MicroRNAs (miRNAs) are short, non-coding strands of RNA found in eukaryotes. They play a role in gene silencing through inhibiting translation or degrading mRNA. Primary miRNA (pri-miRNA) processing is the initial step in producing a mature microRNA molecule. The microprocessor complex (MP) proteins, DROSHA and DGCR8, cleaves the pri-miRNA molecule to a shorter hairpin structure. This cleaved RNA hairpin, precursor miRNA, is sent to the cytoplasm for further processing into the mature miRNA. Previous research has uncovered that the expression and cellular localization of the stress-responsive protein, nucleolin (NCL) affects the processing of several miRNAs, including microRNA 16 (miR16). Nucleolin is an RNA binding protein and is primarily located in the nucleolus but can also be localized in various cellular compartments. When NCL is present in the nucleus, the MP complex works more efficiently in cleaving pri-miR 16-1 to its pre-miRNA form resulting in an upregulation of miR 16-1. It has been proposed that nucleolin binds to pri-miR 16-1 and stabilizes its confirmation for cleavage by the MP complex. However, the mechanistic and structural details on how nucleolin interacts with pri-miRNA 16-1 or the MP are still unclear. It is also unknown if NCL is similarly involved in miR 16-2 biogenesis. NCL and miRNA 16 are also intricately involved in the regulation of the expression of bcl2, an anti-apoptotic and oncogenic protein. When NCL is in the cytoplasm, it stabilizes the 3' untranslated region of bcl2 mRNA leading to an increased expression of the protein. Unlike nucleolin, miR 16 represses the translation of bcl2 mRNA. At high levels of miR 16 when NCL is localized to the nucleus, bcl2 protein expression is low. When cellular stress occurs, NCL returns to the cytoplasm to stabilize bcl2 and this also results in less efficiency in pri-miR 16 processing, resulting in an overall increase in bcl2 protein. It is evident that NCL balances the levels of bcl2 and miR16 through its cellular localization. Since the molecular mechanism underlying NCL's role in the MP-based processing of pri-miR16-1 remains largely unknown, in this study, we used computational approaches including structural alignments, protein-protein, and protein-RNA docking analyses to determine how pri-miR 16-1, nucleolin, and the MP complex interact. In addition, we have investigated if pri-miR 16-2 interacts with the NCL and the MP complex in a similar fashion. We show in our predictive models that the interaction interface of pri-miR 16-1 and pri-miR 16-2 with nucleolin and the MP complex nucleolin is distinct. For pri-miR 16-1, the interaction interface involves NCL and DGCR8 B and C, but in the case of pri-miR 16-2, it involves NCL and DROSHA. Additionally, in the presence of nucleolin, the hydrogen bond interactions are reduced between pri-miR 16-2 and the MP complex. Although the number of interactions between the different components of the MP complex is the same in both scenarios, the specific residues that form the interaction interface differ, suggesting distinct mechanisms. Since the levels of miR16 expression can lead to apoptosis of cancerous cells and prevent cell proliferation, the results of our study provide important clues in understanding how the NCL-miR-MP complex can be targeted in drug design for cancer therapy.

