COVID-19 crisis monitor: assessing the effectiveness of exit strategies in the State of São Paulo, Brazil.

As COVID-19-related health indicators improve after restrictive measures were set in place in different parts of the world, governments are expected to guide how to ease interventions while minimizing the risk of resurgent outbreaks. Whereas epidemiologists track the progress of the disease using daily indicators to understand the pandemic better, economic activity indicators are usually available at a lower frequency and with considerable time lags. We propose and implement a timely trade-based regional economic activity indicator (EAI) that uses high-frequency traffic data to monitor daily sectoral economic activity in different sectors for the Brazilian State of São Paulo, a highly impacted region, overcoming the challenge of real-time assessment of the economy amid the COVID-19 outbreak. We then use this novel set of information combined with hospitalization rates to provide a first assessment of the São Paulo Plan, the COVID-19 exit strategy designed to gradually lifting interventions introduced to control the outbreak in the State. Available data show that, in its first 60 days, the phased strategy pursued in São Paulo has been effective in gradually reactivating economic activity while maintaining the adequate responsiveness of the healthcare system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00168-021-01085-8.

The role of triiodothyronine hormone and mechanically-stressed endothelial cell paracrine signalling synergism in gene reprogramming during hBMSC-stimulated osteogenic phenotype in vitro.

We therefore investigated whether there is synergism between triiodothyronine (T3) hormone and trophic molecules released from mechanically-stressed endothelial cells (EC-enriched medium) in osteogenic phenotype by mapping classical repertory of genes. Although there are studies reporting the efficiency of T3 hormone on bone cells, it is scarce considering their effect in conjunction with other physiologically active molecules, such as those released by the active endothelial cells. To address this issue, human bone marrow-derived mesenchymal stem cells (hBMSCs) were treated with EC-enriched medium subjected to shear-stress up to 72 h in vitro, in conjunction or not with T3 hormone. Although our results found an important synergism considering these parameters on modulating key bone-related gene markers, such as on the alkaline phosphatase (ALP) behavior (at both mRNA and protein content), contributing for osteoblast differentiation, important genes such as OSTERIX and RUNX2 were significantly down-expressed, while a over-expression of RANKL was found when the conjunction effect of T3 and endothelial paracrine signaling was considered. In addition, T3 hormone over expressed both OCT4 and NANOG genes in a DNA epigenetic-independent manner. However, we observed a dynamic reprogramming of DNMT1, DNMT3A, DNMT3B and TET1, important DNA-related epigenetic markers. Specifically, T3 hormone alone up-modulated TET2 transcripts profile. Complimentarily, expression of microRNA (miRs) processing-related genes also was modulated, as well as miR-10b, miR-22, miR-21, miR-143 and miR-145 transcriptional related profiles. Altogether, our results suggested a positive effect of mechanically-stressed endothelial cells-induced paracrine signaling on T3 hormone-obtaining osteogenic phenotype, contributing to understanding the paradoxal effect of T3 hormone on the bone physiology.