During vertebrate embryogenesis, paraxial mesoderm gives rise to somites, which subsequently develop into the dermis, skeletal muscle, ribs and vertebrae of the adult. Mutations that disrupt the patterning of individual somites have dramatic effects on these tissues, including fusions of the ribs and vertebrae. The T-box transcription factor, Tbx6, is expressed in the paraxial mesoderm but is downregulated as somites develop. It is essential for the formation of posterior somites, which are replaced with ectopic neural tubes in Tbx6-null mutant embryos. We show that partial restoration of Tbx6 expression in null mutants rescues somite development, but that rostrocaudal patterning within them is defective, ultimately resulting in rib and vertebral fusions, demonstrating that Tbx6 activity in the paraxial mesoderm is required not simply for somite specification but also for their normal patterning. Somite patterning is dependent upon Notch signaling and we show that Tbx6 genetically interacts with the Notch ligand, deltalike 1 (Dll1). Dll1 expression, which is absent in the Tbx6-null mutant, is restored at reduced levels in the partially rescued mutants, suggesting that Dll1 is a target of Tbx6. We also identify the spontaneous mutation rib-vertebrae as a hypomorphic mutation in Tbx6. The similarity in the phenotypes we describe here and that of some human birth defects, such as spondylocostal dysostosis, raises the possibility that mutations in Tbx6 or components of this pathway may be responsible for these defects.

Electronic health record (EHR) technology use in the educational setting to advance pharmacy practice skills with patient simulation has not been described previously in the literature. Therefore, the purpose of this study was to evaluate the impact of a virtual EHR on learning efficiency, perceptions of clinical skills, communication, and satisfaction. This was a prospective study conducted in a cardiovascular therapeutics course in the Doctor of Pharmacy curriculum. Students were randomized to use of a virtual EHR with patient simulation or to patient simulation alone (control). The efficiency of learning was assessed by the time to optimal recommendation for each scenario. Surveys (n = 12 questions) were administered electronically to evaluate perceptions of clinical skills, communication, and learning satisfaction. Data were analyzed with the Mann–Whitney U or Wilcoxon signed-rank test as appropriate. Use of the virtual EHR decreased the amount of time needed to provide the optimal treatment recommendations by 25% compared to control. The virtual EHR also significantly improved students’ perceptions of their clinical skills, communication, and satisfaction compared to control. The virtual EHR demonstrated value in learning efficiency while providing students with an engaging means of practicing essential pharmacist functions in a simulated setting.

Somites are the first overt sign of segmentation in the vertebrate embryo and form from bilateral strips of paraxial mesoderm. Paraxial mesoderm arises from the primitive streak; it then migrates laterally and comes to lie on both sides of the neural tube. In the mouse, the T-box transcription factor Tbx6 is required for both somite formation and patterning. Tbx6 expression corresponds both temporally and spatially to somite formation, with expression in the primitive streak and presomitic mesoderm. Its expression in the latter could simply be explained by maintenance following its initial activation in the primitive streak. Alternatively, its expression in the presomitic mesoderm may be contributed by separate regulatory elements possibly under the control of different signals. We have begun to investigate how Tbx6 expression is controlled during development using a transgenic approach to identify the cis-acting regulatory regions. We show that it is possible to separate an element required for presomitic mesoderm expression from that driving expression in the primitive streak. Further, we show that a binding site for the Notch transcription factor RBP-Jkappa is necessary for Tbx6 presomitic mesoderm enhancer activity, indicating that Notch signaling is upstream of Tbx6 in the pathway directing somite formation and patterning.

In this article, we describe an Ebola preparedness initiative with implementation across an academic health system. Key stakeholder centers of various disciplines and clinical experts collaborated in the development and design. Subject matter experts in the areas of Centers for Disease Control and Prevention and World Health Organization protocols for personal protective equipment donning and doffing conducted initial train-the-trainer sessions for program instructors. These trainers represented a cross-section of key clinical responders and environmental services. Through a parallel development process, a blended learning curriculum consisting of online modules followed by on-site training sessions was developed and implemented in both the simulation laboratory and the actual clinical care spaces in preparation for a Department of Health inspection. Lessons learned included identification of the need for iterative refinement based on instructor and trainee feedback, the lack of tolerance of practitioners in wearing full-body personal protective equipment for extended periods, and the ability of a large system to mount a rapid response to a potential public health threat through leveraging of expertise of its Simulation Program, Center for Quality, Safety and Innovation as well as a wide variety of clinical departments.