Optimization of TopoIV Potency, ADMET Properties, and hERG Inhibition of 5-Amino-1,3-dioxane-Linked Novel Bacterial Topoisomerase Inhibitors: Identification of a Lead with Efficacy against MRSA.

Novel bacterial topoisomerase inhibitors (NBTIs) are among the most promising new antibiotics in preclinical/clinical development. We previously reported dioxane-linked NBTIs with potent antistaphylococcal activity and reduced hERG inhibition, a key safety liability. Herein, polarity-focused optimization enabled the delineation of clear structure-property relationships for both microsomal metabolic stability and hERG inhibition, resulting in the identification of lead compound .

Fatigue failure and success rate of lithium disilicate table-tops as a function of cement thickness.

Purpose Under thin, partial coverage restoration the proper cement thickness to be clinically employed still remains an issue. The aim of this study was to determine the failure and success rates of simplified lithium disilicate occlusal veneers as a function of cement thickness. The null hypothesis was that cement thickness has no effect on the fatigue resistance.

Formulation, Stability, Pharmacokinetic, and Modeling Studies for Tests of Synergistic Combinations of Orally Available Approved Drugs against Ebola Virus In Vivo.

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses.

Assessment of impression material accuracy in complete-arch restorations on four implants.

Statement Of Problem: New polyvinyl siloxane (PVS) materials with enhanced properties have been developed to improve and facilitate implant impression techniques. However, studies on their accuracy are lacking.

Purpose: The purpose of this in vitro study was to determine the accuracy and precision of implant impressions made with some recently introduced materials on a simulated patient requiring an all-on-4 implant-supported prosthesis.

Novel bacterial topoisomerase inhibitors derived from isomannide.

A series of Novel Bacterial Topoisomerase Inhibitors (NBTIs) employing a linker derived from isomannide were synthesized and evaluated. Reduced hERG inhibition was observed compared to structure-matched analogues with different linkers, and compound 6 showed minimal proarrhythmic potential using an in vitro panel of cardiac ion channels. Compound 6 also displayed excellent activity against fluoroquinolone-resistant MRSA (MIC = 2 μg/mL) and other Gram-positive pathogens.