Quantifying VMAT2 target occupancy at effective valbenazine doses and comparing to a novel VMAT2 inhibitor: a translational PET study.

Positron emission tomography (PET) is frequently used to obtain target occupancy (%TO) of central nervous system (CNS) drug candidates during clinical development. Obtaining %TO with PET can be particularly powerful when the %TO associated with efficacy is known for a protein target. Using the radiotracer [F]AV-133, the relationship between plasma concentration (PK) and %TO of NBI-750142, an experimental inhibitor of the vesicular monoamine transporter type 2 (VMAT2) was obtained in both nonhuman primate (NHP) and human.

Discovery and clinical translation of ceperognastat, an O-GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease.

Introduction: The aggregation and spread of hyperphosphorylated, pathological tau in the human brain is hypothesized to play a key role in Alzheimer's disease (AD) as well as other neurogenerative tauopathies. O-GlcNAcylation, an important post-translational modification of tau and many other proteins, is significantly decreased in brain tissue of AD patients relative to healthy controls. Increased tau O-GlcNAcylation has been shown to reduce tau pathology in mouse in vivo tauopathy models.

Use of cannabis to manage symptoms of mental and physical health conditions during pregnancy: analysis of a pro-cannabis pregnancy forum.

Introduction: Rates of prenatal cannabis use (PCU) have increased in recent years. Despite evidence of developmental health consequences to offspring and birthing person, there has been a reduction in the perception of PCU-related harms. Due to the stigma and risk of legal consequences associated with disclosing PCU, individuals are often cautious to seek information from their healthcare providers.

Implementation strategies to improve adoption of unmet social needs screening and referrals in care management using enabling technologies: study protocol for a cluster randomized trial.

Background: Adverse social determinants of health contribute to health inequities. Practice guidelines now recommend incorporating patient unmet social needs into patient care, and payors increasingly reimburse for screening and providing related referrals to community organizations. Emergent electronic health record (EHR)-based tools can enable clinical-community linkages, but their adoption commonly faces workflow and infrastructure barriers.

Integrating Social Needs into Health Care: An Implementation Science Perspective.

Unmet social needs (e.g., housing instability, food insecurity, transportation barriers) impact a patient's ability to participate in health-seeking behaviors (e.