Severe maternal morbidity contributed by obstetric hemorrhage: Maryland, 2020-2022.

Background: Obstetric hemorrhage is the leading cause of maternal mortality and severe maternal morbidity (SMM) in Maryland and nationally. Currently, through a quality collaborative, the state is implementing the Alliance for Innovation on Maternal Health (AIM) patient safety bundle on obstetric hemorrhage.

Objective: To describe SMM events contributed by obstetric hemorrhage and their preventability in Maryland.

Left Ventrolateral Prefrontal Cortical Activity During Reward Expectancy and Mania Risk.

Importance: Mania/hypomania is the pathognomonic feature of bipolar disorder (BD). As BD is often misdiagnosed as major depressive disorder (MDD), replicable neural markers of mania/hypomania risk are needed for earlier BD diagnosis and pathophysiological treatment development.

Objective: To replicate the previously reported positive association between left ventrolateral prefrontal cortex (vlPFC) activity during reward expectancy (RE) and mania/hypomania risk, to explore the effect of MDD history on this association, and to compare RE-related left vlPFC activity in individuals with and at risk of BD.

The CECR2 bromodomain displays distinct binding modes to select for acetylated histone proteins versus non-histone ligands.

The cat eye syndrome chromosome region candidate 2 (CECR2) protein is an epigenetic regulator involved in chromatin remodeling and transcriptional control. The CECR2 bromodomain (CECR2-BRD) plays a pivotal role in directing the activity of CECR2 through its capacity to recognize and bind acetylated lysine residues on histone proteins. This study elucidates the binding specificity and structural mechanisms of CECR2-BRD interactions with both histone and non-histone ligands, employing techniques such as isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) spectroscopy, and a high-throughput peptide assay.

Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.

Malaria remains a serious global health challenge, yet treatment and control programs are threatened by drug resistance. Dihydroorotate dehydrogenase (DHODH) was clinically validated as a target for treatment and prevention of malaria through human studies with DSM265, but currently no drugs against this target are in clinical use. We used structure-based computational tools including free energy perturbation (FEP+) to discover highly ligand efficient, potent, and selective pyrazole-based DHODH inhibitors through a scaffold hop from a pyrrole-based series.