MTG16 contributes to colonic epithelial integrity in experimental colitis.

OBJECTIVE: The myeloid translocation genes (MTGs) are transcriptional corepressors with both Mtg8(-/-) and Mtgr1(-/-) mice showing developmental and/or differentiation defects in the intestine. We sought to determine the role of MTG16 in intestinal integrity. METHODS: Baseline and stress induced colonic phenotypes were examined in Mtg16(-/-) mice. To unmask phenotypes, we treated Mtg16(-/-) mice with dextran sodium sulphate (DSS) or infected them with Citrobacter rodentium and the colons were examined for ulceration and for changes in proliferation, apoptosis and inflammation. RESULTS: Mtg16(-/-) mice have altered immune subsets, suggesting priming towards Th1 responses. Mtg16(-/-) mice developed increased weight loss, diarrhoea, mortality and histological colitis and there were increased innate (Gr1(+), F4/80(+), CD11c(+) and MHCII(+); CD11c(+)) and Th1 adaptive (CD4) immune cells in Mtg16(-/-) colons after DSS treatment. Additionally, there was increased apoptosis and a compensatory increased proliferation in Mtg16(-/-) colons. Compared with wild-type mice, Mtg16(-/-) mice exhibited increased colonic CD4;IFN-γ cells in vehicle-treated and DSS-treated mice. Adoptive transfer of wild-type marrow into Mtg16(-/-) recipients did not rescue the Mtg16(-/-) injury phenotype. Isolated colonic epithelial cells from DSS-treated Mtg16(-/-) mice exhibited increased KC (Cxcl1) mRNA expression when compared with wild-type mice. Mtg16(-/-) mice infected with C rodentium had more severe colitis and greater bacterial colonisation. Last, MTG16 mRNA levels were reduced in human ulcerative colitis versus normal colon tissues. CONCLUSIONS: These observations indicate that MTG16 is critical for colonocyte survival and regeneration in response to intestinal injury and provide evidence that this transcriptional corepressor regulates inflammatory recruitment in response to injury.

A new measure of the cognitive, metacognitive, and experiential aspects of residents' learning.

PURPOSE: Psychometric data are presented for the Cognitive Behavior Survey: Residency Level (rCBS), a survey that profiles cognitive, metacognitive, and experiential aspects of residents' learning. METHOD: The authors asked 963 residents from seven medicine residencies of large academic medical centers to participate in their study and gathered data from the respondents during a three-year period, 2000-2002. A factor analysis cross-validation design guided the development of rCBS's seven scales: memorization, conceptualization, reflection, independent learning, critical thinking, meaningful learning experience, and attitude toward educational experience. Interscale correlations and MANOVA provided preliminary evidence of scale construct validity. RESULTS: A total of 424 residents (44%) responded. With several minor exceptions, items for each scale loaded .40 or higher. Memorization did not correlate with any other scale, except correlating negatively with critical thinking. Higher-order thinking scales (conceptualization, reflection, independent learning, critical thinking) correlated with one another and with meaningful learning experience and attitude toward educational experience. The one exception: conceptualization did not correlate with critical thinking. MANOVA results reveal that residents who scored in the top 20% on the reflection scale conceptualized, learned independently, and thought critically more than did the bottom 20%. CONCLUSIONS: Results provide preliminary support for scale reliability and construct validity. As residencies seek to meet expectations of the Accreditation Council for Graduate Medical Education's Outcome Project, rCBS could prove useful in program evaluation, residents' self-assessment, and assessment by serving as a means to explore how residents learn, how residency programs affect learning behavior, and how clinically strong and weak residents differ in learning behaviors.