A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this populatio

Cuidando a quienes cuidan, experiencias del servicio de contención virtual en tiempos de pandemia COVID19

Este trabajo tiene como objetivo describir las características del dispositivo creado para la contención y el acompañamiento de profesionales de la salud en tiempos de pandemia por el Coronavirus Covid-19, promoviendo la salud y el bienestar emocional. Se detalla la conformación del equipo de trabajo y la implementación de la atención remota como así también los datos estadísticos obtenidos. Luego de las medidas implementadas por el Gobierno de la Nación, en marco de emergencia sanitaria mundial por el Coronavirus (COVID-19), el 26 de Marzo de 2020 se pone en marcha el servicio. El equipo de trabajo brinda orientación, acompañamiento y contención psicológica a los efectores/efectoras de la Salud que trabajan en diversas instituciones públicas y privadas de nuestra provincia y a docentes y no docentes que se desempeñan en dependencias de la UNC. Desde la Facultad de Psicología de la Universidad Nacional de Córdoba, el Ministerio de Salud, la Secretaría de Salud Mental de la Provincia de Córdoba y la Municipalidad de Córdoba, se gestiona este este servicio surge como un dispositivo de intervención virtual para el cuidado de quienes cuidan la salud de la población y los que brindan transferencia de conocimiento a alumnos de la UNC.publishedVersionFil: López, Nahuel. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Chávez, Lorena Paola. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Salvetti, Marcela Alejandra. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Ré, Ana Carolina. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Scorza, Diana Rita. Ministerio de Salud de la Provincia de Córdoba. Secretaría de Salud Mental; Argentina.Fil: Irueste, Paula. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Serena, Florencia. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Figueroa, Maximiliano Rubén. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Pavan, María Avila. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Alvo, Carolina. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Moreno Andueza, Mayra. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Neme Villarroel, Yanina. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Colombo, Judith J. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Cabanillas, José Ignacio. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Moreno Frías, Ana Virginia. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Espeche, Ana Beatriz. Ministerio de Salud de la Provincia de Córdoba. Secretaría de Salud Mental; Argentina.Fil: Estrada, Ezequiel Matías. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Zandivarez, Paola Fátima. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Wortley, Ana Carolina. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Waigel, Vanina Alejandra. Ministerio de Salud de la Provincia de Córdoba. Secretaría de Salud Mental; Argentina.Fil: Simonini, Claudia. Ministerio de Salud de la Provincia de Córdoba. Secretaría de Salud Mental; Argentina.Fil: Tumas, Paula. Municipalidad de Córdoba. Secretaría de Salud; Argentina

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Advanced Robotic Therapy Integrated Centers (ARTIC): an international collaboration facilitating the application of rehabilitation technologies

Background: The application of rehabilitation robots has grown during the last decade. While meta-analyses have shown beneficial effects of robotic interventions for some patient groups, the evidence is less in others. We established the Advanced Robotic Therapy Integrated Centers (ARTIC) network with the goal of advancing the science and clinical practice of rehabilitation robotics. The investigators hope to exploit variations in practice to learn about current clinical application and outcomes. The aim of this paper is to introduce the ARTIC network to the clinical and research community, present the initial data set and its characteristics and compare the outcome data collected so far with data from prior studies. Methods: ARTIC is a pragmatic observational study of clinical care. The database includes patients with various neurological and gait deficits who used the driven gait orthosis Lokomat® as part of their treatment. Patient characteristics, diagnosis-specific information, and indicators of impairment severity are collected. Core clinical assessments include the 10-Meter Walk Test and the Goal Attainment Scaling. Data from each Lokomat® training session are automatically collected. Results: At time of analysis, the database contained data collected from 595 patients (cerebral palsy: n = 208; stroke: n = 129; spinal cord injury: n = 93; traumatic brain injury: n = 39; and various other diagnoses: n = 126). At onset, average walking speeds were slow. The training intensity increased from the first to the final therapy session and most patients achieved their goals. Conclusions: The characteristics of the patients matched epidemiological data for the target populations. When patient characteristics differed from epidemiological data, this was mainly due to the selection criteria used to assess eligibility for Lokomat® training. While patients included in randomized controlled interventional trials have to fulfill many inclusion and exclusion criteria, the only selection criteria applying to patients in the ARTIC database are those required for use of the Lokomat®. We suggest that the ARTIC network offers an opportunity to investigate the clinical application and effectiveness of rehabilitation technologies for various diagnoses. Due to the standardization of assessments and the use of a common technology, this network could serve as a basis for researchers interested in specific interventional studies expanding beyond the Lokomat®