Clinical features, mutation spectrum and factors related to reaching molecular diagnosis in a cohort of patients with distal myopathies.

Background: Distal myopathies (MPDs) are heterogeneous diseases of complex diagnosis whose prevalence and distribution in specific populations are unknown.

Methods: Demographic, clinical, genetic, neurophysiological, histopathological and muscle imaging characteristics of a MPDs cohort from a neuromuscular reference center were analyzed to study their epidemiology, features, genetic distribution and factors related to diagnosis.

Results: The series included 219 patients (61% were men, 94% Spanish and 41% sporadic cases).

Supplementation with a Whey Protein Concentrate Enriched in Bovine Milk Exosomes Improves Longitudinal Growth and Supports Bone Health During Catch-Up Growth in Rats.

Background: Undernutrition impairs linear growth while restoration of nutritional provisions leads to accelerated growth patterns. However, the composition of the nutrition provided is key to facilitating effective catch-up growth without compromising bone quantity, quality, and long-term health.

Methods: We evaluated the role of a whey protein concentrate enriched in bovine milk exosomes (BMEs) in modulating the proliferative properties of human chondrocytes in vitro and studied how these effects might impact bone quantity and quality measured as longitudinal tibia growth, bone mineral content (BMC) and density (BMD), and trabecular micro-CT parameters in stunted rats during catch-up growth.

ITPR3-associated neuropathy: Report of a further family with adult onset intermediate Charcot-Marie-Tooth disease.

Background And Purpose: ITPR3 encodes type 3 inositol-tri-phosphate receptor (IPR3), a protein expressed in Schwann cells, predominantly in the paranodal region, and involved in the regulation of Ca release from the endoplasmic reticulum. Dominant variants in ITPR3 have recently been recognized as a rare cause of intermediate Charcot-Marie-Tooth disease (CMT).

Methods: We collected the clinical data of a family with autosomal dominant neuropathy whose proband was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) for many years.

Sodium Tungstate Promotes Neurite Outgrowth and Confers Neuroprotection in Neuro2a and SH-SY5Y Cells.

Sodium tungstate (NaWO) normalizes glucose metabolism in the liver and muscle, activating the Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Because this pathway controls neuronal survival and differentiation, we investigated the effects of NaWO in mouse Neuro2a and human SH-SY5Y neuroblastoma monolayer cell cultures. NaWO promotes differentiation to cholinergic neurites via an increased G1/G0 cell cycle in response to the synergic activation of the Phosphatidylinositol 3-kinase (PI3K/Akt) and ERK1/2 signaling pathways.

Thrombocytopenia after transcatheter aortic valve implantation.

Introduction And Objectives: Thrombocytopenia frequently occurs after transcatheter aortic valve implantation (TAVI) but its impact is poorly understood. We aimed to analyze the incidence, clinical impact, and predictors of acquired thrombocytopenia after TAVI.

Methods: This retrospective multicenter registry included 3913 patients undergoing TAVI with a baseline platelet count of ≥ 100 *10/L.

Myosin ATPase inhibition fails to rescue the metabolically dysregulated proteome of nebulin-deficient muscle.

Nemaline myopathy (NM) is a genetic muscle disease, primarily caused by mutations in the NEB gene (NEB-NM) and with muscle myosin dysfunction as a major molecular pathogenic mechanism. Recently, we have observed that the myosin biochemical super-relaxed state was significantly impaired in NEB-NM, inducing an aberrant increase in ATP consumption and remodelling of the energy proteome in diseased muscle fibres. Because the small-molecule Mavacamten is known to promote the myosin super-relaxed state and reduce the ATP demand, we tested its potency in the context of NEB-NM.

Analysis of HLA Alleles in Different Cohorts of Patients Infected by from Southern Spain.

Leishmaniasis is an infectious disease caused by protozoa of the genus , which is endemic in certain areas of Europe, such as southern Spain. The disease manifests in various clinical phenotypes, including visceral, cutaneous, mucosal, or asymptomatic leishmaniasis. This diversity in clinical outcomes may be influenced by the host immune response, with human leukocyte antigen (HLA) molecules playing a crucial role in determining susceptibility and progression of the infection.

Insights into phenotypic variability caused by GARS1 pathogenic variants.

Background And Purpose: Pathogenic variants of the glycyl-tRNA synthetase 1 (GARS1) gene have been described as a cause of Charcot-Marie-Tooth disease type 2D, motor axonal neuropathy with upper limb predominance (distal hereditary motor neuropathy [dHMN] type V), and infantile spinal muscular atrophy.

Methods: This cross-sectional, retrospective, observational study was carried out on 12 patients harboring the c.794C>T (p.

Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial.

Background: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38β MAPK) for the treatment of facioscapulohumeral muscular dystrophy.

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene.

Loss-of-function variants in cause congenital myopathy with prominent facial involvement.

Background: Weakness of facial, ocular, and axial muscles is a common clinical presentation in congenital myopathies caused by pathogenic variants in genes encoding triad proteins. Abnormalities in triad structure and function resulting in disturbed excitation-contraction coupling and Ca homeostasis can contribute to disease pathology.

Methods: We analysed exome and genome sequencing data from three unrelated individuals with congenital myopathy characterised by striking facial, ocular, and bulbar involvement.

Human adipose tissue as a major reservoir of cytomegalovirus-reactive T cells.

Introduction: Cytomegalovirus (CMV) is a common herpesvirus with a high prevalence worldwide. After the acute infection phase, CMV can remain latent in several tissues. CD8 T cells in the lungs and salivary glands mainly control its reactivation control.

Human skeletal myopathy myosin mutations disrupt myosin head sequestration.

Myosin heavy chains encoded by MYH7 and MYH2 are abundant in human skeletal muscle and important for muscle contraction. However, it is unclear how mutations in these genes disrupt myosin structure and function leading to skeletal muscle myopathies termed myosinopathies. Here, we used multiple approaches to analyze the effects of common MYH7 and MYH2 mutations in the light meromyosin (LMM) region of myosin.

Combined Use of a Bacterial Consortium and Early-Colonizing Plants as a Treatment for Soil Recovery after Fire: A Model Based on Los Guájares (Granada, Spain) Wildfire.

During 2022, intense heat waves, together with particularly extreme dry conditions, created a propitious scenario for wildfires, resulting in the area of vegetation consumed in Europe doubling. Mediterranean countries have been particularly affected, reaching 293,155 hectares in Spain, the worst data in the last 15 years. The effects on the vegetation and the soil are devastating, so knowing the recovery factors is essential for after-fire management.

Analysis of muscle magnetic resonance imaging of a large cohort of patient with VCP-mediated disease reveals characteristic features useful for diagnosis.

Background: The diagnosis of patients with mutations in the VCP gene can be complicated due to their broad phenotypic spectrum including myopathy, motor neuron disease and peripheral neuropathy. Muscle MRI guides the diagnosis in neuromuscular diseases (NMDs); however, comprehensive muscle MRI features for VCP patients have not been reported so far.

Methods: We collected muscle MRIs of 80 of the 255 patients who participated in the "VCP International Study" and reviewed the T1-weighted (T1w) and short tau inversion recovery (STIR) sequences.