Muscular Disorders Research Articles

Accurate prenatal diagnosis of facioscapulohumeral muscular dystrophy 1 using nanopore sequencing

BackgroundFacioscapulohumeral muscular dystrophy 1 (FSHD1) is an autosomal dominant muscular disorder mainly caused by the contraction and hypomethylation of the D4Z4 repeat array in chromosome 4q35. Prenatal diagnosis of FSHD1...

Muscular dystrophy associated with the DMD gene in women

Dystrophinopathies are a spectrum of X-linked muscular disorders associated with pathogenic/likely pathogenic variants in the dystrophin gene (DMD). Typically, the condition develops in males, but cases of symptom manifestation have also been described in females. The review presents contemporary data on the manifestations of dystrophinopathies in women with pathogenic variants in the DMD gene, discussing the reasons for the varying degrees of symptom expression in carrier women with pathogenic/ likely pathogenic variants. It discusses the importance of mutation screening in the DMD gene for women presenting with muscular dystrophy symptoms and investigating carrier status in relatives of patients with Duchenne/Becker muscular dystrophy.

Risks, demands, and health damages faced by nursing workers in confronting Covid-19

This article aims to analyze how nursing work processes have impacted the health of workers, taking into consideration the risks, demands, and potential damages. Nursing work is characterised by a demand for care that affects workers on various levels: physical, emotional, and psychological during the pandemic, there has been an exacerbation of labor precarity, increased exposure to risks and demands stemming from their work processes, and consequently, health damage. A mixed-method approach was employed, using the triangulation strategy of three data collection techniques: questionnaire surveys, focus groups, and individual interviews. It was found that the majority of participants are women, aged between 30 and 39, identify as having a brown skin color, work as nursing technicians, and have been employed in hospitals specialising in severe Covid-19 cases. The thematic categories identified were workload overload; lack of breaks or facilities for physiological needs; absence, improvisation, or inadequacy of Personal Protective Equipment (PPE); noise; health damage: fatigue and illness. These categories have corresponding variables that, in turn, were statistically associated with health damage, such as muscular disorders, sleep disturbances, mental health issues, and dermatological problems.

Muscle-enriched microRNA-486-mediated regulation of muscular atrophy and exercise.

The objectives of this review were to understand the impact of microRNA-486 on myogenesis and muscle atrophy, and the change of microRNA-486 following exercise, and provide valuable information for improving muscle atrophy based on exercise intervention targeting microRNA-486. Muscle-enriched microRNAs (miRNAs), also referred to as myomiRs, control various processes in skeletal muscles, from myogenesis and muscle homeostasis to different responses to environmental stimuli such as exercise. MicroRNA-486 is a miRNA in which a stem-loop sequence is embedded within the ANKYRIN1 (ANK1) locus and is strictly conserved across mammals. MicroRNA-486 is involved in the development of muscle atrophy caused by aging, immobility, prolonged exposure to microgravity, or muscular and neuromuscular disorders. PI3K/AKT signaling is a positive pathway, as it increases muscle mass by increasing protein synthesis and decreasing protein degradation. MicroRNA-486 can activate this pathway by inhibiting phosphatase and tensin homolog (PTEN), it may also indirectly inhibit the HIPPO signaling pathway to promote cell growth. Exercises regulate microRNA-486 expression both in blood and muscle. This review focused on the recent elucidation of sarcopenia regulation by microRNA-486 and its effects on pathological states, including primary muscular disease, secondary muscular disorders, and age-related sarcopenia. Additionally, the role of exercise in regulating skeletal muscle-enriched microRNA-486 was highlighted, along with its physiological significance. Growing evidence indicates that microRNA-486 significantly impacts the development of muscle atrophy. MicroRNA-486 has great potential to become a therapeutic target for improving muscle atrophy through exercise intervention.

The Accordion Zebrafish tq206 Mutant in the Assessment of a Novel Pharmaceutical Approach to Brody Myopathy.

