Discovery of VU0467319: an M Positive Allosteric Modulator Candidate That Advanced into Clinical Trials.

Herein we detail the of VU0467319 (VU319), an M Positive Allosteric Modulator (PAM) clinical candidate that successfully completed a Phase I Single Ascending Dose (SAD) clinical trial. VU319 () is a moderately potent M PAM (M PAM EC = 492 nM ± 2.9 nM, 71.

Dupilumab improves sense of smell and clinical outcomes in patients with severe chronic rhinosinusitis with nasal polyps with anosmia.

Objective: Loss of sense of smell is a cardinal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP) and significantly impacts health-related quality-of-life. Dupilumab significantly improved smell outcomes (loss of smell [LoS] score; University of Pennsylvania Smell Identification Test [UPSIT]) versus placebo in the phase 3 SINUS-24/-52 studies (clinicaltrials.gov, NCT02898454/NCT02912468) in patients with severe CRSwNP.

The sclerotome is the source of the dorsal and anal fin skeleton and its expansion is required for median fin development.

Paired locomotion appendages are hypothesized to have redeployed the developmental program of median appendages, such as the dorsal and anal fins. Compared with paired fins, and limbs, median appendages remain surprisingly understudied. Here, we report that a dominant zebrafish mutant, smoothback (smb), fails to develop a dorsal fin.

Self-Induced Nasal Septal Perforation: Rhinotillexomania-A Different Entity From Nose Picking.

Background: Nose picking is a common habit that rarely leads to mutilating self-injury. It is important to distinguish between rhinotillexomania (compulsive nose picking) as a disease and nose picking that results in or contributes to nasal septal perforation (NSP). The aim of this study is to investigate the impact of rhinotillexomania and NSP repair on sinonasal symptoms and quality of life (QoL).