Gastroenterology Commons^™

Novel Fold Of Rotavirus Glycan-Binding Domain Predicted By Alphafold2 And Determined By X-Ray Crystallography, Liya Hu, Wilhelm Salmen, Banumathi Sankaran, Yi Lasanajak, David F Smith, Sue E Crawford, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

The VP8* domain of spike protein VP4 in group A and C rotaviruses, which cause epidemic gastroenteritis in children, exhibits a conserved galectin-like fold for recognizing glycans during cell entry. In group B rotavirus, which causes significant diarrheal outbreaks in adults, the VP8* domain (VP8*B) surprisingly lacks sequence similarity with VP8* of group A or group C rotavirus. Here, by using the recently developed AlphaFold2 for ab initio structure prediction and validating the predicted model by determining a 1.3-Å crystal structure, we show that VP8*B exhibits a novel fold distinct from the galectin fold. This fold with a β-sheet clasping …

Necrotizing Enterocolitis Rates In Preterm Infants, Alexis Howard

The Eleanor Mann School of Nursing Undergraduate Honors Theses

Breast milk and donor human milk is used in the prevention of necrotizing enterocolitis (NEC) in preterm infants born prior to 37 weeks gestation and those with very low birth weight. This process occurs through direct breast feeding and tube feeding. The aim of this study was to compare the use of breast milk and donor milk to the use of formula feed in preterm infants. A systematic review was conducted using articles collected from CINAHL and PubMed and was guided by PRISMA guidelines. A total of 15 studies that met criteria were analyzed by purpose, variables, study design, population …

Natural Killer Cells In Liver Transplantation: Can We Harness The Power Of The Immune Checkpoint To Promote Tolerance?, Jennifer Halma, Stephen Pierce, Rebecca Mclennan, Todd Bradley, Ryan T. Fischer

Manuscripts, Articles, Book Chapters and Other Papers

The roles that natural killer (NK) cells play in liver disease and transplantation remain ill-defined. Reports on the matter are often contradictory, and the mechanisms elucidated are complex and dependent on the context of the model tested. Moreover, NK cell attributes, such as receptor protein expression and function differ among species, make study of primate or rodent transplant models challenging. Recent insights into NK function and NK-mediated therapy in the context of cancer therapy may prove applicable to transplantation. Of specific interest are immune checkpoint molecules and the mechanisms by which they modulate NK cells in the tumor micro-environment. In …

Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh

Dissertations and Theses (Open Access)

Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, incidences of abscopal tumor remission are extremely rare, and the post-irradiation immune escape mechanisms in CRC remain elusive. We report that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate immune activation. This post-irradiation CD47 and PD-L1 upregulation can be observed across various human solid tumor cells. Concordantly, …

Sirolimus (Rapamycin) Induced Mucosal Healing In Anti-Tumor Necrosis Factor Refractory Pediatric Ulcerative Colitis, Richard Kellermayer, Andrew Chang, Kalyani Patel

Faculty, Staff and Students Publications

Sirolimus (rapamycin) has been sparsely reported in the treatment of pediatric ulcerative colitis (PUC). Mucosal healing has not been examined in responders to the drug. We describe a case of infliximab refractory PUC where rapamycin induced sustained clinical remission along with mucosal healing. We conclude that rapamycin should be positioned into the expanding treatment repertoire of PUC.

Prevalence And Clinical Correlates Of Antinuclear Antibody In Patients With Gastroparesis, Henry P Parkman, Mark L Van Natta, Ashima Makol, Madhusudan Grover, Richard W Mccallum, Zubair Malik, Kenneth L Koch, Irene Sarosiek, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Laura Miriel, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Thomas L Abell, Niddk Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

BACKGROUND: Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders.

AIMS: 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA.

METHODS: Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP).

RESULTS: Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), …

Evaluating Eosinophilic Colitis As A Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study, Tetsuo Shoda, Margaret H Collins, Mark Rochman, Ting Wen, Julie M Caldwell, Lydia E Mack, Garrett A Osswald, John A Besse, Yael Haberman, Seema S Aceves, Nicoleta C Arva, Kelley E Capocelli, Mirna Chehade, Carla M Davis, Evan S Dellon, Gary W Falk, Nirmala Gonsalves, Sandeep K Gupta, Ikuo Hirano, Paneez Khoury, Amy Klion, Calies Menard-Katcher, John Leung, Vincent A Mukkada, Philip E Putnam, Jonathan M Spergel, Joshua B Wechsler, Guang-Yu Yang, Glenn T Furuta, Lee A Denson, Marc E Rothenberg, Consortium Of Eosinophilic Gastrointestinal Diseases Researchers (Cegir)

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.

METHODS: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations …

Primer For Development Of Guidelines For Helicobacter Pylori Therapy Using Antimicrobial Stewardship, David Y Graham, Jyh-Ming Liou

Faculty, Staff and Students Publications

We provide a primer to assist in the difficult transition of Helicobacter pylori therapy guidelines to those that adhere to the principles of antimicrobial stewardship. This transition will entail abandonment of many of the principles that heretofore formed the basis of treatment guidelines and recommendations. The goals of antimicrobial stewardship include optimization of the use of antibiotics while reducing antimicrobial resistance. The critical outcome measure is absolute cure rate which largely restricts comparative trials to those which reliably produce high cure rates (eg, ∼95%). Therapies that fail to achieve at least a 90% cure rate should be abandoned as unacceptable. …

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 …

Chromatin State Dynamics Confers Specific Therapeutic Strategies In Enhancer Subtypes Of Colorectal Cancer, Elias Orouji, Ayush T Raman, Anand K Singh, Alexey Sorokin, Emre Arslan, Archit K Ghosh, Jonathan Schulz, Christopher Terranova, Shan Jiang, Ming Tang, Mayinuer Maitituoheti, Scot C Callahan, Praveen Barrodia, Katarzyna Tomczak, Yingda Jiang, Zhiqin Jiang, Jennifer S Davis, Sukhen Ghosh, Hey Min Lee, Laura Reyes-Uribe, Kyle Chang, Yusha Liu, Huiqin Chen, Ali Azhdarinia, Jeffrey Morris, Eduardo Vilar, Kendra S Carmon, Scott E Kopetz, Kunal Rai

Faculty, Staff and Student Publications

Objective: Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described.

Design: We performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer cell lines) for six histone modification marks: H3K4me3 for Pol II-bound and CpG-rich promoters, H3K4me1 for poised enhancers, H3K27ac for enhancers and transcriptionally active promoters, H3K79me2 for transcribed regions, H3K27me3 for polycomb repressed regions and …

The Covid-19 Pandemic: Early Ripple Effects In Pediatric Palliative Care, Linda Marisol Bustamante, Regina Okhuysen-Cawley, Julia Downing, Stephen R Connor, Mary Ann Muckaden, Marianne Phillips, Andrea Icaza, Nicole Garzon, Yuriko Nakashima, Kelsi Morgan, David Mauser, Michelle Grunauer

Faculty, Staff and Students Publications

Palliative care, which aims to provide comprehensive, interdisciplinary, holistic care to children, adolescents and adults with life-threatening, and ultimately life-limiting conditions, is a discipline that has emerged as an integral component of healthcare systems throughout the world. Although the value of life-affirming palliative care (PC) has been shown across many domains, funding and acceptance of palliative care teams have been variable: some hospital systems have free-standing, dedicated interdisciplinary teams while, in many instances, palliative care services are provided "pro bono" by individuals with a special interest in the discipline, who provide PC in addition to other responsibilities. In this article, …

Perceived Roles, Benefits And Barriers Of Virtual Global Health Partnership Initiatives: A Cross-Sectional Exploratory Study, Lisa Umphrey, George Paasi, William Windsor, Grace Abongo, Jessica Evert, Heather Haq, Elizabeth M Keating, Suet Kam Lam, Megan S Mchenry, Carolyne Ndila, Charles Nwobu, Amy Rule, Reena P Tam, Daniel Olson, Peter Olupot-Olupot

Faculty, Staff and Students Publications

BACKGROUND: Virtual global health partnership initiatives (VGHPIs) evolved rapidly during the COVID-19 pandemic to ensure partnership continuity. However the current landscape for VGHPI use and preference is unknown. This study aimed to increase understanding of GH partners' perspectives on VGHPIs.

