Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery

Antarctic marine chemical ecology: what is next?

71 páginas, 1 tabla, 3 figuras.Antarctic ecosystems are exposed to unique environmental characteristics resulting in communities structured both by biotic interactions such as predation and competition, as well as abiotic factors such as seasonality and ice-scouring. It is important to understand how ecological factors may trigger chemical mechanisms in marine Antarctic organisms as a response for survival. However, very little is known yet about the evolution of chemical compounds in Antarctic organisms. Investigations in chemical ecology have demonstrated over the last several years that defensive metabolites have evolved in numerous representative Antarctic species. This contradicts earlier theories concerning biogeographic variation in predation and chemical defenses. As reviewed here, a number of interesting natural products have been isolated from Antarctic organisms. However, we believe many more are still to be discovered. Currently, many groups such as microorganisms, planktonic organisms and deepsea fauna remain almost totally unknown regarding their natural products. Furthermore, for many described compounds, ecological roles have yet to be evaluated. In fact, much of the research carried out to date has been conducted in the laboratory, and only in a few cases in an ecologically relevant context. Therefore, there is a need to extend the experiments to the field, as done in tropical and temperate marine ecosystems, or at least, to test the activity of the chemicals in natural conditions and ecologically meaningful interactions. Defense against predators is always one of the main topics when talking about the roles of natural products in species interactions, but many other interesting aspects, such as competition, chemoattraction, fouling avoidance and ultraviolet (UV) protection, also deserve further attention. In our opinion, challenging future developments are to be expected for Antarctic marine chemical ecology in the years to come.This work would not have been possible without the financial support of the Ministry of Science and Education of Spain through different grants along recent years in the general frame of our ECOQUIM projects (ANT97-1590-E, ANT97-0273, REN2002-12006-E ⁄ANT, REN2003-00545 and CGL2004- 03356 ⁄ANT).Peer reviewe