Repeat Expansions in PLIN4 Cause Autosomal Dominant Vacuolar Myopathy With Sarcolemmal Features.

Objective: We aim to describe and characterize two unrelated Spanish families suffering from an autosomal dominant autophagic vacuolar myopathy caused by repeat expansions in PLIN4.

Methods: We evaluated the clinical phenotype and muscle imaging, and performed a genetic workup that included exome sequencing, muscle RNAseq, and long-read genome sequencing. Muscle pathology was assessed by means of histochemistry, electron microscopy, PLIN4, p62, LC3, and NBR1 immunofluorescence and/or western blotting.

Comparative analysis of the use of autologous exosomes and platelet-derived growth factors in women with premature ovarian insufficiency and infertility: A prospective, randomized, observational, analytical study.

Unlabelled: Stromal fibrosis and ovarian aging depend not only on the age of the patients but also on environmental factors, lifestyle and physiological events such as ovulation itself, which leaves repeated scarring in the ovarian stroma, limiting normal tissue vascularization and the provision of biological signals necessary to maintain folliculogenesis and hormone synthesis. In a fibrosed ovarian stroma, there is a decrease in hyaluronic acid concentrations, loss of synthesis and migration proteins, a decrease in microRNAs, in addition to enzymatic alterations that affect mitochondrial kinases, increasing oxygen free radicals, which accelerate cell death.

Objectives: This study seeks to analyze the effectiveness of autologous exosomes in reversing aging and bioregenerating the ovary of patients with ovarian failure and infertility by improving interstitial fibrosis and providing the necessary elements to activate neofolliculogenesis.

Neuroimmunomodulation induced by mud-bath therapy: clinical benefits and bioregulation of the innate/inflammatory responses induced by a peloid enriched with rosmarinic acid in elderly patients with osteoarthritis.

Balneotherapy using peloids (mud-bath therapy) is one of the most effective non-pharmacological approaches for managing osteoarticular and musculoskeletal disorders, such as osteoarthritis (OA). Recent studies have shown that peloids enriched with rosmarinic acid (RosA) enhance the therapeutic effects of mud therapy in elderly OA patients. The objective of this study was to evaluate whether the normalization of the interaction between the hormetic stress response, mediated by cortisol, and the inflammatory response, mediated by IL-8 (measured in blood by ELISA), underlies the clinical benefits of a hyperthermic mud-bath intervention using a RosA-enriched peloid, a polyphenolic acid with anti-inflammatory and immunomodulatory properties.

A large-scale sORF screen identifies putative microproteins involved in cancer cell fitness.

The human genome contains thousands of potentially coding short open reading frames (sORFs). While a growing set of microproteins translated from these sORFs have been demonstrated to mediate important cellular functions, the majority remains uncharacterized. In our study, we performed a high-throughput CRISPR-Cas9 knock-out screen targeting 11,776 sORFs to identify microproteins essential for cancer cell line growth.

Multiplexed chromatin immunoprecipitation sequencing for quantitative study of histone modifications and chromatin factors.

ChIP-seq is a widely used technique for studying histone post-translational modifications and DNA-binding proteins. DNA fragments associated with a specific protein or histone modification epitope are captured by using antibodies, sequenced and mapped to a reference genome. Albeit versatile and popular, performing many parallel ChIP-seq experiments to compare different conditions, replicates and epitopes is laborious, is prone to experimental variation and does not allow quantitative comparisons unless adequate spike-in chromatin is included.

Morphological Hallmarks of Classical Fabry Disease: An Ultrastructural Study in a Large Spanish Family.

Fabry disease (FD) is a rare lysosomal disorder caused by α-galactosidase A deficiency, and it leads to the systemic deposition of globotriasylceramide. Demonstrations of the storage material in biopsies support this diagnosis. We report a histological and ultrastructural study of biopsies that were performed on 11 individuals from a family with the variant p.

Decalogue to promote the implementation and improvement of recommendations for the early diagnosis of HIV in Emergency Departments.

Early diagnosis of HIV is still a challenge. Emergency Departments (EDs) suppose ideal settings for the early detection of HIV, since patients with high prevalence of hidden HIV infection are frequently attending those services. In 2020, the Spanish Society of Emergency and Emergency Medicine (SEMES) published a series of recommendations for the early diagnosis of patients with suspected HIV infection and their referral and follow-up in the EDs as part of its "Deja tu huella" program.

Dynamic antagonism between key repressive pathways maintains the placental epigenome.

DNA and Histone 3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb repressive complexes regulate the unmethylated CpG-rich promoters of developmental genes. In contrast to this general framework, the extra-embryonic lineages display non-canonical, globally intermediate DNA methylation levels, including disruption of local Polycomb domains.

Meningococcal carriage in men who have sex with men presenting at a sexual health unit in Spain.

Neisseria meningitidis (Nm) is asymptomatically carried in the nasopharynx of 5-10% adults, although certain populations, such as men who have sex with men (MSM), exhibit a higher colonisation rate. Interest in Nm carriage has been renewed, owed to meningitis outbreaks within populations of MSM. The aim of this study was to characterise Nm isolates and risk factors for its carriage among MSM attending a sexual health unit.

Polycomb repressive complex 2 shields naïve human pluripotent cells from trophectoderm differentiation.

The first lineage choice in human embryo development separates trophectoderm from the inner cell mass. Naïve human embryonic stem cells are derived from the inner cell mass and offer possibilities to explore how lineage integrity is maintained. Here, we discover that polycomb repressive complex 2 (PRC2) maintains naïve pluripotency and restricts differentiation to trophectoderm and mesoderm lineages.