Women make up 15% of the total number of practicing gastroenterology (GI) physicians in the US. Despite this disparity, only 33% of the current GI fellows are female. Increasing female GIs is a major goal of all four GI societies. It is known that gender disparity exists in the field of gastroenterology, and women are underrepresented in the leadership ranks and trainee level at academic programs. Whether an increase in female leadership in academic medicine is associated with an increase in female program directors and trainees is unknown. The aim of this study was to assess this relationship in GI. Data were collected via a standardized protocol from all 173 US gastroenterology fellowship programs up until October 2018 from program websites and supplemented by online surveys completed by program coordinators. Any missing information was collected by calling the program coordinators. Data were collected on gender and academic rank of the program director, associate program director, division chief, chair of medicine, program size, academic center affiliation, number, and academic rank of female faculty and geographic region. The association was assessed using a Chi-square test or independent samples t test. In leadership positions, men were listed as comprising 86% of chairs, 82% of division chiefs, 76% of program directors and 63% of associate program directors. Forty-three percent of programs did not have female representation at any leadership level. The presence of a female program director or female associate program director was associated with an increase in the number of female fellows (4.03 vs 3.20; p = 0.076; 4.26 vs 3.36; p = 0.041), respectively. Overall, the presence of a female in any leadership position led to an increase in the number of female fellows (4.04 females vs 2.87 females; p = 0.007) enrolled in a program. If a GI division chief was male, the program director was more likely to be male as well (81% male vs. 18.8% female). Conversely, having a female division chief was likely to lead to a more equitable program director representation, 54% female to 48% male (p value < 0.0001, OR 5.03 95% CI 2.04–12.3). Furthermore, if either the internal medicine department chair or GI chief was female, the proportion of female program directors increased to 41% as compared to 19% if both were male (p value < 0.0001, OR 2.99 95% CI 1.34–6.6). Women are significantly underrepresented in the number of practicing gastroenterologists, at all levels of leadership in GI fellowship programs, and at the fellow level. Increasing the number of women in fellowship leadership positions is associated with an increase in female program directors and trainees. Per our knowledge, this is the first study to examine the relationship between female leadership in fellowship programs and the gender of trainees. Increasing female representation in leadership positions would not only address current gender disparity, but it may also increase the number of female future GI trainees.

INTRODUCTION: Colorectal cancer is the third most cancer diagnosed in USA. Long noncoding RNAs (lncRNAs) are important orchestrators of essential biological networks and regulate cell growth, apoptosis, epigenetics transcription and translation. Multiple lines of evidence link regulatory lncRNAs to diseases. 1,2 METHODS: The project determined the expression of lncRNAs in samples from normal and highly aggressive colorectal cancer. Using paraffin imbedded samples, the epithelial layer was demarcated under the microscope and isolated with a scalpel. Total RNA was isolated and cDNA was used in the LncProfiler qPCR Array (SBI). RESULTS: Results show an increase in lncRNAs DISC2, HAR1A, HAR1B, HULC, NEAT1, NRON, PRINS and RNCR3 in the cancer samples compared to the normal. We further sought to evaluate whether an obese environment could promote the normal colon cells into cancer-like phenotype. To evaluate this, we used exosomes derived from adipose stem cells (ASC) obtained from lean or normal individuals to mimic the obese environment. Colon epithelial cells were cultured and either treated with lean ASC exosomes or obese exosomes for 24 hours. Total RNA was isolated and cDNA was used in the LncProfiler qPCR Array. Amongst the detected lncRNAs, our results showed an increase in DISC-2, NEAT1, NRON, PRINS and RNCR3 lncRNAs which were observed to be increased in the colon cancer samples. Simultaneously, using real time qPCR we saw an increase in pro-survival genes Bcl2, Bcl-xL and caspase 9b in cells treated with exosomes from obese ASC. CONCLUSION: The results suggest that obesity may lead to increased incidence of colon cancer. We have known it for years for obesity to increase the risk od colorectal cancers slightly and now we have some insights into the pathophysiology.

