Muscle Disorders Research Articles

PENYULUHAN IMPLEMENTASI PERSONAL RISK ASSESSMENT TERHADAP WORK RELATED MUSCULOSKELETAL DISORDER SYNDROM (WMSDs) PADA LOADERMAN AREA PACKING PLANT PT SOLUSI BANGUN ANDALAS

Work Related Musculoskeletal Disorder Syndrome (WMSDs) is a group of disorders of muscles, tendons, and nervous system caused by repeated and continuous static loads for a certain period it will cause damage to joints, ligaments, and tendons. The purpose of this research is to find out whether the implementation of the Personal Risk Assessment program has been effective in preventing the risk of musculoskeletal disorders on the loader man at packing plant Solusi Bangun Andalas Inc area, by analyzing the relationship of factors thought to be associated cause WMSDs, namely workload, work posture, repetition, duration, and vibration. This research is quantitative with a cross-sectional method. Data was collected by distributing Rapid Entire Body Assessment (REBA) and Nordic Body Map (NBM) worksheet questionnaires to 30 samples. Data analysis was performed in univariate and bivariate using the Chi-Square test. The results of the workload test with complaints of WMSDs got a p-value of 0.005, work posture with complaints of WMSDs with a result of p 0.004, repetitions with complaints of WMSDs with a result of p 0.013, duration with complaints of WMSDs with a result of 0.008 and vibration with complaints of WMSDs with a result of 0.002, and the conclusion show that the Personal Risk Assessment program is ineffective in preventing WMSDs risk

FRI512 Thyrotoxic Periodic Paralysis With Extreme Hypokalemia Precipitated By Acute Alcohol Intoxication In A Patient With Graves’ Disease

Abstract Disclosure: J. Batra: None. A.R. Ankireddypalli: None. J. Kaur: None. Introduction: Thyrotoxic periodic paralysis (TPP) is a muscle and electrolyte disorder, mostly seen in the setting of hyperthyroidism. It is characterized by reversible painless muscle weakness and hypokalemia. Prevalence is highest in East Asian populations, approximately 2%, and 0.1-0.2% in other populations. Males are much more likely to be affected. Common provoking factors include exercise, fasting, and changes in diet. Clinical case: A 29-year-old male of East Asian ethnicity presented to the hospital with the complaint of multiple bouts of inability to lift his extremities for 1 day. He also complained of generalized weakness. He did not have any changes in his mental status and was fully oriented at the time of the presentation. No breathing difficulty was reported. He had been drinking the night before with his friends and drank 1 L of vodka. His past medical history was significant for hyperthyroidism secondary to Graves’ disease, which was diagnosed a year ago. He had been prescribed methimazole but had not been adherent to the medication. The basic metabolic panel revealed undetectable serum potassium of <1.5 (3.4 to 5.3 mmol/L). The rest of the electrolytes and renal function were unremarkable. TSH was suppressed at <0.01 (0.3 to 4.20 uIU/L) and free T4 levels were significantly elevated at 7.77 (0.9 to 1.70 ng/dL). The thyrotropin receptor antibody was 33 (0.00 to 1.75 IU/L). EKG showed sinus tachycardia with nonspecific T-wave abnormalities. Thyroid ultrasound showed diffusely heterogenous parenchyma with diffusely increased blood flow throughout the thyroid on doppler. Echocardiogram showed a normal ejection fraction of 55-60% with mild concentric left ventricular wall thickening consistent with left ventricular hypertrophy. He was initially treated with intravenous potassium replacement and high doses of propylthiouracil, hydrocortisone, and propranolol, leading to the resolution of his symptoms. He was discharged on methimazole and propranolol therapies. Learning points: • Patients with Graves’ disease are routinely counseled against tobacco use to avoid worsening of orbitopathy. Hyperthyroid patients should also be counseled regarding avoidance or moderation of alcohol intake to avoid this rare but potentially life-threatening complication of thyrotoxic periodic paralysis. • The incidence of TPP is significantly higher in the East Asian populations, especially among males (8.7-13%). Counseling regarding provoking factors, the importance of adherence to medications, and the maintenance of euthyroidism to avoid TPP is essential. Presentation: Friday, June 16, 2023

The Effect of Aerobic Exercise on SREBP-1c Gene Expression in Skeletal Muscle in Obese Female Rats

