Muscle Contractility in Hypokalemic Periodic Paralysis.

Introduction/aims: Primary hypokalemic periodic paralysis (HypoPP) can present with periodic paralysis and/or permanent muscle weakness. Permanent weakness is accompanied by fat replacement of the muscle. It is unknown whether the permanent muscle weakness is solely due to fat replacement or if other factors affect the ability of the remaining muscle fibers to contract.

Pulmonary vascular adaptations to hypoxia in elite breath-hold divers.

Introduction: Elite breath-hold divers (BHD) possess several oxygen conserving adaptations to endure long dives similar to diving mammals. During dives, Bottlenose Dolphins may increase the alveolar ventilation (V) to perfusion (Q) ratio to increase alveolar oxygen delivery. We hypothesized that BHD possess similar adaptive mechanisms during apnea.

Quality of life in hypokalemic periodic paralysis - a survey.

Primary hypokalemic periodic paralysis (HypoPP) is a skeletal muscle channelopathy most commonly caused by pathogenic variants in the calcium channel gene, CACNA1S. HypoPP can present with attacks of paralysis and/or permanent muscle weakness. Previous studies have shown that patients with HypoPP can have impaired quality of life (QoL).

Hemoglobin concentration and blood shift during dry static apnea in elite breath hold divers.

Introduction: Elite breath-hold divers (BHD) enduring apneas of more than 5 min are characterized by tolerance to arterial blood oxygen levels of 4.3 kPa and low oxygen-consumption in their hearts and skeletal muscles, similar to adult seals. Adult seals possess an adaptive higher hemoglobin-concentration and Bohr effect than pups, and when sedated, adult seals demonstrate a blood shift from the spleen towards the brain, lungs, and heart during apnea.

Acetaminophen treatment in children and adults with spinal muscular atrophy: a lower tolerance and higher risk of hepatotoxicity.

Acute liver failure has been reported sporadically in patients with spinal muscular atrophy (SMA) and other neuromuscular disorders with low skeletal muscle mass receiving recommended dosages of acetaminophen. It is suggested that low skeletal muscle mass may add to the risk of toxicity. We aimed to describe the pharmacokinetics and safety of acetaminophen in patients with SMA.

Skeletal Muscle Involvement in Patients With Truncations of Titin and Familial Dilated Cardiomyopathy.

Background: Genetic variants in titin (TTN) are associated with dilated cardiomyopathy (DCM) and skeletal myopathy. However, the skeletal muscle phenotype in individuals carrying heterozygous truncating TTN variants (TTNtv), the leading cause of DCM, is understudied.

Objectives: This study aimed to assess the skeletal muscle phenotype associated with TTNtv.

Humoral immune response to COVID-19 vaccine in patients with myasthenia gravis.

We investigated the humoral response to the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine in patients with myasthenia gravis on or off immunosuppressants and compared this to the response in healthy individuals. The SARS-CoV-2 IgG response and neutralizing capacity were measured in 83 patients (57 on immunosuppressants) and 332 healthy controls at baseline, three weeks, and two and six months after the vaccine. We found that the proportion of positive humoral response was lower in patients on immunosuppressants vs.

Hypokalemic periodic paralysis: a 3-year follow-up study.

Background And Objectives: Primary hypokalemic periodic paralysis (HypoPP) is an inherited channelopathy most commonly caused by mutations in CACNA1S. HypoPP can present with different phenotypes: periodic paralysis (PP), permanent muscle weakness (PW), and mixed weakness (MW) with both periodic and permanent weakness. Little is known about the natural history of HypoPP.

Experiences With In-Person and Virtual Health Care Services for People With Chronic Obstructive Pulmonary Disease: Qualitative Study.

Background: The World Health Organization and the European Commission predict increased use of health technologies in the future care for patients in Europe. Studies have shown that services based on telehealth, which includes components of education, as well as rehabilitation initiatives can support the self-management of individuals living with COPD. This raises an interest in how virtual and in-person interactions and roles can best be organized in a way that suits people living with COPD in relation to their treatment and rehabilitation.

Homozygous splice variant (c.1741-6G>A) of the COL6A1 gene in three patients with Ullrich congenital muscular dystrophy.

The three major collagen VI genes: COL6A1, COL6A2, and COL6A3 encode microfibrillar components of extracellular matrices in multiple tissues including muscles and tendons. Pathogenic variants in the collagen VI genes cause collagen VI-related dystrophies representing a continuum of conditions from Bethlem myopathy at the milder end to Ullrich congenital muscular dystrophy at the more severe end. Here we describe a pathogenic variant in the COL6A1 gene (NM_001848.

Low aerobic capacity in McArdle disease: A role for mitochondrial network impairment?

Background: McArdle disease is caused by myophosphorylase deficiency and results in complete inability for muscle glycogen breakdown. A hallmark of this condition is muscle oxidation impairment (e.g.

β-Galactosidase deficiency in the GLB1 spectrum of lysosomal storage disease can present with severe muscle weakness and atrophy.

Deficiency of the enzyme β-galactosidase due to variants in the -gene is associated with metabolic disorders: Morquio B and GM1-gangliosidosis. Here, we report a case compound heterozygous for variants in the -gene and a severe muscular phenotype. Full body T1-w MRI was conducted for muscular involvement.

