Covalent hits and where to find them.

Covalent hits for drug discovery campaigns are neither fantastic beasts nor mythical creatures, they can be routinely identified through electrophile-first screening campaigns using a suite of different techniques. These include biophysical and biochemical methods, cellular approaches, and DNA-encoded libraries. Employing best practice, however, is critical to success.

Ruggedized Self-Propelling Hemostatic Gauze Delivers Low Dose of Thrombin and Systemic Tranexamic Acid and Achieves High Survival in Swine With Junctional Hemorrhage.

Introduction: Hemorrhage is responsible for 91% of preventable prehospital deaths in combat. Bleeding from anatomic junctions such as the groin, neck, and axillae make up 19% of these deaths, and reports estimate that effective control of junctional hemorrhage could have prevented 5% of fatalities in Afghanistan. Hemostatic dressings are effective but are time-consuming to apply and are limited when proper packing and manual pressure are not feasible, such as during care under fire.

Does pharyngoplasty work? Outcomes of 100 consecutive operations over 10 years.

Background: Velopharyngeal insufficiency is a commonly encountered problem in Cleft Surgery, with pharyngoplasty being the mainstay of surgical management. In this study we aim to investigate the indications and outcomes of a single institution's experience and compare to international literature.

Methods: A retrospective review was performed looking at over 100 consecutive primary pharyngoplasty operations for velopharyngeal dysfunction over a 10-year period at a single institution.

A perspective on the discovery of enzyme activators.

Enzyme activation remains a largely under-represented and poorly exploited area of drug discovery despite some key literature examples of the successful application of enzyme activators by various mechanisms and their importance in a wide range of therapeutic interventions. Here we describe the background nomenclature, present the current position of this field of drug discovery and discuss the challenges of hit identification for enzyme activation, as well as our perspectives on the approaches needed to overcome these challenges in early drug discovery.