Background: Obesity causes skeletal muscle metabolic disorders by altering the expression of the genes involved in lipid metabolism. One of the genes that play an important role in lipid metabolism in skeletal muscle tissue is sterol regulatory element binding protein (SREBP). Objectives: Since the interacting effect of aerobic exercise and high-fat diet on the expression of this gene has not been well studied, the aim of the present study was to determine the effect of aerobic exercise on the expression of the SREBP-1c gene in skeletal muscle in obese female rats. Methods: Eighteen female Wistar rats in the weight range of 180 - 200 grams were selected and randomly divided into three groups: (1) control fed with a normal diet; (2) control fed with a high-fat diet; and (3) aerobic exercise plus a high-fat diet. The high-fat diet contained 40% fat (20% soybean oil and 20% animal fat), 13% protein, and 47% carbohydrates. The rats were initially fed with a high-fat diet for 6 weeks, and then they performed aerobic exercise on a treadmill 5 times a week for 6 weeks. Forty-eight hours after the last training session and after eleven hours of fasting, the rats were anesthetized with ketamine and xylazine. Quadriceps tissues were removed to determine the SREBP-1c gene’s expression by real-time PCR. Results: Feeding with a high-fat diet significantly increased the weight of rats (P = 0.001). The expression of the SREBP-1c gene in the group fed with the high-fat diet decreased significantly compared to the group fed with the normal diet (P = 0.001). Aerobic exercise significantly increased the expression of the SREBP-1c gene in the quadriceps muscle (P = 0.001), contradicting the effect of the high-fat diet on the expression of this gene. Conclusions: Aerobic training may alleviate lipid metabolism disorders in muscles by increasing the expression of the SREBP-1c gene. Therefore, aerobic exercises can be used to contradict the metabolic complications caused by the high-fat diet in skeletal muscles.

Recurrent Toe Walking in Pediatric Orthopedic Patients: Idiopathic vs Concomitant Sensory Processing Disorders

Category: Other Introduction/Purpose: The purpose of this study is to compare rates of recurrent toe-walking following operative intervention between idiopathic toe walkers and toe walkers with associated sensory processing/autism spectrum disorders. Methods: An IRB-approved retrospective review of patients at a single pediatric institution who underwent surgical treatment for toe-walking over a 12-year period was conducted. Children with peripheral or central neurologic disorders, muscle disorders, congenital foot/extremity deformities, prior ankle/foot surgery, and those not managed with an isolated triceps surae procedure were excluded. The remaining patients were divided into those with idiopathic toe-walking (ITW Group) and those with toe- walking associated with sensory processing/autism spectrum disorders (SPD Group). Recurrence of toe walking and need for additional surgery for recurrence were compared between cohorts. Recurrence rates and subsequent operations were assessed for each group. Multivariate regression and Fischer exact test were used to evaluate differences in group characteristics. Results: 106 patients met inclusion criteria. 29 patients (27%) had an associated sensory processing disorder, the remaining 77 patients comprised the ITW group. There were no differences between groups in length of follow-up (p=0.08) or type of initial surgery performed (p=0.48). The SPD group contained a significantly greater percentage of males (75% vs 56%, p=0.01) and were younger at the age of index surgery (8.5 vs 10 years, p=0.03). At an average follow-up time of 1.2 years, 11 patients (10%) developed clinical recurrence, of whom, 4 underwent a subsequent intervention. The SPD group had significantly higher rates of recurrence than idiopathic toe walkers (24% vs 5%, p=0.009). Multivariate regression analysis demonstrated that an underlying sensory processing disorder was an independent predictor of recurrence (p=0.018, OR=7.5). Conclusion: Clinical recurrence following the surgical treatment of toe-walking is over seven times greater in children with autism spectrum and/or other sensory processing disorders than idiopathic counterparts.

P282 Evaluation of gene transfer efficiency in a mild model of dystrophic muscle disorder performed by machine learning and linear discriminant analysis

P282 Evaluation of gene transfer efficiency in a mild model of dystrophic muscle disorder performed by machine learning and linear discriminant analysis

Effects of low-intensity exercise on contractile property of skeletal muscle and the number of motor neurons in diabetic rats.

