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3412 Informed Consent: Refining the Process
- Courtney Perry, Terrence Barrett
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 123
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OBJECTIVES/SPECIFIC AIMS: -This study aims to evaluate our retention rate into our prospective clinical trial. We will be comparing the rate of withdrawal both before and after our revamped informed consent process. -We aim to assess patient satisfaction with our study and u METHODS/STUDY POPULATION: -The informed consent process for an observational prospective study at our institution has been modified to lengthen the recruitment and consenting process. -In brief, the research protocol for this observational prospective aims to evaluate the role of steroids on ulcer healing in patients with ulcerative colitis. This study involves an initial standard of care colonoscopy with biopsies and photos. The areas biopsied are marked with a tattoo. The patients are started on steroids for management of their Ulcerative Colitis, and must return for two research colonoscopies at one week post- initial diagnostic visit, and at one month. Additional study biopsies are obtained at the one week visit and photo documentation is obtained. At the one month visit, only photos are obtained to document healing. -In addition to patients with active ulcerative colitis, this study recruits control groups of patients with UC in remission, as well as two groups of normal control patients (one group on steroids for non-IBD reasons, and one group not on steroids. -Prior to our informed consent intervention, patients were screened for eligibility on the day of their standard of care endoscopy. The study was explained to the patient prior to their endoscopy, often in the “pre-op” endoscopy suite. -Our intervention seeks to draw out the consent and recruitment process. All patients scheduled for upcoming endoscopies will be mailed a generic flyer announcing research studies occurring in the endoscopy suite. Patients will be pre-screened at least a week prior to endoscopy with the aid of the endoscopy scheduler. Patients interested in hearing about research will be contacted via phone by study personnel, and a copy of the consent as well as a brief summary will be mailed to the patient. -Patients potentially interested in study participation will be asked to arrive 30 minutes earlier than they typically would for their procedure, and they will be consented in a quiet and private consultation room. They will be given ample time to ask clarifying questions regarding the study. -At the conclusion of their participation, patients will receive an anonymous post-participation survey that seeks to assess their feelings regarding the study and their understanding of the research process. RESULTS/ANTICIPATED RESULTS: DISCUSSION/SIGNIFICANCE OF IMPACT: This study adds to the ongoing body of evidence suggesting that the informed consent process is more than the three key elements initially described by the Belmont Report 40 years ago. Several factors can impact patient’s willingness to participate in research, and the amount of time it takes for patients to achieve all three elements of consent can vary from person to person. The traditional method of consent just prior to study entrance is one that needs to be revisited, and we propose that prolonging the consenting process will positively impact not only patients, but also the overall research process by ensuring that those who decide to participate remain adherent to study protocols.
2523 Noninvasive biomarkers for inflammatory bowel disease: Drawbacks and potential
- Vihang Patel, Sherif Seif, Terrence Barrett
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- Journal:
- Journal of Clinical and Translational Science / Volume 2 / Issue S1 / June 2018
- Published online by Cambridge University Press:
- 21 November 2018, p. 22
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OBJECTIVES/SPECIFIC AIMS: Approximately 1.6 million Americans suffer from inflammatory bowel diseases (IBD), ulcerative colitis, and Crohn’s disease. It is a challenge for both physicians and patients alike to manage the disease, primarily due to lack of disease specific biomarkers. Endoscopy remains the gold standard to diagnose and evaluate IBD activity. Current biomarkers or their combinations cannot adequately predict IBD progression or relapse, and response to therapy. METHODS/STUDY POPULATION: In total, 97 IBD patients recruited at University of Kentucky undergoing endoscopy. Patients medical information was collected from electronic database including C-reactive protein (CRP), fecal calprotectin (FC), endoscopy/pathology report. RESULTS/ANTICIPATED RESULTS: The mean CRP and FC levels were 1.3 (normal <1) and 679 (normal <162), respectively. FC (sensitivity 74%) was more reliable to predict mucosal inflammation compare to CRP (sensitivity 36%). However, 52% of patients did not have FC performed (vs. CRP only 4%), and 45% of these patients failed to submit stool sample for analysis. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggests FC is the most promising noninvasive marker for disease monitoring in IBD. It correlates well with endoscopic activity and mucosal inflammation. However, further analysis must be done to evaluate barriers to testing and issues with compliance from patients. We feel strongly that a blood biomarker for disease activity is vital for disease monitoring and response to therapy in IBD.