Three novel FHL1 variants cause a mild phenotype of Emery-Dreifuss muscular dystrophy.

Emery-Dreifuss muscular dystrophy (EDMD) is a hereditary muscle disease, characterized by the clinical triade of early-onset joint contractures, progressive muscle weakness, and cardiac involvement. Pathogenic variants in FHL1 can cause a rare X-linked recessive form of EDMD, type 6. We report three men with novel variants in FHL1 leading to EDMD6.

Growth Factors Do Not Improve Muscle Function in Young or Adult Mice.

Muscular dystrophies constitute a broad group of genetic disorders leading to muscle wasting. We have previously demonstrated that treating a muscular atrophy mouse model with growth factors resulted in increased muscle mass. In the present study, we treated the Duchenne mouse model for 12 weeks with myogenic growth factors peri- and post-onset of muscular degeneration to explore the effects in the oxidative muscle soleus and the glycolytic muscle extensor digitorum longus (EDL).

Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies.

McArdle disease is an autosomal recessive disorder of muscle glycogen metabolism caused by pathogenic mutations in the gene, which encodes the skeletal muscle-specific isoform of glycogen phosphorylase. Clinical symptoms are mainly characterized by transient acute "crises" of early fatigue, myalgia and contractures, which can be accompanied by rhabdomyolysis. Owing to the difficulty of performing mechanistic studies in patients that often rely on invasive techniques, preclinical models have been used for decades, thereby contributing to gain insight into the pathophysiology and pathobiology of human diseases.

Extreme Hypoxia Causing Brady-Arrythmias During Apnea in Elite Breath-Hold Divers.

The cardiac electrical conduction system is very sensitive to hypoglycemia and hypoxia, and the consequence may be brady-arrythmias. Weddell seals endure brady-arrythmias during their dives when desaturating to 3.2 kPa and elite breath-hold-divers (BHD), who share metabolic and cardiovascular adaptions including bradycardia with diving mammals, endure similar desaturation during maximum apnea.

Muscle biopsy and MRI findings in ANO5-related myopathy.

Introduction/aims: Mutations in the anoctamin 5 (ANO5) gene are a common cause of muscular dystrophy. We aimed to investigate whether inflammatory changes in muscle are present in patients with ANO5 myopathy when assessed by muscle biopsy and muscle magnetic resonance imaging (MRI).

Methods: Adults with pathogenic variations in ANO5 known to cause muscular dystrophy were included in our study.

Novel Homozygous Truncating Variant Widens the Spectrum of Early-Onset Multisystemic SYNE1 Ataxia.

Pathogenic variants in the SYNE1 gene are associated with a phenotypic spectrum spanning from late-onset, slowly progressive, relatively pure ataxia to early-onset, fast progressive multisystemic disease. Since its first description in 2007 as an adult-onset ataxia in French Canadian families, subsequent identification of patients worldwide has widened the clinical spectrum and increased the number of identified pathogenic variants. We report a 20-year-old Faroese female with early-onset progressive gait problems, weakness, dysphagia, slurred speech, orthostatic dizziness, and urge incontinence.

Myopathy can be a key phenotype of membrin (GOSR2) deficiency.

T1-weighted, cross-sectional MR images showing shoulder girdle, abdominal, paraspinal, gluteal and thigh muscles almost completely replaced by fat, whereas lower leg muscles are almost unaffected i a patient who is compound heterozygous for pathogenic variants in GOSR2.

Autophagy is affected in patients with hypokalemic periodic paralysis: an involvement in vacuolar myopathy?

Hypokalemic periodic paralysis is an autosomal dominant, rare disorder caused by variants in the genes for voltage-gated calcium channel Ca1.1 (CACNA1S) and Na1.4 (SCN4A).

No effect of resveratrol in patients with mitochondrial myopathy: A cross-over randomized controlled trial.

Mitochondrial myopathies (MM) are caused by mutations that typically affect genes involved in oxidative phosphorylation. Main symptoms are exercise intolerance and fatigue. Currently, there is no specific treatment for MM.

Antimyostatin Treatment in Health and Disease: The Story of Great Expectations and Limited Success.

In the past 20 years, myostatin, a negative regulator of muscle mass, has attracted attention as a potential therapeutic target in muscular dystrophies and other conditions. Preclinical studies have shown potential for increasing muscular mass and ameliorating the pathological features of dystrophic muscle by the inhibition of myostatin in various ways. However, hardly any clinical trials have proven to translate the promising results from the animal models into patient populations.

Preclinical Research in Glycogen Storage Diseases: A Comprehensive Review of Current Animal Models.

GSD are a group of disorders characterized by a defect in gene expression of specific enzymes involved in glycogen breakdown or synthesis, commonly resulting in the accumulation of glycogen in various tissues (primarily the liver and skeletal muscle). Several different GSD animal models have been found to naturally present spontaneous mutations and others have been developed and characterized in order to further understand the physiopathology of these diseases and as a useful tool to evaluate potential therapeutic strategies. In the present work we have reviewed a total of 42 different animal models of GSD, including 26 genetically modified mouse models, 15 naturally occurring models (encompassing quails, cats, dogs, sheep, cattle and horses), and one genetically modified zebrafish model.