The mode of diabetes-induced muscle and motor neuron damage depends on the type of muscle and motor neuron. One of the purposes of exercise therapy for diabetes is to improve blood glucose levels; however, information on the effects of low-intensity exercise on muscle and motor neuron disorders remain unknown. Therefore, this study aimed to examine the effects of low-intensity exercise on diabetes-induced muscle and motor neuron damage in a rat model of type 1 diabetes mellitus. We subjected adult male Wistar rats treated with streptozotocin to develop type 1 diabetes and age-matched rats to low-intensity treadmill exercise for 12weeks. We recorded electrically evoked maximum twitch tension in leg muscles, and examined the number of motor neurons and cell body sizes. Low-intensity exercise ameliorated the prolonged half-relaxation time and the decreased numbers of the retrograde-labeled motor neurons observed in the soleus muscle of type 1 diabetic rats. However, no effect was observed in the diabetic group, as atrophy was not improved and the twitch force in the medial gastrocnemius muscle was decreased in the diabetic group. In addition, there was no improvement in the blood glucose levels after exercise. These data indicate that low-intensity exercise may relieve the onset of muscle and motor neuron damage in the soleus muscle of type 1 diabetic rats.

Synchronization of discrete time fractional order neuromuscular models in the presence and absence of stimulus

This article proposes a fractional order discrete-time neuromuscular model incorporating calcium kinetics to study the essential role of the neuromuscular system in facilitating rapid information transmission between nerve cells and muscles for bodily functions. The study conducts a dynamical analysis to investigate the stability and periodic oscillations of the system in the presence and absence of tetanus stimuli from neurons. Bifurcation diagrams are generated for different fractional orders and rate constants, highlighting the occurrence of chaotic dynamics. The region of chaos is determined using the largest Lyapunov exponents and the Jacobian matrix method. The study also achieves synchronization of the systems by employing nonlinear control functions with feedback gains. Emphasizing the significance of constructing the biological model using fractional order operators, the article provides a chemical interpretation of the analytical findings. Moreover, the article employs dynamic plots to visually depict the changing system variables over time, allowing for an examination of the concurrent presence of multiple attractors through bifurcation diagrams and phase plane portraits. By studying how chemical kinetics and muscle activation are interrelated, the article uncovers captivating revelations that could guide the formulation of strategies to combat muscle disorders. The article also underscores the potential utility of synchronization in managing neuromuscular conditions, thus emphasizing its practical implications in disease control.

Loss of Sec-1 Family Domain-Containing 1 (scfd1) Causes Severe Cardiac Defects and Endoplasmic Reticulum Stress in Zebrafish.

Dilated cardiomyopathy (DCM) is a common heart muscle disorder that frequently leads to heart failure, arrhythmias, and death. While DCM is often heritable, disease-causing mutations are identified in only ~30% of cases. In a forward genetic mutagenesis screen, we identified a novel zebrafish mutant, heart and head (hahvcc43), characterized by early-onset cardiomyopathy and craniofacial defects. Linkage analysis and next-generation sequencing identified a nonsense variant in the highly conserved scfd1 gene, also known as sly1, that encodes sec1 family domain-containing 1. Sec1/Munc18 proteins, such as Scfd1, are involved in membrane fusion regulating endoplasmic reticulum (ER)/Golgi transport. CRISPR/Cas9-engineered scfd1vcc44 null mutants showed severe cardiac and craniofacial defects and embryonic lethality that recapitulated the phenotype of hahvcc43 mutants. Electron micrographs of scfd1-depleted cardiomyocytes showed reduced myofibril width and sarcomere density, as well as reticular network disorganization and fragmentation of Golgi stacks. Furthermore, quantitative PCR analysis showed upregulation of ER stress response and apoptosis markers. Both heterozygous hahvcc43 mutants and scfd1vcc44 mutants survived to adulthood, showing chamber dilation and reduced ventricular contraction. Collectively, our data implicate scfd1 loss-of-function as the genetic defect at the hahvcc43 locus and provide new insights into the role of scfd1 in cardiac development and function.

COVID-19 related to sarcopenia: Current perspectives on etiology, clinical implications, and nutritional rehabilitation

Sarcopenia is a progressive skeletal muscle disorder characterized by reduced strength and quality. Pathophysiological mechanisms, clinical aspects, and nutritional points were related to sarcopenia in COVID-19 found in skeletal muscle during and after the disease course, which corroborated the development of adverse events. Declining physical activity, insufficient protein intake, and worsened proinflammatory response have been shown to have negative consequences on muscle protein synthesis, potentiating the risk of acute sarcopenia. Obesity sarcopenia has also been shown to worsen the prognosis of patients with SARS-CoV-2. Nutritional rehabilitation is used to prevent or minimize the development of acute sarcopenia. Dietary recommendations include increased energy supply and protein intake of 1.2 to 2.0 g/kg of body weight. Evidence suggests that aging with sedentary behaviors, pathophysiological changes, and inflammation alter body composition. In addition, nutritional deficiencies are predictors and aggravators of acute sarcopenia in COVID-19.

