constipation is a prevalent gastrointestinal disorder, with its prevalence showing an annual upward trend. There are many factors involved in the occurrence of constipation, such as abnormal smooth muscle contraction and disorders of gastrointestinal hormone secretion. Amomum villosum (A. villosum) has been proven to be effective in improving digestive system diseases, but there is no report on improving constipation. Therefore, we used network pharmacology prediction combined with animal experiments to explore the key active components of A. villosum and their pharmacological mechanisms. The results of network pharmacological prediction showed that β-sitosterol was the key laxative compound of A. villosum, which may play a laxative role by activating the adrenoceptor alpha 1 A-myosin light chain (ADRA1A-MLC) pathway. Further animal experiments showed that β-sitosterol could significantly shorten the time to first black stool; increase faecal weight, faecal number, and faecal water content; and promote gastrointestinal motility. β-sitosterol may promote intestinal motility by upregulating the expression of ADRA1A and myosin light chain 9 (Myl9) mRNA and protein in the colon, thereby activating the ADRA1A-MLC signalling pathway. In addition, it is possible to improve constipation symptoms by regulating serum neurotransmitters and gastrointestinal motility-related factors, such as the serum content of 5-hydroxytryptamine (5-HT) and acetylcholinesterase (AchE) and the mRNA expression of 5-hydroxytryptamine receptor 4 (5-HT4), stem cell factor (SCF), stem cell factor receptor (c-Kit) and smooth muscle myosin light chain kinase (smMLCK) in the colon. These results lay a foundation for the application of A. villosum and β-sitosterol in constipation.

Raised CK and acute kidney injury following intense exercise in three patients with a history of exercise intolerance due to homozygous mutations in SLC2A9

Acute rhabdomyolysis (AR) leading to acute kidney injury has many underlying etiologies, however, when the primary trigger is exercise, the most usual underlying cause is either a genetic muscle disorder or unaccustomed intense exercise in a healthy individual. Three adult men presented with a history of exercise intolerance and episodes of acute renal impairment following intense exercise, thought to be due to AR in the case of two, and dehydration in one. The baseline serum CK was mildly raised between attacks in all three patients and acutely raised during attacks in two of the three patients. Following referral to a specialized neuromuscular centre, further investigation identified very low serum urate (<12 umol/L). In all three men, genetic studies confirmed homozygous mutations in SLC2A9, which encodes for facilitated glucose transporter member 9 (GLUT9), a major regulator of urate homeostasis. Hereditary hypouricaemia should be considered in people presenting with acute kidney injury related to intense exercise. Serum urate evaluation is a useful screening test best undertaken after recovery.

Myosteatosis for Early Detection of Muscle Disorder in Patients With Liver Cirrhosis

Background and AimsMuscle disorders in cirrhosis is associated with poor outcome and needs early identification. Anthropometric measures lack sensitivity, and CT-based L3-skeletal muscle Index(L3-SMI) may miss early sarcopenia. The study aimed to find if SM-RA can identify more patients with muscle disorder than L3-SMI and anthropometry. Methods388 patients with cirrhosis underwent nutritional assessment by anthropometry, short-physical-performance-battery (SPPB) <9, L3-SMI (<36.5 cm2/m2 (males); <30.2 cm2/m2 (females), and myosteatosis assessment by skeletal muscle radiation attenuation (SM-RA)(<41 HU for body mass index [BMI] <24.9 kg8m2 and <33 HU for ≥25 kg/m2) and results were compared. ResultsSarcopenia based on SPPB was 38.9% with scores (9 ±1.48 vs. 10.74 ±1.25, p=0.001 in males; and 8.43 ±1.59 vs. 9.89 ±1.57, p=0.001in females). Mid-arm muscle circumference was lower in sarcopenic males [20.5 ±2.42 vs. 22.9 ±2.19 cm, p=0.001] but not in females [19.4 ± 2.73 vs. 21.1 ± 2.51, p =0.18]. L3-SMI-based sarcopenia was found in 44.8% (additional 5.92%) compared to SPPB, mostly in cryptogenic cirrhosis (19.2% vs. 35.08%, δ change +15.9%). Myosteatosis (71.64%) identified an additional 26.85% and 32.74% of patients with muscle disorder compared to L3SMI and SPPB, respectively, with the majority of new detection in non-alcoholic fatty liver disease (NAFLD) 39.4% vs. 77.06%, δ change +37.66%) CTP-A patients (16.6% vs. 36.8%, δ change +20.2%). Myosteatosis was found in 48.3% of patients with normal L3-SMI. ConclusionSM-RA can identify more patients with muscle-disorder than L3-SMI and SPPB.

