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

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Genome-wide study of the defective sucrose fermenter strain of Vibrio cholerae from the Latin American cholera epidemic.

Contains fulltext : 108030.pdf (publisher's version ) (Open Access)The 7th cholera pandemic reached Latin America in 1991, spreading from Peru to virtually all Latin American countries. During the late epidemic period, a strain that failed to ferment sucrose dominated cholera outbreaks in the Northern Brazilian Amazon region. In order to understand the genomic characteristics and the determinants of this altered sucrose fermenting phenotype, the genome of the strain IEC224 was sequenced. This paper reports a broad genomic study of this strain, showing its correlation with the major epidemic lineage. The potentially mobile genomic regions are shown to possess GC content deviation, and harbor the main V. cholera virulence genes. A novel bioinformatic approach was applied in order to identify the putative functions of hypothetical proteins, and was compared with the automatic annotation by RAST. The genome of a large bacteriophage was found to be integrated to the IEC224's alanine aminopeptidase gene. The presence of this phage is shown to be a common characteristic of the El Tor strains from the Latin American epidemic, as well as its putative ancestor from Angola. The defective sucrose fermenting phenotype is shown to be due to a single nucleotide insertion in the V. cholerae sucrose-specific transportation gene. This frame-shift mutation truncated a membrane protein, altering its structural pore-like conformation. Further, the identification of a common bacteriophage reinforces both the monophyletic and African-Origin hypotheses for the main causative agent of the 1991 Latin America cholera epidemics

Aps Sustainable and Inclusive Social Volunteering: learning by doing a service stop the community (II)

El objetivo principal es consolidar el desarrollo de competencias genéricas y específicas que capacite a los y las participantes para transmitir la importancia de la Agenda 2030 en la universidad y la comunidad, desarrollando capacidades de reafirmación social para canalizar acciones encaminadas hacia los Objetivos de Desarrollo Sostenible (ODS). A través de la metodología del Aprendizaje-Servicio se busca promover un encuentro para el trabajo conjunto, mediante la conexión entre la individualidad de las personas, el trabajo grupal y comunitario. Los fundamentos del Trabajo Social nos permitirán trabajar un enfoque de derechos, valores y compromiso. Además, se promoverá el desarrollo de habilidades para la vida desde la educación popular, la educación eco-social, el diseño universal del aprendizaje, los entornos inclusivos, la lectura fácil y los huertos eco-didácticos. En el proyecto participará un grupo de veinte voluntarios/as (estudiantes de grado y máster de la Facultad de Trabajo Social y personas externas con diversidad intelectual), puntualmente estudiantes de Bellas Artes y Estudios Estadísticos. Como Aprendizaje, las actividades formativas programadas buscan formar al voluntariado tanto en los ODS como en las capacidades comentadas anteriormente. Para su desarrollo, se contará con recursos de las entidades colaboradoras, tanto propias de la UCM como externas. Como Servicio a la Comunidad, se propondrá al voluntariado el reto de ser embajadores/as de los ODS, compartiendo su mensaje en la universidad y comunidad, desde el conocimiento científico y el reconocimiento a los demás (cultura, saberes y procesos distintos a los nuestros). La gestión operativa se realizará a tres niveles: equipo técnico, para el seguimiento y evaluación del proyecto; equipo de acompañamiento, para coordinar actividades con el voluntariado y garantizar cohesión grupal; y equipo de relaciones institucionales, para coordinar con entidades colaboradoras los espacios y agenda para las actividades con el voluntariado.The main objective is to consolidate the development of generic and specific skills that train the participants to convey the importance of the 2030 Agenda in the university and the community, developing capacities for social reaffirmation to channel actions aimed at the Sustainable Development Goals ( ODS). Through the Service-Learning methodology, it seeks to promote a meeting for joint work, through the connection between the individuality of people, group and community work. The foundations of Social Work will allow us to work on a focus on rights, values ​​and commitment. In addition, the development of life skills will be promoted from popular education, eco-social education, universal learning design, inclusive environments, easy reading and eco-didactic gardens. A group of twenty volunteers will participate in the project (undergraduate and master's students from the Faculty of Social Work and external people with intellectual diversity), occasionally students of Fine Arts and Statistical Studies. As Learning, the programmed training activities seek to train volunteers both in the SDGs and in the capacities mentioned above. For its development, there will be resources from collaborating entities, both from the UCM and from outside. As Community Service, the challenge of being ambassadors of the SDGs will be proposed to volunteers, sharing their message in the university and community, based on scientific knowledge and recognition of others (culture, knowledge and processes different from ours). Operational management will be carried out at three levels: technical team, for the monitoring and evaluation of the project; support team, to coordinate activities with volunteers and guarantee group cohesion; and institutional relations team, to coordinate with collaborating entities the spaces and agenda for volunteer activities.Depto. de Trabajo Social y Servicios SocialesFac. de Trabajo SocialTRUEServicio ApS. Universidad Complutense de Madridunpu

Mexican Asthma Guidelines: GUIMA 2017

Background: The need for a national guideline, with a broad basis among specialists and primary care physicians was felt in Mexico, to try unifying asthma management. As several high-quality asthma guidelines exist worldwide, it was decided to select the best three for transculturation. Methods: Following the internationally recommended methodology for guideline transculturation, ADAPTE, a literature search for asthma guidelines, published 1-1-2007 through 31-12-2015 was conducted. AGREE-II evaluations yielded 3/40 most suitable for transculturation. Their compound evidence was fused with local reality, patient preference, cost and safety considerations to draft the guideline document. Subsequently, this was adjusted by physicians from 12 national medical societies in several rounds of a Delphi process and 3 face-to-face meetings to reach the final version. Results: Evidence was fused from British Thoracic Society Asthma Guideline 2014, Global Initiative on Asthma 2015, and Guía Española del Manejo del Asma 2015 (2016 updates included). After 3 Delphi-rounds we developed an evidence-based document taking into account patient characteristics, including age, treatment costs and safety and best locally available medication. Conclusion: In cooperation pulmonologists, allergists, ENT physicians, paediatricians and GPs were able to develop an evidence-based document for the prevention, diagnosis and treatment of asthma and its exacerbations in Mexico