Effect of Muscle Forces on Femur During Level Walking Using a Virtual Population of Older Women.

Aging is associated with a greater risk of muscle and bone disorders such as sarcopenia and osteoporosis. These conditions substantially affect one's mobility and quality of life. In the past, muscles and bones are often studied separately using generic or scaled information that are not personal-specific, nor are they representative of the large variations seen in the elderly population. Consequently, the mechanical interaction between the aged muscle and bone is not well understood, especially when carrying out daily activities. This study presents a coupling approach across the body and the organ level, using fully personal-specific musculoskeletal and finite element models in order to study femoral loading during level walking. Variations in lower limb muscle volume/force were examined using a virtual population. These muscle forces were then applied to the finite element model of the femur to study the variations in predicted strains. The study shows that effective coupling across two scales can be carried out to study the muscle-bone interaction in elderly women. The generation of a virtual population is a feasible approach to augment anatomical variations based on a small population that could mimic variations seen in a larger cohort. This is a valuable alternative to overcome the limitation or the need to collect dataset from a large population, which is both time and resource consuming.

Investigating the Microwave-Assisted Extraction Conditions and Antioxidative and Anti-Inflammatory Capacities of Symphytum officinale WL Leaves

Symphytum officinale (comfrey) is a perennial herb native to West Asia and Europe. Its root extracts are commonly used as a natural remedy to treat muscle, joint, skin, and bone disorders, especially in Europe. However, more information is needed on the biomedical functions of comfrey leaves. This study’s sequencing results of internal transcribed spacer and trnL–trnF genes showed that plants purchased from the local market were comfrey and named S. officinale WL (WL). The suitable extraction conditions of the WL leaves with the highest extract yield and total phenols and flavonoid contents by microwave-assisted extraction were identified. The antioxidative and anti-inflammatory activities and possible molecular mechanism(s) of the WL leaf extract (WLE) were evaluated. Furthermore, the major component of WLE was identified as rosmarinic acid by HPLC. Results showed that the optimal extract condition was obtained with 750 W microwave power, 50 °C, 75% methanol, the solid-to-solvent ratio of 1:10, and 15 min. Results of all DPPH, ABTS, and superoxide radical scavenging activities, reducing power, ferrous ion chelating activity, and ferric reducing antioxidant power showed high antioxidative capacities of WLE. Furthermore, WLE showed prominent DNA-protecting activity. WLE attenuated lipopolysaccharide-stimulated inflammation by suppressing iNOS, COX-2, IL-1β, IL-6, and TNF-α expressions in the RAW264.7 macrophages. These attenuations are involved in the inactivation of lipopolysaccharide-stimulated NF-κB and MAPK signaling pathways. Therefore, the comfrey leaf extract obtained via a time- and energy-saving microwave-assisted extraction may be a potential antioxidative and anti-inflammatory biomedicinal agent.

100 Prevalence of probable sarcopenia and associated factors in older adults undergoing Comprehensive Geriatric Assessment

Abstract Background Sarcopenia is a skeletal muscle disorder, underpinned by adverse muscle changes that accrue across the lifespan. It is associated with increased likelihood of falls, fractures, physical disability and mortality. Low muscle strength is a principal parameter of sarcopenia. Sarcopenia is probable when low muscle strength (grip strength) is detected. The aim of this study was to evaluate the prevalence of low grip strength in older adults referred for Comprehensive Geriatric Assessment (CGA). The relationship between grip strength and sarcopenia- related factors was evaluated. Methods A period prevalence study was undertaken between September 2022 and March 2023. All patients ≥65 years who underwent CGA by a Community Specialist Team were included. Grip strength was measured using the Southampton Protocol. Associated factors measured were age, gender, frailty (CFS: Clinical Frailty Scale score), risk of malnutrition (MST: Malnutrition Screening Tool), co-morbidity, cognitive change on Dementia Screening Interview (AD8), falls history and mobility impairment. Probable sarcopenia was based on EWGSOP2 definition. Descriptive statistics, odds ratio (OR) with 95% confidence intervals (CI) and cross tabulation using Persons Chi squared test were used to determine if there was correlation between probable sarcopenia and associated factors. Results In total, 173 people attended for CGA (69 male, 104 female), mean age was 80 years (SD =7) and the median CFS score was 5 (mildly frail). The percentage of people who had their grip measured was 84% (n = 145). The prevalence of probable sarcopenia was 52% (n = 75). A positive correlation was identified between probable sarcopenia and age (p = 0.039), Clinical Frailty Scale score (p = 0.025), mobility impairment (p = 0.033) and those reporting cognitive change (p = 0.008). A positive association was identified between those with probable sarcopenia and ≥ 6 co-morbidities (OR 2.13; 95%CI 1.1–4.2). Conclusion Probable sarcopenia is associated with frailty, multi-morbidity, impaired mobility and cognitive change. Grip strength can identify older people who require CGA and targeted multimodal intervention.

