ABSTRACT
Objective: We investigated the educational value of implementing a web-based e-learning program into a medical student emergency medicine rotation. We created "UltrasoundBox," a browser-based application where students interpret ultrasound (US) images. Our goal was to assess how this form of e-learning performs when compared to more passive, lecture-based online US education. We also assessed the how the students interpreted the addition this learning modality to the rotation. Methods: This is a randomized, controlled study to assess the educational outcomes of implementing UltrasoundBox compared to lecture-based US education. Fourth-year medical students on their emergency medicine rotation were enrolled in the study. Students randomized to the control arm were instructed to watch widely available educational lecture videos. Students randomized to the intervention arm received access to UltrasoundBox and were instructed to complete the clinical modules. Both groups completed the same standardized US examination before and after the trial. All the trial participants were given a survey to complete after the trial. Results: We enrolled 42 students, with 23 in the control group and 19 in the intervention group. On the post-intervention examination, the control and intervention groups were found to have mean examination scores of 61.6% and 73.6% respectively, with a statistically significant difference of 12% (95% confidence interval 1.611 to 5.56; p < 0.0005). A total of 92% of survey respondents in the intervention group indicated that UltrasoundBox was an effective tool in meeting the intended learning objectives, while only 36.8% of the control group indicated this for the online lectures (p < 0.005). Conclusions: We found that medical students using the web-based e-learning platform UltrasoundBox achieved better scores on the examination when compared to the medical students using existing online lecture-based US educational resources. The students reported that the addition of UltrasoundBox added educational value to the rotation.
ABSTRACT
B cells, which are critical for intestinal homeostasis, remain understudied in ulcerative colitis (UC). In this study, we recruited three cohorts of patients with UC (primary cohort, n = 145; validation cohort 1, n = 664; and validation cohort 2, n = 143) to comprehensively define the landscape of B cells during UC-associated intestinal inflammation. Using single-cell RNA sequencing, single-cell IgH gene sequencing and protein-level validation, we mapped the compositional, transcriptional and clonotypic landscape of mucosal and circulating B cells. We found major perturbations within the mucosal B cell compartment, including an expansion of naive B cells and IgG+ plasma cells with curtailed diversity and maturation. Furthermore, we isolated an auto-reactive plasma cell clone targeting integrin αvß6 from inflamed UC intestines. We also identified a subset of intestinal CXCL13-expressing TFH-like T peripheral helper cells that were associated with the pathogenic B cell response. Finally, across all three cohorts, we confirmed that changes in intestinal humoral immunity are reflected in circulation by the expansion of gut-homing plasmablasts that correlates with disease activity and predicts disease complications. Our data demonstrate a highly dysregulated B cell response in UC and highlight a potential role of B cells in disease pathogenesis.
Subject(s)
Colitis, Ulcerative , Plasma Cells , B-Lymphocytes , Colitis, Ulcerative/genetics , Humans , Intestinal Mucosa/pathology , Lymphocyte Count , T-Lymphocytes, Helper-InducerABSTRACT
GPR15 is a chemoattractant receptor that facilitates colon homing of regulatory and effector CD4+ T cells in health and colitis. The molecular mechanisms that control GPR15 expression are not fully known. Here we report the presence of two highly conserved aryl hydrocarbon receptor (AHR) binding sequences in a 3' enhancer of GPR15, leading us to investigate AHR function in regulating GPR15 expression. Using luciferase reporter assays, we show that AHR activation increased GPR15 expression and requires both the AHR binding sites. Consistent with a transcriptional regulatory role, treatment with AHR agonists induce GPR15 expression on human CD4+ T cells. Using AHR-deficient mice, we demonstrate that the lack of AHR signaling drastically reduces GPR15 expression on effector/memory and Foxp3+ CD4+ T cells. In mixed bone marrow chimeras of AHR-deficient and wildtype cells, GPR15 expression was similarly diminished on AHR-deficient CD4+ effector/memory and regulatory T cells in the colon and small intestine. Furthermore, administration of AHR agonists upregulated GPR15 expression on CD4+ effector/memory T cells and increased their homing capability, especially to the colon. Collectively, our studies reveal a novel function of the AHR in regulation of GPR15 expression and increased colon trafficking of CD4+ T cells expressing GPR15.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Gene Expression Regulation , Receptors, Aryl Hydrocarbon , Receptors, G-Protein-Coupled , Receptors, Peptide , Humans , Basic Helix-Loop-Helix Transcription Factors/metabolism , Binding Sites , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Forkhead Transcription Factors , GATA3 Transcription Factor/metabolism , Promoter Regions, Genetic , Protein Binding , Receptors, Aryl Hydrocarbon/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, Peptide/genetics , Receptors, Peptide/metabolism , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Animals , MiceABSTRACT
Physiologic stress associated with illness and hospitalization is known to result in gastrointestinal ulceration, especially among the critically ill. The complication of this stress-related mucosal disease could be prevented with appropriate application of pharmacologic prophylaxis. Vigilance by the nursing staff is required to properly detect and manage the condition.