INTRODUCTION: Capsule endoscopy is an important tool for noninvasive identification of gastrointestinal pathology. It requires a physician to review images which can be tedious and time consuming. The use of artificial intelligence has increased in popularity for colonoscopy for identification of polyps and vascular lesions. We aim to use computer-assisted image analysis using convolutional neural networks (CNNs) for the identification of inflammatory and vascular lesions on capsule endoscopy. METHODS: We examined a total of 2371 publicly available wireless capsule endoscopy (WCE) images obtained using MiroCam® (IntroMedic Co, Seoul, Korea) capsule endoscopes. The capsule images illustrated normal and assorted small bowel findings including polypoid, vascular and, inflammatory lesions and were notated with each finding. Images were divided into “normal” (725 images), “inflammatory” (225 images), and “vascular” (300 images) for the purposes of this analysis. Pre-processing was performed on these images. Augmentation of the image was performed by flipping and rotating the image to obtain multiple views of pathologic and normal images. The machine learning algorithm was trained on the original and augmented images, testing was only performed on original images. RESULTS: Using this machine learning architecture, a total testing accuracy of 73.7% was able to be achieved for the differentiation of normal versus inflammatory and a total testing accuracy of 70.2% was able to be achieved for the differentiation of normal versus vascular capsule endoscopy images. In a set of 2371 capsule endoscopy images, the CNN identified both vascular and inflammatory images using a 5-Fold Cross validation with an accuracy of 73.7% for normal compared to inflammatory images (Figure 1) and 70.20% for normal versus vascular images. The area under the receiver operating characteristic curve (ROC) for identification of inflammatory images was 0.70 (95% CI 0.664-0.736) compared to 0.68 (95% CI 0.646-0.714) for vascular lesions. CONCLUSION: This system demonstrates that AI can be used to find more subtle inflammatory and vascular lesions. The CNN system detected and localized polyps well within real-time constraints using an ordinary desktop machine with a contemporary graphics-processing unit. It can increase the findings of pathology and decrease time needed to review capsule endoscopy studies, but requires further validation in large multicenter trials.

INTRODUCTION: Approximately 5–10% of patients who present with an acute gastrointestinal (GI) hemorrhage have a primary small bowel source. While small bowel angioectasias are one of the most common causes of small bowel hemorrhage, it is rare to find large vascular anomalies in the small bowel as a cause of chronic GI bleed. CASE DESCRIPTION/METHODS: We present a case of a 56-year-old woman referred to our institution for management of obscure GI bleeding, associated with severe iron deficiency anemia. She had intermittent melena and occasional dark red blood mixed with stool. Extensive work up in an outside facility including 2 endoscopies, 2 colonoscopies, and a capsule endoscopy were unrevealing. After referral to our institution; push enteroscopy, colonoscopy and retrograde single balloon enteroscopy were performed and were negative for source of bleeding. Capsule endoscopy revealed a small oozing angioectasia in proximal jejunum. The lesion was treated with heater probe via anterograde single-balloon enteroscopy. Due to persistent melena and anemia, antegrade balloon enteroscopy was repeated and demonstrated an abnormal cluster of vascular-appearing lesions in the proximal jejunum that were marked with two hemostatic clips. CT angiogram was consistent with a large arteriovenous malformation (AVM). Interventional radiology performed glue embolization of the high-flow jejunal arteriovenous malformation. The post procedure course was complicated by ischemic proximal jejunum which was confirmed on repeat enteroscopy. Fortunately, her symptoms completely resolved with conservative management without surgical intervention. DISCUSSION: AVMs are abnormal lesions with a direct connection between the arterial and venous blood supply without any true capillary bed connecting them. While extremely rare within the GI tract, they can cause significant amount of bleeding and must be considered in patients with obscure GI bleeding or chronic iron deficiency anemia. Studies have shown that AVMs typically only account for 1–2% of upper GI bleeds. More common sites for AVMs include the cecum and ascending colon, while other sites like the small bowel are much more rare. Diagnostic work up typically begins with upper endoscopy followed by colonoscopy. However, these tests are often unrevealing when dealing with small bowel AVMs. Patient’s typically undergo capsule endoscopy for further evaluation, as seen in our patient. If the source of bleeding is still un-identified, then angiography or bleeding scans may be required.