165 Improving sarcopenia with a physiotherapy-dietetics sarcopenia management pathway in a post-acute rehabilitation unit

Abstract Background Sarcopenia is a progressive and generalised skeletal muscle disorder. The prevalence of sarcopenia in Irish studies ranges from 30 to 41%. The European Working Group on Sarcopenia in Older People (EWGSOP2) recommends that management of sarcopenia includes optimal protein intake and resistance training. The objectives of this study were to: (1) Implement a structured physiotherapy-dietetics sarcopenia management pathway for older persons identified as severely sarcopenic in a Post-Acute Rehabilitation Unit, to align with the (EWGSOP2) recommendations and (2) Assess the effect of the combination of protein optimisation and progressive resistance training (PRT) in reducing sarcopenia in those identified as severely sarcopenic. Methods Patients admitted to a post-acute rehabilitation unit from January to April 2023 were screened for sarcopenia using Grip strength and the Timed Up & Go test. All patients identified as being severely sarcopenic were referred to dietetics and attended a PRT class three times per week. Results There were 38 participants in this study. 73.7% were screened for sarcopenia on admission. From this, 71.4% were classified as having probable sarcopenia and 50% were identified as having severe sarcopenia. On discharge, 28.6% of participants had their sarcopenia completely reversed and 40% had their sarcopenia reduced from ‘severe’ to ‘probable’. Conclusion The results demonstrate that implementing a structured sarcopenia pathway for older persons in a post-acute rehabilitation unit has a positive effect on sarcopenia.

The gut microbiota from maintenance hemodialysis patients with sarcopenia influences muscle function in mice.

Sarcopenia is a common complication in patients undergoing maintenance hemodialysis (MHD). Growing evidence suggests a close relationship between the gut microbiota and skeletal muscle. However, research on gut microbiota in patients with sarcopenia undergoing MHD (MS) remains scarce. To bridge this knowledge gap, we aimed to evaluate the pathogenic influence of gut microbiota in the skeletal muscle of patients with MS, to clarify the causal association between gut microbiota and skeletal muscle symptoms in patients with MS and identify the potential mechanisms underlying this causal association. Fecal samples were collected from 10 patients with MS and 10 patients without MS (MNS). Bacteria were extracted from these samples for transplantation. Mice (n=42) were randomly divided into three groups and, after antibiotic treatment, fecal microbiota transplantation (FMT) was performed once a day for 3 weeks. Skeletal muscle and fecal samples from the mice were collected for 16S rRNA gene sequencing and for histological, real-time PCR, and metabolomic analyses. Mice colonized with gut microbiota from MS patients exhibited notable decreases in muscle function and muscle mass, compared with FMT from patients with MNS. Moreover, 16S rRNA sequencing revealed that the colonization of MS gut microbiota reduced the abundance of Akkermansia in the mouse intestines. Metabolome analysis revealed that seven metabolic pathways were notably disrupted in mice transplanted with MS microbiota. This study established a connection between skeletal muscle and the gut microbiota of patients with MS, implying that disruption of the gut microbiota may be a driving factor in the development of skeletal muscle disorders in patients undergoing MHD. This finding lays the foundation for understanding the pathogenesis and potential treatment methods for sarcopenia in patients undergoing MHD.

Soft Bioelectronics for Therapeutics.

