Development, implementation, and evaluation of a simulation-based educational curriculum for pediatric hospitalists.

BACKGROUND AND OBJECTIVES: Minimal published simulation-based educational training exists for practicing pediatric hospitalists. Our aim was to determine specific pediatric hospital medicine (PHM) knowledge, skill, and competency needs aligned with our scope of practice and evaluate the impact of a simulation-based training curriculum. DESIGN AND METHODS: Baseline and post-training surveys were administered to 48 physicians providing self-ratings on a 5-point scale from Novice to Expert on published PHM competencies. Results were used to develop a targeted simulation curriculum. Participants were considered competent in a domain if their mean score was 3 or greater. We categorized participant responses to individual questions into nine domain scores on survey self-assessments. Score analysis was performed using the signed-rank test and McNemar's test. Post-training evaluations solicited curriculum acceptance and perceived clinical value. RESULTS: The baseline response rate was 98% and the post-training response rate was 85%. Areas with the lowest competency on baseline self-assessment included advanced airway management (38%), vascular access and emergency medications (38%), code cart skills (19%), team communication (51%), and medically complex care (49%). Post-training scores improved significantly for five of nine domains, with the largest gains in the "not competent" at baseline group. Percent competent (% with mean score >3) increased significantly in three domains (advanced airway management, code cart skills, and complex care). Participants rated educational sessions favorably (98%) and most (95%) reported using knowledge/skills learned for patient care. CONCLUSION: Baseline self-assessment results were instrumental in curriculum design. Post-training analysis revealed gains in multiple domains and identified opportunities for future interventions. Most hospitalists reported participation positively impacted patient care with high learner satisfaction.

Dystrophin and dysferlin double mutant mice: a novel model for rhabdomyosarcoma.

Although researchers have yet to establish a link between muscular dystrophy (MD) and sarcomas in human patients, literature suggests that the MD genes dystrophin and dysferlin act as tumor suppressor genes in mouse models of MD. For instance, dystrophin-deficient mdx and dysferlin-deficient A/J mice, models of human Duchenne MD and limb-girdle MD type 2B, respectively, develop mixed sarcomas with variable penetrance and latency. To further establish the correlation between MD and sarcoma development, and to test whether a combined deletion of dystrophin and dysferlin exacerbates MD and augments the incidence of sarcomas, we generated dystrophin and dysferlin double mutant mice (STOCK-Dysf(prmd)Dmd(mdx-5Cv)). Not surprisingly, the double mutant mice develop severe MD symptoms and, moreover, develop rhabdomyosarcoma (RMS) at an average age of 12 months, with an incidence of >90%. Histological and immunohistochemical analyses, using a panel of antibodies against skeletal muscle cell proteins, electron microscopy, cytogenetics, and molecular analysis reveal that the double mutant mice develop RMS. The present finding bolsters the correlation between MD and sarcomas, and provides a model not only to examine the cellular origins but also to identify mechanisms and signal transduction pathways triggering development of RMS.

Mouse neutrophils lacking lamin B-receptor expression exhibit aberrant development and lack critical functional responses.

OBJECTIVE: The capacity of neutrophils to eradicate bacterial infections is dependent on normal development and activation of functional responses, which include chemotaxis and generation of oxygen radicals during the respiratory burst. A unique feature of the neutrophil is its highly lobulated nucleus, which is thought to facilitate chemotaxis, but may also play a role in other critical neutrophil functions. Nuclear lobulation is dependent on expression of the inner nuclear envelope protein, the lamin B receptor (LBR), mutations of which cause hypolobulated neutrophil nuclei in human Pelger-Huët anomaly and the "ichthyosis" (ic) phenotype in mice. In this study, we have investigated roles for LBR in mediating neutrophil development and activation of multiple neutrophil functions, including chemotaxis and the respiratory burst. MATERIALS AND METHODS: A progenitor EML cell line was generated from an ic/ic mouse, and derived cells that lacked LBR expression were induced to mature neutrophils and then examined for abnormal morphology and functional responses. RESULTS: Neutrophils derived from EML-ic/ic cells exhibited nuclear hypolobulation identical to that observed in ichthyosis mice. The ic/ic neutrophils also displayed abnormal chemotaxis, supporting the notion that nuclear segmentation augments neutrophil extravasation. Furthermore, promyelocytic forms of ic/ic cells displayed decreased proliferative responses and produced a deficient respiratory burst upon terminal maturation. CONCLUSIONS: Our studies of promyelocytes that lack LBR expression have identified roles for LBR in regulating not only the morphologic maturation of the neutrophil nucleus, but also proliferative and functional responses that are critical to innate immunity.

Humanized NOD/LtSz-scid IL2 receptor common gamma chain knockout mice in diabetes research.

There are many rodent models of autoimmune diabetes that have been used to study the pathogenesis of human type 1 diabetes (T1D), including the non-obese diabetic (NOD) mouse, the biobreeding (BB) rat, and the transgenic mouse models. However, mice and rats are not humans, and these rodent models do not completely recapitulate the autoimmune pathogenesis of the human disease. In addition, many of the reagents, tools, and therapeutics proposed for use in humans may be species specific and cannot be investigated in rodents. Researchers have used nonhuman primates to more closely mimic the human immune system and, to study species-specific therapeutics, but these studies are associated with additional ethical and economic constraints and, to date, no model of autoimmune diabetes in this species has been described. New animal models are needed that will permit the in vivo investigation of human immune systems and analyses of the pathogenesis of human T1D without putting individuals at risk. To fill this need, we are developing humanized mouse models for the in vivo study of T1D. These models are based on our newly generated stock of NOD-scid IL2rgamma(null) mice, which engraft at higher levels with human hematolymphoid cells and exhibit enhanced function of the engrafted human immune systems compared with previous humanized mouse models. Overall, development of these new generations of humanized mice should facilitate in vivo studies of the human immune system as well as permit the investigation of the pathogenesis and effector phases of human T1D.