A Selection Protocol to Identify Therapeutics to Target NLRP3-Associated Sensory Hearing Loss.

Objective: We propose a selection process to identify a small molecule inhibitor to treat NLRP3-associated sensory hearing loss.

Background: The NLRP3 inflammasome is an innate immune sensor and present in monocytes and macrophages. Once the inflammasome is activated, a cleavage cascade is initiated leading to the release of proinflammatory cytokines IL-1β and IL-18.

Localized application of SAG21k-loaded fibrin hydrogels for targeted modulation of the hedgehog pathway in facial nerve injury.

Given the broad biological effects of the Hedgehog (Hh) pathway, there is potential clinical value in local application of Hh pathway modulators to restrict pathway activation of target tissues and avoid systemic pathway activation. One option to limit Hh pathway activation is using fibrin hydrogels to deliver pathway modulators directly to tissues of interest, bypassing systemic distribution of the drug. In this study, we loaded the potent Hh pathway agonist, SAG21k, into fibrin hydrogels.

Eradication of Bacterial Persister Cells By Leveraging Their Low Metabolic Activity Using Adenosine Triphosphate Coated Gold Nanoclusters.

Bacteria first develop tolerance after antibiotic exposure; later genetic resistance emerges through the population of tolerant bacteria. Bacterial persister cells are the multidrug-tolerant subpopulation within an isogenic bacteria culture that maintains genetic susceptibility to antibiotics. Because of this link between antibiotic tolerance and resistance and the rise of antibiotic resistance, there is a pressing need to develop treatments to eradicate persister cells.

Povidone-Iodine Fails to Eradicate Chronic Suppurative Otitis Media and Demonstrates Ototoxic Risk in Mice.

Hypothesis: Commercially available povidone-iodine solution can eliminate biofilms and persister cells rapidly in in vivo achievable concentrations without inducing ototoxicity.

Background: Chronic suppurative otitis media (CSOM) is a substantial global problem. Current treatment options often induce a temporary remission without leading to a permanent cessation of symptoms secondary to the treatments' inability to eliminate persister cells.

Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss.

Background: Chronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model.