Rescue of Familial Lecithin:Cholesterol Acyltranferase Deficiency Mutations with an Allosteric Activator.

Lecithin:cholesterol acyltransferase (LCAT) deficiencies represent severe disorders characterized by aberrant cholesterol esterification in plasma, leading to life-threatening conditions. This study investigates the efficacy of Compound 2, a piperidinyl pyrazolopyridine allosteric activator that binds the membrane-binding domain of LCAT, in rescuing the activity of LCAT variants associated with disease. The variants K218N, N228K, and G230R, all located in the cap and lid domains of LCAT, demonstrated notable activity restoration in response to Compound 2.

Early Lessons From Implementation of Holistic Review for Pediatric Surgery Fellowship Applicants.

Purpose: Holistic review (HR) considers applicants' unique identities and experiences rather than focusing on academic metrics. Though several residency programs have demonstrated increases in women and those underrepresented in medicine (URiM), this is the first study to examine HR in pediatric surgery (PS).

Methods: Using a retrospective review of applicants, demographic, academic, and non-academic metrics of traditional review (TR) [2015-2017] were compared to HR [2018-2022].