The RAST-NP Pilot: Preparing New Graduate Nurse Practitioners for Emergent Procedures in Remote Settings Using a Novel Training Program.

With more new graduate primary care nurse practitioners (NPs) practicing in remote locales than ever before, their preparation for performing emergency procedural skills (EPSs) is critical for safe and effective care. Emergency procedural skills are not uniformly taught in primary care academic programs but are easily imparted via additional training and practice. The purpose of this project was to develop and pilot an expert panel-validated training program specifically for NPs bound for remote practice and to evaluate how the participants rated their self-efficacy in performing specific EPSs before and after completing the training, called the Remote Advanced Skills Training for NPs (RAST-NP).

Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease.

HCV serine protease NS3 represents an attractive drug target because it is not only essential for viral replication but also implicated in the viral evasion of the host immune response pathway through direct cleavage of key proteins in the human innate immune system. Through structure-based drug design and optimization, macrocyclic peptidomimetic molecules bearing both a lipophilic P2 isoindoline carbamate and a P1/P1' acylsulfonamide/acylsulfamide carboxylic acid bioisostere were prepared that possessed subnanomolar potency against the NS3 protease in a subgenomic replicon-based cellular assay (Huh-7). Danoprevir (compound 49) was selected as the clinical development candidate for its favorable potency profile across multiple HCV genotypes and key mutant strains and for its good in vitro ADME profiles and in vivo target tissue (liver) exposures across multiple animal species.

2,2-Disubstituted analogues of the natural hormone 1 alpha,25-dihydroxyvitamin D(3): chemistry and biology.

Six new 2,2-disubstituted analogues of the natural hormone calcitriol have been prepared. Chemical novelty includes (1) the first example of an inverse-electron-demand Diels-Alder cycloaddition using a pyrone diene and a difluorinated vinyl ether dienophile, leading to difluorinated analogues 7 and (2) a conceptually streamlined approach to dimethylated 19-nor analogues. Analogues 7a and are similar to calcitriol in terms of in vitro antiproliferative activity, but they are different from calcitriol in terms of transcriptional activity: difluorinated analogue 7a is 2-3 times more active transcriptionally than calcitriol, whereas dimethylated analogue is 7.