Hearing impairment as an unusual presenting sign of meningoencephalitis.

Hearing loss is an unusual presenting feature of meningoencephalitis. Two cases of HIV-negative patients who presented with hearing loss are discussed and a literature review of published cases was conducted. Possible mechanisms for hearing loss with infection are explored.

Medical students' perceptions and expectations regarding digital health education and training: A qualitative study.

Introduction: Digital health - the convergence of digital technologies within health and health care to enhance the efficiency of health-care delivery - is fast becoming an integral part of routine medical practice. The integration of digital health into traditional practice brings significant changes. Logic dictates that for medical practitioners to operate in this new digitally enabled environment, they require specific knowledge, skills and competencies relating to digital health.

Development of Human in vitro Brain-blood Barrier Model from Induced Pluripotent Stem Cell-derived Endothelial Cells to Predict the in vivo Permeability of Drugs.

An in vitro blood-brain barrier (BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system. Though many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug transport.

Quantitative Algorithm-Based Paired Imaging Measurement for Antibody-Triggered Endocytosis in Cultured Cells.

Antibody-triggered endocytosis (ATE) is a biological mechanism on which many therapeutic strategies are grounded, such as delivery of antibody-drug conjugates (ADCs). Current methods monitoring ATE include confocal Z-stack analysis, acid wash, antibody quenching, and pH-sensitive dye labeling. However, those generate less quantifiable results with low throughput.

Discovery of Novel 1-Cyclopentenyl-3-phenylureas as Selective, Brain Penetrant, and Orally Bioavailable CXCR2 Antagonists.

CXCR2 has emerged as a therapeutic target for not only peripheral inflammatory diseases but also neurological abnormalities in the central nervous system (CNS). Herein, we describe the discovery of a novel 1-cyclopentenyl-3-phenylurea series as potent and CNS penetrant CXCR2 antagonists. Extensive SAR studies, wherein molecules' property forecast index (PFI) was carefully optimized for overall balanced developability profiles, led to the discovery of the advanced lead compound 68 with a desirable PFI.

Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders.

Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-induced demyelination model with twice daily oral administration, thereby supporting CXCR2 to be a potential therapeutic target for the treatment of demyelinating diseases such as multiple sclerosis.