Comparative Analysis of Small-Molecule LIMK1/2 Inhibitors: Chemical Synthesis, Biochemistry, and Cellular Activity.

LIM domain kinases 1 and 2 (LIMK1 and LIMK2) regulate actin dynamics and subsequently key cellular functions such as proliferation and migration. LIMK1 and LIMK2 phosphorylate and inactivate cofilin leading to increased actin polymerization. As a result, LIMK inhibitors are emerging as a promising treatment strategy for certain cancers and neurological disorders. High-quality chemical probes are required if the role of these kinases in health and disease is to be understood. To that end, we report the results of a comparative assessment of 17 reported LIMK1/2 inhibitors in a variety of in vitro enzymatic and cellular assays. Our evaluation has identified three compounds (TH-257, LIJTF500025, and LIMKi3) as potent and selective inhibitors suitable for use as in vitro and in vivo pharmacological tools for the study of LIMK function in cell biology.

Developing Core Competency-Based Learning Objectives for Postgraduate Curricula for Postanesthesia Nurses-A Delphi Study.

PURPOSE: Postanesthesia care unit (PACU) nurse competencies involve the ability to care for patients receiving complex treatment. Well-educated PACU nurses are required to provide safe patient care, and accordingly, they require investment in their education. However, core competencies for PACU nurses that are based on systematic methods for curriculum development and consensus have not been established. The purpose of this study was to develop a nationwide consensus on core competency-based learning objectives for a postgraduate PACU nursing curriculum. DESIGN: Nationwide Delphi Study using Kern's six steps of curriculum development as a framework. METHODS: Forty-one anesthesiologists and 38 PACU nurses from 37 Danish departments of anesthesiology were invited to participate. In Delphi round 1, the participants listed core competencies for PACU nurses within 12 predefined categories. We analyzed the responses using an inductive and manifest approach to content analysis and developed learning objectives in accordance with the Structure of Observed Learning Outcomes and Simpson taxonomies. In Delphi round 2 and 3, the participants rated and rerated the learning objectives on a 7-point Likert scale, measuring statements of agreement. Consensus was predefined as a median score of 6 and or greater. The main outcome was a prioritized list of competency-based learning objectives for a postgraduate PACU nurse curriculum. FINDINGS: Twenty-six nurses and 14 anesthesiologists (51%) completed all Delphi rounds, representing 22 (60%) departments of anesthesiology. Consensus was reached on 180 learning objectives. The learning objectives described competencies ranging from basic to complex nursing tasks and emphasized the knowledge and skills needed to identify and initiate treatment of postoperative complications. CONCLUSIONS: Nationwide consensus on core competencies for postgraduate curricula for PACU nurses was achieved through the Delphi method. Our study exemplifies the range of complex knowledge and skills needed to work as a PACU nurse. The learning objectives are applicable in postgraduate curricula designed for PACU nurses.