Muscle Disorders Research Articles

Functional Food Mixture Extricates D-Galactose-Induced Skeletal Muscle Impairment in Rats.

Aging-related muscle atrophy/sarcopenia is the most common type of muscle impairment that affects the quality of life. In the current study, we examined the effect of a functional food mixture of amla, turmeric, black pepper, cinnamon, and ginger on D-galactose-induced muscle alterations in rats. Wistar rats were randomly divided into three groups: Control (C), D-galactose (G), and D-galactose + functional food mixture intervention (G + I). Rats in group-G and -G + I were injected with D-galactose (300 mg/kg/day) for 90 days. After 3 months of the experimental period, the rats were sacrificed to collect gastrocnemius muscle. Group-G rats showed elevated levels of inflammatory cytokines (TNFα and NF-kB), atrogenes (atrogin-1 and MuRF1), decreased insulin/IGF1 signaling (decreased AKT phosphorylation), altered mitochondrial dynamics (increased fission and decreased fusion proteins), increased apoptotic mediators (Bax/Bcl-2, and caspase-3), and decreased muscle cell cross-sectional area when compared with group-C (p < 0.05). Interestingly, supplementation with the functional food mixture prevented galactose-induced alterations in the muscle. The observed anti-inflammatory, insulin-sensitizing, mitochondria-protective, and antiapoptotic effects of the functional food could be the underlying mechanisms in displaying positive effects against galactose-induced muscle atrophy and, hence, may be useful for the prevention of age-related muscle disorders.

Phenotype-Genotype Correlation of a Cohort of Patients with Congenital Myopathy: A Single Centre Experience from India.

Congenital myopathies (CMs) are a diverse group of inherited muscle disorders with broad genotypic and phenotypic heterogeneity. While the literature on CM is available from European countries, comprehensive data from the Indian subcontinent is lacking. This study aims to describe the clinical and histopathological characteristics of a cohort of genetically confirmed CMs from India and attempts to do phenotype-genotype correlation. A retrospective chart review of genetically confirmed CMs was evaluated between January 2016 and December 2020 at the neuromuscular clinic. The clinical, genetic, and follow-up data were recorded in a pre-structured proforma as per the medical records, and the data was analyzed. A total of 31(M: F = 14 : 17) unrelated patients were included. The median age at onset and duration of illness are 2.0(IQR:1-8) years and 6.0(IQR:3-10) years respectively. Clinical features observed were proximodistal weakness (54.8%), facial weakness (64.5%), and myopathic facies (54.8%), followed by ptosis (33.3%), and ophthalmoplegia (19.4%). Muscle histopathology was available in 38.7% of patients, and centronuclear myopathy was the most common histopathology finding. The pathogenic genetic variants were identified in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), KBTBD13 (9.7%), NEB (6.5%), and MYPN (6.5%) genes. Novel mutations were observed in 30.3% of the cohort. Follow-up details were available in 77.4% of children, and the median duration of follow-up and age at last follow-up was 4.5 (Range 0.5-11) years and 13 (Range 3-35) years, respectively. The majority were ambulant with minimal assistance at the last follow-up. Mortality was noted in 8.3% due to respiratory failure in Centronuclear myopathy 1 and congenital myopathy 3 with rigid spines (SELENON). This study highlights the various phenotypes and patterns of genetic mutations in a cohort of pediatric patients with congenital myopathy from India. Centronuclear myopathy was the most common histological classification and the mutations in RYR1 followed by DNM2 gene were the common pathogenic variants identified. The majority were independent in their activities of daily living during the last follow-up, highlighting the fact that the disease has slow progression irrespective of the genotype.

