Organotin pollution at Arraial do Cabo, Rio de Janeiro State, Brazil: increasing levels after the TBT ban

O imposex, um fenômeno de desregulação endócrina, é um biomarcador da exposição ao tributilestanho (TBT) em populações de gastrópodes marinhos. A ocorrência e intensidade dessa síndrome nas populações do neogastrópode Stramonita haemastoma foram verificadas em nove estações amostrais em outubro de 2008 em Arraial do Cabo, uma área de grande importância turística no Rio de Janeiro (Brasil) e integrante da Reserva Extrativista Marinha de Arraial do Cabo. Com os resultados obtidos foi possível avaliar as alterações ocorridas desde o último biomonitoramento realizado em 2001, nessas mesmas estações. Mesmo após o banimento do TBT pela Marinha do Brasil em 2003, a entrada em vigor dos controles ao uso deste agente com o estabelecimento da NORMAM 23, no Brasil em 2007 pela Marinha, e o banimento completo do TBT nas fórmulas de tintas antiincrustantes pela IMO em escala global, em 2008, o imposex continua a ser detectado. Ao invés de um declínio esperado, observou-se um aumento da extensão das áreas afetadas pelo imposex. Além disso, observou-se a ausência de populações em áreas que em 2001 estavam gravemente afetadas pelo imposex. Esses resultados sugerem um aumento da poluição por TBT na área de estudo, indicando a ineficácia das medidas legislativas.Imposex, an endocrine disruption phenomenon, is a biomarker of tributyltin (TBT) exposure in marine gastropod populations. The occurrence and intensity of the syndrome in populations of the neogastropod Stramonita haemastoma were ascertained at nine sampling stations in October 2008 at Arraial do Cabo, a very important tourist resort in Rio de Janeiro state (Brazil) and part of the Marine Extractive Reserve of Arraial do Cabo. The results obtained made it possible to evaluate the changes which had occurred since the last biomonitoring campaign, undertaken in 2001, at these same stations. Despite the ban on the use of TBT imposed by the Brazilian Navy in 2003, the controls on the use of this agent in Brazil resulting from the establishment of NORMAM 23 by the Navy in 2007 and the complete ban of organotin compounds in antifouling paint formulae by the IMO on a global scale in 2008, imposex was still detected. Instead of the expected reduction, an increase was observed in the areas affected by imposex. Furthermore, populations in the areas seriously affected by imposex in 2001 were absent in the 2008 sampling campaign. These results suggest an increase in TBT pollution in the study area, indicating the inefficacy of legislative measures

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease