Latin American study of hereditary breast and ovarian cancer LACAM : a genomic epidemiology approach

Q2Q1Artículo original1-13Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5–10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations

Primer Encuentro virtual de los docentes de facultad de administración de empresas.

Primer Encuentro virtual de los docentes de facultades de administración de empresas USTA Colombia - En busca de la consolidación multicampus. Un espacio de diálogo que permitió   Palabras clave: facultades de administración, docentes administración, multicampus, trabajo colaborativo.http://unidadinvestigacion.usta.edu.c

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

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

IV Congreso internacional 2019: memorias II

La Red de Dirección Estratégica en la Educación Superior (RED-DEES) celebró hace poco tiempo su 10mo Aniversario de constitución. Por ello, con mucho orgullo este libro permite crear un puente en el tiempo y la emoción para Ias 54 Instituciones de Educación Superior que hoy tienen el honor de ser parte de sus miembros. Hace unos 10 años pocos podrían soñar con que la Red hubiera recorrido el camino que nos ha traído hasta aquí; era una idea inicial, tan solo una semilla, que abriría las puertas a un futuro prometedor; se convirtió en un camino hacia la ilusión, ya que en los primeros años nos movíamos entre el deseo y la incertidumbre. Hoy no dejamos de reconocer que fue una decisión riesgosa, pero estábamos dispuestos a asumirla con muchos esfuerzos entre todos. (Apartes del texto)Contiene: 1. La Planificación Estratégica en la Educación Superior: Monitoreo y Seguimiento a la planificación operativa: Herramienta de apoyo para la toma de decisiones / Isaías Hernández Sánchez, María Catalina Tapia López -- La Planificación y su vinculación con los modelos para la calidad, caso UNAH / Javier Alexis Martínez Moncada -- Resultados de un trabajo planificado en la facultad de medicina de la UNNE- Argentina / Erika Sánchez, Silvia García, Patricia Demuth -- Rediseño estratégico y prospectivo de la arquitectura organizacional: experiencia en la Universidad de Managua. Nicaragua / Fernando Valle Meza, Mario Valle Dávila, Dora María Meza Cornavaca -- Factores que favorecen y dificultan la aplicación de la dirección estratégica en la educación superior / Jorge Juan Domínguez Menéndez -- La evaluación de la práctica de la planificación estratégica en instituciones de educación superior de Cuba. Metodología aplicada y principales resultados / José Luis Almuiñas Rivero, Judith Galarza López -- Modelo para el control de la estrategia institucional en la Universidad de Cienfuegos / Katia Rivero Alonso, Judith Galarza López -- Reconstrucción de la senda que se recorrió en los procesos de planificación y evaluación institucional de comunitaria intercultural / Adrián Puerta Ch., Julia Arguello M. -- 2. Evaluación Institucional y gestión de la calidad en las IES: Hacia la instauración de una cultura de mejora continua: Modelo de evaluación del desempeño en la UNAN -Managua / Isaías Hernández Sánchez, Saira del Rosario Figueroa Aguirre -- Estrategias para mejorar la gestión del proceso de autoevaluación institucional con fines de acreditación en la Universidad San Gregorio de Portoviejo / Ximena Guillén Vivas, José Luis Almuiñas Rivero, Judith Galarza López -- Visita de condiciones iniciales para la acreditación institucional en tiempos de pandemia y sus impactos. Relato de una experiencia. Fundación Universitaria Los Libertadores - Colombia / Patricia Martínez Barrios, Orlando Salinas Gómez, Luz Mercedes Flechas Mendoza -- 3. La formación profesional y la calidad de los procesos universitarios: La formación profesional y la calidad de los procesos universitarios / Observal - Honduras, Celeo Emilio Arias -- Describir la satisfacción estudiantil delos egresados del instituto tecnológico superior de tela, ubicado en la ciudad de tela, Atlantida, Honduras / Gustavo Adolfo Rodríguez, Espinoza Carlos Agurcia, Jairo Núñez -- La cadena valor percibido, satisfacción y lealtad para los egresados de la universidad / Katty Johanna Loor Avila, José Antonio Pedraza Rodríguez, Leonor Pérez Naranjo -- El avance del seguimiento a graduados en la universidad nacional de ingeniería / Melvis Daviel Martínez Cano -- Programa de seguimiento de egresados: estudio preliminar de tres servicios universitarios / Rodrigo Horjales -- La formación de valores éticos en los estudiantes de la carrera de derecho con un enfoque RSU: propuesta de una estrategia / Roger Martínez Isaac, Odette Martínez Pérez, Noemí Delgado Álvarez -- El seguimiento de graduados; oferta y demanda de profesionales veterinarios en el Uruguay / José Passarini, Paola Cabral, Brasiliano Rodríguez, Claudia Borlido -- 4. Vinculación con medio y responsabilidad social universitaria: Responsabilidad social y aprendizaje: ideas preliminares / Odette Martínez Pérez, Roxana Chiquito Chillán, Víctor Gómez Rodríguez -- Transversalización de los Objetivos de Desarrollo Sostenible en la Planeación Institucional de la UNAN-León / Marcos Vinicio Sandino Montes -- La Universidad de Pinar del Río del conocimiento y la innovación en función del desarrollo local sostenible / Maricela González Pérez, Carlos Cesar Torres Paez, Saray Nuñez González -- Educación superior socialmente responsable: propuesta de una metodología para su evaluación e implementación en la educación superior ecuatoriana / Odette Martínez Pérez, Luis Alberto Alzate Peralta, Rudy García Cobas -- 5. La Gestión de la Internacionalización de la educación superior: La gestión del proceso de internacionalización: experiencias en la movilidad académica, la formación doctoral del docente / Bernal Álava AF, Borroto Leal OE, Campozano Pluas, Vanessa Daniela -- La gestión de la internacionalización desde la perspectiva de la formación tecnológica: la experiencia del Instituto Superior Tecnológico Bolivariano de Tecnología ITB / Luis Alberto Alzate Peralta, Odette Martínez Pérez Elena Tolozano Benites -- 6.Las TIC y las Redes Sociales en la formación de los estudiantes / Las Redes sociales como gestoras de conocimiento formal en los participantes / Esteban de Jesús Gutiérrez Ortiz, Andrés Ernesto Manrique de la Cruz, Sheyla Monsait Valero Estrada, Carlos Jesús Rodríguez Saucedo -- Las NTIC como plataformas de nuevas habilidades digitales y cocreadoras de ecosistemas virtuales educomunicativos / Martín Hernández Oseguera, Oscar Ricardo Castillo BribiescaFundación Universitaria Los Libertadore

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

International audienc