Digestive System Diseases Commons^™

Health-Related Quality Of Life In Pediatric Acute Recurrent Or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors, See Wan Tham, Fuchenchu Wang, Cheryl E Gariepy, Gretchen A Cress, Maisam A Abu-El-Haija, Melena D Bellin, Kate M Ellery, Douglas S Fishman, Tanja Gonska, Melvin B Heyman, Tom K Lin, Asim Maqbool, Brian A Mcferron, Veronique D Morinville, Jaimie D Nathan, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Uzma Shah, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Tonya M Palermo, International Study Group Of Pediatric Pancreatitis: In Search For A Cure (Insppire) And Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

OBJECTIVES: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL.

METHODS: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment.

RESULTS: The sample included …

Perceptions Of Weight Status And Energy Balance Behaviors Among Patients With Non-Alcoholic Fatty Liver Disease, Natalia I Heredia, Ruchi Gaba, Yan Liu, Shilpa Jain, Manasi Rungta, Manav Rungta, Hashem B El-Serag, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Students Publications

Weight loss through behavioral modification is central to treating non-alcoholic fatty liver disease (NAFLD). To achieve this, patients need to accurately self-perceive their health behaviors. We aimed to identify predictors of concordance between self-perception and objective measures of body weight, physical activity (PA) and dietary behaviors. We used data from the Harris County NAFLD Cohort, an ongoing prospective study in a regional safety-net healthcare system. Patients completed self-administered baseline questionnaires on demographics, diet, PA, and self-perceptions. We assessed concordance between actual and self-perceived body weight and energy-balance behaviors. Multivariable logistic regression identified predictors of concordance. Patients (n = 458; average …

Regulation Of The Double-Stranded Rna Response Through Adar1 Licenses Metaplastic Reprogramming In Gastric Epithelium, José B Sáenz, Nancy Vargas, Charles J Cho, Jason C Mills

Faculty, Staff and Students Publications

Cells recognize both foreign and host-derived double-stranded RNA (dsRNA) via a signaling pathway that is usually studied in the context of viral infection. It has become increasingly clear that the sensing and handling of endogenous dsRNA is also critical for cellular differentiation and development. The adenosine RNA deaminase, ADAR1, has been implicated as a central regulator of the dsRNA response, but how regulation of the dsRNA response might mediate cell fate during injury and whether such signaling is cell intrinsic remain unclear. Here, we show that the ADAR1-mediated response to dsRNA was dramatically induced in 2 distinct injury models of …

Comparative Performance Of Risk Prediction Models For Hepatitis B-Related Hepatocellular Carcinoma In The United States, Hyun-Seok Kim, Xian Yu, Jennifer Kramer, Aaron P Thrift, Pete Richardson, Yao-Chun Hsu, Avegail Flores, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Guidelines recommend hepatocellular carcinoma (HCC) surveillance in patients with chronic HBV infection. Several HCC risk prediction models are available to guide surveillance decisions, but their comparative performance remains unclear.

METHODS: Using a retrospective cohort of patients with HBV treated with nucleos(t)ide analogues at 130 Veterans Administration facilities between 9/1/2008 and 12/31/2018, we calculated risk scores from 10 HCC risk prediction models (REACH-B, PAGE-B, m-PAGE-B, CU-HCC, HCC-RESCUE, CAMD, APA-B, REAL-B, AASL-HCC, RWS-HCC). We estimated the models' discrimination and calibration. We calculated HCC incidence in risk categories defined by the reported cut-offs for all models.

RESULTS: Of 3,101 patients …

Depression And Anxiety Are Common Among Patients With Cirrhosis, Ruben Hernaez, Jennifer R Kramer, Aisha Khan, Jessica Phillips, Katharine Mccallister, Kassie Chaffin, Adriana Portela Hernandez, Hannah Fullington, Cynthia Ortiz, James-Michael Blackwell, Adam Loewen, Yan Liu, Jasmin A Tiro, Simon C Lee, Amit G Singal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Depression and anxiety can have negative effects on patients and are important to treat. There have been few studies of their prevalence among patients with cirrhosis. We aimed to characterize the prevalence and risk factors for depression and anxiety in a large multi-center cohort of patients with cirrhosis.

