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

Los principios de comprensividad y diversificación como respuesta a la diversidad en una escuela multicultural dentro de la Enseñanza Obligatoria

Analizar la interacción, en la práctica real del aula, entre el principio de comprensividad curricular y la estrategia didáctica de la diversidad.. Alumnado y profesorado de cuatro centros públicos de Educación Primaria de la Comunidad de Madrid. Se presentan las cuestiones que pretenden analizarse en cada centro: 1. Cultura escolar, 2. Tareas del aula, 3. Dimensiones espacio-temporales, 4. Recursos y materiales didácticos, 5. Participación y comunicación en el aula, 6. Evaluación, 7. Diversidad y profesorado. Para la obtención de los datos, se emplea la estrategia de la observación participante en el aula, el estudio de casos y la realización de entrevistas al profesorado. Los datos obtenidos se sistematizan en categorías. Se adjuntan los informes de los 4 centros estudiados. En los casos analizados, la diversidad se entiende, bien como dificultades en el aprendizaje o se reduce a la dimensión disciplinar. En el centro A, la diversidad se reduce a esta última dimensión, mientras que en el centro B se percibe como una característica natural de las personas. En el centro A se ofrece una respuesta precaria a la diversidad, sin existir ni adaptaciones curriculares ni materiales. En cuanto a la distribución espacio-temporal, en el centro A, la organización del centro contempla el aula de Compensatoria como único lugar para este alumnado y la distribución del tiempo es rígida. En el centro B se intenta adecuar el espacio a las necesidades educativas de este alumnado y la distribución del tiempo se realiza por áreas de conocimiento. En la práctica del profesorado del centro A, la tradición intelectualista está muy presente y las necesidades educativas se subordinan a la transmisión de los saberes intelectuales. En el centro B se consideran más importantes los contenidos actitudinales y procedimentales que los conceptuales. En el centro A, el libro de texto condiciona las tareas educativas, que se estructuran en torno a unidades didácticas, y en el centro B se emplean recursos alternativos y las tareas se organizan a través de los planes de trabajo. La evaluación, en el centro A, se refiere casi exclusivamente a contenidos conceptuales y en el centro B se favorece la autoevaluación y se realizan evaluaciones continuas y formativas. Se resalta la necesidad y la exigencia, surgidas de la práctica, de flexibilizar los planteamientos metodológicos y adaptar las condiciones del contexto educativo a cada situación específica. La lógica de la homogeneidad orienta y determina todos los modos de actuación profesional de los docentes. En el profesorado se observa un predominio de las influencias psicológicas sobre las socioculturales que, junto con las presiones curriculares a las que se le somete en el tercer ciclo de Educación Primaria, hacen que, en la diversificación curricular, se ponga más énfasis en los aspectos metodológicos que en los culturales.Ministerio Educación CIDEBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; Fax +34917748026; [email protected]

Acceleration of the DNA methylation clock among lynch syndrome-associated mutation carriers.

DNA methylation (DNAm) age metrics have been widely accepted as an epigenetic biomarker for biological aging and disease. The purpose of this study is to assess whether or not individuals carrying Lynch Syndrome-associated mutations are affected in their rate of biological aging, as measured by the epigenetic clock. Genome-wide bisulfite DNA sequencing data were generated using DNA from CD4 + T-cells obtained from peripheral blood using 27 patient samples from Lynch syndrome families. Horvath's DNAm age model based on penalized linear regression was applied to estimate DNAm age from patient samples with distinct clinical and genetic characteristics to investigate cancer mutation-related aging effects. Both Lynch mutation carriers and controls exhibited high variability in their estimated DNAm age, but regression analysis showed steeper slope for the Lynch mutation carriers. Remarkably, six Lynch Syndrome-associated mutation carriers showed a strong correlation to the control group, and two sisters carrying Lynch Syndrome-associated mutations, with no significant difference in lifestyle and similar chronological age, were assigned very different DNAm age. Future studies will be required to explore, in larger patient populations, whether specific epigenetic age acceleration is predictive of time-to-cancer development, treatment response, and survival. Epigenetic clock DNAm metrics may be affected by the presence of cancer mutations in the germline, and thus show promise of potential clinical utility for stratified surveillance strategies based on the relative risk for imminent emergence of tumor lesions in otherwise healthy Lynch Syndrome-associated mutation carriers

Cáncer de cabeza y cuello: proceso asistencial integrado

YesLa denominación de carcinomas de cabeza y cuello, o tracto aero-digestivo superior, supone un agrupamiento, no sólo por su mera localización anatómica, sino porque existen elementos comunes compartidos por estas neoplasias: etiología, epidemiología, histología, evolución clínica, procedimientos diagnósticos, enfoques terapéuticos, medidas de seguimiento. No obstante, la variabilidad en la localización, afectando órganos que participan en la fonación y la deglución, funciones fundamentales para el paciente, y su comportamiento evolutivo, exigen que los cánceres de cabeza y cuello sean abordados desde una perspectiva multidisciplinar, tanto en las actividades de detección precoz como en el diagnóstico y tratamiento, al estar implicados una gran variedad de profesionales tanto del ámbito de la Atención Primaria como de Atención Hospitalaria, siendo además imprescindible una perfecta coordinación que garantice la continuidad asistencial

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

Novel genes and sex differences in COVID-19 severity.

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided