New prophylaxis regimen for SARS-CoV-2 infection in health professionals with low doses of hydroxychloroquine and bromhexine: a randomised, double-blind placebo clinical trial (ELEVATE Trial).

INTRODUCTION: SARS-CoV-2 infection in Mexico has caused ~2.7 million confirmed cases; around 20%-25% of health workers will be infected by the virus at their workplace, with approximately 4.4% of mortality. High infectivity of SARS-CoV-2 is related with cell entry mechanism, through the ACE receptor. SARS-CoV-2 requires transmembrane protease serine 2 to cleave its spike glycoprotein and ensure fusion of host cell and virus membrane. We propose studying prophylactic treatment with hydroxychloroquine (HCQ) and bromhexine (BHH), which have been shown to be effective in preventing SARS-CoV-2 infection progression when administered in early stages. The aim of this study is to assess the efficacy of HCQ and BHH as prophylactic treatments for SARS-CoV-2 infection in healthy health workers exposed to the virus. METHODS AND ANALYSIS: Double-blind randomised clinical trial, with parallel allocation at a 1:1 ratio with placebo, of low doses of HCQ plus BHH, for 60 days. Study groups will be defined as follows: (1) HCQ 200 mg/day+BHH 8 mg/8 hours versus (2) HCQ placebo plus BHH placebo. Primary endpoint will be efficacy of both interventions for the prevention of SARS-CoV-2 infection, determined by the risk ratio of infected personnel and the absolute risk. At least a 16% reduction in absolute risk is expected between the intervention and placebo groups; a minimum of 20% infection is expected in the placebo group. The sample size calculation estimated a total of 214 patients assigned: two groups of 107 participants each. ETHICS AND DISSEMINATION: This protocol has been approved by the local Medical Ethics Committee (National Institute of Rehabilitation 'Luis Guillermo Ibarra Ibarra', approval number INRLGII/25/20) and by the Federal Commission for Protection against Sanitary Risks (COFEPRIS, approval number 203 300 410A0058/2020). The results of the study will be submitted for publication in peer-reviewed journals and disseminated through conferences. TRIAL REGISTRATION NUMBER: NCT04340349.

G protein-coupled receptors: Key molecules in metabolic associated fatty liver disease development.

Metabolic associated fatty liver disease (MAFLD) is a range of hepatic disorders with progression to steatohepatitis with risk of development of fibrosis, cirrhosis, and hepatocellular carcinoma. MAFLD is strongly related to metabolic disorders of active fatty acids, which seem to be selective according to their specific ligand of G protein-coupled receptors (GPRs) located in immune response cells. An approach to study the pathophysiological mechanisms of MAFLD could be through the expression of active fatty acids ligands. The expression of GPRs is associated with obesity, microbiota environment, and dietary characteristics in patients with MAFLD. More specifically, GPR41, GPR43, GPR20, and GPR120 have been associated with alteration of lipid metabolism in hepatic and intestinal cells, and consequently they have a key role in metabolic diseases. We observed that GPR120 is not expressed in nonoverweight/obese patients, regardless of the presence of MAFLD; meanwhile the expression of GPR41 is increased in patients with lean MAFLD. GPRs role in liver disease is intriguing and a field of research opportunity. More studies are necessary to define the role of active fatty acids in the development of metabolic diseases.

Neurogenesis From Neural Crest Cells: Molecular Mechanisms in the Formation of Cranial Nerves and Ganglia.

The neural crest (NC) is a transient multipotent cell population that originates in the dorsal neural tube. Cells of the NC are highly migratory, as they travel considerable distances through the body to reach their final sites. Derivatives of the NC are neurons and glia of the peripheral nervous system (PNS) and the enteric nervous system as well as non-neural cells. Different signaling pathways triggered by Bone Morphogenetic Proteins (BMPs), Fibroblast Growth Factors (FGFs), Wnt proteins, Notch ligands, retinoic acid (RA), and Receptor Tyrosine Kinases (RTKs) participate in the processes of induction, specification, cell migration and neural differentiation of the NC. A specific set of signaling pathways and transcription factors are initially expressed in the neural plate border and then in the NC cell precursors to the formation of cranial nerves. The molecular mechanisms of control during embryonic development have been gradually elucidated, pointing to an important role of transcriptional regulators when neural differentiation occurs. However, some of these proteins have an important participation in malformations of the cranial portion and their mutation results in aberrant neurogenesis. This review aims to give an overview of the role of cell signaling and of the function of transcription factors involved in the specification of ganglia precursors and neurogenesis to form the NC-derived cranial nerves during organogenesis.