Lifelong dietary protein restriction accelerates skeletal muscle loss and reduces muscle fibre size by impairing proteostasis and mitochondrial homeostasis

The early life environment significantly affects the development of age-related skeletal muscle disorders. However, the long-term effects of lactational protein restriction on skeletal muscle are still poorly defined. Our study revealed that male mice nursed by dams fed a low-protein diet during lactation exhibited skeletal muscle growth restriction. This was associated with a dysregulation in the expression levels of genes related to the ribosome, mitochondria and skeletal muscle development. We reported that lifelong protein restriction accelerated loss of type-IIa muscle fibres and reduced muscle fibre size by impairing mitochondrial homeostasis and proteostasis at 18 months of age. However, feeding a normal-protein diet following lactational protein restriction prevented accelerated fibre loss and fibre size reduction in later life. These findings provide novel insight into the mechanisms by which lactational protein restriction hinders skeletal muscle growth and includes evidence that lifelong dietary protein restriction accelerated skeletal muscle loss in later life.

Potential application of anti-osteoporotic therapy to relieve sarcopenia in the elderly

Sarcopenia is a progressive and systemic skeletal muscle disorder associated with aging that usually occurs with age in the elderly. Sarcopenia currently lacks effective pharmacological treatment modalities. Multiple pharmacological intervention modalities are available for osteoporosis, a comprehensive disease characterized by decreased systemic bone mass, degradation of bone microarchitecture, and increased bone fragility. Several recent studies have shown an extremely strong correlation between sarcopenia and osteoporosis, leading to the concept of “osteosarcopenia”. Therefore, it is possible to alleviate sarcopenia simultaneously by improving osteoporosis.

Relationship between the preoperative grip strength and postoperative shoulder strength of patients treated via reverse shoulder arthroplasty.

Systemic disorders including diabetes mellitus, obesity, and depression affect the outcomes of reverse shoulder arthroplasty (RSA). Sarcopenia (a general skeletal muscle disorder) is common in elderly people, but its effect on patients after RSA is not clear. We hypothesized that the preoperative sarcopenia indices of grip strength and general skeletal muscle mass would correlate with the clinical outcomes of RSA. Grip strength and general skeletal muscle mass were measured in patients scheduled (between 2016 and 2021) for primary RSA to treat cuff tear arthropathy, an unrepairable cuff tear, or osteoarthritis with a large cuff tear. Before surgery, grip strength was measured using a hydraulic dynamometer and general skeletal muscle mass was calculated from the appendicular relative skeletal muscle mass index (aRSMI) using dual-energy X-ray absorptiometry. In all, 58 patients were included; the minimal follow-up duration was 12months. The postoperative clinical results (pain, active range of motion, shoulder strength, and functional scores) were evaluated during scheduled outpatient visits. We calculated correlations between the preoperative sarcopenia indices, and the clinical results at the final follow-up. The mean preoperative grip strength and aRSMI were 21.6±4.0kg and 5.98±0.84kg/m2 in females and 30.6±7.5kg and 7.21±0.94kg/m2 in males, respectively; the grip strength and aRSMI were not associated with each other (P=.083). Ten females (25%) and 10 males (56%) met the criteria for sarcopenia. The postoperative abduction shoulder strength and Constant-Murley shoulder score increased significantly with higher preoperative grip strength (R=0.420 and P=.001; and R=0.497 and P<.001, respectively) and the American Shoulder and Elbow Surgeons score was related to the preoperative aRSMI (R=0.320, P=.039). The shoulder strength and functional score after RSA correlated positively with the preoperative grip strength. Measuring grip strength before RSA allows the surgeon to predict shoulder strength after RSA.