Brody disease (BD) is an "ultra-rare" human genetic disorder of skeletal muscle function due to defects in the atp2a1 gene causing deficiency of the SERCA protein, isoform1. The main clinical signs are exercise-induced stiffness and delayed muscular relaxation after physical exercises, even mild ones. No mouse model nor specific therapies exist for Brody myopathy, which is therefore considered an orphan disease. Bovine congenital pseudomyotonia (PMT) is a muscular disorder characterized by an impairment of muscle relaxation and is the only mammalian model of human BD. The pathogenetic mechanism underlying bovine PMT has been recently clarified. These findings prompted us to purpose a potential pharmacological approach addressing a specific population of BD patients who exhibit reduced expression but still exhibit activity of the SERCA1 pump. Preclinical research involving in vivo studies is essential and necessary before clinical trials can be pursued and SERCA protein shows a high degree of conservation among species. So far, the only animal models available to study BD in vivo are a group of zebrafish mutant lines known as accordion zebrafish (acc). In this paper, we focused on a comprehensive characterization of the "acctq206" zebrafish variant. Our aim was to use this mutant line as an experimental animal model for testing the novel therapeutic approach for BD.

Structural biology and molecular pharmacology of voltage-gated ion channels.

Voltage-gated ion channels (VGICs), including those for Na+, Ca2+ and K+, selectively permeate ions across the cell membrane in response to changes in membrane potential, thus participating in physiological processes involving electrical signalling, such as neurotransmission, muscle contraction and hormone secretion. Aberrant function or dysregulation of VGICs is associated with a diversity of neurological, psychiatric, cardiovascular and muscular disorders, and approximately 10% of FDA-approved drugs directly target VGICs. Understanding the structure-function relationship of VGICs is crucial for our comprehension of their working mechanisms and role in diseases. In this Review, we discuss how advances in single-particle cryo-electron microscopy have afforded unprecedented structural insights into VGICs, especially on their interactions with clinical and investigational drugs. We present a comprehensive overview of the recent advances in the structural biology of VGICs, with a focus on how prototypical drugs and toxins modulate VGIC activities. We explore how these structures elucidate the molecular basis for drug actions, reveal novel pharmacological sites, and provide critical clues to future drug discovery.

Protein-extending ACTN2 frameshift variants cause variable myopathy phenotypes by protein aggregation.

The objective of the study is to characterize the pathomechanisms underlying actininopathies. Distal myopathies are a group of rare, inherited muscular disorders characterized by progressive loss of muscle fibers that begin in the distal parts of arms and legs. Recently, variants in a new disease gene, ACTN2, have been shown to cause distal myopathy. ACTN2, a gene previously only associated with cardiomyopathies, encodes alpha-actinin-2, a protein expressed in both cardiac and skeletal sarcomeres. The primary function of alpha-actinin-2 is to link actin and titin to the sarcomere Z-disk. New ACTN2 variants are continuously discovered; however, the clinical significance of many variants remains unknown. Thus, lack of clear genotype-phenotype correlations in ACTN2-related diseases, actininopathies, persists. Functional characterization in C2C12 cell model of several ACTN2 variants is conducted, including frameshift and missense variants associated with dominant and recessive actininopathies. We assess the genotype-phenotype correlations of actininopathies using clinical data from several patients carrying these variants. The results show that the missense variants associated with a recessive form of actininopathy do not cause detectable alpha-actinin-2 aggregates in the cell model. Conversely, dominant frameshift variants causing a protein extension do form alpha-actinin-2 aggregates. The results suggest that alpha-actinin-2 aggregation is the disease mechanism underlying some dominant actininopathies, and thus, we recommend that protein-extending frameshift variants in ACTN2 should be classified as pathogenic. However, this mechanism is likely elicited by only a limited number of variants. Alternative functional characterization methods should be explored to further investigate other molecular mechanisms underlying actininopathies.

Histone β-hydroxybutyrylation is critical in reversal of sarcopenia.

Sarcopenia, a leading cause for global disability and mortality, is an age-related muscular disorder, characterized by accelerated muscle mass loss and functional decline. It is known that caloric restriction (CR), ketogenic diet or endurance exercise lessen sarcopenia and elevate circulating β-hydroxybutyrate (β-HB) levels. Whether the elevated β-HB is essential to the reversal of sarcopenia, however, remains unclear. Here we show in both Caenorhabditis elegans and mouse models that an increase of β-HB reverse myofiber atrophy and improves motor functions at advanced ages. β-HB-induced histone lysine β-hydroxybutyrylation (Kbhb) is indispensable for the reversal of sarcopenia. Histone Kbhb enhances transcription of genes associated with mitochondrial pathways, including oxidative phosphorylation, ATP metabolic process and aerobic respiration. This ultimately leads to improve mitochondrial integrity and enhance mitochondrial respiration. The histone Kbhb are validated in mouse model with CR. Thus, we demonstrate that β-HB induces histone Kbhb, increases mitochondrial function, and reverses sarcopenia.

