muscular disease

Duchenne muscular dystrophy (DMD) represents one of the most devastating types of muscular dystrophies which affect boys already at early childhood. Despite the fact that the primary cause of the disease, namely the lack of functional dystrophin is known already for more than 30 years, DMD still remains an incurable disease. Thus, an enormous effort has been made during recent years to reveal novel mechanisms that could provide therapeutic targets for DMD, especially because glucocorticoids treatment acts mostly symptomatic and exerts many side effects, whereas the effectiveness of genetic approaches aiming at the restoration of functional dystrophin is under the constant debate...

Glycogen storage disease type II, or Pompe disease, is an autosomal recessive disorder caused by deficiency of lysosomal acid alpha-glucosidase (GAA). We performed genetic analysis to confirm the diagnosis of Pompe disease in a 61-year-old patient with progressive weakness in extremities, severe Sleep Apnea-Hypopnea Syndrome, a significant reduction of alpha-glucosidase in liquid sample of peripheral blood and muscular biopsy diagnosis. GAA gene sequencing showed the patient is homozygous for the splice-site mutation c...

Impaired aerobic function is a potential mechanism of exercise intolerance in patients with combined cardiorespiratory disease. We investigated the pathophysiological and sensory consequences of a low Δ O2 uptake (V̇O2 )/Δ work rate (WR) relationship during incremental exercise in patients with coexisting chronic obstructive pulmonary disease (COPD) and systolic heart failure (HF).After clinical stabilisation, 51 COPD-HF patients performed an incremental cardiopulmonary exercise test to symptom limitation...

BACKGROUND: Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophy (LGMD2C, LGMD2D, LGMD2E, and LGMD2F) that are caused, respectively, by mutations in the SGCG, SGCA, SGCB, and SGCD genes. Knowledge about the clinical and genetic features of sarcoglycanopathies in Chinese patients is limited. The aims of this study were to investigate in detail the clinical manifestations, sarcoglycan expression, and gene mutations in Chinese patients with sarcoglycanopathies and to identify possible correlations between them...

BACKGROUND: Cardiomyopathies affect more than 0.5% of the general population. They are associated with high risk of sudden cardiac death, which can result from either heart failure or electrical abnormalities. Although different mechanisms underlie the various types of cardiomyopathies, a principal pathology is common to all and is usually at the level of the cardiac muscle. With a relatively high incidence rate in most countries, and a subsequent major health burden on both the families and governments, cardiomyopathies are gaining more attention by researchers and pharmaceutical companies as well as health government bodies...

BACKGROUND: Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Standard cardiac biomarkers are poor indicators of DMD cardiovascular disease. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate collagen turnover. Given the cardiac fibrosis seen in DMD, we hypothesized that MMPs and TIMPs correlate with severity of DMD cardiomyopathy. METHODS AND RESULTS: Prospectively enrolled DMD subjects (n=42) underwent cardiac MRI for function and late gadolinium enhancement (LGE), including LGE severity from 0 (no LGE) to 4 (severe)...

PURPOSE OF REVIEW: The purpose of this review article is to present the spectrum of abnormalities and multi-modality imaging evaluations in patients with musculoskeletal sarcoidosis. RECENT FINDINGS: The articular manifestations of sarcoidosis are difficult to distinguish from those of the other inflammatory and degenerative arthropathies, and the muscular lesions in sarcoidosis are generally clinically silent and therefore often missed. Magnetic resonance imaging has shown these manifestations to be very common in active sarcoidosis, and should thus be included in the screening if musculoskeletal sarcoidosis is suspected...

There is a need to support individuals with Duchenne Muscular Dystrophy (DMD) to achieve optimal functionality in everyday life and with meaningful tasks and activities, throughout stages of the disease progression. Thus, technological developments have created an exciting opportunity for the use of affordable virtual reality (VR) systems with different kinds of interaction devices, providing an efficient and fun tool for enabling improvement in motor performance. Objective: To compare performance on a virtual task using interfaces with and without physical contact in order to identify functionality by using different devices in individuals with DMD...

PURPOSE: Carrier screening identifies couples at high risk for conceiving offspring affected with serious heritable conditions. Minimal guidelines recommend offering testing for cystic fibrosis and spinal muscular atrophy, but expanded carrier screening (ECS) assesses hundreds of conditions simultaneously. Although medical societies consider ECS an acceptable practice, the health economics of ECS remain incompletely characterized. METHODS: Preconception screening was modeled using a decision tree comparing minimal screening and a 176-condition ECS panel...

Mineralocorticoid receptor (MR) drugs have been used clinically for decades to treat cardiovascular diseases. MR antagonists show preclinical efficacy not only for heart in Duchenne muscular dystrophy models, but also improve skeletal muscle force and muscle membrane integrity. The mechanisms of action of MR antagonists in skeletal muscles are entirely unknown. Since MR are present in many cell types in the muscle microenvironment, it is critical to define cell-intrinsic functions in each cell type to ultimately optimize antagonist efficacy for use in the widest variety of diseases...

BACKGROUND: Patients with end stage kidney disease on dialysis have increased mortality and reduced physical activity contributing to impaired physical function. While exercise programmes have demonstrated a positive effect on physiological outcomes such as cardiovascular function and strength, there is a reduced focus on physical function. The aim of this review was to determine whether exercise programmes improve objective measures of physical function indicative of activities of daily living for end stage kidney disease patients on dialysis...

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. It remains unresolved whether increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscle's disrupted contractile machinery. This knowledge has important implications for patients, as potential physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones...

Context: The lifetime prevalence of anabolic androgenic steroid (AAS) use is estimated at 1-5% worldwide. AAS use occurs primarily male elite athletes and men who want a muscular appearance. The evidence for effective, safe management of AAS cessation and withdrawal is weak. Evidence Acquisition: Key studies were extracted from Pubmed (1990-2018) and Google Scholar with reference searches from relevant retrieved articles. Evidence synthesis: The proven adverse effects of AAS include suppression of the gonadal axis and infertility, hirsutism and defeminization in women, and erythrocytosis...

Background: Chronic kidney disease (CKD) patients experience a high symptom burden including fatigue, sleep difficulties, muscle weakness and pain. These symptoms reduce levels of physical function (PF) and activity, and contribute to poor health-related quality of life (HRQoL). Despite the gathering evidence of positive physiological changes following exercise in CKD, there is limited evidence on its effect on self-reported symptom burden, fatigue, HRQoL and physical activity. Methods: Thirty-six patients [mean ± SD 61...

BACKGROUND: B-cell activating factor (BAFF) is considered to have a role in the pathogenesis of systemic sclerosis (SSc). AIM: We conducted a longitudinal study on early SSc patients to determine the change in BAFF serum level after treatment and its association with organ involvements. METHODS: A total of 46 patients (32 diffuse, 14 limited) were recruited, among which 35 patients (24 diffuse, 11 limited) completed 12-month follow-up. RESULTS: Higher pretreatment BAFF levels were observed in patients with positive anti-topoisomerase antibody (ATA) (2252...

Congenital generalized lipodystrophy type 4 (CGL4) is a rare disease caused by mutations in the gene polymerase I and transcript release factor ( PTRF ), the main symptoms of which are systemic reductions in adipose tissue and muscular dystrophy. The strategy of treating CGL4 is to improve the insulin resistance and hypertriglyceridemia that result from systemic reductions in adipose tissue. Metreleptin, a synthetic analog of human leptin, is effective against generalized lipodystrophies; however, there are no reports of the use of metreleptin in the treatment of CGL4...

BACKGROUND: Exercise is considered important in the management of patients with rheumatic diseases, but the effect of high intensity exercises on disease activity is unknown. OBJECTIVE: To investigate the effectiveness of high intensity exercises on disease activity in patients with axial spondyloarthritis (axSpA). METHOD: Assessor blinded multicentre randomised controlled trial. 100 patients (aged from their 20s to their 60s) with axSpA were randomly assigned to an exercise group or to a no-intervention control group...

OBJECTIVES: Respiratory syncytial virus (RSV) causes respiratory infection across the world, with infants and the elderly at particular risk of developing severe disease and death. The replication-defective chimpanzee adenovirus (PanAd3-RSV) and modified vaccinia virus Ankara (MVA-RSV) vaccines were shown to be safe and immunogenic in young healthy adults. Here we report an extension to this first-in-man vaccine trial to include healthy older adults aged 60-75 years. METHODS: We evaluated the safety and immunogenicity of a single dose of MVA-RSV given by intra-muscular (IM) injection (n=6), two doses of IM PanAd3-RSV given 4-weeks apart (n=6), IM PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n=6), intra-nasal (IN) spray of PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n=6), or no vaccine (n=6)...

Heterozygous variants in the bicaudal D homolog 2 gene ( BICD2 ) are associated with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). This disease is usually characterized by congenital or early-onset muscle weakness and atrophy of the lower extremities with benign or slow progression. We herein described an autosomal dominant inherited pedigree with SMALED2 in which the affected individuals presented with late adult-onset muscle weakness and wasting in the lower extremities...

A triathlon, which consists of swimming, bicycling, and running, is a high-intensity and long-term form of exercise that can cause injuries such as muscular damage, inflammation, oxidative stress, and energy imbalance. Probiotics are thought to play an important role in disease incidence, health promotion, and nutrient metabolism, but only a few studies have focused on physiological adaptations to exercise in sports science. Previous studies indicated that Lactobacillus supplementation could improve oxidative stress and inflammatory responses...