Contribution of bacterial and host factors to pathogen "blooming" in a gnotobiotic mouse model for Salmonella enterica serovar Typhimurium-induced enterocolitis.

Inflammation has a pronounced impact on the intestinal ecosystem by driving an expansion of facultative anaerobic bacteria at the cost of obligate anaerobic microbiota. This pathogen "blooming" is also a hallmark of enteric Salmonella enterica serovar Typhimurium (S. Tm) infection. Here, we analyzed the contribution of bacterial and host factors to S. Tm "blooming" in a gnotobiotic mouse model for S. Tm-induced enterocolitis. Mice colonized with the Oligo-Mouse-Microbiota (OMM12), a minimal bacterial community, develop fulminant colitis by day 4 after oral infection with wild-type S. Tm but not with an avirulent mutant. Inflammation leads to a pronounced reduction in overall intestinal bacterial loads, distinct microbial community shifts, and pathogen blooming (relative abundance >50%). S. Tm mutants attenuated in inducing gut inflammation generally elicit less pronounced microbiota shifts and reduction in total bacterial loads. In contrast, S. Tm mutants in nitrate respiration, salmochelin production, and ethanolamine utilization induced strong inflammation and S. Tm "blooming." Therefore, individual Salmonella-specific inflammation-fitness factors seem to be of minor importance for competition against this minimal microbiota in the inflamed gut. Finally, we show that antibody-mediated neutrophil depletion normalized gut microbiota loads but not intestinal inflammation or microbiota shifts. This suggests that neutrophils equally reduce pathogen and commensal bacterial loads in the inflamed gut.

Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation.

CKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α3-deficient mice with Alport syndrome-related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen-presenting cells, CD4 and CD8 T cells, and Th17- or IFNγ-producing T cells in the spleen as well as regulatory T cell suppression. CKD-related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD-related systemic inflammation and its consequences.

Radiology Education in Medical School and Residency: The Views and Needs of Program Directors.

RATIONALE AND OBJECTIVES: The authors of this study used the perspectives of residency program directors (PDs) nationally to explore whether trainees are adequately prepared to utilize and interpret medical imaging as interns, to identify the types of imaging skills most important for residency, and to begin to address current shortcomings in radiology education. MATERIALS AND METHODS: The authors created a survey using a modified version of Accreditation Council for Graduate Medical Education radiology milestones and sent it to 100 randomly selected PDs each in pediatrics, internal medicine, obstetrics and gynecology, and general surgery. The survey asked PDs to assess the actual and desired imaging skills of their incoming interns, the incoming interns' variability of skill level upon matriculation, and which imaging skills were most important from the PDs' perspective. RESULTS: PDs from all specialties identified a significant shortcoming relative to their expectations for both image interpretation and utilization skills. Additionally, PDs identified a significant variability in imaging skills, and described that variability as a hindrance to their programs. All of the potential imaging skills were rated as highly important with little clinically relevant difference between them. DISCUSSION: This multidisciplinary national survey found a deficiency in imaging education among interns across specialties and substantiates calls for formalized and improved radiology education in undergraduate medical education. Additionally, PDs had difficulty distinguishing which skills were most important, suggesting an unclear understanding of imaging ability needs for interns in respective specialties. More specific needs assessments are warranted on a national level.