Soft bioelectronics play an increasingly crucial role in high-precision therapeutics due to their softness, biocompatibility, clinical accuracy, long-term stability, and patient-friendliness. In this review, we provide a comprehensive overview of the latest representative therapeutic applications of advanced soft bioelectronics, ranging from wearable therapeutics for skin wounds, diabetes, ophthalmic diseases, muscle disorders, and other diseases to implantable therapeutics against complex diseases, such as cardiac arrhythmias, cancer, neurological diseases, and others. We also highlight key challenges and opportunities for future clinical translation and commercialization of soft therapeutic bioelectronics toward personalized medicine.

Use of occlusal splint in subjects with TMJ disorders by general dental practitioners in Indian scenario

Temporomandibular disorders (TMDs) constitute a global health concern, giving rise to both physical and financial burdens, as evidenced by symptoms and indications indicative of masticatory muscle imbalances. These symptoms encompass manifestations associated with disorders of the masticatory muscles. Scant literature exists regarding the utilization of occlusal splints by general dentists for addressing TMDs within the Indian context. Employing a cross-sectional questionnaire survey, the present study aimed to evaluate the application of occlusal splints in the treatment of temporomandibular issues by Indian dental practitioners. The inquiry involved the administration of a questionnaire designed to investigate the diagnosis, management, and treatment of TMDs by general dentists in India. Responses to the survey questions, provided by 314 general dental practitioners, were subjected to assessment and analysis through statistical methodologies. For practitioners with less than five years of experience, 77.63% (n=118) of participants reported no attendance at Certified Diabetes Educator (CDE) programs, whereas 14.47% (n=22) attended a single CDE session, and 7.89% (n=12) attended multiple CDE sessions related to TMDs. Among those practicing for five to ten years, 57.77% (n=52) did not participate in any TMD-related CDE programs, while 24.4% (n=22) attended one, and 17.7% (n=16) attended more than one. Among practitioners with over ten years of experience, 34.48% (n=20) did not attend any CDE, 24.13% (n=14) attended one, and 37.93% (n=22) attended multiple TMD-related CDE sessions. Diagnosis of TMDs was carried out by 64.33% (n=193) of participants using a combination of study models, imaging, patient history, and medical history. Among a total of 300 subjects, 64.6% (n=194) of participants responded affirmatively to the treatment of patients with TMDs. Hinge and mean value articulators were utilized in conjunction with soft materials for the fabrication of occlusal splints. The survey results suggest a paucity of knowledge among general dental practitioners regarding the application of occlusal splints in the treatment of TMDs.

The transcriptional regulator KLF15 is necessary for myoblast differentiation and muscle regeneration by activating FKBP5

Successful muscle regeneration following injury is essential for functional homeostasis of skeletal muscles. Krüppel-like factor 15 (KLF15) is a metabolic transcriptional regulator in the muscles. However, little is known regarding its function in muscle regeneration. Here, we examined microarray datasets from the Gene Expression Omnibus database, which indicated downregulated KLF15 in muscles from patients with various muscle diseases. Additionally, we found that Klf15 knockout (Klf15KO) impaired muscle regeneration following injury in mice. Furthermore, KLF15 expression was robustly induced during myoblast differentiation. Myoblasts with KLF15 deficiency showed a marked reduction in their fusion capacity. Unbiased transcriptome analysis of muscles on day 7 postinjury revealed downregulated genes involved in cell differentiation and metabolic processes in Klf15KO muscles. The FK506-binding protein 51 (FKBP5), a positive regulator of myoblast differentiation, was ranked as one of the most strongly downregulated genes in the Klf15KO group. A mechanistic search revealed that KLF15 binds directly to the promoter region of FKBP5 and activates FKBP5 expression. Local delivery of FKBP5 rescued the impaired muscle regeneration in Klf15KO mice. Our findings reveal a positive regulatory role of KLF15 in myoblast differentiation and muscle regeneration by activating FKBP5 expression. KLF15 signaling may be a novel therapeutic target for muscle disorders associated with injuries or diseases.

