Asymmetric Synthesis of CIDD-0072424 via an Enantioselective Nitro-Mannich Reaction: A Central Nervous System Penetrant, Selective Small Molecule Inhibitor of Protein Kinase C Epsilon.

CIDD-0072424 is a novel small molecule developed with remarkable activity for the inhibition of protein kinase C (PKC)-epsilon to treat alcohol use disorder. We developed a concise synthesis of ()- that is highly enantioselective, scalable, and amenable for 3-point structure-activity relationship (SAR) studies for compound optimization. The highly enantioselective nitro-Mannich reaction was achieved through a dual-reagent catalysis system.

PM threshold exceedances during the prenatal period and risk of intellectual disability.

Background: Research demonstrates that chronic exposure to fine particulates (PM) increases risks of neurodevelopmental conditions, such as intellectual disability (ID). Few studies have examined neurodevelopmental health impacts of pollution spikes exceeding 24-h (24-h) PM guidelines, despite relevance to the regulatory landscape. The current potential for regulatory changes to 24-h PM standards in the United States makes research on exceedances relevant.

Does Outness Function the Same for All Sexual Minority Youth? Testing Its Associations With Different Aspects of Well-Being in a Sample of Youth With Diverse Sexual Identities.

While research generally supports that greater outness about one's sexual identity is associated with improved well-being, emerging evidence suggests that outness may have negative consequences for bisexual individuals. Yet, few studies have examined sexual identity as a moderator of the associations between outness and well-being, especially among youth. As such, the role of outness in the mental health of diverse sexual minority youth (including pansexual, queer, questioning, and asexual youth) remains unclear.

Chronic alcohol exposure differentially alters calcium activity of striatal cell populations during actions.

Alcohol Use Disorder (AUD) can induce long lasting alterations to executive function. This includes altered action control, which can manifest as dysfunctional goal-directed control. Cortical and striatal circuits mediate goal-directed control over behavior, and prior research has found chronic alcohol disrupts these circuits.