Stereodivergent Synthesis of the Vicinal Difluorinated Tetralin of Casdatifan Enabled by Ru-Catalyzed Transfer Hydrogenation.

We disclose a stereodivergent strategy to prepare difluorinated tetralins from γ-substituted tetralones via a combination of catalyst-controlled transfer hydrogenation and substrate-controlled fluorinations. This process is easily scalable and amenable to highly functionalized substrates, as demonstrated here in the late-stage synthesis of casdatifan, a clinical-stage inhibitor of hypoxia-inducible factor-2α. Analysis of the physicochemical properties of casdatifan, which features a difluoride, revealed a higher level of facial polarization compared to its difluoride isomers.

C7-T1 Full-Endoscopic Posterior Foraminotomy and Sequestrectomy Using Navigation.

The main objective of this case and video is to demonstrate the surgical technique of navigated full-endoscopic decompression and sequestrectomy at the C7-T1 level to alleviate C8 nerve root compression and manage cervicobrachialgia. Cervicobrachialgia resulting from C7-T1 disc herniation is a quite rare yet painful condition that can significantly impair motor function in the upper limb. Traditionally, open surgeries can be invasive, with prolonged recovery times and/or fusion of the level with adjacent segment disease.

Cerebral oxidative stress, inflammation and apoptosis induced by intermittent hypoxia: a systematic review and meta-analysis of rodent data.

Obstructive sleep apnoea (OSA) contributes to cerebrovascular diseases and cognitive decline. Preclinical studies support the deleterious impact on the brain of intermittent hypoxia (IH), one of the main components of OSA, but heterogeneity in rodent species and brain regions studied, or induced by IH paradigms, can challenge interpretation of the studies. Hence, we conducted a systematic review and meta-analysis to evaluate the impact of IH on rodent brain oxidative stress, inflammation, apoptosis and the expression of brain-derived neurotrophic factor (BDNF) and hypoxia-inducible factor 1 (HIF-1).

Effect of a Feedback Visit and a Clinical Decision Support System Based on Antibiotic Prescription Audit in Primary Care: Multiarm Cluster-Randomized Controlled Trial.

Background: While numerous antimicrobial stewardship programs aim to decrease inappropriate antibiotic prescriptions, evidence of their positive impact is needed to optimize future interventions.

Objective: This study aimed to evaluate 2 multifaceted antibiotic stewardship interventions for inappropriate systemic antibiotic prescription in primary care.

Methods: An open-label, cluster-randomized controlled trial of 2501 general practitioners (GPs) working in western France was conducted from July 2019 to January 2021.