Discovery, synthesis and SAR of 2-acyl-1-biarylmethyl pyrazolidines, dual orexin receptor antagonists designed as fast and short-acting sleeping drugs.

Dual orexin receptor antagonists (DORAs) are approved for the treatment of sleep onset and/or sleep maintenance insomnia. In the present disclosure, we report the discovery of a new class of DORAs designed to treat sleep disorders requiring a fast onset and a short duration of action (<4 h). We used early human pharmacokinetic-pharmacodynamic (PK-PD) predictions and in vivo experiments to identify DORAs eliciting this specific hypnotic profile.

Vulnerability and coping strategies within wild meat trade networks during the COVID-19 pandemic.

Measures adopted to prevent the spread of COVID-19 and economic shocks caused by the pandemic have affected food networks globally, including wild meat trade networks that support the livelihoods and food security of millions of people around the world. In this article, we examine how COVID-related shocks have affected the vulnerability and coping strategies of different actors along wild meat trade networks. Informed by 1,876 questionnaires carried out with wild meat hunters, traders, vendors, and consumers in Cameroon, Colombia, Democratic Republic of Congo (DRC), and Guyana, the article presents qualitative evidence as to how COVID-19 impacted different segments of society involved in wild meat trade networks.

Understanding Factors that Shape Exposure to Zoonotic and Food-Borne Diseases Across Wild Meat Trade Chains.

The rise of zoonotic disease-related public health crises has sparked calls for policy action, including calls to close wildlife markets. Yet, these calls often reflect limited understanding of where, precisely, exposure to risk occurs along wildlife and wild meat trade chains. They also threaten to negatively impact food security and livelihoods.

Six-month change in gait speed to discriminate between those with and without falls history in older people with Mild Cognitive Impairment and mild Alzheimer disease.

The purposes of this study were to identify differences in gait speed performance over 6 months between older people with Preserved Cognition (PrC), with Mild Cognitive Impairment (MCI) and with Alzheimer disease (AD) in mild stage; and to verify if the change in gait speed could discriminate fallers in older people with MCI and AD in a mild stage METHODS: A longitudinal study was conducted with community-dwelling older adults, including 40 with PrC, 36 with MCI and 34 with AD in the mild stage. Gait speed (in m/s) changes were captured through a 10-meter walk test. We documented the number of self-reported falls by monthly calendars that were returned after a 6-month follow-up.

Monitoring weekly progress of front crawl swimmers using IMU-based performance evaluation goal metrics.

Technical evaluation of swimming performance is an essential factor in preparing elite swimmers for their competitions. Inertial measurement units (IMUs) have attracted much attention recently because they can provide coaches with a detailed analysis of swimmers' performance during training. A coach can obtain a quantitative and objective evaluation from IMU.