Terapia ocupacional y estado de ánimo del adulto mayor en dos asilos, Departamento de Cortés / Occupational Therapy and state of mind of elderls in two nursing homes, Cortés Departament

La terapia ocupacional lleva a cabo su labor en lo que se refiere a la promoción de la salud, prevención de enfermedades y rehabilitación de la salud mediante estrategias de ocupación del adulto con actividades diarias que permitan y estimulen su independencia física. Objetivo: Identificar las actividades de terapia ocupacional y su impacto en el estado de animo de los ancianos que viven en dos asilos del departamento de Cortés. Pacientes y Métodos: Estudio cuantitativo, descriptivo-transversal, realizado en dos asilos de ancianos del departamento de Cortés, en el primer semestre del año 2017. Muestra no probabilistíca de 30 adultos mayores institucionalizadas en dos asilos. Instrumento tipo cuestionario para las actividades de salud ocupacional y la escala de depresión geriatrica-Test de Yesavage. Resultados: Se encontró que el 50% de los adultos mayores institucionalizados no realizan ninguna terapia ocupacional, el otro 50% refieren hacer terapia ocupacional como; manualidades con papel, ir a la iglesia, pintar, sembrar, hacer ejercicios. Se encontró que 18 (60%) a menudo se sienten desmoralizados y tristes; 21 (70%) presentan un nivel de depresión que va de leve a grave. Conclusión: El estudio indicó que más del 50% de los ancianos realizarón algún tipo de terapia ocupacional y en su estado de animo presentaron un nivel de depresión geriátrica que va desde leve a grave,lo que indica que tiene un impacto directo en su estado de ánimo y salud física...(AU)

Hypoxia inducible transcription factor (HIF-1) regulates CXCL13 expression: Clinical implications in pediatric non-Hodgkin's lymphoma

Background: Lymphomas are B and/or T cell clonal neoplasms in various states of differentiation, characteristically compromising lymph nodes. They are constituted by B and T lymphocytes that reach the node by chemokine-mediated recruitment including CXCL13. Hypoxia-inducible transcription factor (HIF-1α) plays a role in cellular adaptation to oxygen concentration changes. It also regulates expression of chemokines such as CXCL12, CCL20, and CCL5 as well as some of their receptors such as CCR7 and CXCR4. Methods: We performed in silico analysis of the CXCL13 promoter, pharmacologic modulation of HIF-1α activity and, using reporter plasmids, site-directed mutation and DNA-protein interaction analysis we analyzed the relation between HIF-1α activity and CXCL13 expression. Moreover, we did tissue microarray and immunohistochemistry to see the expression of HIF-1α and CXCL13. Results: This study detected three possible HIF-1α binding sites suggesting that this chemokine may be regulated by the CXCL13 transcription factor. We showed that CXCL13 expression is directly dependent, whereby an increase in HIF-1α activity increases CXCL13 expression and decreased HIF-1α activity in turn decreases CXCL13 expression. We proved that HIF-1α transcriptionally regulates the expression of CXCL13 in a direct manner. We established that HIF-1α and CXCL13 are greatly overexpressed in the most aggressive pediatric lymphomas. Conclusions: For the first time, this study showed that HIF-1α directly regulates transcriptional CXCL13 and that both proteins are overexpressed in the most aggressive forms of pediatric lymphoma. This suggests that they may play a significant role in the pathogenesis of pediatric non-Hodgkin's lymphoma.

Multi-allelic major effect genes interact with minor effect QTLs to control adaptive color pattern variation in Heliconius erato.

Recent studies indicate that relatively few genomic regions are repeatedly involved in the evolution of Heliconius butterfly wing patterns. Although this work demonstrates a number of cases where homologous loci underlie both convergent and divergent wing pattern change among different Heliconius species, it is still unclear exactly how many loci underlie pattern variation across the genus. To address this question for Heliconius erato, we created fifteen independent crosses utilizing the four most distinct color pattern races and analyzed color pattern segregation across a total of 1271 F2 and backcross offspring. Additionally, we used the most variable brood, an F2 cross between H. himera and the east Ecuadorian H. erato notabilis, to perform a quantitative genetic analysis of color pattern variation and produce a detailed map of the loci likely involved in the H. erato color pattern radiation. Using AFLP and gene based markers, we show that fewer major genes than previously envisioned control the color pattern variation in H. erato. We describe for the first time the genetic architecture of H. erato wing color pattern by assessing quantitative variation in addition to traditional linkage mapping. In particular, our data suggest three genomic intervals modulate the bulk of the observed variation in color. Furthermore, we also identify several modifier loci of moderate effect size that contribute to the quantitative wing pattern variation. Our results are consistent with the two-step model for the evolution of mimetic wing patterns in Heliconius and support a growing body of empirical data demonstrating the importance of major effect loci in adaptive change.