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

Ciencia Odontológica 2.0

Libro que muestra avances de la Investigación Odontológica en MéxicoEs para los integrantes de la Red de Investigación en Estomatología (RIE) una enorme alegría presentar el segundo de una serie de 6 libros sobre casos clínicos, revisiones de la literatura e investigaciones. La RIE está integrada por cuerpos académicos de la UAEH, UAEM, UAC y UdeG

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

SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV

The serine incorporator 5 (SERINC5) is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef), S2, and glycosylated Gag (glycoGag). These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env) that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy

Gene Expression Profile in Persistent Pulmonary Hypertension of Newborn, Preliminary Report

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition with high morbidity and mortality. The therapeutic approach, even today, represents a major challenge. There is considerable interest in the understanding of the signaling pathways that regulate vasoconstriction and pulmonary vascular remodeling. Objective: We set out to identify the expression of genes S100A9 and solutes transporter, as well as their participation in the physiopathological events of PPHN. Design and methods: This is a cross-sectional study that focuses mainly on up- and down-regulated genes involved in endothelial metabolism, hypoxia transporters, ionic and nucleotides metabolism. The total RNA was obtained from blood samples of healthy full-term newborns (negative controls) and patients with PPHN. The preparation of samples for microarray analysis was as follows: control samples were stained with fluorescent nucleotides dUTP-Cy3 and pathological samples with dUTP-Cy5; samples were co-hybridized, a microarray analysis was performed using an Array Scanner Packard. Additionally, reverse transcriptase polymerase chain reaction (RT-PCR) for the genes S100A9 and solutes transporter was done. Comparative and descriptive analyses were done using t-test for independent variables, considering a p \u3c 0.05 as significant. The elements with a z-score of more than 2 standard deviations are genes likely to be differentially expressed. Results: From the total (10,000) genes analyzed, 364 (3.64%) were differentially regulated in their expression; those that registered an up-regulation were 1.13%, while 2.51% were down-regulated. S100 proteins type A9 and A12 were the most over-expressed, as well as Rho family GTPase 3. Down-regulation in the hypoxia-inducible factor 1 (HIF-1) and HIF-1 alpha subunit inhibitor was found. S100A9 and RSC1A1 had increased mRNA expression under PPHN conditions compared to healthy newborn infants. Conclusions: The up-regulation from both genes could explain, in part, the vasoreactivity and vascular remodeling characteristic of PPHN. A deeper understanding of the pathophysiology of PPHN could have a positive impact on the development of specific therapies

Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns

Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae. In an attempt to improve prognostic estimates, neurological research envisaged various biochemical markers detectable in the umbilical cord blood of newborns (NB). Few studies examining these biochemical factors in the whole blood of newborns exist. Thus, the aim of this study was to determine the expression and concentrations of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and specific CNS enzymes (S-100 and enolase) in infants with perinatal asphyxia. These data were compared between the affected infants and controls and were related to the degree of HIE to determine their utilities as biochemical markers for early diagnosis and prognosis. Methods: The levels of the proinflammatory cytokines and enzymes were measured by enzyme-linked immunosorbent assay (ELISA) and Reverse Transcription polymerase chain reaction (RT-PCR). Results: The expression and serum levels of the proinflammatory cytokines, enolase and S-100 were significantly increased in the children with asphyxia compared with the controls. Conclusion: The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models

Effect of Rituximab Compared with Natalizumab and Fingolimod in Patients with Relapsing–Remitting Multiple Sclerosis: A Cohort Study

The objective of this study was to evaluate the clinical files of patients with RRMS who started rituximab (RTX) compared with a second-line treatment (natalizumab (NTZ) or fingolimod (FTY)). This was a historical cohort study. We compared the effect according to the Expanded Disability Status Scale (EDSS) and the number of relapses in RRMS patients receiving these treatments after a mean period of 12 months. We found a statistically significant difference (p < 0.001) when comparing the EDSS scores and the annual relapse rates of patients receiving RTX with those receiving NTZ or FTY. This study is essential for our clinical practice, since patients with limited treatment options represent a challenge with regard to the management of their medical care. However, clinical trials and prospective studies with long follow-up periods are necessary to provide sufficient evidence on the efficacy of RTX and thus include this treatment in the therapeutic profile of patients with MS