2325: Steroid therapy limits stem cell activation required to enact mucosal healing in inflammatory bowel disease
- Evan Brady Lynch, Tatiana Goretsky, Emily Bradford, Tianyan Gao, Terrence Barrett
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, pp. 61-62
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OBJECTIVES/SPECIFIC AIMS: Intestinal stem cells (ISC) primarily act in the repair of ulcerated epithelium, and their proliferative capacity relies on Wnt/β-catenin signaling. However, the role of GCs on basal epithelial cell signaling has not been fully characterized. The objective of this study was to interrogate a mechanism by which steroids may limit ISC activation. GCs inhibit NFκB signaling, which has been shown to play a role in nuclear β-catenin activation in epithelial cells. We hypothesized that GCs limit Wnt/β-catenin signaling required for ISC activation and epithelial restitution by inhibiting NFκB activation in epithelial cells. METHODS/STUDY POPULATION: To examine the effects of GCs on intestinal epithelial cells, we treated a nontransformed human colonic epithelial cell line (NCM460) with dexamethasone and observed the effects on NFκB and Wnt/β-catenin signaling events. We isolated mouse epithelial cells from the distal colon for stem cell culture as 3D “organoids.” We obtained pure epithelial cell preparations from mucosal biopsies isolated from patients treated at GI clinics at the University of Kentucky Chandler Hospital and VA Medical Center, Lexington. Steroid treated patients with equivalent levels of inflammation, but no mucosal ulceration were used as controls. RESULTS/ANTICIPATED RESULTS: In steroid-treated NCM460 cells, we saw an increase in steroid-responsive genes GILZ and SGK1. We saw a significant decrease in transcripts for Wnt target genes, including Axin2 and cmyc; NFκB target genes, including IFNG and IL6; and the shared NFκB and Wnt pathway co-activator CREBBP, despite unchanged transcript levels for β-catenin (CTNNB1). This data was corroborated in 3D stem cell cultures from cells isolated from mouse colon tissue, which had significant decreases in transcripts for stem cell markers Lgr5 and Ascl2, proliferative markers KI67 and PCNA, and Wnt target Axin2. NCM460s transfected with a lentivirus carrying a TCF/LEF luciferase construct showed a 2.5-fold decrease in TNF-stimulated luciferase activity with dexamethasone treatment. Interestingly, this effect can be rescued by glucocorticoid receptor (GR) blockade with RU-486. Intestinal epithelial cells from patient biopsies showed significant decreases in colitis-induced Axin2, p-LRP6 (a positive marker of Wnt Signaling) and nuclear β-catenin, which correlated with decreased p-p65 protein levels. DISCUSSION/SIGNIFICANCE OF IMPACT: Together, these data suggest that steroid therapy inhibits Wnt/β-catenin signaling at multiple levels, and effects stem cell proliferation in pure stem cell cultures. Decreases in TCF/LEF transcriptional activation (nuclear β-catenin’s DNA binding target) can be reversed with steroid receptor blockade with RU-486, suggesting that a receptor level interaction may be occurring. Interestingly, the required co-activator CBP, shared between NFκB and Wnt pathways, has decreased transcription following steroid treatment, which may provide a mechanism for limited Wnt activation following steroid therapy. Although steroids play a significant role in regulating the amount of inflammatory damage that occurs during IBD treatment, our data suggest that they may be limiting pathways required for effective healing as well.
The effects of exercise and diet on olfactory capability in detection dogs*
- Craig T. Angle, Joseph J. Wakshlag, Robert L. Gillette, Todd Steury, Pamela Haney, Jay Barrett, Terrence Fisher
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- Journal:
- Journal of Nutritional Science / Volume 3 / 2014
- Published online by Cambridge University Press:
- 13 October 2014, e44
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A previous work suggests that dietary fat may influence canine olfaction. The present study evaluated whether olfactory performance could be influenced by forms of dietary fat and exercise. Seventeen certified detection dogs were fed three different diets (high fat, low fat or high polyunsaturated fat) for 12 weeks. After 12 weeks, olfactory testing was performed using a scent wheel in an olfaction laboratory using three explosive materials. The dogs completed eight to twelve scent trials before and after a 30 min treadmill exercise on five consecutive days. A mixed-effect logistic regression model was used to examine how diet, pre- or post-exercise, trial number, odourant, mass of target and target position influenced the probability of dogs alerting on the target odour. There were no significant changes in the dog's ability to find a target odour at threshold amounts. Dogs were 1·42 (1·08, 1·87; 95 % CI) times as likely to find a target on the high polyunsaturated fat diet relative to the high-fat diet (P = 0·009). The low-fat diet was not significantly different from either the high-fat diet or the high polyunsaturated fat diet (P = 0·12). Dogs were 1·49 (1·26, 1·76; 95 % CI) times as likely to find a target prior to exercise relative to after exercise (P < 0·001). Dogs on the high PUFA diet utilising maize oil showed mild improvement in olfaction. The exact reasons are unknown; however, the higher relative amount of linoleic acid in the diet may play a role in olfactory sensation which warrants further examination of optimal diets for detection dogs.