Quantification of volumetric thigh and paravertebral muscle fat content: comparison of quantitative Dixon (Q-Dixon) magnetic resonance imaging (MRI) with high-speed T2-corrected multiecho MR spectroscopy.

Muscle fat infiltration (MFI) is increasingly recognized as a critical factor influencing muscle function and metabolic health. Accurate quantification of MFI is essential for diagnosing and monitoring various muscular and metabolic disorders. Quantitative Dixon (Q-Dixon) magnetic resonance imaging (MRI) and high-speed T2-corrected multi-echo (HISTO) magnetic resonance spectroscopy (MRS) are both advanced imaging techniques that offer potential for detailed assessment of MFI. However, the validity and reliability of these methods in measuring volumetric changes in muscle composition, particularly in both thigh and paravertebral muscles, have not been thoroughly compared. This study aims to validate volumetric measurements using Q-Dixon MRI against HISTO MRS in thigh and paravertebral muscles, taking into account the heterogeneity of MFI. A retrospective study was conducted with 54 subjects [mean age, 60 years; 38 male (M)/16 female (F)] for thigh muscle and 56 subjects (mean age, 50 years; 22 M/34 F) for paravertebral muscle assessment using a 3-Tesla MRI. The proton density fat fraction (PDFF) was measured with Q-Dixon MRI and HISTO MRS within the upper-middle part of quadriceps femoris and paravertebral muscles at L4/5 level in volumes-of-interest (VOIs). The corresponding volumetric Q-Dixon freehand VOI PDFF was measured. Scatterplots, Bland-Altman plots, Spearman correlation coefficients, and Wilcoxon signed rank test with Bonferroni correction were employed. The Kruskal-Wallis H tests followed by Bonferroni-corrected post hoc tests were analyzed to compare parameter differences with visual MFI grades. Q-Dixon cubic VOI PDFF correlated positively with HISTO MRS PDFF in thigh (r=0.96, P<0.001) and paravertebral groups (r=0.98, P<0.001), with insignificant differences (P=0.29, 0.82, respectively). Both PDFF values from cubic VOIs in Q-Dixon and HISTO MRS differed from the freehand Q-Dixon PDFF (all P<0.001). Only for <5% HISTO MRS PDFF, there was a difference between HISTO MRS PDFF and Q-Dixon cubic VOI PDFF (P=0.002). Volumetric Q-Dixon cubic VOI PDFF exhibited good correlation and consistency with HISTO MRS PDFF for quantitative fat assessment in thigh and paravertebral muscles except for muscles with fat fraction <5%, and the Q-Dixon freehand VOI PDFF offers a more comprehensive assessment of the actual MFI compared to cubic VOI.

Diapocynin treatment induces functional and structural improvements in an advanced disease state in the mdx5Cv mice

Duchenne muscular dystrophy (DMD) is the most common muscular disorder affecting children. It affects nearly 1 male birth over 5000. Oxidative stress is a pervasive feature in the pathogenesis of DMD. Recent work shows that the main generators of ROS are NADPH oxidases (NOX), suggesting that they are an early and promising target in DMD. In addition, skeletal muscles of mdx mice, a murine model of DMD, overexpress NOXes. We investigated the impact of diapocynin, a dimer of the NOX inhibitor apocynin, on the chronic disease phase of mdx5Cv mice. Treatment of these mice with diapocynin from 7 to 10 months of age resulted in decreased hypertrophy of several muscles, prevented force loss induced by tetanic and eccentric contractions, improved muscle and respiratory functions, decreased fibrosis of the diaphragm and positively regulated the expression of disease modifiers. These encouraging results ensure the potential role of diapocynin in future treatment strategies.

Application of whole exome sequencing in the diagnosis of muscular disorders: a study of Taiwanese pediatric patients.

Muscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity. This study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification-negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%). WES analysis of these groups found pathogenic variants in 100.0% (3/3), 57.1% (12/21), and 68.2% (15/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes. WES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling.

Cyclo His-Pro Attenuates Muscle Degeneration in Murine Myopathy Models.

Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progressive degeneration of muscle fibers, resulting in inflammation and fibrosis that ultimately affect the overall muscle biomechanics. At the opposite end of the spectrum of muscle diseases, age-related sarcopenia is a common condition that affects an increasing proportion of the elderly. Although characterized by different pathological mechanisms, DMD and sarcopenia share the development of progressive muscle weakness and tissue inflammation. Here, the therapeutic effects of Cyclo Histidine-Proline (CHP) against DMD and sarcopenia are evaluated. In the mdx mouse model of DMD, it is shown that CHP restored muscle contractility and force production, accompanied by the reduction of fibrosis and inflammation in skeletal muscle. CHP furthermore prevented the development of cardiomyopathy and fibrosis in the diaphragm, the two leading causes of death for DMD patients. CHP also attenuated muscle atrophy and functional deterioration in a mouse model of age-related sarcopenia. These findings from two different models of muscle dysfunction hence warrant further investigation into the effects of CHP on muscle pathologies in animal models and eventually in patients.

Anaesthesia management of a patient with Bethlem Myopathy for elective tonsillectomy: a case report

BackgroundBethlem Myopathy is a collagen VI-related myopathy presenting as a rare hereditary muscular disorder with progressive muscular weakness and joint contractures. Despite its milder clinical course relative to other myopathies, anaesthetic management can be challenging. High arched palates and fixed flexion deformities may contribute to a difficult airway. A progressive decline in pulmonary function can present later into adulthood. This respiratory decline can carry secondary cardiovascular consequences due to the progressive nature of restrictive lung disease, including right sided heart disease and pulmonary hypertension. We describe a case of a male patient with Bethlem Myopathy undergoing anaesthesia, to contribute to the limited body of literature on this condition and enhance awareness and guidance amongst anaesthesiologists on approaching patients with this condition. This is the first case report within the literature of its kind.Case presentationThis case details a 33-year-old male with Bethlem Myopathy undergoing tonsillectomy. Diagnosed in childhood following developmental delays, the patient had no prior anaesthetic exposure and no family history of anaesthetic complications. Anaesthetic induction was achieved without complications, avoiding depolarizing muscle relaxants and careful airway management. Extreme care was taken in patient positioning to prevent complications. The surgery proceeded without incident and muscle paralysis was reversed with Suggammadex, resulting in no adverse post-operative respiratory complications. The patient was discharged on the first post-operative day without any respiratory or cardiovascular compromise.ConclusionsBethlem Myopathy, while often exhibiting a mild clinical course, can present anaesthetic challenges. Awareness of potential complications including a difficult airway, cardiovascular and respiratory implications as well as the need for specialised monitoring and positioning is crucial to ensure a safe peri-operative course.

Impact of Orthodontic-Surgical Treatments on the Signs and Symptoms of Temporomandibular Disorders: A Systematic Review.

Some patients exhibit temporomandibular joint or muscular disorders of the masticatory system before, during, or after orthognathic surgery (OS). These are collectively referred to as temporomandibular disorders (TMDs). This systematic literature review aimed to determine the relationship between orthodontic-surgical treatment and TMDs. An electronic search of the PubMed database, supplemented by a manual search, was performed; the search included any studies published between 2021 (date of the last search in a systematic review of the literature on the subject) and June 2023 that evaluate the prevalence of TMDs during orthodontic-surgical treatment. The diagnosis of TMDs had to be established using the diagnostic algorithm "diagnostic criteria for temporomandibular disorders (DC/TMDs)", and the diagnosis of disc displacement had to be confirmed using magnetic resonance imaging (MRI). The data were extracted and statistically analyzed. Of the 100 results, seven eligible articles were included, representing a total of 529 cases undergoing orthodontic-surgical treatment. A reduction in joint noises (64.8%), arthralgia (57 to 77%), and myalgia (73 to 100%) was found after orthodontic-surgical treatment despite the fact that a minority of patients exhibited these signs and symptoms even though they were asymptomatic before treatment. The effects of OS on disc position were objectively unpredictable. After surgery, the presence of headaches decreased without significance and the risk of their occurrence was very low (1%). The studies converged toward a reduction in the amplitudes of mouth opening and lateral/protrusion movements. Finally, after the treatment, mandibular function was improved. Under the conditions of this study, OS seems to have a positive impact on the signs and symptoms of TMDs; however, it is not possible to predict the consequential effects on the position of the TMJ disc, whether it is initially in a normal position or displaced.

