Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

Sequential Chikungunya and Zika Virus Infections in a Traveler from Honduras.

Zika virus (ZIKV) and chikungunya virus (CHIKV) are currently circulating in overlapping areas in the American continents and may both be transmitted by Aedes spp. mosquitoes. The first documented case, to the authors' knowledge, of sequential CHIKV and ZIKV infections diagnosed in a nonendemic area in a returning traveler is reported. The implications for heightened clinical surveillance for these infections and specific patient recommendations are emphasized.

Descripción anatómica de un aneurisma de la aorta abdominal postmortem / Anatomic description of an abdominal aorta postmortemaneurism

Un aneurisma es una dilatación de las paredes de una arteria10. Un aneurisma de aorta abdominal (AAA) es una dilatación de la aorta mayor a 3.0 cm de diámetro². Dicha dilatación se encuentra en el abdomen a nivel de la cicatriz umbilical, anterior a la columna vertebral6. Se ha encontrado, por medio de estudios ultrasonográfico, que el 5% de los hombres mayores de 65 años tienen un aneurisma oculto que mide de 3 a 5 cm de diámetro. Si bien hasta la actualidad no existe un consenso general de cómo definir a un aneurisma de la aorta abdominal, la mayoría de los autores revisados lo define como una dilatación con un diámetro igual o mayor a 3.0 cm8. Su importancia radica principalmente en el gran número de casos no diagnosticados y las consecuencias fatales que pueden ocurrir en ausencia de un adecuado tratamiento, en la mayoría asociados con un aumento crónico de la tensión arterial. 2,3 Presentamos en el siguiente caso la descripción de un aneurisma abdominal postmortem, correspondiente a un individuo de sexo masculino de 77 años, de procedencia mexicana, cuya causa de defunción fue infarto agudo al miocardio.

An aneurism is an expansion of the walls of an artery; an aneurism of abdominal aorta is a dilatation of the greater aorta with more than 3.0 cm. in diameter. This dilatation is in the abdomen, located deeply from the umbilical scar, anterior to the vertebral column. Ultrasonographic screening studies show that 5% of men above 65 years old have an occult aneurysm, measuring 3 to 5 cm in diameter. Although there is no general consensusup to date on how to define an aneurysm of the abdominal aorta, the majority of the reviewed authors define it as a dilatation with a diameter of 3.0 cm or more. Its relevance consists of the large number of undetected cases and its fatal consequences when untreated, mostly associated with a chronic elevation of the arterial pressure. We presentin the following casea description of a postmortem abdominal aneurism, corresponding to a 77 year-old Mexican male, whose cause of death was myocardialinfarction.

Bacterias con alta tasa de mutación: los riesgos de una vida acelerada / High mutation rate bacteria: Risks of a high-speed life

El proceso evolutivo de un ser vivo se acelera cuanto mayor sea su capacidad para producir variabilidad genética, bien por mutación, bien por recombinación.Sin embargo, cuanto mayor sea esta capacidad, mayor también será el riesgo de acumular mutaciones deletéreas. La variabilidad genética es, por tanto, un proceso altamente regulado, de tal manera que las bacterias tienden a mantener una baja tasa de mutación. En diferentes poblaciones bacterianas analizadas hay siempre un porcentaje variable de cepas con una tasa de mutación superior a la frecuencia modal del resto de la población. Existe una relación directa entre la proporción de cepas que mutan y el grado de estrés del ambiente. Así, en los procesos infecciosos crónicos, en los que el tratamiento antibiótico es constante durante períodos prolongados, se observan los mayores porcentajes de bacterias que mutan, cercano al 50 por ciento de la población. Esta selección positiva de bacterias que mutan es debida al enorme potencial que presentan para desarrollar resistencia antibiótica (100 veces superior a una bacteria normal). Esta capacidad ha sido explotada, en algunos centros de investigación, como un modelo natural de evolución acelerada para predecir la facilidad con la que determinadas variantes resistentes pueden aparecer, saber qué posiciones serán las más susceptibles a los cambios y cuál será el costo para la bacteria. El laboratorio de microbiología debe hacer un esfuerzo por detectar estas cepas mutadoras antes de que desarrollen mecanismos de resistencia e induzcan el fracaso terapéutico

The potential of producing genetic variability, eitherby mutation or by recombination, is the driving for-ce of evolution in a living organism. Geneticvariability is a quite regulated process in which bac-teria tend to maintain a low mutation rate. However,a variable proportion of bacteria with a highermutation rate than that of the modal is alwayspresent in any population. Moreover, a direct rela-tionship exists between the proportion of mutatorstrains and environmental stress. In chronicinfectious diseases, due to prolonged antibioticregimens, nearly 50% of the population may berepresented by mutating bacteria. Such a positiveselection is due to the capacity of this type of strainsto develop antibiotic resistance (100 fold higherthan normal bacteria) This trait has been used asan accelerated-evolution model to predict the easeof certain resistant variants to emerge as well asto infer which targets are more prone to bemodified and the concomitant cost that suchvariability would imply to the organism.The Microbiology laboratory might then doan effort to detect mutating strains before theappearance of resistance mechanisms that maylead to therapeutic failures.Keywords: evolution, genetic recombination,mutagenesis, bacterial drug resistance.Fecha de recepción