METHODS: From 15 October to 30 November 2020, An online, international survey was conducted using snowball sampling to document pandemic-related changes in partnership activities, preferences for VGHPIs, and perceived acceptability and barriers. The survey underwent iterative development within a diverse author group, representing academic and clinical institutions, and the non-profit sector. Participants from their professional global health networks were invited, …

Variability Of Care And Access To Transplantation For Children With Biliary Atresia Who Need A Liver Replacement, Jean De Ville De Goyet, Toni Illhardt, Christophe Chardot, Peace N Dike, Ulrich Baumann, Katherine Brandt, Barbara E Wildhaber, Mikko Pakarinen, Fabrizio Di Francesco, Ekkehard Sturm, Marianna Cornet, Caroline Lemoine, Eva Doreen Pfister, Ana M Calinescu, Maria Hukkinen, Sanjiv Harpavat, Fabio Tuzzolino, Riccardo Superina

Faculty, Staff and Students Publications

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed—from diagnosis to LT—with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life …

The Chromosome-Level Rambutan Genome Reveals A Significant Role Of Segmental Duplication In The Expansion Of Resistance Genes, Jinfang Zheng1, Lyndel W. Meinhardt, Ricardo Goenaga, Tracie Matsumoto, Dapeng Zhang, Yanbin Yin

Food for Health: Publications

Rambutan (Nephelium lappaceum var. lappaceum), a tropical fruit tree native to southeastern Asia, belongs to the family Sapindaceae. Rambutan is a popular table fruit and is also processed into preserves, juices, wines, and sorbets [1]. At present, only three Sapindaceae genomes are publicly available: Xanthoceras sorbifolium [2], Dimocarpus longan (longan) [3], and Acer yangbiense [4]. During the process of submitting this manuscript, the genome paper for the rambutan cultivar Baoyan7 became available online, but its genome sequence has not yet been released [5].

Methylation Quantitative Trait Loci Are Largely Consistent Across Disease States In Crohn’S Disease, Suresh Venkateswaran, Hari K Somineni, Varun Kilaru, Seyma Katrinli, Jarod Prince, David T Okou, Jeffrey S Hyams, Lee A Denson, Richard Kellermayer, Greg Gibson, David J Cutler, Alicia K Smith, Subra Kugathasan, Karen N Conneely

Faculty, Staff and Students Publications

Recently, we identified 1,189 CpG sites whose DNA methylation level in blood associated with Crohn's disease. Here, we examined associations between DNA methylation and genetic variants to identify methylation quantitative trait loci across disease states in (1) 402 blood samples from 164 newly diagnosed pediatric Crohn's disease patients taken at 2 time points (diagnosis and follow-up), and 74 non-inflammatory bowel disease controls, (2) 780 blood samples from a non-Crohn's disease adult population, and (3) 40 ileal biopsies (17 Crohn's disease cases and 23 non-inflammatory bowel disease controls) from group (1). Genome-wide DNAm profiling and genotyping were performed using the Illumina …

Antimicrobial Susceptibility Testing For Helicobacter Pylori Is Now Widely Available: When, How, Why, David Y Graham, Steven F Moss

Faculty, Staff and Students Publications

No abstract provided.

Prevalence And Predictors Of Missed Dysplasia On Index Barrett's Esophagus Diagnosing Endoscopy In A Veteran Population, Theresa H Nguyen, Aaron P Thrift, Rollin George, Daniel G Rosen, Hashem B El-Serag, Gyanprakash A Ketwaroo

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis.

METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up …

Comparison Of Endoscopic Ultrasound-Directed Transgastric Endoscopic Retrograde Cholangiopancreatography Outcomes Using Various Technical Approaches, Firas Bahdi, Rollin George, Kavea Paneerselvam, Dang Nguyen, Wasif M Abidi, Mohamed O Othman, Isaac Raijman

Faculty, Staff and Students Publications

Background and study aims  Roux-en-Y gastric bypass presents an anatomic challenge for patients needing ERCP. EUS-directed transgastric ERCP (EDGE) offers high clinical success but carries considerable risk of adverse events (AEs) with no standardized technical approach. In our study, we review the safety and efficacy of our various EDGE technical approaches.

Patients and methods  A retrospective single-center study of all patients who underwent EDGE procedures between February 2018 and November 2019. Primary outcomes included comparing the technical and clinical success, AEs, and lumen-apposing metal stent (LAMS) migration rates per access route (gastrogastric vs jejuno-gastric), number of procedure stages (single-stage vs …

Prevalence And Predictors Of Missed Dysplasia On Index Barrett's Esophagus Diagnosing Endoscopy In A Veteran Population, Theresa H Nguyen, Aaron P Thrift, Rollin George, Daniel G Rosen, Hashem B El-Serag, Gyanprakash A Ketwaroo

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis.

METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up …

Loss Of Rnf43 Accelerates Kras-Mediated Neoplasia And Remodels The Tumor Immune Microenvironment In Pancreatic Adenocarcinoma, Abdel Nasser Hosein, Gita Dangol, Takashi Okumura, Jason Roszik, Kimal Rajapakshe, Megan Siemann, Mohamed Zaid, Bidyut Ghosh, Maria Monberg, Paola A Guerrero, Aatur Singhi, Cara L Haymaker, Hans Clevers, Lotfi Abou-Elkacem, Sonja M Woermann, Anirban Maitra

Faculty, Staff and Student Publications

Background & aims: RNF43 is an E3 ubiquitin ligase that is recurrently mutated in pancreatic ductal adenocarcinoma (PDAC) and precursor cystic neoplasms of the pancreas. The impact of RNF43 mutations on PDAC is poorly understood and autochthonous models have not been characterized sufficiently. In this study, we describe a genetically engineered mouse model (GEMM) of PDAC with conditional expression of oncogenic Kras and deletion of the catalytic domain of Rnf43 in exocrine cells.

Methods: We generated Ptf1a-Cre;LSL-KrasG12D;Rnf43flox/flox (KRC) and Ptf1a-Cre; LSL-KrasG12D (KC) mice and animal survival was assessed. KRC mice were sacrificed at 2 months, 4 months, and at moribund …

Skp2 Stabilizes Mcl-1 And Confers Radioresistance In Colorectal Cancer, Xinfang Yu, Li Zhou, Wenbin Liu, Lijun Liu, Feng Gao, Wei Li, Haidan Liu

Faculty, Staff and Students Publications

Overexpression of Skp2 plays a critical role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, Skp2 has been proposed as an attractive target for anti-tumor interventions. The expression of Skp2 in human colorectal cancer (CRC) and the role of Skp2 in tumorigenic properties and irradiation sensitivities of CRC cells were examined by anchorage-dependent and -independent growth assays, immunoblot, flow cytometry, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiments. Skp2 is highly expressed in CRC patient tissues. Blocking Skp2 expression reduces the tumorigenic properties of CRC cells in vitro and in vivo. Depletion of …

Atomic Structure Of The Predominant Gii4 Human Norovirus Capsid Reveals Novel Stability And Plasticity, Liya Hu, Wilhelm Salmen, Rong Chen, Yi Zhou, Frederick Neill, James E Crowe, Robert L Atmar, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) cause sporadic and epidemic viral gastroenteritis worldwide. The GII.4 variants are responsible for most HuNoV infections, and GII.4 virus-like particles (VLPs) are being used in vaccine development. The atomic structure of the GII.4 capsid in the native T = 3 state has not been determined. Here we present the GII.4 VLP structure with T = 3 symmetry determined using X-ray crystallography and cryo-EM at 3.0 Å and 3.8 Å resolution, respectively, which reveals unanticipated novel features. A novel aspect in the crystal structure determined without imposing icosahedral symmetry is the remarkable adaptability of the capsid protein VP1 …

Depletion Of Transmembrane Mucin 4 (Muc4) Alters Intestinal Homeostasis In A Genetically Engineered Mouse Model Of Colorectal Cancer, Ramesh Pothuraju, Priya Pai, Sanjib Chaudhary, Jawed A Siddiqui, Jesse L Cox, Sukhwinder Kaur, Satyanarayana Rachagani, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

Mucins are components of the mucus layer overlying the intestinal epithelial cells, which maintains physiological homeostasis. Altered mucin expression is associated with disease progression. Expression of MUC4 decreases in colorectal cancer (CRC); however, its functional role and implications in the intestinal pathology in CRC are not studied well. Therefore, we generated a genetically engineered Muc4 knockout (Muc4-/-) CRC mouse model by crossing with Muc4-/- and Apc^flox/flox mice in the presence of colon-specific inducible Cre. We observed that deficiency of Muc4 results in an increased number of macroscopic tumors in the colon and rectal region and leads to poor survival. …

Increased Inflammatory Low-Density Neutrophils In Severe Obesity And Effect Of Bariatric Surgery: Results From Case-Control And Prospective Cohort Studies, Maria Dulfary Sanchez-Pino, William S. Richardson, Jovanny Zabaleta, Ramesh Thylur Puttalingaiah, Andrew G. Chapple, Jiao Liu, Yonghyan Kim, Michelle Ponder, Randi Dearmitt, Lyndsey Buckner Baiamonte, Dorota Wyczechowska, Liqin Zheng, Amir A. Al-Khami, Jone Garai, Rachel Martini, Melissa Davis, Jessica Koller Gorham, James B. Wooldridge, Paulo C. Rodriguez, Lucio Miele, Augusto C. Ochoa

