Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure

Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted

Cultura clásica : propuesta de currículum

La bibliografía está dividida en bibliografía de documentos clásicos y bibliografía generalEl objetivo fundamental del trabajo es que la materia Cultura Clásica constituya para el alumno una ayuda en el conocimiento y análisis de su entorno, cuyas raices están en el mundo clásico, al que pretenden acercarle mediante la comprensión del entorno histórico heredado, literario y lingüístico que forman parte de su vivencia cotidiana. Se centran en cuatro ejes temáticos, que a nivel procedimental y actitudinal, se adecúan a los objetivos que les parecen fundamentales en esta etapa, sin perder de vista la posibilidad de conexión, entre sí y con el resto de materias de la ESO. Los ejes temáticos son: Histórico. La romanización en Asturias; Mitológico: Mitología greco-latina y asturiana; Literario: La literatura clásica como fuente de inspiración de la actual; Lingüístico: Lenguas clásicas y lenguas modernas. El modelo de DCB propuesto está concebido para las características e intereses de alumnos asturianos de la cuenca del Nalón, pero a los autoeres les parece lo suficientemente flexible como para adaptarse a otros entornos y necesidades. El trabajo está presentado en dos partes, en la primera la propuesta de Diseño Curricular Base y en la segunda se ejemplifica el diseño mediante una unidad didáctica, Mitos y mitos, ya dispuesta para ser llevada al aula y que consta de dos partes diferentes pero inseparables: la guía del profesor y los documentos del alumno.AsturiasES

La lengua asturiana en los libros de texto : tratamiento y ajuste al marco curricular

Conocer el tratamiento que la lengua asturiana recibe en los libros de texto que utilizan en los centros educativos del Principado de Asturias. Editoriales que comercializan sus textos en el Principado de Asturias en las asignaturas de Cultura Clásica, Lengua Latina y Lengua Castellana y Literatura. En total se manejan 36 libros de texto que corresponden a ediciones posteriores al año 2002. El informe proporciona, en primer lugar, una revisión de las distintas bases legales referidas, por un lado, al tratamiento de las lenguas minoritarias y, por otro, a los contenidos curriculares vigentes sobre el asturiano en las materias de Lengua Castellana y Literatura, Cultura Clásica y Latín para Educación Secundaria Obligatoria y Bachillerato. En esta primera parte se recopilan todos aquellos contenidos curriculares referidos a la lengua asturiana. Una segunda parte está compuesta por el estudio de datos. En ella se ofrece un resumen estadístico del tratamiento que recibe la lengua asturiana en los libros de texto en cuanto a su denominación, su ámbito geográfico, su descripción lingüística e histórica, la aparición de ejemplos y ejercicios y el tratamiento de la literatura en asturiano. La tercera parte plantea un conjunto de conclusiones sobre la coherencia entre la información que aparece en los libros de texto y las exigencias de los currículos oficiales y las bases legales que promueven la difusión y el conocimiento de la lengua asturiana. Para la toma de datos se diseña una ficha de referencia que sirve para unificar los criterios de análisis. El tipo de datos que se extraen responden a una doble determinación; por un lado, a las exigencias que se imponen en los documentos curriculares de la región y, por otro, la denominación, la cartografía, la descripción lingüística y la ejemplificación de esa lengua. A) La práctica totalidad de los manuales han optado por una interpretación restrictiva de la legislación. La mención expresa de la lengua asturiana en los decretos obliga a que los libros de texto, en su mayoría, planteen la situación lingüística asturiana dentro de la realidad plurilingüe de España. Sin embargo, cuando lo hacen, presentan esa situación desde una perspectiva histórica que, si bien puede tener su valor y su fundamento dentro del conjunto de contenidos que se exigen, se encuentra totalmente alejada de la realidad actual. B) El conjunto de los libros de texto no sigue la pauta que marca la redacción del currículo del Principado de Asturias en lo que se refiere a la denominación de la lengua asturiana, asturiano o bable. C) En el tratamiento cartográfico los libros de texto incumplen las prescripciones del currículo determinado para Asturias. D) Los escasos ejercicios que aparecen en los manuales no están planteados específicamente para la lengua asturiana: lenguas del Estado Español, 'historia de la lengua que hablas', dialectos latinos en el norte peninsular, toponimia local y patronímicos y topónimos prerrománicos. E) Escasas alusiones a la geografía lingüística, ya sea de época medieval ya sea referida a la actualidad. F) Ninguno de los textos alude a la literatura en asturiano ni a la literatura que refleja la situación cultural de Asturias. G) Solo dos editoriales ofertan monográficos o suplementos específicos para Asturias con objeto de complementar sus libros de texto y adaptarlos a los contenidos del currículo del Principado de Asturias.AsturiasUniversidad de Oviedo. Facultad de Ciencias de la Educación; Calle Aniceto Sela s. n.; 33005 Oviedo; Tel. +34985103215; Fax +34985103214;ES

Festival Juvenil de Teatro Grecolatino de Segóbriga : historia, actividades, dimensión educativa del festival, guías didácticas y trabajos escolares

Resumen tomado de la publicaciónLos profesores asturianos de lenguas clásicas pretenden acercar el teatro clásico a los escolares. Estructurada en cuatro apartados (Historia y actividades del festival; Dimensión educativa del festival; Guías didácticas; Trabajos escolares premiados en la sede de Gijón),la publicación repasa las actividades que el festival ha llevado a cabo en sus trece años de existencia, presenta veintisiete guías didácticas con el fin de facilitar y ahondar en la lectura de los escritores grecolatinos en el aula y recoge los trabajos realizados por alumnos de ESO y bachillerato premiados en los concursos que cada primavera convoca este Festival.AsturiasUniversidad de Oviedo. Facultad de Ciencias de la Educación; Calle Aniceto Sela s. n.; 33005 Oviedo; +34985103215; +34985103214;ES

Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure

Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)