Discovery of Potent and Orally Bioavailable Pyrimidine Amide cGAS Inhibitors via Structure-Guided Hybridization.

Using a high-throughput screening (HTS) approach, a new GTP-site binding pyridine-carboxylate series of cGAS inhibitors was discovered. The biochemical potency of this new pyridine carboxylate series was improved 166-fold from the original hit to double-digit nanomolar levels using structure-based design insights, but the series was found to suffer from low permeability and low bioavailability. A structure-based hybridization of the metal-binding motifs of the pyridine carboxylate series and our previously disclosed tetrahydrocarboline GTP-site ligand identified pyrimidine amide compound .

A comparison of foot fractures relative to other fragility fractures: a review and analysis of the American Orthopaedic Association's Own the Bone Database.

Unlabelled: Evidence regarding the risk factors and characteristics of those with foot fragility fractures compared to non-foot fragility fractures is limited. Foot fragility fracture patients are more likely to be younger female with a higher BMI. A foot fragility fracture is strongly predictive of a subsequent foot fragility fracture.

A Comparison of Ankle Fractures Relative to Other Fragility Fractures: A Review and Analysis of the American Orthopaedic Association's Database.

Background: Ankle fragility fractures (AFX) continue to increase in the elderly population. There is limited knowledge of AFX characteristics compared to nonankle fragility fractures (NAFX). The American Orthopaedic Association's (OTB) is a fragility fracture initiative.

Exposure-Related Anxiety and Improving Patient Satisfaction with Medical Undergarments During Surgery: A Randomized Controlled Trial.

Background: The standard of care for patients undergoing a surgical procedure is to have patients remove all clothing and don a hospital-provided gown. A growing number of patients have anxiety when exposing their bodies in a medical setting, which increases stress for those patients.

Methods: This study prospectively enrolled patients at a single orthopaedic specialty hospital into 1 of 2 garment groups in a block-randomized design.

Implementing stakeholder engagement to explore alternative models of consent: An example from the PREP-IT trials.

Introduction: Cluster randomized crossover trials are often faced with a dilemma when selecting an optimal model of consent, as the traditional model of obtaining informed consent from participant's before initiating any trial related activities may not be suitable. We describe our experience of engaging patient advisors to identify an optimal model of consent for the PREP-IT trials. This paper also examines surrogate measures of success for the selected model of consent.