G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis

G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion. Importantly, GPR35 is required for the rapid onset of ETBF-induced colitis in mouse models. GPR35-deficient mice showed reduced death and disease severity compared to wild-type C57Bl6 mice. Our data support a role for GPR35 in the CEC and mucosal response to BFT and underscore the importance of this molecule for sensing ETBF in the colon

The effectiveness of clinical teaching of mental health courses in nursing using clinical supervision and Kirkpatrick’s model

Background: Clinical experience associated with the fear and anxiety of nursing students in the psychiatric unit. Mental health nursing instructors find it challenging to teach nursing students to deal with patients with mental disorders in an environment where they need to provide patient teaching and clinical decision-making based on evidence and new technology. Objective: To measure the effectiveness of clinical teaching of mental health courses in nursing using clinical supervision and Kirkpatrick’s model evaluation in the psychiatry unit of Imam Reza Hospital, Bojnurd, Iran. Methods: This cross-sectional study was carried out from 2011 to 2016 on 76 nursing students from a university as part of a clinical mental health course in two semesters. The students were selected by a non-probable convenient sampling method. After completing their clinical education, each student responded to checklist questions based on the four-level Kirkpatrick’s model evaluation and open questions relating to clinical supervision. Finally, all data was analyzed using the SPSS version 16. Results: The students have evaluated clinical supervision as a useful approach, and appreciated the instructor’s supportive behavior during teaching and imparting clinical skills. This has made them feel relaxed at the end of the clinical teaching course. In addition, in the evaluation through Kirkpatrick’s model, more than 70% of the students have been satisfied with the method of conducting the teaching and average score of nursing students’ attitude toward mental health students: Their mean self-confidence score was 18.33±1.69, and the mean score of their performance in the study was evaluated to be 93.74±5.3 from 100 points. Conclusion: The results of clinical mental health teaching through clinical supervision and Kirkpatrick’s model evaluation show that the satisfaction, self-esteem, attitude, and skill of nursing students are excellent, thereby portraying the effectiveness of clinical teaching. But this program still needs to be reformed. To establish longterm goals and obtain knowledge and clinical skills of nursing, it is recommended to develop a curriculum and evaluate it appropriately

Predictors of incomplete optical colonoscopy using computed tomographic colonography

Background/Aims: Optical colonoscopy (OC) is the primary modality for investigation of colonic pathology. Although there is data on demographic factors for incomplete OC, paucity of data exists for anatomic variables that are associated with an incomplete OC. These anatomic variables can be visualized using computed tomographic colonography (CTC). We aim to retrospectively identify variables associated with incomplete OC using CTC and develop a scoring method to predict the outcome of OC. Patients and Methods: In this case-control study, 70 cases ( with incomplete OC) and 70 controls (with complete OC) were identified. CTC images of cases and controls were independently reviewed by a single CTC radiologist. Demographic and anatomical parameters were recorded. Data was examined using descriptive linear statistics and multivariate logistic regression model. Results: On analysis, female gender (80% vs 58.6% P = 0.007), prior abdominal/pelvic surgeries (51.4% vs 14.3% P < 0.001), colonic length (187.6 ± 30.0 cm vs 163.8 ± 27.2 cm P < 0.001), and number of flexures (11.4 ± 3.1 vs 8.4 ± 2.9 P < 0.001) increased the risk for incomplete OC. No significant association was observed for increasing age (P = 0.881) and history of severe diverticulosis (P = 0.867) with incomplete OC. A scoring system to predict the outcome of OC is proposed based on CTC findings. Conclusion: Female gender, prior surgery, and increasing colonic length and tortuosity were associated with incomplete OC, whereas increasing age and history of severe diverticulosis were not. These factors may be used in the future to predict those patients who are at risk of incomplete OC

PD-L1 (Programmed Death Ligand 1) as a Marker of Acute Cellular Rejection After Heart Transplantation

International audienceNo abstract availabl

LIN28B induces a differentiation program through CDX2 in colon cancer

Most colorectal cancers (CRCs) are moderately differentiated or well differentiated, a status that is preserved even in metastatic tumors. However, the molecular mechanisms underlying CRC differentiation remain to be elucidated. Herein, we unravel a potentially novel posttranscriptional regulatory mechanism via a LIN28B/CDX2 signaling axis that plays a critical role in mediating CRC differentiation. Owing to a large number of mRNA targets, the mRNA-binding protein LIN28B has diverse functions in development, metabolism, tissue regeneration, and tumorigenesis. Our RNA-binding protein IP (RIP) assay revealed that LIN28B directly binds CDX2 mRNA, which is a pivotal homeobox transcription factor in normal intestinal epithelial cell identity and differentiation. Furthermore, LIN28B overexpression resulted in enhanced CDX2 expression to promote differentiation in subcutaneous xenograft tumors generated from CRC cells and metastatic tumor colonization through mesenchymal-epithelial transition in CRC liver metastasis mouse models. A ChIP sequence for CDX2 identified α-methylacyl-CoA racemase (AMACR) as a potentially novel transcriptional target of CDX2 in the context of LIN28B overexpression. We also found that AMACR enhanced intestinal alkaline phosphatase activity, which is known as a key component of intestinal differentiation, through the upregulation of butyric acid. Overall, we demonstrated that LIN28B promotes CRC differentiation through the CDX2/AMACR axis