Description of the first Spanish case of Gerstmann-Sträussler-Scheinker disease with A117V variant: clinical, histopathological and biochemical characterization.

Gerstmann-Sträussler-Scheinker disease (GSS) is a rare neurodegenerative illness that belongs to the group of hereditary or familial Transmissible Spongiform Encephalopathies (TSE). Due to the presence of different pathogenic alterations in the prion protein (PrP) coding gene, it shows an enhanced proneness to misfolding into its pathogenic isoform, leading to prion formation and propagation. This aberrantly folded protein is able to induce its conformation to the native counterparts forming amyloid fibrils and plaques partially resistant to protease degradation and showing neurotoxic properties.

Targeted screening for human immunodeficiency virus infection in Spanish emergency departments: an analysis of epidemiologic and economic impact.

Objectives: To evaluate the potential epidemiologic and economic impact of applying an HIV screening protocol in hospital emergency departments (ED) and compare it to current clinical practice in Spain.

Material And Methods: We estimated the cumulative incidence of human immunodeficiency virus (HIV) infections and associated costs in Spain for a 20-year time horizon based on a model comprised of various health states with different risks for HIV transmission. The impact of current clinical practices in Spain, in which there is no established protocol for HIV screening, was compared to the potential impact of applying a targeted screening protocol in persons who come to the ED with certain conditions suggestive of HIV infection (diagnosis of a sexually transmitted infection, mononucleosis, herpes zoster infection, community-acquired pneumonia; practice of chemsex, and need for postexposure prophylaxis).

Large Increase in Azithromycin-Resistant in Northern Spain.

The aim of this study was to characterize the evolution of gonorrhea in the general population by correlating epidemiological, genotypic, and antimicrobial resistance data of isolates collected in northern Spain from 2014 to 2018. One hundred ninety-four strains underwent antimicrobial susceptibility testing and were genetically analyzed by multiantigen sequence typing. Increasing cases of gonococcal infections have been observed after 2015.

Development and validation of a laboratory-based risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19.

Background: Early identification of patients with COVID-19 who may develop critical illness is of great importance.

Methods: In this study a retrospective cohort of 264 COVID-19 cases admitted at Macarena University was used for development and internal validation of a risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. Backward stepwise logistic regression was used to derive the model, including clinical and laboratory variables predictive of critical illness.

Mediterranean Diet and Risk of Dementia and Alzheimer's Disease in the EPIC-Spain Dementia Cohort Study.

The Mediterranean diet (MD) has shown to reduce the occurrence of several chronic diseases. To evaluate its potential protective role on dementia incidence we studied 16,160 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort study recruited between 1992-1996 and followed up for a mean (±SD) of 21.6 (±3.

Creation and implementation of a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC registry).

Background: International patient registries are of particular importance for rare disorders, as they may contribute to overcome the lack of knowledge derived from low number of patients and limited awareness of these diseases, and help to learn more about their geographical or population-based specificities, which is relevant for research purposes and for promoting better standards of care and diagnosis. Our objective was to create and implement a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) and to disseminate the knowledge of these disorders.

Results: Teams from nine different countries (United Kingdom, Spain, Italy, France, Germany, Denmark, Greece, Turkey and USA) created a consortium that developed the first European registry dedicated to rare muscle glycogenoses.

An embryonic stem cell-specific heterochromatin state promotes core histone exchange in the absence of DNA accessibility.

Nucleosome turnover concomitant with incorporation of the replication-independent histone variant H3.3 is a hallmark of regulatory regions in the animal genome. Nucleosome turnover is known to be universally linked to DNA accessibility and histone acetylation.

Incidence of Dementia and Associated Factors in the EPIC-Spain Dementia Cohort.

Background: Dementia has become a public health priority as the number of cases continues to grow worldwide.

Objective: To assess dementia incidence and determinants in the EPIC-Spain Dementia Cohort.

Methods: 25,015 participants (57% women) were recruited from three Spanish regions between 1992-1996 and followed-up for over 20 years.

Modification of the risk of post-traumatic stress disorder (PTSD) by the 5-HTTLPR polymorphisms after Lorca's earthquakes (Murcia, Spain).

Information of the modulation effect of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on post-traumatic stress disorder (PTSD) after earthquakes is scarce and contradictory. A cross-sectional face-to-face interview survey of a representative sample of the adults was carried out after the Lorca (Spain) earthquakes (May 11, 2011). Socio-demographic variables, DSM-IV diagnostic assessment and earthquake-related stressors were obtained from the Composite International Diagnostic Interview (CIDI).

[Food policies to prevent obesity and the main non-transmissible diseases in Spain: where there's a will there's a way].

Introduction: In Spain, one third of all children and two-thirds of adults suffer from excess weight, a condition that generates a direct excess medical cost of 2000 million Euros. Obesogenic food environments cause obesity by promoting the consumption of sugar-sweetened beverages and ultra-processed foods. Accordingly, we propose five priority policies capable of reversing the epidemic of obesity and related non-communicable diseases through the creation of healthy food environments.

Childhood adversities and 5-HTTLPR polymorphism as risk factors of substance use disorders: retrospective case-control study in Murcia (Spain).

Objective: To explore the separate and joint associations of childhood adversities and 5-HTTLPR polymorphism as risk factors for substance use disorders among adults. : : Retrospective case-control study.

Setting: Cases from the substance unit and controls from a representative sample of the adult general population in the metropolitan area of Murcia (Spain).

Socioeconomic Effect of Education on Pancreatic Cancer Risk in Western Europe: An Update on the EPIC Cohorts Study.

Background: To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up.

Methods: Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations.