Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Management of a Hypomineralisation of the Enamel by Applying a Remineraliser Based on Zinc Hydroxyapatite (microRepair)

According to our experience, the treatment with remineralising mousse based on biomimetic nanohydroxyapatite has the advantage of being easily implemented by all patients as it is economical and absolutely noninvasive. The following case report reports the results obtained from the use of a mousse based on biomimetic nanohydroxyapatite for the treatment of incisor and molar hypomineralisation. This case report illustrates the case of a 4-year-old patient who was diagnosed with MIH and was subjected to remineralising treatments at home for six months, at alternating periods. Throughout the observation period, the painful perception of the lesions was detected through an assessment scale, and the clinical appearance was documented photographically. One year after the diagnosis, all the elements involved no longer showed any symptoms

Effects of transcranial direct current stimulation on joint flexibility and pain in sedentary male individuals

The aim of this study was to analyze the effects of cathodal tDCS (c-tDCS) on joint flexibility and pain perception in a sedentary male. Eight male healthy, sedentary right-leg-dominant and novice in muscle stretching aged between 19 and 30 years (24.0 ± 4.0 years) were recruited. Subjects performed three experimental conditions in a randomized, double-blinded crossover design: anodal stimulation (a-tDCS), c-tDCS and sham-tDCS (2 mA for 20 minutes targeting the bilaterally motor cortex). Before and immediately after the experimental conditions (baseline and post-condition, respectively), subjects completed the range of motion (ROM) of right hip test and the Visual Analogic Scale for Pain (VAS pain; level of significance P < 0.05). In post-condition, c-tDCS was greater than to a-tDCS (P < 0.001), and sham-tDCS (P < 0.001) in the right hip ROM. Hip ROM increased in the post-condition compared to baseline in the c-tDCS condition (P < 0.001). In the a-tDCS condition, hip ROM decreased in the post-condition compared to baseline (P < 0.001). For VAS pain, in post-condition, c-tDCS was less than a-tDCS (P < 0.001), and sham-tDCS (P < 0.001). In the c-tDCS condition, the VAS pain decreased in the post-condition compared to baseline (P < 0.001). This study suggests that c-tDCS applied to SM1 may promote increased in ROM of the hip and decreased and perception of pain.Le but de cette étude était d’analyser les effets du tDCS cathodique (c-tDCS) sur la flexibilité des articulations et la perception de la douleur chez un homme sédentaire. Huit hommes en bonne santé, sédentaires, dominants de la jambe droite et novices en étirement musculaire âgés de 19 à 30 ans (24,0 ± 4,0 ans) ont été recrutés. Les sujets ont réalisé trois conditions expérimentales dans un plan croisé randomisé à double insu : stimulation anodale (a-tDCS), c-tDCS et sham-tDCS (2 mA pendant 20 minutes en ciblant le cortex moteur bilatéral). Avant et immédiatement après les conditions expérimentales (de base et post-condition, respectivement), les sujets ont complété l’amplitude de mouvement (ROM) du test de la hanche droite et l’échelle visuelle-analogique de la douleur (douleur EVA ; niveau de signification p < 0,05). En post-condition, c-tDCS était supérieur à a-tDCS (p < 0,001) et à sham-tDCS (p < 0,001) dans la ROM de la hanche droite. La ROM de la hanche a augmenté dans la post-condition par rapport aux valeurs de base dans la condition c-tDCS (p < 0,001). Dans la condition a-tDCS, la ROM sous hanche a diminué dans la post-condition par rapport au niveau de base (p < 0,001). Pour la douleur liée à l’EVA, en post-condition, le c-tDCS était inférieur à a-tDCS (p < 0,001) et au sham-tDCS (p < 0,001). Dans les conditions c-tDCS, la douleur liée à l’EVA diminuait après la condition par rapport à la situation initiale (p < 0,001). Cette étude suggère que le c-tDCS appliqué à SM1 pourrait favoriser une augmentation de la ROM de la hanche et une diminution de la perception de la douleur.info:eu-repo/semantics/publishedVersio