Heilungshindernis bei klaffender Tube – ein Fallbericht

A 65-year-old female patient presented with a diagnosis of PET (patulous Eustachian tube). For years, she had been suffering from severely disabling autophonia and had already undergone various unsuccessful treatments. Surgery was discussed as the last resort.The osteopathic treatments I carried out primarily only led to a short-lasting improvement in the symptoms. An unconscious permanent tension of the cervical muscles, shoulder – and temporomandibular joint muscles – subjectively unperceived by the patient – in combination with a coordination disorder of the orofacial muscles prevented a lasting healing success. In addition to the osteopathic treatment an intensive perception training and daily coordination excercises were necessary for a successful treatment.

Diarylpropionitrile-stimulated ERβ nuclear accumulation promotes MyoD-induced muscle regeneration in mdx mice by interacting with FOXO3A

Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive degenerative disease of skeletal muscle, characterized by intramuscular inflammation, muscle regeneration disorder and replacement of muscle with fibroadipose tissue. DMD is caused by the absence of normal dystrophy. Impaired self-renew ability and limited differentiation capacity of satellite cells are proved as main reasons for muscle regeneration failure. The deficiency of estrogen impedes the process of muscle regeneration. However, the role of estrogen receptor β (ERβ) in muscle regeneration is still unclear. This study aims to investigate the role and the pharmacological effect of ERβ activation on muscle regeneration in mdx mice. This study showed that mRNA levels of ERβ and myogenic-related genes both witnessed increasing trends in dystrophic context. Our results revealed that treatment with selective ERβ agonist (DPN, diarylpropionitrile) significantly increased myogenic differentiation 1 (MyoD-1) level and promoted muscle regeneration in mdx mice. Similarly, in mdx mice with muscle-specific estrogen receptor α (ERα) ablation, DPN treatment still promoted muscle regeneration. Moreover, we demonstrated that myoblasts differentiation was accompanied by raised nuclear accumulation of ERβ. DPN treatment augmented the nuclear accumulation of ERβ and, thus, contributed to myotubes formation. One important finding was that forkhead box O3A (FOXO3A), as a pivotal transcription factor in Myod-1 transcription, participated in the ERβ-promoted muscle regeneration. Overall, we offered an interesting explanation about the crucial role of ERβ during myogenesis.

The Hox-based positional memory in muscle stem cells.

The skeletal muscle is a contractile tissue distributed throughout the body with various anatomical sizes, shapes and functions. In pathological conditions, such as muscular dystrophy, age-related sarcopenia and cancer cachexia, skeletal muscles are not uniformly affected throughout the body. This region-specific vulnerability cannot be fully explained by known physiological classifications, including muscle fiber types. Accumulating evidence indicates that the expression patterns of topographic homeobox (Hox) genes provide a molecular signature of positional memory, reflecting the anatomical locations and embryonic history of muscles and their associated muscle stem cells in adult mice and humans. Hox-based positional memory is not merely a remnant of embryonic development but is expected to be an intrinsic determinant controlling muscle function because recent studies have shown that aberrant Hox genes affect muscle stem cells. In this review, we discuss the concept of Hox-based positional memory, which may offer a new perspective on the region-specific pathophysiology of muscle disorders.

Genetic susceptibility to temporomandibular joint involvement in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Temporomandibular joint (TMJ) is among the most commonly affected joints in JIA patients. When JIA involves the TMJ, it may affect condylar growth in the joint; therefore, JIA patients are at risk of unfavourable long-term outcomes from associated joint damage. If undetected, TMJ involvement can lead to various functional disabilities such as reduced mandibular mobility and disorders of the mastication muscles. Limitations in sagittal and vertical mandibular growth can result in micrognathia and anterior open bite with aesthetic and functional restrictions. Genetic factors may play a role in determining which individuals are more prone to develop TMJ disorders or in predicting the severity of the disease process. Therefore, we applied a GWAS approach to identify loci associated with TMJ involvement in a sample of Estonian patients with JIA. Our aim was to address the potential role of genetic susceptibility factors in TMJ-JIA, a condition not previously studied in this context. The case group consisted of 55 JIA patients with TMJ involvement and 208 patients without TMJ involvement comprised the control group. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. Imputation was performed using a nationwide reference panel obtained of 2240 individuals whose data were obtained from the Estonian Biobank. We identified six loci as being associated with the risk of TMJ-JIA in Estonian JIA patients. The strongest associations were identified at CD6 rs3019551 (P = 3.80 × 10-6), SLC26A8/MAPK14 rs9470191 (P = 6.15 × 10-6), NLRP3 rs2056795 (P = 8.91 × 10-6) and MAP2K4 rs7225328 (P = 1.64 × 10-5). This study provides first insights into the risk-associated loci between JIA and its manifestation in the TMJ. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that render the TMJ susceptible to involvement by JIA in Estonian patients.