METHODS: We conducted a telephone-based survey of patients with cirrhosis at 3 health systems in the United States (a tertiary-care referral center, a safety net system, and a Veterans hospital) from April through December 2018. Of 2871 patients approached, 1021 (35.6%) completed the survey. Depression and anxiety were assessed …

The Autophagic Protein P62 Is A Target Of Reactive Aldehydes In Human And Murine Cholestatic Liver Disease, Colin T Shearn, Aimee L Anderson, Michael W Devereux, David J Orlicky, Cole Michel, Dennis R Petersen, Colin G Miller, Sanjiv Harpavat, Edward E Schmidt, Ronald J Sokol

Faculty, Staff and Students Publications

Inflammatory cholestatic liver diseases, including Primary Sclerosing Cholangitis (PSC), are characterized by periportal inflammation with progression to cirrhosis. The objective of this study was to examine interactions between oxidative stress and autophagy in cholestasis. Using hepatic tissue from male acute cholestatic (bile duct ligated) as well as chronic cholestatic (Mdr2KO) mice, localization of oxidative stress, the antioxidant response and induction of autophagy were analyzed and compared to human PSC liver. Concurrently, the ability of reactive aldehydes to post-translationally modify the autophagosome marker p62 was assessed in PSC liver tissue and in cell culture. Expression of autophagy markers was upregulated in …

Palliative Endoscopic Salvage Of A Functionally Obstructed Gastrojejunostomy - Report Of Technique, Elias A Chamely, Bryan Hoang, Nadim S Jafri, Melissa M Felinski, Kulvinder S Bajwa, Peter A Walker, Jaideep Barge, Erik B Wilson, Putao Cen, Shinil K Shah

Faculty, Staff and Student Publications

BACKGROUND: Gastric outlet obstruction secondary to foregut gastrointestinal malignancies can be managed with a variety of medical, endoscopic, and surgical options. Laparoscopic gastrojejunostomy is an option for those patients who are able to tolerate an operation as a long-term palliative option. This operation may be associated with some significant postoperative technical and nontechnical complications, including delayed gastric emptying. This paper describes an incision-less, endoscopic option that we propose can be used to salvage a functionally obstructed gastrojejunostomy.

CASE DESCRIPTION: A 57-year old male patient had a history of pancreatic adenocarcinoma causing gastric outlet obstruction and underwent a previously created surgical …

Classifying Esophageal Motility By Flip Panometry: A Study Of 722 Subjects With Manometry, Dustin A Carlson, C Prakash Gyawali, Abraham Khan, Rena Yadlapati, Joan Chen, Reena V Chokshi, John O Clarke, Jose M Garza, Anand S Jain, Philip Katz, Vani Konda, Kristle Lynch, Felice H Schnoll-Sussman, Stuart J Spechler, Marcelo F Vela, Jacqueline E Prescott, Alexandra J Baumann, Erica N Donnan, Wenjun Kou, Peter J Kahrilas, John E Pandolfino

Faculty, Staff and Students Publications

INTRODUCTION: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0).

METHODS: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers ("controls") and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., …

Atypical Idiopathic Intracranial Hypertension Presenting As Cyclic Vomiting Syndrome: A Case Report, Nafee T Talukder, Amanda H Clorfeine, Moira K Black, Shade B Moody

Faculty, Staff and Student Publications

BACKGROUND: Idiopathic intracranial hypertension is a disorder of increased intracranial pressure in the absence of cerebrospinal outflow obstruction, mass lesion, or other underlying cause. It is a rare phenomenon in prepubertal children and is most typically found in women of childbearing age. The classic presentation consists of headaches, nausea, vomiting, and visual changes; however, children present more atypically. We report a case of idiopathic intracranial hypertension in an otherwise healthy, 4-year-old child with atypical symptoms resembling those of cyclic vomiting syndrome.

