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

Dysphagia Lusoria and Zenker`s Diverticulum

Una mujer de 81 años fue remitida para evaluación de una disfagia que padecía desde hacía cuatro años. Una endoscopia gastrointestinal reveló un divertículo de Zenker y una compresión extrínseca del esófago. Un escaneo computadorizado del tórax confirmó la presencia de la comprensión extrínseca, causada por una arteria subclavia derecha aberrada, que comprometía la pared esofágica posterior, lo que confirmó un diagnóstico de disfagia lusoria. Una asociación entre el divertículo de Zenker y la disfagia lusoria es tan poco común que no han sido publicados sus casos con anterioridad

Development and validation of a TaqMan-MGB real-time RT-PCR assay for simultaneous detection and characterization of infectious bursal disease virus

Rapid and reliable detection and classification of infectious bursal disease viruses (IBDVs) is of crucial importance for disease surveillance and control. This study presents the development and validation of a real-time RT-PCR assay to detect and discriminate very virulent (vv) from non-vv (classic and variant) IBDV strains. The assay uses two fluorogenic, minor groove-binding (MGB) TaqMan probes targeted to a single nucleotide polymorphism (SNP) embedded in a highly conserved genomic region. The analyti- cal sensitivity of the assay was determined using serial dilutions of in vitro-transcribed RNA. The assay demonstrated a wide dynamic range between 102 and 108 standard RNA copies per reaction. Good repro- ducibility was also detected, with intra- and inter-assay coefficients of variation ranging from 0.13% to 2.23% and 0.26% to 1.92%, respectively. The assay detected successfully all the assessed vv, classical, and variant field and vaccine strains and correctly discriminated all vvIBDV strains from non-vvIBDV strains. Other common avian RNA viruses tested negative, indicating high specificity of the assay. The high sensi- tivity, rapidity, reproducibility, and specificity of the real-time RT-PCR assay make this method suitable for general and genotype-specific detection and quantitation.Fil: Tomás, Gonzalo. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Hernández, Martín. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Marandino, Ana. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Panzera, Yanina. Universidad de la República. Facultad de Ciencias; UruguayFil: Maya, Leticia. Universidad de la República. Facultad de Ciencias; UruguayFil: Hernández, Diego. Universidad de la República. Facultad de Ciencias; UruguayFil: Pereda, Ariel Julián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Banda, Alejandro. Mississippi State University; Estados UnidosFil: Villegas, Pedro. Georgia State University; Estados UnidosFil: Aguirre, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Pérez, Ruben. Universidad de la República. Facultad de Ciencias; Urugua

Reactivity of TpMe2Ir(C2H4)(DMAD) with carboxylic acids. A DFT study on geometrical isomers and structural characterization

The thermally unstable adduct TpMe2Ir(C2H4)(DMAD), which was generated “in situ” by the reaction of DMAD with TpMe2Ir(C2H4)2 (1) at low temperature, reacted with different carboxylic acids to produce the following compounds: TpMe2Ir(E-C(CO2Me)double bond; length as m-dashCH(CO2Me))(H2O)(OC(O)C6H4R), (R = H, 2a; o-OH, 2b; o-Cl, 2c; m-Cl, 2d; o-NO2, 2e; m-NO2, 2f;o-Me, 2g;p-Me, 2h) and TpMe2Ir(E-C(CO2Me)double bond; length as m-dashCH(CO2Me))(H2O)(OC(O)Me) 3. In the reaction of derivative 2a with Lewis bases, TpMe2Ir(E-C(CO2Me)double bond; length as m-dashCH(CO2Me))(L)(OC(O)C6H5), (L = Py, 4a; m-Br–Py, 4b; m-Cl–Py, 4c; NCMe, 5) were obtained, of which 4b and 4c were isolated as a mixture of two isomers in which the substituted pyridine ring was present at different rotational orientations. All new compounds prepared were characterized by 1H and 13C{1H} NMR spectroscopy, the structure of compounds 2d, 2h and 4a being determined by X-ray diffraction analysis. DFT was used to analyze the relative stability and the structural orientation of the isomers.CCDC 768172, 768174 and 768173 contain the supplementary crystallographic data for 2d, 2h and 4a. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Also, all NMR spectra including 1-D, 2-D heteronuclear experiments and long range bond correlations are available for this article from the author.Peer Reviewe