Unsupervised Learning of Eye State Prototypes for Semantically Rich Blinking Detection.

Blinking contributes to the health and protection of the eye and also holds potential in the context of muscle or nerve disorder diagnosis. Traditional methods of classifying eye blinking as open or closed are insufficient, as they do not capture medical-relevant aspects like closure speed, duration, or percentage. The issue could be solved by reliably detecting blinking intervals in high-temporal recordings. Our research demonstrates the reliable detection of blinking events through data-driven analysis of the eye aspect ratio. In an unsupervised manner, we establish an eye state prototype to identify blink intervals and measure inter-eye synchronicity between moments of peak closure. Additionally, our research shows that manually defined prototypes yield comparable results. Our results demonstrate inter-eye synchronicity up to 4.16 ms. We anticipate that medical professionals could utilize our methods to identify or define disease-specific prototypes as potential diagnostic tools.

Molecular mechanism of skeletal muscle loss and its prevention by natural resources.

A skeletal muscle disorder has drawn attention due to the global aging issues. The loss of skeletal muscle mass has been suggested to be from the reduced muscle regeneration by dysfunction of muscle satellite cell/fibro-adipogenic progenitor cells and the muscle atrophy by dysfunction of mitochondria, ubiquitin-proteasome system, and autophagy. In this review, we highlighted the underlying mechanisms of skeletal muscle mass loss including Notch signaling, Wnt/β-catenin signaling, Hedgehog signaling, AMP-activated protein kinase (AMPK) signaling, and mammalian target of rapamycin (mTOR) signaling. In addition, we summarized accumulated studies of natural resources investigating their roles in ameliorating the loss of skeletal muscle mass and demonstrating the underlying mechanisms in vitro and in vivo. In conclusion, following the studies of natural resources exerting the preventive activity in muscle mass loss, the signaling-based approaches may accelerate the development of functional foods for sarcopenia prevention.

Polyunsaturated fatty acids prevent myosteatosis and lipotoxicity

Myosteatosis occurs in response to excess circulating fatty acids and is associated with muscle dysfunction. This study aimed to characterize the sequence of events of lipid-induced toxicity within muscle cells and the role of polyunsaturated fatty acids (PUFA) as potential preventive factors. Myosteatosis was induced in C2C12 myotubes exposed to palmitic acid (PAL 500µM). Furthermore, cells were co-incubated with PUFA (α-linolenic acid = ALA, Eicosapentaenoic acid = EPA, Docosahexaenoic acid = DHA; Arachidonic acid = ARA) over a period of 48 h. Cell viability, morphology, and measures of lipid and protein metabolism were assessed at 6, 12, 24, and 48 h. We observed that myotube integrity was rapidly and progressively disrupted by PAL treatment after 12 h, ultimately leading to cell death (41.7% cell survival at 48 h, p < .05). Cell death did not occur in cells exposed to PAL+ARA and PAL+DHA. After 6 h of PAL treatment, an accumulation of large lipid droplets was observed within the cell (6 folds, p < .05). This was associated with an increase in ceramides (CER x3 fold change) and diacylglycerol (DAG x150 fold change) contents (p < .05). At the same time, insulin was no longer able to stimulate protein synthesis (p < .05) nor leverage autophagic flux (p < .05). DHA and ARA were able to completely reverse the defect in protein synthesis and partially modulate the accumulation of CER and DAG. These findings present new and intriguing research avenues in the field of muscle metabolism and nutrition, particularly in the context of aging, chronic muscle disorders, and insulin resistance.

Cytochrome c Oxidase Detection in Human Fibroblasts Using Scanning Electrochemical Microscopy

Cytochrome C Oxidase Deficiency (COXD) is a disorder caused by the mutation in genes encoding for the cytochrome c oxidase enzyme (COX),1 a mitochondrial multimeric enzyme which acts as the terminal electron acceptor in the electron transport chain.2 COXD causes serious health issues in affected individuals, including severe muscle weakness, brain damage and disorders in organs such as heart, liver and kidneys.1 Diagnosis is mostly performed by muscle biopsy,3,4 which is invasive and time-consuming. Finding new effective and early diagnostic strategies is therefore crucial to minimize symptoms and long-term disabilities. This research proposes the use of scanning electrochemical microscopy (SECM) as a promising method to quantify COX activity in normal and COXD fibroblasts as cell models. We explore the interaction of the redox probe N,N,N’,N’-tetramethyl-p-phenylene diamine (TMPD) with COX as an indicator of enzymatic activity.5,6 A platinum ultramicroelectrode was used to monitor electrochemical currents at different scan speeds, which were later used to determine an apparent heterogeneous rate constant (k 0) for TMPD regeneration by each cell line using numerical modelling. A significant difference in k 0 values (p < 0.1) was observed when comparing normal and COXD fibroblasts. The further treatment of normal fibroblasts with a COX inhibitor, NaN3,7 induced significant decreases in k 0 (p < 0.01). The COX activity results determined using SECM were in good agreement with a standard spectrophotometric assay. Taken together, our findings confirm SECM as an effective and rapid method to detect COXD in living tissues and provides a foundation for the development of new assays to diagnose COXD in infants. References M. Brischigliaro and M. Zeviani, Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1862, 148335 (2021).A. Timón-Gómez et al., Semin Cell Dev Biol, 76, 163–178 (2018).M. L. Simard, A. Mourier, L. C. Greaves, R. W. Taylor, and J. B. Stewart, Journal of Pathology, 245, 311–323 (2018).S. B. Wortmann, J. A. Mayr, J. M. Nuoffer, H. Prokisch, and W. Sperl, Neuropediatrics, 48, 309–314 (2017).S. Kuss, E. E. L. Tanner, M. Ordovas-Montanes, and R. G. Compton, Chem Sci, 8, 7682–7688 (2017).S. Thind et al., Proc Natl Acad Sci U S A (2023). In press.M. J. Fei et al., Acta Crystallogr D Biol Crystallogr, 56, 529–535 (2000).

Levothyroxine sodium tablets reversed Hashimoto thyroiditis-induced kidney injury, muscle injury, and lipid metabolism disorder: A case report and literature review.

Hashimoto thyroiditis (HT), a common cause of hypothyroidism, has shown an increasing incidence in recent years, particularly among women. In addition to the common complications such as lipid metabolism disorders, patients with HT may also experience some serious complications, acute kidney injury and severe muscle damage for instance. This article explored the effectiveness of levothyroxine sodium tablets (L-T4) replacement therapy in severe complications of hypothyroidism, including treatment dosage, duration of complication recovery, and whether additional treatment is needed. We described a case of a 52-year-old woman with HT who exhibited kidney injury, muscle injury, and lipid metabolism disorders. The increased levels of serum creatinine, creatine kinase, cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and the decreased levels of estimated glomerular filtration rate were obviously observed. This patient was started on L-T4 (75 and 100 µg, alternate). Following a two-month treatment, the serum creatine kinase level decreased to within normal range. The estimated glomerular filtration rate level was restored, and the serum creatinine level was down-regulated, although slightly higher than the normal range. L-T4 partially reversed HT-induced the disorders of muscle, renal function, and lipid profile of this patient and remarkably alleviated her HT-related symptoms.

