Situación epidemiológica del Covid-19 en Sudamérica: Epidemiological situation of COVID-19 in South America

Currently the coronavirus (COVID-19) infection has become a public health problem worldwide. In December 2019, in the city of Wuhan, province of Hubei, China, the first cases of pneumonia of unknown etiology were reported, which incremented rapidly in other provinces of the country. Subsequently, SARS-CoV2 was identified as the causal agent and in mid-January 2020, the World Health Organization (WHO) reported over 280 confirmed cases of COVID-19 in China, Thailand, Japan and Korea. In South America, the first case of COVID-19 is made known on February 26, 2020 in the city of Sao Paulo, Brazil, identified as a male patient of 61 years of age from the region of Lombardy in Italy. Soon after there were other confirmed cases imported from the Asian and European continents in other south American countries.Actualmente la infección por coronavirus (COVID-19) se ha convertido en un problema de salud públicaa nivel mundial. En diciembre del 2019, en la ciudad de Wuhan, provincia de Hubei, China, se reportaronlos primeros casos de neumonía de etiología desconocida, los cuales se incrementaron rápidamente enotras provincias del país. Posteriormente, se identificó al coronavirus SARS-CoV-2 como agente causal y, a mediados de enero del2020 la Organización Mundial de la Salud (OMS) reportó más de 280 casos confirmados de COVID-19 enChina, Tailandia, Japón y Corea

Bending Stiffness in Cadaveric and Composite Long Bones Following Total Joint Replacement

Several biomechanics studies have utilized commercially available replicate bone models as an alternative to cadaveric tissue specimens, in part due to their ease of handling and reduced expense. In an effort to validate the use of replicate bone specimens in biomechanics research, a number of studies have compared material properties of whole tibia and femur specimens to those of similar cadaveric specimens. Many of these validation studies have ascertained that the material properties of whole bone composite models fall within the range of those properties of cadaveric specimens, while offering reduced interspecimen variability. Current literature lacks, however, the direct comparison between cadaveric and composite specimens after the implantation of joint replacement components. Because of this, the interactions between orthopaedic implant and replicate bone model, and how those interactions compare with those between implants and cadaveric tissue, are relatively unknown. The purpose of this study was to evaluate the use of composite femur specimens in test scenarios aside from the whole-bone instances currently evaluated in the literature. Six cadaveric and six composite tibias and femurs were tested at different stages of surgical intervention. Flexural rigidity was measured using a 4-point bending test as a whole bone, after unicompartimental cut and implantation (UKA), and after total knee cut and implantation (TKA) or total hip arthroplasty (THA). The data did not show a definite trend between tests and specimens but is conclusive enough to use composite models for cadaveric specimens

Natural drivers of multidecadal Arctic sea ice variability over the last millennium

This is the final version. Available from Nature Research via the DOI in this record.The climate varies due to human activity, natural climate cycles, and natural events external to the climate system. Understanding the different roles played by these drivers of variability is fundamental to predicting near-term climate change and changing extremes, and to attributing observed change to anthropogenic or natural factors. Natural drivers such as large explosive volcanic eruptions or multidecadal cycles in ocean circulation occur infrequently and are therefore poorly represented within the observational record. Here we turn to the first high-latitude annually-resolved and absolutely dated marine record spanning the last millennium, and the Paleoclimate Modelling Intercomparison Project (PMIP) Phase 3 Last Millennium climate model ensemble spanning the same time period, to examine the influence of natural climate drivers on Arctic sea ice. We show that bivalve oxygen isotope data are recording multidecadal Arctic sea ice variability and through the climate model ensemble demonstrate that external natural drivers explain up to third of this variability. Natural external forcing causes changes in sea-ice mediated export of freshwater into areas of active deep convection, affecting the strength of the Atlantic Meridional Overturning Circulation (AMOC) and thereby northward heat transport to the Arctic. This in turn leads to sustained anomalies in sea ice extent. The models capture these positive feedbacks, giving us improved confidence in their ability to simulate future sea ice in in a rapidly evolving Arctic.Natural Environment Research Council (NERC)Natural Environment Research Council (NERC)Natural Environment Research Council (NERC)Leverhulme TrustAustralian Research CouncilEuropean Union’s Horizon 202

Phenobarbital Indirectly Activates the Constitutive Active Androstane Receptor (CAR) by Inhibition of Epidermal Growth Factor Receptor Signaling

Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. We found that phenobarbital activated CAR by inhibiting epidermal growth factor receptor (EGFR) signaling. Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of receptor for activated C kinase 1 (RACK1) at Tyr52, which then promoted the dephosphorylation of CAR at Thr38 by the catalytic core subunit of protein phosphatase 2A. The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR

Global Well-posedness of an Inviscid Three-dimensional Pseudo-Hasegawa-Mima Model

The three-dimensional inviscid Hasegawa-Mima model is one of the fundamental models that describe plasma turbulence. The model also appears as a simplified reduced Rayleigh-B\'enard convection model. The mathematical analysis the Hasegawa-Mima equation is challenging due to the absence of any smoothing viscous terms, as well as to the presence of an analogue of the vortex stretching terms. In this paper, we introduce and study a model which is inspired by the inviscid Hasegawa-Mima model, which we call a pseudo-Hasegawa-Mima model. The introduced model is easier to investigate analytically than the original inviscid Hasegawa-Mima model, as it has a nicer mathematical structure. The resemblance between this model and the Euler equations of inviscid incompressible fluids inspired us to adapt the techniques and ideas introduced for the two-dimensional and the three-dimensional Euler equations to prove the global existence and uniqueness of solutions for our model. Moreover, we prove the continuous dependence on initial data of solutions for the pseudo-Hasegawa-Mima model. These are the first results on existence and uniqueness of solutions for a model that is related to the three-dimensional inviscid Hasegawa-Mima equations

Relative Activation of Human Pregnane X Receptor versus Constitutive Androstane Receptor Defines Distinct Classes of CYP2B6 and CYP3A4 Inducers

Both the human pregnane X receptor (hPXR) and constitutive androstane receptor (hCAR) are capable of regulating CYP3A4 and CYP2B6 gene expression. However, the majority of currently identified CYP3A4 and CYP2B6 inducers are confirmed activators of hPXR but not hCAR. To compare these receptors with respect to their chemical selectivities, 16 drugs known to induce CYP3A4 and/or CYP2B expression were evaluated for relative activation of hPXR versus hCAR. Because of the high basal but low chemical-induced activation of hCAR in immortalized cells, alternative methods were used to evaluate hCAR activation potential. Thirteen of the 16 compounds were classified as moderate to strong hPXR activators. In contrast, carbamazepine (CMZ), efavirenz (EFV), and nevirapine (NVP) were classified as negligible or weak hPXR activators at concentrations associated with efficacious CYP2B6 reporter or endogenous gene induction in primary human hepatocytes, suggesting potential activation of hCAR. Subsequent experiments demonstrated that these three drugs efficiently induced nuclear accumulation of in vivo-transfected enhanced yellow fluorescent protein-hCAR and significantly increased expression of a CYP2B6 reporter gene when hCAR was expressed in CAR−/− mice. In addition, using a recently identified, chemically responsive splice variant of hCAR (hCAR3), the hCAR activation profiles of the 16 compounds were evaluated. By combining results from the hPXR- and hCAR3-based reporter gene assays, these inducers were classified as hPXR, hCAR, or hPXR/hCAR dual activators. Our results demonstrate that CMZ, EFV, and NVP induce CYP2B6 and CYP3A4 preferentially through hCAR and that hCAR3 represents a sensitive tool for in vitro prediction of chemical-mediated human CAR activation