A series of small-molecule full agonists of the prostaglandin E type 4 (EP) receptor have been generated and evaluated for binding affinity and cellular potency. KMN-80 and its gem-difluoro analog KMN-159 possess high selectivity relative to other prostanoid receptors. Difluoro substitution is positioned alpha to the lactam ring carbonyl and results in KMN-159's fivefold increase in potency versus KMN-80.
View Article and Find Full Text PDFThe decision to introduce canines (K9s) to a law enforcement (LE) agency does not typically involve the evaluation of the fiscal or clinical impact on local hospitals. This study compared injury, cost, and care associated with K9s to a common nonlethal force method, the Thomas A Swift Electrical Rifle (TASER), to highlight the cost and resources required to treat both patient types. Patients treated for LE-related K9 and TASER injuries at a Level I community-based trauma center (2011-2016) were evaluated for level of care required (, surgeon/specialist), clinical interventions, proxy medical costs, and length of stay (LOS).
View Article and Find Full Text PDFAutism spectrum disorder in children is a group of neurodevelopmental disorders characterized by difficulties with social communication and behavior. Growing scientific evidence in addition to clinical practice has led the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to categorize several disorders into the broader category of autism spectrum disorder. As more is learned about how autism spectrum disorder manifests, progress has been made toward better clinical management including earlier diagnosis, care, and when specific interventions are required.
View Article and Find Full Text PDFDuring mitosis in budding yeast, cortically anchored dynein generates pulling forces on astral microtubules to position the mitotic spindle across the mother-bud neck. The attachment molecule Num1 is required for dynein anchoring at the cell membrane, but how Num1 assembles into stationary cortical patches and interacts with dynein is unknown. We show that an N-terminal Bin/Amphiphysin/Rvs (BAR)-like domain in Num1 mediates the assembly of morphologically distinct patches and its interaction with dynein for spindle translocation into the bud.
View Article and Find Full Text PDF