Have a Little Heart (or Not): Highly Minimized Skeletal Muscle Regulatory Cassettes with Low or No Activity in the Heart.

Adeno-associated virus-mediated gene therapies for certain muscle disorders require regulatory cassettes that provide high-level, striated muscle-specific activity. However, cardiotoxicity has emerged as a serious concern in clinical trials for Duchenne muscular dystrophy and X-linked myotubular myopathy. While this may be caused by systemic inflammatory effects of the treatment, high transgene expression in the heart may also play a role. Thus, certain muscle disorders may require a modulated level of therapeutic expression in the heart, while others may not require any cardiac expression at all. Additionally, the size of some cargos requires regulatory cassettes to be small enough that large cDNAs and other therapeutic payloads can be accommodated. Thus, we have performed enhancer/promoter optimization to develop highly minimized regulatory cassettes that are active in skeletal muscles, with either low or no detectable activity in cardiac muscle. Our No-heart (NH) cassette is active in most skeletal muscles, but exhibits only very low activity in extensor digitorum longus (EDL), soleus, and diaphragm, and no activity in the heart. By contrast, our Have a Little Heart (HLH) cassette displays high activity in most skeletal muscles, comparable to the ∼800-bp CK8 cassette, with increased activity in EDL, soleus, and diaphragm, and low activity in the heart. Due to their small size, these cassettes can be used in therapeutic strategies with both flexible (e.g., antisense) and stringent (e.g., CRISPR/Cas or bicistronic) size limitations. Thus, our new cassettes may be useful for gene therapies of muscle disorders in which the need for low or almost no expression in cardiac muscle would outweigh the need for high levels of therapeutic product in certain skeletal muscles.

Fucoxanthin Mitigates High-Fat-Induced Lipid Deposition and Insulin Resistance in Skeletal Muscle through Inhibiting PKM1 Activity.

Glucose and lipid metabolism dysregulation in skeletal muscle contributes to the development of metabolic disorders. The efficacy of fucoxanthin in alleviating lipid metabolic disorders in skeletal muscle remains poorly understood. In this study, we systematically investigated the impact of fucoxanthin on mitigating lipid deposition and insulin resistance in skeletal muscle employing palmitic acid-induced lipid deposition in C2C12 cells and ob/ob mice. Fucoxanthin significantly alleviated PA-induced skeletal muscle lipid deposition and insulin resistance. In addition, fucoxanthin prominently upregulated the expression of lipid metabolism-related genes (Pparα and Cpt-1), promoting fatty acid β-oxidation metabolism. Additionally, fucoxanthin significantly increased the expression of Pgc-1α and Tfam, elevated the mtDNA/nDNA ratio, and reduced ROS levels. Further, we identified pyruvate kinase muscle isozyme 1 (PKM1) as a high-affinity protein for fucoxanthin by drug affinity-responsive target stability and LC-MS and confirmed their robust interaction by CETSA, microscale thermophoresis, and circular dichroism. Supplementation with pyruvate, the product of PKM1, significantly attenuated the beneficial effects of fucoxanthin on lipid deposition and insulin resistance. Mechanistically, fucoxanthin reduced glucose glycolysis rate and enhanced mitochondrial biosynthesis and fatty acid β-oxidation through inhibiting PKM1 activity, thereby alleviating lipid metabolic stress. These findings present a novel clinical strategy for treating metabolic diseases using fucoxanthin.

RBP4 promotes denervation-induced muscle atrophy through STRA6-dependent pathway.

Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. Denervation-induced muscle atrophy model was constructed in wild-type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) or oral gavage of RBP4 inhibitor A1120. Holo-RBP4-stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross-sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. The expression levels of RBP4 in skeletal muscles were significantly up-regulated more than 2-fold from 7days and sustained for 28days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation-induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin-1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol-bound holo-RBP4 aggregated denervation-induced ectopic fat accumulation and muscle atrophy. Consistently, holo-RBP4 stimulation also had a dose-dependent effect on the reduction of C2C12 myotube diameter and myofibre cross-sectional area, as well as on the increase of Atrogin-1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo-RBP4 treatment increased the expression of its membrane receptor STRA6 (>3-fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin-1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3-fold) in holo-RBP4-treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation-induced muscle atrophy (30% increased myofibre cross-sectional area) in mice. In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6-dependent and JAK2/STAT3 pathway-mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.

Pendampingan Kesehatan Fisik bagi Pembatik sebagai Upaya Mengurangi Risiko dan Keluhan Work-related Musculoskeletal Disorder (WMSD) di Kampung Batik Laweyan

The high incidence of Work-related Musculoskeletal Disorder (WMSD) in workers is caused by various factors from the individual and the work environment. Musculoskeletal complaints in workers also occur and disrupt productivity for batik workers. Batik itself has several types and several divisions of work. Workload, duration, and poor work posture cause excess work on the muscles which results in functional disorders of the structural muscles in the neck and causes myofascial trigger point syndrome (MTPS). This service activity is carried out to resolve complaints, prevent further impacts, and increase worker productivity. The program is provided in the form of Integrated Neuromuscular Inhibition Technique (INIT) and Self Stretching combined with infrared radiation. Apart from that, educational efforts are also being made regarding Musculoskeletal Disorders and ergonomic working positions. Measurement of activity effectiveness is carried out using the VAS, NDI, NBM and WERA instruments. Based on the results of the activities carried out, it can be concluded that health assistance efforts for batik workers in Laweyan Batik Village in the form of providing therapeutic and educational measures have proven effective in reducing complaints and incidents of WMSD. By reducing complaints, the work output and productivity of batik makers increases.

Muscle ultrasound in myopathies.

This review highlights recent developments in the field of muscle ultrasound (MUS) for the diagnosis and follow up of muscle disorders. The diagnostic screening capacity of quantitative grayscale analysis is still sufficient to assess children suspected of a neuromuscular disorder. A combination of visual and quantitative assessment is advised for optimal interpretation. MUS was more sensitive but less specific than MRI for detecting pathology in limb girdle dystrophies and inflammatory myopathies. New techniques such as shearwave elastography and artificial intelligence algorithms for automated image segmentation show promise but need further development for use in everyday practice.Muscle ultrasound has high correlations with clinical measures of function in skeletal and respiratory muscles and the orofacial region, in most of the myopathies and dystrophies studied. Over time, imaging changes precede changes in clinical status, making them attractive for biomarker use in trials. In Duchenne muscular dystrophy MUS was also responsive to the effects of steroid treatment. Muscle ultrasound is a sensitive technique to diagnose and follow up of skeletal, facial and respiratory muscles in neuromuscular disorders. Its role is both complementary to and partially overlapping with that of MRI.

System Design and Development of a Novel, Unique Neuro Physical Medical Treatment Method for Spinal Muscular Atrophy and Similar Neurological Muscle Diseases.

The project is entirely original to the author. It proposes the theory of a method under development aimed at treating SMA and other related neurological muscle disorders The study will utilize a 14-channel EEG device to analyze brain data. The brain signals recorded by this device will be transmitted to the patient's muscles, potentially restoring functions lost in SMA patients. These functions include coughing, swallowing, breathing, chewing, walking, and movements of the hands, arms, and other muscles. By using this EEG device, brain signals can be visualized as waves, and its specialized software allows users to manipulate objects on a computer screen with thought alone. The system also simulates facial movements and expressions on-screen

Prevalence of sarcopenia among people living with HIV defined by the revised European working group on sarcopenia in older people.