Deubiquitinases in muscle physiology and disorders.

In vivo, muscle and neuronal cells are post-mitotic, and their function is predominantly regulated by proteostasis, a multilayer molecular process that maintains a delicate balance of protein homeostasis. The ubiquitin-proteasome system (UPS) is a key regulator of proteostasis. A dysfunctional UPS is a hallmark of muscle ageing and is often impacted in neuromuscular disorders (NMDs). Malfunction of the UPS often results in aberrant protein accumulation which can lead to protein aggregation and/or mis-localization affecting its function. Deubiquitinating enzymes (DUBs) are key players in the UPS, controlling protein turnover and maintaining the free ubiquitin pool. Several mutations in DUB encoding genes are linked to human NMDs, such as ATXN3, OTUD7A, UCHL1 and USP14, whilst other NMDs are associated with dysregulation of DUB expression. USP5, USP9X and USP14 are implicated in synaptic transmission and remodeling at the neuromuscular junction. Mice lacking USP19 show increased maintenance of lean muscle mass. In this review, we highlight the involvement of DUBs in muscle physiology and NMDs, particularly in processes affecting muscle regeneration, degeneration and inflammation following muscle injury. DUBs have recently garnered much respect as promising drug targets, and their roles in muscle maturation, regeneration and degeneration may provide the framework for novel therapeutics to treat muscular disorders including NMDs, sarcopenia and cachexia.

Treatment Outcomes in Patients with Muscular Temporomandibular Joint Disorders: A Prospective Case-Control Study.

Muscular temporomandibular joint disorders (M-TMDs) encompass a wide range of painful muscular conditions, which can provoke functional limitation and severely affect quality of life. The aim of the present study was to assess the treatment outcomes in patients affected by M-TMDs in terms of pain scores assessed with pressure pain threshold (PPT). The levels of depression, anxiety, and the Oral Health Impact Profile were also assessed and compared to healthy controls. Patients with a clinical diagnosis of M-TMDs and a control group of healthy subjects were enrolled. At baseline, OHIP-14, PHQ-9, and GAD-7 were administered. PPT was registered at the level of masseter and temporalis muscles. The patients affected by M-TMDs were then treated with oral splints and physio-kinesiotherapy following a standardized treatment protocol. At the 6-month follow-up of M-TMD-affected patients, PPT was registered, and the questionnaires were re-administered to evaluate treatment outcomes. In total, sixty patients and sixty controls were enrolled. The treatment of M-TMDs produced a significant improvement in PPT at the level of the masseter muscle. OHIP-14 at baseline in the M-TMD group was significantly higher compared to the control group (p < 0.05). At the 6-month follow-up, a significant reduction in OHIP-14 scores was registered, although with higher scores compared to the control group (p < 0.05). PHQ-9 was significantly higher at baseline in the M-TMD group (p < 0.05) and decreased to values comparable to the control group after treatment. GAD-7 presented statistically significant differences between the control group and M-TMD patients at baseline (p < 0.05) and between pre- and post-treatment in the M-TMD group. Following treatment, the GAD-7 scores were comparable to the control group. The symptom burden associated with M-TMDs negatively affects quality of life, with higher oral health impairment and a tendency towards depression and anxiety compared to healthy subjects. Following treatment, an improvement in both PPT and quality of life was observed.

Minimally invasive techniques in the management of muscular temporomandibular joint disorders: A five-year observational study.

