Lectura crítica de evidencia médica en el contexto de COVID-19: ¿Cómo leer estudios observacionales?

Objetive. The critical reading of scientific articles allows the medical community, above all, to improve the context of decision making. The great amount of scientific production worldwide makes use of observational studies, however, a significant proportion is not useful for decision making, not because of its methodological limitations but because of errors in its application. Many studies published in relation to coronavirus 2019 disease have limitations and require statistical, epidemiological and clinical tools to be able to assess them and incorporate them into the practice of evidence-based medicine. In this review, we analyze the different observational research designs and with the help of examples we will see the different steps in the research process.Objetivo. La lectura crítica de artículos científicos, permite a la comunidad médica, sobre todo, a mejorar el contexto de la toma de decisiones. La gran cantidad de producción científica mundial hace uso de los estudios observacionales, sin embargo, una proporción significativa no sirve para la toma de decisiones, no por sus limitaciones metodológicas sino por los errores en su aplicación. Muchos estudios publicados en relación a la enfermedad por coronavirus 2019 tienen limitaciones y requieren herramientas estadísticas, epidemiológicas y clínicas para poder valorarlas e incorporarlas en la práctica de la medicina basada en evidencias. En esta revisión, analizamos los diferentes diseños de investigación observacionales y con la ayuda de ejemplos veremos los diferentes pasos en el proceso de investigación

Correlation of gene expression and protein production rate - a system wide study

<p>Abstract</p> <p>Background</p> <p>Growth rate is a major determinant of intracellular function. However its effects can only be properly dissected with technically demanding chemostat cultivations in which it can be controlled. Recent work on <it>Saccharomyces cerevisiae </it>chemostat cultivations provided the first analysis on genome wide effects of growth rate. In this work we study the filamentous fungus <it>Trichoderma reesei </it>(<it>Hypocrea jecorina</it>) that is an industrial protein production host known for its exceptional protein secretion capability. Interestingly, it exhibits a low growth rate protein production phenotype.</p> <p>Results</p> <p>We have used transcriptomics and proteomics to study the effect of growth rate and cell density on protein production in chemostat cultivations of <it>T. reesei</it>. Use of chemostat allowed control of growth rate and exact estimation of the extracellular specific protein production rate (SPPR). We find that major biosynthetic activities are all negatively correlated with SPPR. We also find that expression of many genes of secreted proteins and secondary metabolism, as well as various lineage specific, mostly unknown genes are positively correlated with SPPR. Finally, we enumerate possible regulators and regulatory mechanisms, arising from the data, for this response.</p> <p>Conclusions</p> <p>Based on these results it appears that in low growth rate protein production energy is very efficiently used primarly for protein production. Also, we propose that flux through early glycolysis or the TCA cycle is a more fundamental determining factor than growth rate for low growth rate protein production and we propose a novel eukaryotic response to this i.e. the lineage specific response (LSR).</p

Diabetes mellitus tipo 2 y toxicidad por quimioterapia en adultos mayores con cáncer prostático

Introduction: Prostate cancer is considered a predominant type of neoplasia and aging is a factor for chemotherapeutic toxicity, which can increase due to chronic diseases, particularly diabetes. Despite all this knowledge, there are no studies to evaluate the association between diabetes and the risk of chemotherapeutic toxicity in these patients.Objective: To determine the association between Type 2 Diabetes Mellitus and the risk of chemotherapy toxicity in in older adults with prostate cancer in the Geriatric Service of the Peruvian Naval Medical Center.Material and methods: Analytical retrospective cohort study and secondary database analysis.  The adverse effects of chemotherapy and the associated factors of 161 retired sailors with prostate cancer were evaluated between 2013 and 2015. Cox Regression Model for Adjusted Toxicity was constructed for antecedents of diabetes, age, pathological antecedents, smoking antecedents, calf circumference, physical activity, dependence on ABVD, falls, polypharmacy, fragility, and vulnerability.Results: The 23.6% of patients had diabetes. The prevalence of fragility was 39.7% and the one of vulnerability was 24.2% (G8) and 26.71% (VES-13). The frequent adverse effects were: gastrointestinal (13.04%) and hematological (8.07%). The most significant associations by adjusted regression model were the antecedent of Type 2 Diabetes Mellitus, 3 or more pathological antecedents, smoking antecedents, calf circumference, physical activity, dependence on ABVD, falls, polypharmacy, fragility, and vulnerability.Conclusions: The antecedent of Type 2 Diabetes Mellitus is a predictive factor for the risk of chemotherapy toxicity in older adults with prostate cancer.Keywords: Diabetes Mellitus, toxicity, chemotherapy, older adults, cancer, prostate, cohort.Introducción: Siendo el cáncer prostático una neoplasia prevalente, el envejecimiento es un factor para la toxicidad quimioterapéutica, adicionalmente puede incrementarse por enfermedades crónicas, destacando la diabetes. A pesar de estos conocimientos, no hay estudios que evalúen la asociación entre la diabetes y el riesgo de toxicidad quimioterapéutica en estos pacientes. Objetivo: Determinar la asociación entre diabetes mellitus tipo 2 y riesgo de toxicidad por quimioterapia en adultos mayores con cáncer prostático del Servicio de Geriatría del Centro Médico Naval del Perú.Material y métodos: Estudio analítico de cohorte retrospectiva, análisis secundario de una base de datos. Se evaluaron los efectos adversos de quimioterapia y factores asociados de 161 marinos retirados con cáncer prostático entre 2013 y 2015. Se construyó un modelo de regresión de Cox sobre la toxicidad ajustado por el antecedente de diabetes, edad, antecedentes patológicos, antecedentes de consumo de tabaco, circunferencia de pantorrilla, actividad física, dependencia para ABVD, caídas, polifarmacia, fragilidad y vulnerabilidad.Resultados: El 23.6% presentó diabetes. La prevalencia de fragilidad fue del 39.7% y de vulnerabilidad, del 24.2% (G8) y 26.71% (VES-13). Los efectos adversos frecuentes fueron gastrointestinales (13.04%) y hematológicos (8.07%). Mediante el modelo de regresión ajustado, el antecedente de diabetes mellitus tipo 2, 3 o más antecedentes patológicos, antecedente de consumo de tabaco, circunferencia de pantorrilla, actividad física, dependencia de ABVD, caídas, polifarmacia, vulnerabilidad y fragilidad presentaron asociación significativa.Conclusiones: El antecedente de diabetes mellitus tipo 2 es un factor predictivo para el riesgo de toxicidad por quimioterapia en adultos mayores con cáncer prostático

Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection

Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity