Integrating Prolonged Field Care Into Rough Terrain and Mountain Warfare Training: The Mountain Critical Care Course.

Current prolonged field care (PFC) training routinely occurs in simulated physical locations that force providers to continue care until evacuation to definitive care, as based on the staged Ruck-Truck-House-Plane model. As PFC-capable teams move further forward into austere environments in support of the fight, they are in physical locations that do not fit this staged model and may require teams to execute their own casualty evacuation through rough terrain. The physical constraints that come specifically with austere, mountainous terrain can challenge PFC providers to initiate resuscitative interventions and challenge their ability to sustain these interventions during lengthy, dismounted movement over unimproved terrain. In this brief report, we describe our experience with a novel training course designed for PFC-capable medical teams to integrate their level of advanced resuscitative care within a mountainous, rough terrain evacuation-training program. Our goals were to identify training gaps for Special Operations Forces medical units tasked to operate in a cold-weather, mountain environment with limited evacuation resources and the challenges related to maintaining PFC interventions during dismounted casualty movement.

Synthesis of natural product-inspired inhibitors of Mycobacterium tuberculosis mycothiol-associated enzymes: the first inhibitors of GlcNAc-Ins deacetylase.

Synthesis and evaluation of a chemical library of inhibitors of the mycothiol biosynthesis enzyme GlcNAc-Ins deacetylase (MshB) and the mycothiol-dependent detoxification enzyme mycothiol- S-conjugate amidase (MCA) from Mycobacterium tuberculosis are reported. The library was biased to include structural features of a group of natural products previously shown to competitively inhibit MCA. Molecular docking studies that reproducibly placed the inhibitors in the active site of the enzyme MshB reveal the mode of binding and are consistent with observed biological activity.

Synthesis of a bromotyrosine-derived natural product inhibitor of mycothiol-S-conjugate amidase.

Recently we described the structures of two new bromotyrosine-derived alkaloids that inhibit the detoxification enzyme mycothiol-S-conjugate amidase (MCA) from Mycobacterium tuberculosis. Here we describe a concise total synthesis of bromotyrosine oxime 1. The six-step synthesis of 1 utilized a trifluoromethyloxazole intermediate, whose hydrolysis product underwent alkylation and coupling to agmatine to give the inhibitor in approximately 40% overall yield. Oxime 1 inhibited MCA and its homolog AcGI deacetylase with IC(50) values of 30 and 150 microM, respectively.