Taking More Society for Academic Emergency Medicine Practice Tests Does Not Lead to Improved National EM-M4 Exam Scores.

INTRODUCTION: Emergency medicine (EM) is a required clerkship for third-year medical students, and an elective EM acting internship (AI) is available to fourth-year students at our institution. The Society for Academic Emergency Medicine's (SAEM) National Emergency Medicine M4 Examination (EM-M4) is administered to students at the end of the EM AI experience. To prepare for the exam, students gain access to 23 practice tests available from SAEM. In this study we investigate the correlation between the number of practice tests taken and EM-M4 performance. METHODS: We collected data for EM-M4 and the US Medical Licensing Exam (USMLE) Step 2 Clinical Knowledge (CK) from students completing a MS4 EM clerkship in consecutive medical school classes from 2014-2017 at a private medical school. In addition, we collected data during the clerkship on the number of practice exams taken and whether a comprehensive practice exam was taken. We analyzed the study population three ways to determine whether the number of practice tests impacted final exam results: a binary distribution (1-11 or 12-23 tests taken); quaternary distribution (1-6, 7-12, 13-18, or 19-23 tests taken); and individual test variability (1,2,3,…22,23 tests taken). Complete data for 147 students was used for data analysis. RESULTS: The EM-M4 showed moderate (r = 0.49) correlations with USMLE Step 2 CK. There was no significant difference in EM-M4 performance in the binary analysis (P ≤ 0.09), the quaternary analysis (P ≤ 0.09), or the continuous variable analysis (P ≤ 0.52). Inclusion of a comprehensive practice test also did not correlate with EM-M4 performance (P ≤ 0.78). CONCLUSION: Degree of utilization of SAEM practice tests did not seem to correlate with performance on the EM-M4 examination at our institution. This could be due to many factors including that the question bank is composed of items that had poor item discrimination, possible inadequate coverage of EM curriculum, and/or use of alternative study methods. While further investigation is needed, if our conclusions prove generalizable, then using the SAEM practice tests is an extraneous cognitive load from a modality without proven benefit.

Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte-myelin dysfunction.

Although the underlying neurobiology of major mental illness (MMI) remains unknown, emerging evidence implicates a role for oligodendrocyte-myelin abnormalities. Here, we took advantage of a large family carrying a balanced t(1;11) translocation, which substantially increases risk of MMI, to undertake both diffusion tensor imaging and cellular studies to evaluate the consequences of the t(1;11) translocation on white matter structural integrity and oligodendrocyte-myelin biology. This translocation disrupts among others the DISC1 gene which plays a crucial role in brain development. We show that translocation-carrying patients display significant disruption of  white matter integrity compared with familial controls. At a cellular level, we observe dysregulation of key pathways controlling oligodendrocyte development and morphogenesis in induced pluripotent stem cell (iPSC) derived case oligodendrocytes. This is associated with reduced proliferation and a stunted morphology in vitro. Further, myelin internodes in a humanized mouse model that recapitulates the human translocation as well as after transplantation of t(1;11) oligodendrocyte progenitors were significantly reduced when  compared with controls. Thus we provide evidence that the t(1;11) translocation has biological effects at both the systems and cellular level that together suggest oligodendrocyte-myelin dysfunction.

Axonal mRNAs: characterisation and role in the growth and regeneration of dorsal root ganglion axons and growth cones.

We have developed a compartmentalised culture model for the purification of axonal mRNA from embryonic, neonatal and adult rat dorsal root ganglia. This mRNA was used un-amplified for RT-qPCR. We assayed for the presence of axonal mRNAs encoding molecules known to be involved in axon growth and guidance. mRNAs for beta-actin, beta-tubulin, and several molecules involved in the control of actin dynamics and signalling during axon growth were found, but mRNAs for microtubule-associated proteins, integrins and cell surface adhesion molecules were absent. Quantification of beta-actin mRNA by means of qPCR showed that the transcript is present at the same level in embryonic, newborn and adult axons. Using the photoconvertible reporter Kaede we showed that there is local translation of beta-actin in axons, the rate being increased by axotomy. Knock down of beta-actin mRNA by RNAi inhibited the regeneration of new axon growth cones after in vitro axotomy, indicating that local translation of actin-related molecules is important for successful axon regeneration.

Modulation and lack of cross-talk between signal transducer and activator of transcription 5 and Suppressor of cytokine signaling-3 in insulin and growth hormone signaling in 3T3-L1 adipocytes.

OBJECTIVE: To examine the role of signal transducer and activator of transcription (STAT) 5 and suppressor of cytokine signaling (SOCS)-3 in the cross-talk between growth hormone and insulin (INS) signaling in fat cells. RESEARCH METHODS AND PROCEDURES: Fully differentiated 3T3-L1 adipocytes were exposed to INS, growth hormone (GH), or both of these growth factors, and the activation of STAT5 proteins and mitogen-activated protein kinase was examined using phospho-specific antibodies. The induction of SOCS-3 mRNA was assessed by Northern blot analysis. INS-stimulated glucose transport was also measured. RESULTS: We observed that GH, not INS, induced STAT5 activation in adipocytes in a manner that was independent of extracellular signal-regulated kinase (ERK) activation or new protein synthesis. GH strongly induced SOCS-3 mRNA expression, whereas INS had a much less potent effect on SOCS-3 mRNA expression. Because SOCS-3 has been implicated in the attenuation of GH and INS signaling, we examined the cross-talk between these signaling pathways. GH pretreatment of adipocytes inhibited GH signaling. Similarly, INS pretreatment inhibited INS signaling. However, INS did not block the GH-induced activation of STAT5, and GH did not block the INS induction of ERK activity or of increased glucose uptake. We observed that neither new protein synthesis nor activation of ERKs 1 and 2 were required for the inhibition of GH signaling. DISCUSSION: These results demonstrate that blocking the induction of the SOCS-3 protein has no effect on the attenuation of GH signaling and support recent studies suggesting that SOCS proteins have additional functions. In addition, these studies demonstrate that GH-induced SOCS-3 expression is insufficient to inhibit INS-induced glucose uptake in adipocytes.

Growth hormone, but not insulin, activates STAT5 proteins in adipocytes in vitro and in vivo.

STAT 5 proteins are latent transcription factors which have been shown to be activated by growth hormone (GH) in many cell types. However, some recent studies also suggest that STAT 5B is a physiological substrate of the insulin receptor. In our studies, we have shown that physiological levels of insulin do not induce STAT 5 tyrosine phosphorylation or affect the nuclear distribution of STATs 5A or 5B in 3T3-L1 adipocytes. Moreover, we did not observe the activation of STAT 5 in the adipose tissue or skeletal muscle of mice following an acute intraperitoneal injection of insulin. However, acute GH administration, both in vitro and in vivo, resulted in the activation of STAT 5 proteins. In summary, our results indicate that STAT 5 proteins are not activated by physiological levels of insulin in adipose tissue.