CASE PRESENTATION: A 4-year-old Caucasian, otherwise healthy, male child presented to our emergency department with episodic intermittent early-morning vomiting …

Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Na Li, Mingyang Huang, Mason Bartels, Sophie Dogné, Shangang Zhao, Xi Chen, Clair Crewe, Leon Straub, Lavanya Vishvanath, Zhuzhen Zhang, Mengle Shao, Yongjie Yang, Christy M Gliniak, Ruth Gordillo, Gordon I Smith, William L Holland, Rana K Gupta, Bingning Dong, Nathalie Caron, Yong Xu, Yucel Akgul, Samuel Klein, Philipp E Scherer

Faculty, Staff and Students Publications

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma …

Advantage Of 16s Rrna Amplicon Sequencing In Helicobacter Pylori Diagnosis, Boldbaatar Gantuya, Hashem B El Serag, Batsaikhan Saruuljavkhlan, Dashdorj Azzaya, Takashi Matsumoto, Tomohisa Uchida, Khasag Oyuntsetseg, Nyamdorj Oyunbileg, Duger Davaadorj, Yoshio Yamaoka

Faculty, Staff and Students Publications

BACKGROUND: 16S rRNA amplicon sequencing is an accurate method of detecting microbial infection without culture. It is unclear if sequencing has additional benefits over routine diagnostic methods for Helicobacter pylori testing.

METHODS: We enrolled Mongolian volunteers with dyspepsia. Using routine diagnostic methods, positive H. pylori was defined as positive results on histology/immunohistochemistry, culture, rapid urease test, or serology; negative H. pylori was defined by negative results from all these tests. We performed 16S rRNA sequencing on gastric biopsy specimens and calculated cutoffs for operational taxonomic units (OTUs) and relative abundance (RA) to define positive results using ROC curves.

RESULTS: We …

A Novel Biomarker Panel For The Early Detection And Risk Assessment Of Hepatocellular Carcinoma In Patients With Cirrhosis, Ilvira M Khan, Donjeta Gjuka, Jingjing Jiao, Xiaoling Song, Ying Wang, Jing Wang, Peng Wei, Hashem B El-Serag, Jorge A Marrero, Laura Beretta

Faculty, Staff and Students Publications

Novel biomarkers for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis are urgently needed. We previously identified osteopontin (OPN) as a promising biomarker for the early detection of HCC. This study is to further validate the performance of OPN and identify fatty acids (FA) that could improve OPN's performance in HCC risk assessment in patients with cirrhosis. To that end, we selected 103 patients with cirrhosis under surveillance. Among them, 40 patients developed HCC during follow-up. We investigated in these 103 patients, the association between HCC incidence and prediagnostic serum levels of AFP, OPN, and 46 FAs. OPN performance was …

Dietary Factors And Gastric Intestinal Metaplasia Risk Among Us Veterans, Mimi C Tan, Niharika Mallepally, Quynh Ho, Yan Liu, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Studies on diet and gastric intestinal metaplasia (GIM) risk are lacking in US populations.

AIM: To determine the associations of dietary factors and risk of GIM among a US population with typical American diet.

METHODS: We analyzed data from a cross-sectional study of veterans attending primary care and endoscopy clinics at the Houston VA Medical Center. Patients completed a 110-item Block Food Frequency Questionnaire then underwent upper endoscopy with gastric mapping biopsies. We compared cases defined by GIM on ≥ 1 non-cardia gastric biopsy to controls without GIM. Associations of dietary factors and GIM were estimated using logistic regression …

Prevalence And Factors Associated With Nafld Detected By Vibration Controlled Transient Elastography Among Us Adults: Results From Nhanes 2017–2018, Xiaotao Zhang, Natalia I Heredia, Maya Balakrishnan, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasingly common in the adult population. In the United States, the overall burden of NAFLD is unknown due to challenges with population-level NAFLD detection. The purpose of this study was to estimate prevalence of NAFLD and significant NAFLD fibrosis and identify factors associated with them in the U.S.

METHODS: Data came from the 2017-2018 cycle of National Health and Nutrition Examination Survey. We defined NAFLD by controlled attenuation parameter (CAP) scores of ≥248 dB/m in absence of excessive alcohol use and viral hepatitis. We defined significant fibrosis as Vibration controlled transient elastography (VCTE) …

Meld-Na Is More Strongly Associated With Risk Of Infection And Outcomes Than Other Characteristics Of Patients With Cirrhosis, Zachary P Fricker, V V Pavan Kedar Mukthinuthalapati, Samuel Akinyeye, Naga Chalasani, Bashar M Attar, Maya Balakrishnan, Marwan Ghabril, Michelle T Long

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The nature and outcomes of infection among patients with cirrhosis in safety-net hospitals are not well described. We aimed to characterize the rate of and risk factors for infection, both present on admission and nosocomial, in this unique population. We hypothesized that infections would be associated with adverse outcomes such as short-term mortality.

