Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs

In order to understand the role of microRNAs (miRNAs) in vascular physiopathology, we took advantage of deep-sequencing techniques to accurately and comprehensively profile the entire miRNA population expressed by endothelial cells exposed to hypoxia. SOLiD sequencing of small RNAs derived from human umbilical vein endothelial cells (HUVECs) exposed to 1% O or normoxia for 24 h yielded more than 22 million reads per library. A customized bioinformatic pipeline identified more than 400 annotated microRNA/ microRNA*species with a broad abundance range: miR-21 and miR-126 totaled almost 40% of all miRNAs. A complex repertoire of isomiRs was found, displaying also 5′ variations, potentially affecting target recognition. Highstringency bioinformatic analysis identified microRNA candidates, whose predicted pre-miRNAs folded into a stable hairpin. Validation of a subset by qPCR identified 18 high-confidence novel miRNAs as detectable in independent HUVEC cultures and associated to the RISC complex. The expression of two novel miRNAs was significantly down-modulated by hypoxia, while miR- 210 was significantly induced. Gene ontology analysis of their predicted targets revealed a significant association to hypoxiainducible factor signaling, cardiovascular diseases, and cancer. Overexpression of the novel miRNAs in hypoxic endothelial cells affected cell growth and confirmed the biological relevance of their down-modulation. In conclusion, deep-sequencing accurately profiled known, variant, and novel microRNAs expressed by endothelial cells in normoxia and hypoxia

Delirium symptoms duration and mortality in SARS-COV2 elderly: results of a multicenter retrospective cohort study

BACKGROUND: Since the occurrence of the SARS-COV2 pandemic, there has been an increasing interest in investigating the epidemiology of delirium. Delirium is frequent in SARS-COV2 patients and it is associated with increased mortality; however, no information is available on the association between delirium duration in SARS-COV2 patients and related outcomes. AIMS: The aim of this study is to investigate the association between the duration of delirium symptoms and in-hospital mortality in older patients with SARS-COV2 infection. METHODS: Retrospective cohort study of patients 65 years of age and older with SARS-CoV 2 infection admitted to two acute geriatric wards and one rehabilitation ward. Delirium symptoms duration was assessed retrospectively with a chart-based validated method. In-hospital mortality was ascertained via medical records. RESULTS: A total of 241 patients were included. The prevalence of delirium on admission was 16%. The median number of days with delirium symptoms was 4 (IQR 2–6.5) vs. 0 (IQR 0–2) in patients with and without delirium on admission. In the multivariable Cox regression model, each day with a delirium symptom in a patient with the same length of stay was associated with a 10% increase in in-hospital mortality (Hazard ratio 1.1, 95% Confidence interval 1.01–1.2; p = 0.03). Other variables associated with increased risk of in-hospital death were age, comorbidity, CPAP, CRP levels and total number of drugs on admission. CONCLUSIONS: The study supports the necessity to establish protocols for the monitoring and management of delirium during emergency conditions to allow an appropriate care for older patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40520-021-01899-8