A role for plasma membrane Ca ATPases in regulation of cellular Ca homeostasis by sphingosine kinase-1.

Sphingosine-1-phosphate (S1P) is a ubiquitous lipid mediator, acting via specific G-protein-coupled receptors (GPCR) and intracellularly. Previous work has shown that deletion of S1P lyase caused a chronic elevation of cytosolic [Ca] and enhanced Ca storage in mouse embryonic fibroblasts. Here, we studied the role of sphingosine kinase (SphK)-1 in Ca signaling, using two independently generated EA.

WWC2 modulates GABA-receptor-mediated synaptic transmission, revealing class-specific mechanisms of synapse regulation by WWC family proteins.

The WW and C2 domain-containing protein (WWC2) is implicated in several neurological disorders. Here, we demonstrate that WWC2 interacts with inhibitory, but not excitatory, postsynaptic scaffolds, consistent with prior proteomic identification of WWC2 as a putative component of the inhibitory postsynaptic density. Using mice lacking WWC2 expression in excitatory forebrain neurons, we show that WWC2 suppresses γ-aminobutyric acid type-A receptor (GABAR) incorporation into the plasma membrane and regulates HAP1 and GRIP1, which form a complex promoting GABAR recycling to the membrane.

A machine learning technology for addressing medication-related risk in older, multimorbid patients.

Objectives: To evaluate the FeelBetter machine learning system's ability to accurately identify older patients with multimorbidity at Brigham and Women's Hospital at highest risk of medication-associated emergency department (ED) visits and hospitalizations, and to assess the system's ability to provide accurate medication recommendations for these patients.

Study Design: Retrospective cohort study.

Methods: The system uses medications, demographics, diagnoses, laboratory results, health care utilization patterns, and costs to stratify patients' risk of ED visits and hospitalizations.

Straight to the point: evaluation of a Point of Care Information (POCI) resource in answering disease-related questions.

Objective: To evaluate the ability of DynaMedex, an evidence-based drug and disease Point of Care Information (POCI) resource, in answering clinical queries using keyword searches.

Methods: Real-world disease-related questions compiled from clinicians at an academic medical center, DynaMedex search query data, and medical board review resources were categorized into five clinical categories (complications & prognosis, diagnosis & clinical presentation, epidemiology, prevention & screening/monitoring, and treatment) and six specialties (cardiology, endocrinology, hematology-oncology, infectious disease, internal medicine, and neurology). A total of 265 disease-related questions were evaluated by pharmacist reviewers based on if an answer was found (yes, no), whether the answer was relevant (yes, no), difficulty in finding the answer (easy, not easy), cited best evidence available (yes, no), clinical practice guidelines included (yes, no), and level of detail provided (detailed, limited details).