Genetic Neuromuscular Disorders and Health Services Access, Utilization, and Needs in Zambia

BackgroundMedical and rehabilitative advances increasingly transform management of rare genetic neuromuscular diseases (GNMDs) for children in the global north. Lack of information about GNMDs and related health care needs in sub-Saharan Africa threatens to widen pre-existing health disparities. MethodsThis is a cross-sectional study of probands enrolling in a study of GNMDs at the University Teaching Hospital in Lusaka, Zambia, a member of the International Consortium for Genomic Medicine in Neuromuscular Disease. Probands/caregivers were interviewed about utilization of medical, rehabilitative, and other support services by a research assistant. A neuromuscular neurologist and/or physiotherapist examined each case and completed an independent questionnaire regarding health service utilization for each proband. Diagnoses were made on available clinical and electrophysiologic data. Molecular findings were unavailable at the time of this analysis. ResultsAmong 50 probands, 52% were male with median age 12 (absolute range 2 months to 54 years). Motor neuron diseases (n = 16; 32%), muscle disorders (n = 20; 40%), and inherited polyneuropathies (n = 5; 10%) were most common. Six (15%) cases had insufficient clinical data to classify the GNMDs. Outside of primary care, patient/caregiver-reported access to recommended health services (n = 34; 69%) was challenging. Large disparities in current utilization of health care services versus clinician-recommended services are reported. ConclusionsParadigms to improve access to diagnostics and therapeutic interventions are needed for GNMDs in Zambia. Multidisciplinary clinics may improve access and utilization of needed health services. Qualitative and other research focused on improving referrals, access, and quality of available health services are greatly needed.

Clinical implications and mechanism of complement C1q in polymyositis.

Polymyositis (PM) is the most common autoimmune disease in neurology and among muscle disorders; it is of great significance to thoroughly understand the mechanism of PM to find new diagnosis and treatment methods. This research intends to elucidate the clinical implications and mechanisms of complement C1q in polymyositis (PM). One hundred fifteen PM patients (research group, RG) and 120 healthy subjects (control group, CG) who visited our hospital between March 2017 and March 2020 were selected. Peripheral blood C1q and creatine kinase (CK) levels of both groups were measured, and their correlations with clinical symptoms and prognostic recurrence of PM. Additionally, to further understand the mechanism of action of C1q in PM, we purchased BALB/c mice and grouped them as follows: control group with normal feeding, PM group with PM modeling, intervention group with PM modeling, and intraperitoneal injection of gC1qR monoclonal antibody 60.11, a C1q protein receptor. Inflammatory factors and muscle histopathology were detected in all groups of mice. Finally, rat macrophages (mø) were isolated, and changes in the biological behavior of mø were observed after silencing the expression of gC1qR. Serum C1q and CK were both higher in RG than in CG, with favorable diagnostic effects on PM (P < 0.05). C1q and CK increased in symptomatic anti-ribonuclear protein antibody (RNP)-positive patients but decreased in anti Jo-1 antibody (Jo-1)- and anti-neutrophil cytoplasmic antibody (ANCA)-positive patients (P < 0.05). PM mice were observed with elevated gC1qR, while model mice exhibited severe infiltration of inflammatory cells in muscle tissue, increased pro-IFs, and reduced anti-IFs, and the animals in the intervention group showed improved conditions (P < 0.05). Finally, it was found that CD68, CD86 protein, and invasion capacity of gC1qR-sh-transfected cells decreased, while CD206 and CD163 increased (P < 0.05). C1q is elevated in PM and is strongly linked to the pathological process of PM. Inhibition of gC1qR expression reduced inflammatory infiltration in PM mice.

Caenorhabditis elegans models for striated muscle disorders caused by missense variants of human LMNA.

Striated muscle laminopathies caused by missense mutations in the nuclear lamin gene LMNA are characterized by cardiac dysfunction and often skeletal muscle defects. Attempts to predict which LMNA variants are pathogenic and to understand their physiological effects lag behind variant discovery. We created Caenorhabditis elegans models for striated muscle laminopathies by introducing pathogenic human LMNA variants and variants of unknown significance at conserved residues within the lmn-1 gene. Severe missense variants reduced fertility and/or motility in C. elegans. Nuclear morphology defects were evident in the hypodermal nuclei of many lamin variant strains, indicating a loss of nuclear envelope integrity. Phenotypic severity varied within the two classes of missense mutations involved in striated muscle disease, but overall, variants associated with both skeletal and cardiac muscle defects in humans lead to more severe phenotypes in our model than variants predicted to disrupt cardiac function alone. We also identified a separation of function allele, lmn-1(R204W), that exhibited normal viability and swimming behavior but had a severe nuclear migration defect. Thus, we established C. elegans avatars for striated muscle laminopathies and identified LMNA variants that offer insight into lamin mechanisms during normal development.