Sarcopenia is a progressive and systemic skeletal muscle disorder associated with an increased risk of hospitalization and adverse effects on survival. This study aims to investigate the prevalence and related risk factors of sarcopenia in people living with HIV using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) definition. This cross-sectional study comprising 379 patients with confirmed HIV infection evaluated the appendicular skeletal muscle mass by employing the bioelectrical impedance analysis method. Muscle strength and functional mobility were analyzed using the five-time sit-to-stand test and the timed "Up and Go" test. The prevalence rates of pre-sarcopenia and sarcopenia among people living with HIV were 3.4 % and 2.1 % according to the revised EWGSOP2 definition. Advanced age (Odds Ratio 1.07, p = .03), lower body mass index (Odds Ratio 0.79, p = .012) and CD4+ T-cell count below 500/μl (Odds Ratio 2.22, p = .007) were identified as significant factors associated with sarcopenia. Sarcopenia was also identified as a significant correlate of frailty (p < .001). This is the first study examining the prevalence of sarcopenia in people living with HIV according to the revised EWGSOP2 clinical algorithm. Advanced age, lower body mass index and a poor immune status are determined as promoting factors of sarcopenia. Sarcopenia significantly correlates with frailty. Standardized clinical algorithms are essential for reliable sarcopenia diagnosis in people living with HIV in order to promote intervention strategies and to prevent adverse health outcomes.

Heterogenic Genetic Background of Distal Arthrogryposis-Review of the Literature and Case Report.

Distal arthrogryposis (DA) is a skeletal muscle disorder that is characterized by the presence of joint contractures in various parts of the body, particularly in the distal extremities. In this study, after a systematic review of the literature, we present a case report of a non-consanguineous family. In our case, the first-trimester ultrasound was negative, and the presence of the affected mother was not enough for the parents to consent to us performing invasive amniotic fluid sampling. The second-trimester ultrasound showed clear abnormalities suggestive of arthrogryposis. Whole-exome sequencing was performed and an autosomal dominantly inherited disease-associated gene was identified. In our case, a pathogenic variant in the TNNT3 gene c.188G>A, p.Arg63His variant was identified. The mother, who had bilateral clubfoot and hand involvement in childhood, carried the same variant. The TNNT3 gene is associated with distal arthrogryposis type 2B2, which is characterized by congenital contractures of the distal limb joints and facial dysmorphism. In the ultrasound, prominent clubfoot was identified, and the mother, who also carried the same mutation, had undergone surgeries to correct the clubfoot, but facial dysmorphism was not detected. Our study highlights the importance of proper genetic counseling, especially in an affected parent(s), and close follow-up during pregnancy.

Protective properties of melanin from lichen Lobaria pulmonaria (L.) HOFFM. In models of oxidative stress in skeletal muscle

Melanin is a dark pigment from the group of phenolic or indole polymers with inherent biocompatibility and antioxidant capacity. In extremophilic lichen Lobaria pulmonaria, melanin is responsible for protective properties against hostile environments. Herein, the ability of melanin extracted from L. pulmonaria to counteract oxidative stress and related damages was studied in the mouse diaphragm, the main respiratory muscle. Initial in vitro experiments demonstrated ultraviolet (UV)-absorbing, antioxidant and metal chelating activities of melanin. This melanin can form nanoparticles and stabile colloidal system at concentration of 5 μg/ml. Pretreatment of the muscle with melanin (5 μg/ml) markedly reduced UV-induced increase in intracellular and extracellular reactive oxygen species (ROS) as well as antimycin A-mediated enhancement in mitochondrial ROS production accompanied by lipid peroxidation and membrane asymmetry loss. In addition, melanin attenuated suppression of neuromuscular transmission and alterations of contractile responses provoked by hydrogen peroxide. Thus, this study shed the light on the perspectives of the application of a lichen melanin as a protective component for treatment of skeletal muscle disorders, which are accompanied with an increased ROS production.