INTRODUCTION: This retrospective cohort study aims to address the overall incidence of formal malnutrition assessments of U.S. veteran patients with decompensated cirrhosis and how these assessments impact clinical outcomes. METHODS: All consecutive adult U.S. veteran patients with a diagnosis of decompensated cirrhosis were identified in the James A. Haley VA Computerized Patient Record System using ICD-9 and ICD-10 codes associated with decompensated cirrhosis. Patients were included in the study if they had at least 2 cross-sectional imaging studies (CT or MRI) approximately 2 years apart from one another in order to identify significant changes in skeletal muscle composition and body fat as a primary outcome. These studies were reviewed and compared by one independent radiologist. Demographic and clinical data were also extracted. Malnutrition assessments were evaluated by one registered dietician (RD) based on review of prior dietician consultation notes that documented clinical evidence of malnutrition. RESULTS: 101 subjects with decompensated cirrhosis met inclusion criteria; 97% were male with a median age of 60 years. The most common etiology of cirrhosis was due to hepatitis C virus. The overall incidence of at least one documented nutritional assessment conducted by a registered dietician (RD) was 69% (70/101). Approximately 41% of those patients evaluated by an RD were confirmed as being malnourished and had significant reductions in the dimensions of their gluteus maximus, erector spinae muscles and flank fat while their BMI and MELD scores were relatively unchanged over a 2-year period. Cirrhotic veterans that were not evaluated by an RD had similar reductions in fat and muscle mass compositions. Only 17% of malnourished subjects that were evaluated by an RD had a billing code (ICD-9 or ICD-10) in their medical record that corresponded to their malnutrition. CONCLUSION: Nearly one-third of U.S. veterans with decompensated cirrhosis had a documented diagnosis of malnutrition. There were significant reductions in skeletal muscle mass and fat mass over a 2-year time period that correlated with their chronic disease-related malnutrition. Interestingly, the presence or absence of an RD evaluation had no significant impact on these reductions. Corresponding ICD-9/ICD-10 billing codes associated with malnutrition were underreported, which may be a potential barrier in identifying and optimally treating malnutrition in U.S. veteran patients with decompensated cirrhosis.

INTRODUCTION: IBD is growing at an alarming rate from than 1 per100,000 in 1960s to 4.1 in 1980s in the western world. This sharp increase is unlikely to be explained by genetic factors alone and an environmental factor is strongly incriminated. Diet has been proposed by some as a plausible culprit with significant effect on the course of IBD. Western diet which is high in refined sugar and processed food has been associated with altered immune response and thought to contribute to the pathogenesis of inflammatory bowel disease. Food rich in fruits and vegetables have a lower incidence of IBD. In this regard elemental diet has been studies extensively However there appears to be a taste fatigue leading to poor tolerance and there is lack of data for its long-term effectiveness. Another diet which has shown promise, is specific carbohydrate diet (SCD) and has the potential for better tolerance. Patient unwillingness and lack of familiarity with this diet by providers has been reported as causes for limited use. Here we are reporting patient willingness to participate when provider training is present. METHODS: We have a gastroenterologist at our Institution who is also Board Certified in Nutrition by American Society of Enteral Nutrition (A.S.P.E.N.). Provider knowledge in SCD increased with giving National talks and attending nutrition conferences. This led to creation of an inner core group team by training of registered dietician (RD). Via a grant, books were obtained for patient distribution and hundreds of recipes. Patients who were seen in clinic or inpatients were offered SCD when provider felt it was appropriate. Inclusion criteria was presence of IBD. Exclusion criteria was stable disease, fulminant colitis. Treatment was offered with one-on-one session with a RD and a second meeting the next day if patient had any questions. Patients were given books, recipes. A telephone call was planned in 2 weeks and a follow-up. RESULTS: Eight patients were offered SCD of which 7 patients agreed to participate. When this result was compared prior to training of the inner core team no patient was offered this. CONCLUSION/DISCUSSION: Our numbers are small and out study has just started but it does reveal that when a team trained in Nutrition is involved more patient participation is seen as several patients want to avoid side-effects of expensive and toxic medications. Our goal is to check patient compliance, its impact on the course of disease.