METHODS: We used descriptive statistics to characterize infections within a retrospective cohort characterized previously. We used multivariable logistic regression models to assess potential risk factors for infection and associations with key outcomes such as short-term mortality and length of stay.

RESULTS: The study cohort …

Alcohol Consumption And The Risk Of Gastric Intestinal Metaplasia In A Us Veterans Population, Hudson M Holmes, Andre G Jove, Mimi C Tan, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Chronic alcohol use is a risk factor for non-cardia gastric adenocarcinoma. However, it is less well understood whether alcohol use is a risk factor for premalignant mucosal changes, namely gastric intestinal metaplasia. We examined the association between various parameters of alcohol use and risk of gastric intestinal metaplasia.

METHODS: We used data from 2084 participants (including 403 with gastric intestinal metaplasia) recruited between February 2008-August 2013 into a cross-sectional study at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. All participants underwent a study upper endoscopy with systematic gastric mapping biopsies. Cases had intestinal metaplasia on …

Model For End-Stage Liver Disease-Sodium Underestimates 90-Day Mortality Risk In Patients With Acute-On-Chronic Liver Failure, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Abbas Rana, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: It is unclear whether the model for end-stage liver disease-sodium (MELD-Na) score captures the clinical severity of acute-on-chronic liver failure (ACLF). We compared observed 90-day mortality in patients with ACLF with expected mortality based on the calculated MELD-Na and examined the consequences of underestimating clinical severity.

METHODS: We identified patients with ACLF during hospitalization for cirrhosis in 127 VA hospitals between 01/01/2004 and 12/31/2014. We examined MELD-Na scores by ACLF presence and grade. We used actual and observed 90-day mortality to estimate a standardized mortality ratio (SMR) by ACLF presence and grade. We used transplant center-specific median …

Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND: Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

PATIENTS AND METHODS: We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

RESULTS: Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line …

Prevalence Of Helicobacter Pylori Positive Non-Cardia Gastric Adenocarcinoma Is Low And Decreasing In A Us Population, Theresa H Nguyen, Niharika Mallepally, Tariq Hammad, Yan Liu, Aaron P Thrift, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND: Helicobacter pylori infection is an established causal factor for non-cardia gastric cancer. H. pylori negative gastric cancer prevalence among US patients is unclear.

METHODS: This retrospective cohort study examined H. pylori prevalence among consecutive patients with incident non-cardia gastric adenocarcinoma at the Houston VA Hospital (11/2007-10/2018). H. pylori positivity was defined by H. pylori on histopathology, positive antibody serology, stool antigen, or urea breath testing. We examined for trends in H. pylori negative gastric cancer based on year of diagnosis. Associations between histopathologic and cancer-related outcomes with H. pylori positivity were determined using regression models.

RESULTS: Of 91 patients …

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …

Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function In Mouse Hepatocytes, Sungwoo Choi, Bingning Dong, Chih-Chun Janet Lin, Mi Jeong Heo, Kang Ho Kim, Zhen Sun, Martin Wagner, Nagireddy Putluri, Jae Myoung Suh, Meng C Wang, David D Moore

Faculty, Staff and Students Publications

Liver receptor homologue-1 (LRH-1; NR5A2) is a nuclear receptor that regulates metabolic homeostasis in the liver. Previous studies identified phosphatidylcholines as potential endogenous agonist ligands for LRH-1. In the liver, distinct subsets of phosphatidylcholine species are generated by two different pathways: choline addition to phosphatidic acid via the Kennedy pathway, or trimethylation of phosphatidylethanolamine via Phosphatidylethanolamine N-methyl Transferase (PEMT). Here we report that a PEMT - LRH-1 pathway specifically couples methyl metabolism and mitochondrial activities in hepatocytes. We show that the loss of Lrh-1 reduces mitochondrial number, basal respiration, beta-oxidation and ATP production in hepatocytes, and decreases expression of mitochondrial …

Comparison Of Microneutralization And Histo-Blood Group Antigen-Blocking Assays For Functional Norovirus Antibody Detection, Robert L Atmar, Khalil Ettayebi, B Vijayalakshmi Ayyar, Frederick H Neill, Ralph P Braun, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels.

METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays.

RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking.

CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses.

Prevalence Of Chronic Hepatitis B In Oro Province, Papua New Guinea, Alice Unah Lee, Luke Mair, Bob Kevin, Lily Gandi, Olive Tarumuri, Caroline Lee, Sue Huntley, David Carl Hilmers

Faculty, Staff and Students Publications

Chronic hepatitis B (CHB) affects over 250 million people worldwide. In Papua New Guinea, the prevalence of CHB has been estimated to be over 8%, and it is a leading cause of death. To address this problem, an alliance was formed between the government of Oro Province, a large private employer and an Australian nongovernmental organization, which established a CHB test and treatment programme. Between 2014 and 2019, rapid hepatitis B surface antigen testing was performed on 4068 individuals in Oro Province. The crude prevalence rate was 12.98% and was significantly higher in males (15.26%) than females (10.94%) (P < 0.001). The rate was 4.72% among children aged 10 years and under, 12.81% among women of childbearing age (19–35 years) and 18.48% among health-care workers. These results indicate that the rates of vaccination at birth and later among women of childbearing age and health-care workers must be improved to prevent transmission of CHB.

A Nationwide Study On The Prevalence Of Functional Gastrointestinal Disorders In School-Children., Miguel Saps, Jairo Enrique Moreno-Gomez, Carmen Rossy Ramírez-Hernández, John M. Rosen, C A. Velasco-Benitez

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Functional gastrointestinal disorders (FGIDs) are highly prevalent worldwide and are thought to result from the interplay of multiple factors that can vary from region to region. Nationwide studies can help understand the regional epidemiology and the pathogenesis of FGIDs. The objectives of this study were to determine the prevalence of FGIDs in school-children of Colombia and assess associated factors.

Methods: A cross-sectional study was carried out at twelve private and public schools in ten cities distributed through the four main geographic regions of Colombia. School-children completed a validated questionnaire to assess functional gastrointestinal disorders according to Rome III criteria. …

Exome Analysis Of Rare And Common Variants Within The Nod Signaling Pathway., Gaia Andreoletti, Valentina Shakhnovich, Kathy Christenson, Tracy Coelho, Rachel Haggarty, Nadeem A. Afzal, Akshay Batra, Britt-Sabina Petersen, Matthew Mort, R Mark Beattie, Sarah Ennis

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort …

Ibd Live Case Series-Case 6., Dhyan Rajan, Julia B. Greer, Miguel D. Regueiro, Leonard Baidoo, David G. Binion, Hans H. Herfarth, Corey A. Siegel, Douglas J. Hartman, Francis A. Farraye, Ioannis E. Koutroubakis, Myron H. Brand, Emmanuelle D. Williams, Alka Goyal, Raymond K. Cross

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Are Immune Modulating Single Nucleotide Polymorphisms Associated With Necrotizing Enterocolitis?, Ashanti L Franklin, Mariam Said, Clint D Cappiello, Heather Gordish-Dressman, Zohreh Tatari-Calderone, Stanislav Vukmanovic, Khodayar Rais-Bahrami, Naomi L C Luban, Joseph M Devaney, Anthony D Sandler

Genomics and Precision Medicine Faculty Publications

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over …

Repression Of Esophageal Neoplasia And Inflammatory Signaling By Anti-Mir-31 Delivery In Vivo., Cristian Taccioli, Michela Garofalo, Hongping Chen, Yubao Jiang, Guidantonio Malagoli Tagliazucchi, Gianpiero Di Leva, Hansjuerg Alder, Paolo Fadda, Justin Middleton, Karl J. Smalley, Tommaso Selmi, Srivatsava Naidu, John L. Farber, Carlo M. Croce, Louise Fong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Overexpression of microRNA-31 (miR-31) is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary zinc deficiency. Using a rat model that recapitulates features of human ESCC, the mechanism whereby Zn regulates miR-31 expression to promote ESCC is examined.

METHODS: To inhibit in vivo esophageal miR-31 overexpression in Zn-deficient rats (n = 12-20 per group), locked nucleic acid-modified anti-miR-31 oligonucleotides were administered over five weeks. miR-31 expression was determined by northern blotting, quantitative polymerase chain reaction, and in situ hybridization. Physiological miR-31 targets were identified by microarray analysis and verified by luciferase reporter …