To evaluate the effectiveness of three minimally invasive techniques for managing patients with myofascial pain dysfunction, determine their association with sociodemographic factors, habits, medication usage, comorbidities, treatment history, pain duration, complaint intensity, and diagnosis limitations. This five-year observational study scrutinized 1,000 medical records from individuals treated at the TMD Orofacial Dental Research Center. TMD treatments were organized into Group 1 (thermotherapy, exercises, and CBT), Group 2 (Group 1 plus intramuscular manual therapy), and Group 3 (Group 1 and Group 2 plus occlusal appliances) and correlated with sociodemographic factors, habits, prior medication usage, comorbidities, history of prior treatments, duration of pain, intensity of complaint, and diagnosis limitations or without limitations regarding the symptoms of muscular temporomandibular disorders (TMD). Treatment durability was proportionally higher in Groups II and III (p<0.05). Although no significant differences were found for habits (p= 0.051) and pain duration (p= 0.001), clenching was more prevalent in Groups II n= 77 (57.0%) and III n= 39 (63.9%) and among those with therapy duration equal to or greater than 6 months for n=102 (59.3%). Statistically significant correlations were noted between age and education (rho=-0.198; p<0.001) and between pain duration and treatment durability (rho=0.317; p<0.001). Intraoral devices do not constitute the primary treatment for myofascial pain. For cases of prolonged pain, comorbidities, limited mouth opening, and a history of prior medication or treatments, a splint combined with other therapies is recommended for effective management. Key words:Temporomandibular disorders, myofascial pain, occlusal appliances, clinical diagnosis, thermotherapy, exercise therapy, cognitive behavioral therapy.

Equine Musculoskeletal Pathologies: Clinical Approaches and Therapeutical Perspectives-A Review.

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, polysulfated glycosaminoglycans, pentosan polysulfate, and polyacrylamides, to promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for the intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies have emerged as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

Determining a musculoskeletal system’s pre-stretched state using continuum–mechanical forward modelling and joint range optimization

The subject-specific range of motion (RoM) of a musculoskeletal joint system is balanced by pre-tension levels of individual muscles, which affects their contraction capability. Such an inherent pre-tension or pre-stretch of muscles is not measureable with in vivo experiments. Using a 3D continuum mechanical forward simulation approach for motion analysis of the musculoskeletal system of the forearm with 3 flexor and 2 extensor muscles, we developed an optimization process to determine the muscle fibre pre-stretches for an initial arm position, which is given human dataset. We used RoM values of a healthy person to balance the motion in extension and flexion. The performed sensitivity study shows that the fibre pre-stretches of the m. brachialis, m. biceps brachii and m. triceps brachii with 91%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$91\\%$$\\end{document} dominate the objective flexion ratio, while m. brachiradialis and m. anconeus amount 7.8%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$7.8\\%$$\\end{document} and 1.2%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$1.2\\%$$\\end{document}. Within the multi-dimensional space of the surrogate model, 3D sub-spaces of primary variables, namely the dominant muscles and the global objective, flexion ratio, exhibit a path of optimal solutions. Within this optimal path, the muscle fibre pre-stretch of two flexors demonstrate a negative correlation, while, in contrast, the primary extensor, m. triceps brachii correlates positively to each of the flexors. Comparing the global optimum with four other designs along the optimal path, we saw large deviations, e.g., up to 15∘\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{\\circ }$$\\end{document} in motion and up to 40% in muscle force. This underlines the importance of accurate determination of fibre pre-stretch in muscles, especially, their role in pathological muscular disorders and surgical applications such as free muscle or tendon transfer.

Allele frequency of muscular genetic disorders in bull-catching (vaquejada) quarter horses

Quarter horses (QH), a prominent athletic breed in Brazil, are affected by muscular genetic disorders such as myosin-heavy chain myopathy (MYHM), polysaccharide storage myopathy (PSSM1), hyperkalemic periodic paralysis (HyPP), and malignant hyperthermia (MH). Bull-catching (vaquejada), primarily involving QH, is a significant equestrian sport in Brazil. Since the allele frequencies (AF) of MYHM, PSSM1, HyPP, and MH in vaquejada QH remain unknown, this study evaluated the AF in 129 QH vaquejada athletes, specifically from the Brazilian Northeast. These variants were exclusively observed in heterozygosity. The MYHM exhibited the highest AF (0.04 ±0.01), followed by PSSM1 (0.01 ±0.01) and the HyPP variant (0.004 ±0.01), while the MH variant was not identified in this study. This study represents the first identification of these variants in vaquejada QH, emphasizing the need to implement measures to prevent the transmission of pathogenic alleles and reduce the occurrence of clinical cases of these genetic diseases.