Discovery of BI-9508, a Brain-Penetrant GPR88-Receptor-Agonist Tool Compound for Mouse Studies.

Decreased activity and expression of the G-protein coupled receptor GPR88 is linked to many behavior-linked neurological disorders. Published preclinical GPR88 allosteric agonists all have pharmacokinetic properties that preclude their progression to the clinic, including high lipophilicity and poor brain penetration. Here, we describe our attempts to improve GPR88 agonists' drug-like properties and our analysis of the trade-offs required to successfully target GPR88's allosteric pocket.

A master regulator of opioid reward in the ventral prefrontal cortex.

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone.

Development of Gerontological Learning Objectives to Enhance Nursing Educational Curricula.

Background: Many nursing schools are challenged to provide adequate gerontological education to students despite the enormous benefits to students' careers and society. This project developed student learning objectives to be used by nursing faculty to facilitate enriched gerontology courses and program curricula.

Method: The project team drafted a comprehensive list of nursing student learning objectives based on the 2020 Canadian Gerontological Nursing Association Standards of Practice and Competencies and included relevant supportive references.

Does Cardiac Contractility Modulation Therapy Reduce Atrial Fibrillation Burden?

Cardiac contractility modulation (CCM) is an implantable technology approved by the U.S. Food and Drug Administration and intended for heart failure patients without a cardiac resynchronization therapy indication.