Aldosterone synthase inhibitors: a potential revival for treatment of renal and cardiovascular diseases.

Inappropriate aldosterone excess plays a key role in the pathophysiology of various cardiovascular, endocrine and renal diseases. Mineralocorticoid receptor (MR) antagonists (MRAs) such as spironolactone block of the harmful effects of aldosterone and are recommended treatment in these various conditions. However, the sexual adverse effects of spironolactone due to its lack of specificity for the MR and the risk of hyperkalemia in patients with decreased renal function, limit its use.

Temporo-spatial analysis of amyotrophic lateral sclerosis in Spain: Altitude and land use as new determinants of the disease.

Introduction: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Currently, ALS is conceived as the result of the interaction between genetics, environmental factors, and aging. This study analyzed the spatial and temporal patterns of ALS in Spain, delving into the potential relationships between altitude, land cover, and this disease.

Changes in choroidal thickness and lamina cribrosa position in subjects with overdipper pattern of arterial pressure.

Introduction: The purpose is to analyze the changes produced in subjects with an overdipper pattern of ambulatory blood pressure monitoring with the aim of understanding the pathophysiology of normal tension glaucoma.

Methods: A cross sectional study was performed in patients exhibiting overdipper and non-overdipper blood pressure patterns, respectively. Different optic parameters were assessed including the analysis of ganglion cell layer (GCL), peripapillary retinal nerve fiber layer (pRNFL) and Bruch's membrane opening-minimum rim width (BMO-MRW), as well as changes produced in choroidal thickness (CT) and lamina cribrosa (LC) position at two different periods of the day (early morning and evening).

Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study.

Background: Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment.

Objectives: This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction.

Spatial analysis of ischemic stroke in Spain: the roles of accessibility to healthcare and economic development.

Ischemic stroke is a major cause of mortality worldwide; however, few studies have been conducted to measure the impact of the distribution of healthcare services on ischemic stroke fatality. This study aimed to explore the relationship between three ischemic stroke outcomes (incidence, mortality, and fatality) and accessibility to hospitals in Spain, considering its economic development. A cross-sectional ecological study was performed using data on hospital admissions and mortality due to ischemic stroke during 2016-2018.

Etiology of hypophosphatemia in adults.

Long-term hypophosphatemia, defined by serum phosphorus (P) levels <2.5mg/dL, impairs the development and quality of mineralized tissue of the skeletal, dental, and auditory systems. P homeostasis depends mainly on intestinal absorption and renal excretion.

Worldwide distribution of genetic factors related to severity of COVID-19 infection.

Background: Genome-wide association studies of COVID-19 severity have been carried out mostly on European or East Asian populations with small representation of other world regions. Here we explore the worldwide distribution and linkage disequilibrium (LD) patterns of genetic variants previously associated with COVID-19 severity.

Methods: We followed up the results of a large Spanish genome-wide meta-analysis on 26 populations from the 1000 Genomes Project by calculating allele frequencies and LD scores of the nine most significant SNPs.

Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.

Background: Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown.

Genetic causes of hypophosphatemia.

Phosphate is a key component of mineralized tissues and is also part of many organic compounds. Phosphorus homeostasis depends especially upon intestinal absorption, and renal excretion, which are regulated by various hormones, such as PTH, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23. In this review we provide an update of several genetic disorders that affect phosphate transporters through cell membranes or the phosphate-regulating hormones, and, consequently, result in hypophosphatemia.

A Missense Variant in Could Be a Genetic Biomarker Associated with Bone Tissue Alterations.

Metabolic bone diseases cover a broad spectrum of disorders that share alterations in bone metabolism that lead to a defective skeleton, which is associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, with being one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of is a genetic factor associated with several pathologies, including cancer, stroke, and osteoporosis.

Erdheim-Chester Disease Due to a Novel Internal Duplication of NRAS: Response to Targeted Therapy with Cobimetinib.

Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim-Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatment of ECD has been challenging.

Engineering a Pro-Osteogenic Secretome through the Transient Silencing of the Gene Encoding Secreted Frizzled Related Protein 1.

The evidence sustaining the regenerative properties of mesenchymal stem cells' (MSCs) secretome has prompted a paradigm change, where MSCs have shifted from being considered direct contributors to tissue regeneration toward being seen as cell factories for producing biotech medicines. We have previously designed a method to prime MSCs towards osteogenic differentiation by silencing the Wnt/β-Catenin inhibitor . This approach produces a significant increase in bone formation in osteoporotic mice.

HLA-A*11:01 and HLA-C*04:01 are associated with severe COVID-19.

We analyzed the association between HLA polymorphisms and susceptibility to SARS-CoV-2 infection and disease severity. Genotyping data from a total of 9373 COVID-19-positive cases from the Spanish Coalition to Unlock Research on Host Genetics on COVID-19 (SCOURGE) consortium and 5943 population controls were included in the study. We found an association of the alleles HLA-B*14:02 and HLA-C*08:02 with a lower risk to COVID-19 infection (p = 0.

Erratum: Cumulative Genetic Score and C9orf72 Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies.

[This corrects the article DOI: 10.1212/NXG.0000000000200079.

Cumulative Genetic Score and Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies.

Background And Objectives: Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores.

Methods: Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion.

Psychiatric polygenic risk as a predictor of COVID-19 risk and severity: insight into the genetic overlap between schizophrenia and COVID-19.

Despite the high contagion and mortality rates that have accompanied the coronavirus disease-19 (COVID-19) pandemic, the clinical presentation of the syndrome varies greatly from one individual to another. Potential host factors that accompany greater risk from COVID-19 have been sought and schizophrenia (SCZ) patients seem to present more severe COVID-19 than control counterparts, with certain gene expression similarities between psychiatric and COVID-19 patients reported. We used summary statistics from the last SCZ, bipolar disorder (BD), and depression (DEP) meta-analyses available on the Psychiatric Genomics Consortium webpage to calculate polygenic risk scores (PRSs) for a target sample of 11,977 COVID-19 cases and 5943 subjects with unknown COVID-19 status.

Influence of meteorological factors on the severity of COVID-19 in Spain: Observational ecological study.

Objectives: Evaluating whether meteorological and geographical variables could be associated with the severity of COVID-19 in Spain.

Methods: An ecological study was performed to analyze the influence of meteorological and geographical factors in hospital admissions and deaths due to COVID-19 in the 52 provinces of Spain (24 coastal and 28 inland regions), during the first three pandemic waves. Medical and mortality data were collected from the Carlos III Health Institute (ISCIII) and meteorological variables were requested to the Spanish State Meteorological Agency (AEMET).