Zebrafish as an Emerging Model for Sarcopenia: Considerations, Current Insights, and Future Directions.

Sarcopenia poses a significant challenge to public health and can severely impact the quality of life of aging populations. Despite extensive efforts to study muscle degeneration using traditional animal models, there is still a lack of effective diagnostic tools, precise biomarkers, and treatments for sarcopenia. Zebrafish models have emerged as powerful tools in biomedical research, providing unique insights into age-related muscle disorders like sarcopenia. The advantages of using zebrafish models include their rapid growth outside of the embryo, optical transparency during early developmental stages, high reproductive potential, ease of husbandry, compact size, and genetic tractability. By deepening our understanding of the molecular processes underlying sarcopenia, we may develop novel diagnostic tools and effective treatments that can improve the lives of aging individuals affected by this condition. This review aims to explore the unique advantages of zebrafish as a model for sarcopenia research, highlight recent breakthroughs, outline potential avenues for future investigations, and emphasize the distinctive contributions that zebrafish models offer. Our research endeavors to contribute significantly to address the urgent need for practical solutions to reduce the impact of sarcopenia on aging populations, ultimately striving to enhance the quality of life for individuals affected by this condition.

Self-reported functioning among patients with ultra-rare nemaline myopathy or a related disorder in Finland: a pilot study

BackgroundNemaline myopathy (NM) and related disorders (NMr) form a heterogenous group of ultra-rare (1:50,000 live births or less) congenital muscle disorders. To elucidate the self-reported physical, psychological, and social functioning in the daily lives of adult persons with congenital muscle disorders, we designed a survey using items primarily from the Patient Reported Outcomes Measurement Information System, PROMIS®, and conducted a pilot study in patients with NM and NMr in Finland. The items were linked to International Classification of Functioning, Disability and Health (ICF) categories.ResultsIn total, 20 (62.5%) out of 32 invited persons resident in Finland participated in the study; 12 had NM and 8 NMr, 15 were women and 5 men aged 19–75 years. Sixteen (80%) were ambulatory and 4 (20%) NM patients used wheelchairs. The results from the PROMIS measuring system and ICF categories both indicated that non-ambulatory patients of this study faced more challenges in all areas of functioning than ambulatory ones, but the differences were smaller in the domains measuring psychological and social functioning than in physical functioning. In addition, the COVID-19 pandemic adversely affected the functioning of non-ambulatory patients more than that of ambulatory patients. The interindividual differences were, however, noticeable.ConclusionsTo our knowledge, this pilot study is the first comprehensive survey-based study of the physical, psychological, and social functioning of adult persons with nemaline myopathy or related disorders. The results indicate vulnerability of non-ambulatory patients being at higher risk to a decrease in general functioning during global or national exceptional periods. The responses also gave directions for modifying and improving the survey for future studies.

Exercise induced muscle weakness in a young adult: McArdle’s disease unusual presentation

McArdle’s disease (Glycogen storage disease type V) is a rare inherited autosomal recessive disease involving defect in enzyme, glycogen phosphorylase (PYGM) which results in accumulation of glycogen mainly affecting skeletal muscles. It commonly presents in childhood and rarely in adults with symptoms like exercise intolerance, muscle weakness, cramps and fatigue. Herein, we report an unusual case of a 22 years old male in Pakistan with probable McArdle’s Disease presenting with repeated episodes of generalized cramping muscle pain, exercise intolerance and haematuria. The diagnostic approach to identifying this disease as well as the differentials of other rare types of skeletal muscle disorders that should be kept in mind while dealing with a similar clinical picture, irrespective of the age of presentation, have been discussed. Keywords: Glycogen Storage Disease Type V, Myoglobinuria.