School of Medicine Faculty Publications

Background: Low-density neutrophils (LDN) are increased in several inflammatory diseases and may also play a role in the low-grade chronic inflammation associated with obesity. Here we explored their role in obesity, determined their gene signatures, and assessed the effect of bariatric surgery. Methods: We compared the number, function, and gene expression profiles of circulating LDN in morbidly obese patients (MOP, n=27; body mass index (BMI) > 40 Kg/m2) and normal-weight controls (NWC, n=20; BMI < 25 Kg/m2) in a case-control study. Additionally, in a prospective longitudinal study, we measured changes in the frequency of LDN after bariatric surgery (n=36) and tested for associations with metabolic and inflammatory parameters. Findings: LDN and inflammatory markers were significantly increased in MOP compared to NWC. Transcriptome analysis showed increased neutrophil-related gene expression signatures associated with inflammation, neutrophil activation, and immunosuppressive function. However, LDN did not suppress T cells proliferation and produced low levels of reactive oxygen species (ROS). Circulating LDN in MOP significantly decreased after bariatric surgery in parallel with BMI, metabolic syndrome, and inflammatory markers. Interpretation: Obesity increases LDN displaying an inflammatory gene signature. Our results suggest that LDN may represent a neutrophil subset associated with chronic inflammation, a feature of obesity that has been previously associated with the appearance and progression of co-morbidities. Furthermore, bariatric surgery, as an efficient therapy for severe obesity, reduces LDN in circulation and improves several components of the metabolic syndrome supporting its recognized anti-inflammatory and beneficial metabolic effects. Funding: This work was supported in part by grants from the National Institutes of Health (NIH; 5P30GM114732-02, P20CA233374 – A. Ochoa and L. Miele), Pennington Biomedical NORC (P30DK072476 – E. Ravussin & LSU-NO Stanley S. Scott Cancer Center and Louisiana Clinical and Translational Science Center (LACaTS; U54-GM104940 – J. Kirwan).

The Impact Of Radiation Dose To Heart Substructures On Major Coronary Events And Patient Survival After Chemoradiation Therapy For Esophageal Cancer, Xin Wang, Nicolas L Palaskas, Brian P Hobbs, Jun-Ichi Abe, Kevin T Nead, Syed Wamique Yusuf, Joerg Hermann, Anita Deswal, Steven H Lin

Faculty, Staff and Student Publications

Simple Summary

Whether it is necessary to evaluate the radiation exposure of cardiac substructures when making radiotherapy plans is one of the current research hotspots. In this cohort study of 355 patients with esophageal cancer, the radiation dose to key coronary substructures such as the left anterior descending artery V30_Gy and mean left main coronary artery was closely associated with major coronary events and overall patient survival, and showed better predictive value than the mean heart dose or heart V30_Gy recommended by current guidelines. Our findings suggest that, in addition to the whole heart, key coronary substructures should …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD+GI), 10 children with ASD but no GI symptoms (ASD−GI), and 20 from typically developing (TD) children (TD) in this pilot study. Fecal mycobiome taxa were analyzed by ITS sequencing. GI symptoms (GI Severity Index (GSI)), behavioral symptoms (Social Responsiveness Scale −2 (SRS-2)), inflammation and fungal immunity (fecal calprotectin and serum dectin-1 (ELISA)) were evaluated. …

Constipation In Patients With Symptoms Of Gastroparesis: Analysis Of Symptoms And Gastrointestinal Transit, Henry P Parkman, Emily Sharkey, Richard W Mccallum, William L Hasler, Kenneth L Koch, Irene Sarosiek, Thomas L Abell, Braden Kuo, Robert J Shulman, Madhusudan Grover, Gianrico Farrugia, Ron Schey, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Nih/Niddk Gastroparesis Consortium

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC).

METHODS: Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper …

Randomised Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain, Robert J Shulman, Bruno P Chumpitazi, Susan M Abdel-Rahman, Uttam Garg, Salma Musaad, Gregory L Kearns

Faculty, Staff and Students Publications

AIMS: Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit.

METHODS: Thirty children ages 7-12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, …

Effect Of Domperidone Therapy On Gastroparesis Symptoms: Results Of A Dynamic Cohort Study By Niddk Gastroparesis Consortium, Irene Sarosiek, Mark Van Natta, Henry P Parkman, Thomas Abell, Kenneth L Koch, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Madhusudan Grover, Frank A Hamilton, Pankaj J Pasricha, Katherine P Yates, Laura Miriel, Laura Wilson, Goro Yamada, James Tonascia, Richard W Mccallum

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR).

METHODS: The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. …