Team-based learning in large enrollment classes.

The goal of this review is to highlight the key elements needed to successfully deploy team-based learning (TBL) in any class, but especially in large enrolment classes, where smooth logistics are essential. The text is based on a lecture and workshop given at the American Physiological Society's Institute on Teaching and Learning in Madison, WI, in June 2016. After a short overview of the TBL method, its underpinning in learning theory, and a summary of current evidence for its effectiveness, we present two case studies from our own teaching practices in a new medical school. The first case study explores critical elements of design and planning for a TBL module, and the second explores best practices in classroom management. As medical educators in the fields of physiology, pediatrics, nephrology, and family medicine, we present the objective views of subject matter experts who adopted TBL as one teaching method rather than TBL experts or advocates per se. The review is aimed primarily at faculty contemplating using TBL for the first time who are interested in exploring the significant benefits and challenges of TBL.

Histone deacetylase (HDAC) activity is critical for embryonic kidney gene expression, growth, and differentiation.

Histone deacetylases (HDACs) regulate fundamental biological processes such as cellular proliferation, differentiation, and survival via genomic and nongenomic effects. This study examined the importance of HDAC activity in the regulation of gene expression and differentiation of the developing mouse kidney. Class I HDAC1-3 and class II HDAC4, -7, and -9 genes are developmentally regulated. Moreover, HDAC1-3 are highly expressed in nephron precursors. Short term treatment of cultured mouse embryonic kidneys with HDAC inhibitors (HDACi) induced global histone H3 and H4 hyperacetylation and H3K4 hypermethylation. However, genome-wide profiling revealed that the HDAC-regulated transcriptome is restricted and encompasses regulators of the cell cycle, Wnt/ß-catenin, TGF-ß/Smad, and PI3K-AKT pathways. Further analysis demonstrated that base-line expression of key developmental renal regulators, including Osr1, Eya1, Pax2/8, WT1, Gdnf, Wnt9b, Sfrp1/2, and Emx2, is dependent on intact HDAC activity. Treatment of cultured embryonic kidney cells with HDACi recapitulated these gene expression changes, and chromatin immunoprecipitation assays revealed that HDACi is associated with histone hyperacetylation of Pax2/Pax8, Gdnf, Sfrp1, and p21. Gene knockdown studies demonstrated that HDAC1 and HDAC2 play a redundant role in regulation of Pax2/8 and Sfrp1 but not Gdnf. Long term treatment of embryonic kidneys with HDACi impairs the ureteric bud branching morphogenesis program and provokes growth arrest and apoptosis. We conclude that HDAC activity is critical for normal embryonic kidney homeostasis, and we implicate class I HDACs in the regulation of early nephron gene expression, differentiation, and survival.

High incidence of initial and late steroid resistance in childhood nephrotic syndrome.

BACKGROUND: Conventional wisdom states that greater than 80% of children with nephrotic syndrome (NS) respond to steroid treatment, remain steroid-sensitive during subsequent relapses, and consequently have a favorable long-term prognosis. In contrast, steroid resistance is believed to be associated with a high risk of developing chronic renal failure. Recent reports suggest that the histologic pattern of NS in children may be changing, but whether the change is accompanied by a parallel change in steroid sensitivity is unknown. METHODS: Initial and subsequent steroid responsiveness was evaluated in all children aged 1 to 18 years who presented with newly diagnosed NS to the 2 pediatric nephrology referral centers in southeastern Louisiana between 1994 and 2003. NS was defined as presence of edema, heavy proteinuria, and serum albumin concentration below 2.5 g/dL. Steroid sensitivity (SS) was defined as total resolution of proteinuria and edema, and partial response to steroids (PR) was defined as loss of edema with continuing proteinuria. RESULTS: There were 210 new cases of NS. Forty-one patients (20%) had immune complex glomerulonephritis. Six patients were excluded because of incomplete data availability. Of the remaining 163 patients, 115 (71%) were SS and 23 (14%) achieved PR during the initial 4 weeks of treatment; 25 (15%) were steroid-resistant (SR). Follow-up data were available for 91 of the 115 initially SS patients; 19 subsequently became steroid-resistant. Thus, at least 45% of the patients with new-onset NS did not have typical childhood steroid-responsive NS. Initial steroid resistance was more likely in African American children and in children with older age at onset (11.5 vs. 4.6 years). Development of steroid resistance after initial SS was associated with shorter interval to the first relapse (2.2 vs. 5.4 months) and having the first relapse during the initial steroid treatment. CONCLUSION: Compared to previous reports, our results show a higher incidence of initial and subsequent steroid resistance, characteristics not consistent with typical minimal change NS with a benign prognosis. The results suggest that in the current era, NS in children may not be as benign as indicated by earlier studies.