Left Ventricular Assist Device Multialarm Emergency: A High-Fidelity Simulation Case for Emergency Medicine Residents.

Introduction: As left ventricular assist devices (LVADs) become more prevalent in the treatment of patients with end-stage heart failure, emergency physicians must become experts in the management and resuscitation of patients with LVADs. As with other high-acuity, low-occurrence scenarios, managing the unstable LVAD patient makes for an ideal topic for simulation-based resident education. Methods: By incorporating a high-fidelity HeartMate 3 LVAD task trainer, our program developed and executed a novel LVAD simulation activity for our emergency medicine resident physicians. In the scenario, a 65-year-old male with recent LVAD placement arrived at a community hospital with undifferentiated hypotension. Various device alarms activated during the scenario and required intervention. Ultimately, the patient was found to be in septic/hypovolemic shock and only survived with appropriate resuscitation. We implemented a postscenario survey to assess the effectiveness of the simulation activity and administered it to 27 residents. Results: Content and delivery of our simulation were found to be effective; all survey questions regarding content and delivery obtained a mean score of 4.5 or greater on a 5-point Likert scale. Residents reported an overall high level of confidence in achieving most of the skill-based learning objectives (most scores > 4.1). The two objectives with the lowest confidence ratings were troubleshooting an LVAD and its various alarms (3.8) and demonstrating the ability to assess an LVAD patient (3.9). Discussion: Our LVAD simulation activity was successful and also revealed several potential areas for future research and simulation improvement.

Deregulated KLF4 Expression in Myeloid Leukemias Alters Cell Proliferation and Differentiation through MicroRNA and Gene Targets.

Acute myeloid leukemia (AML) is characterized by increased proliferation and blocked differentiation of hematopoietic progenitors mediated, in part, by altered myeloid transcription factor expression. Decreased Krüppel-like factor 4 (KLF4) expression has been observed in AML, but how decreased KLF4 contributes to AML pathogenesis is largely unknown. We demonstrate decreased KLF4 expression in AML patient samples with various cytogenetic aberrations, confirm that KLF4 overexpression promotes myeloid differentiation and inhibits cell proliferation in AML cell lines, and identify new targets of KLF4. We have demonstrated that microRNA 150 (miR-150) expression is decreased in AML and that reintroducing miR-150 expression induces myeloid differentiation and inhibits proliferation of AML cells. We show that KLF family DNA binding sites are necessary for miR-150 promoter activity and that KLF2 or KLF4 overexpression induces miR-150 expression. miR-150 silencing, alone or in combination with silencing of CDKN1A, a well-described KLF4 target, did not fully reverse KLF4-mediated effects. Gene expression profiling and validation identified putative KLF4-regulated genes, including decreased MYC and downstream MYC-regulated gene expression in KLF4-overexpressing cells. Our findings indicate that decreased KLF4 expression mediates antileukemic effects through regulation of gene and microRNA networks, containing miR-150, CDKN1A, and MYC, and provide mechanistic support for therapeutic strategies increasing KLF4 expression.

Molecular Phylogeny Supports Repeated Adaptation to Burrowing within Small-Eared Shrews Genus of Cryptotis (Eulipotyphla, Soricidae).

Small-eared shrews of the New World genus Cryptotis (Eulipotyphla, Soricidae) comprise at least 42 species that traditionally have been partitioned among four or more species groups based on morphological characters. The Cryptotis mexicana species group is of particular interest, because its member species inhibit a subtly graded series of forelimb adaptations that appear to correspond to locomotory behaviors that range from more ambulatory to more fossorial. Unfortunately, the evolutionary relationships both among species in the C. mexicana group and among the species groups remain unclear. To better understand the phylogeny of this group of shrews, we sequenced two mitochondrial and two nuclear genes. To help interpret the pattern and direction of morphological changes, we also generated a matrix of morphological characters focused on the evolutionarily plastic humerus. We found significant discordant between the resulting molecular and morphological trees, suggesting considerable convergence in the evolution of the humerus. Our results indicate that adaptations for increased burrowing ability evolved repeatedly within the genus Cryptotis.