A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-Cell Fusion

10.1371/journal.ppat.1003297PLoS Pathogens94

Effects of nanosuspension and inclusion complex techniques on the in vitro protease inhibitory activity of naproxen

This study investigated the effects of nanosuspension and inclusion complex techniques on in vitro trypsin inhibitory activity of naproxen—a member of the propionic acid derivatives, which are a group of antipyretic, analgesic, and non-steroidal anti-inflammatory drugs. Nanosuspension and inclusion complex techniques were used to increase the solubility and anti-inflammatory efficacy of naproxen. The evaporative precipitation into aqueous solution (EPAS) technique and the kneading methods were used to prepare the nanosuspension and inclusion complex of naproxen, respectively. We also used an in vitro protease inhibitory assay to investigate the anti-inflammatory effect of modified naproxen formulations. Physiochemical properties of modified naproxen formulations were analyzed using UV, IR spectra, and solubility studies. Beta-cyclodextrin inclusion complex of naproxen was found to have a lower percentage of antitryptic activity than a pure nanosuspension of naproxen did. In conclusion, nanosuspension of naproxen has a greater anti-inflammatory effect than the other two tested formulations. This is because the nanosuspension formulation reduces the particle size of naproxen. Based on these results, the antitryptic activity of naproxen nanosuspension was noteworthy; therefore, this formulation can be used for the management of inflammatory disorders

SL(2,Z) symmetries, Supermembranes and Symplectic Torus Bundles

We give the explicit formulation of the 11D supermembrane as a symplectic torus bundle with non trivial monodromy and non vanishing Euler class. This construction allows a classification of all supermembranes showing explicitly the discrete SL(2,Z) symmetries associated to dualities. It hints as the origin in M-theory of the gauging of the effective theories associated to string theories.Comment: 13 pages, Late

Controle alternativo de podridões pós‑colheita de framboesas

O objetivo deste trabalho foi avaliar o efeito de tratamentos pré-colheita sobre a ocorrência de podridões pós-colheita e sobre os atributos de qualidade de framboesas (Rubus idaeus L.) 'Heritage'. As frutas foram pulverizadas com um dos seguintes tratamentos: água destilada (controle), 6 g L-1 de quitosana, 100 mg L-1 de dióxido de cloro, Bacillus amyloliquefaciens, Curtobacterium pusillum ou Saccharomyces cerevisiae. Foram realizadas colheitas aos 3, 7 e 14 dias após a aplicação dos tratamentos. Após cada uma das colheitas, realizadas no estádio de maturação comercial (coloração rosa), as frutas foram inoculadas individualmente com suspensão de conídios (2x10(5) conídios mL-1) de Botrytis cinerea ou Rhizopus stolonifer. As frutas foram mantidas a 12±0,5ºC por sete dias e avaliadas quanto à incidência de podridões e quanto aos principais atributos de qualidade. Bacillus amyloliquefaciens, C. pusillum e S. cerevisiae proporcionaram menor área abaixo da curva de progresso da incidência das podridões por Botrytis e Rhizopus. Os agentes de controle biológico avaliados não interferem negativamente sobre os atributos de qualidade das frutas, e, portanto, são alternativas potenciais no controle de podridões pós-colheita de framboesas

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