Digestive System Diseases Commons^™

Synergistic Effects Of Novel Penicillin-Binding Protein 1a Amino Acid Substitutions Contribute To High-Level Amoxicillin Resistance Of, Alain Cimuanga-Mukanya, Evariste Tshibangu-Kabamba, Patrick De Jesus Ngoma Kisoko, Kartika Afrida Fauzia, Fabien Mbaya Tshibangu, Antoine Tshimpi Wola, Pascal Tshiamala Kashala, Dieudonné Mumba Ngoyi, Steve Ahuka-Mundeke, Gunturu Revathi, Ghislain Disashi-Tumba, Yasutoshi Kido, Takashi Matsumoto, Junko Akada, Yoshio Yamaoka

Faculty, Staff and Students Publications

The growing resistance to amoxicillin (AMX)—one of the main antibiotics used in Helicobacter pylori eradication therapy—is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene …

Preventive Effects Of Quercetin On The Leaky Gut By Suppression Of Il-1beta-Induced Transcription Factors Involved In An Inflammatory Pathway In Colonic Epithelial Cells, Wannaporn Chayalak, Sumpun Thammacharoen, Chatsri Deachapunya, Sutthasinee Poonyachoti

The Thai Journal of Veterinary Medicine

Flavonol quercetin (Q), found in vegetables and fruits, demonstrates the most potent anti-inflammatory effect. The preventive effect and cellular mechanisms of Q (Q1, Q10, and Q100 µM) on IL-1β induced leaky gut via the signaling molecules of inflammatory pathway, NF-κB p65-iκB/or p38/ERK1/2/MLCK/phospho(p)-MLC were investigated in Caco-2 cells. The cytotoxic effect of Q was initially determined by MTT assay. Transepithelial electrical resistance (TER) and apical-to-basolateral fluorescein isothiocyanate-labeled dextran (FD-4) flux were used to determine paracellular permeability. The protein expression of signaling molecules was examined by Western blot analysis, and their target MLCK mRNA expression was determined using real-time PCR. All Q …

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …

The Impact Of Bariatric Surgery On Glutathione Synthesis In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine is deficient in individuals with obesity but improves following bariatric surgery. Glycine deficiency could impair glutathione (GSH) synthesis and worsen oxidative stress. We examined the impact of obesity-associated glycine deficiency and bariatric surgery on GSH synthesis. Twenty-one participants with severe obesity and twenty-one healthy weight controls were recruited. [1,2-13C2] glycine was infused to measure the erythrocyte (RBC) GSH synthesis rate. Participants with obesity underwent bariatric surgery, and 19 were restudied six months post-surgery. Compared to healthy weight controls, individuals with obesity had significantly lower concentrations of RBC GSH (2.43 ± 0.23 vs. 2.63 ± 0.26 mmol/L, p < 0.01). However, there were no differences in GSH fractional synthesis rate [78.0 (51.4–123.7) vs. 76.9 (49.3–110.1) % pool/day, p = …

Missing The Overlap, Rutwik Pradeep Sharma, Mohamed Mohamed Ahmed, Ryan Tam, Alexander T. Kusnik, Ali Jaan, Ari Chodos, Krishna Tangirala

Advances in Clinical Medical Research and Healthcare Delivery

A 43-year-old female presented with painful obstructive jaundice, a mixed pattern of elevation of liver injury markers and neutrophilic leukocytosis. Evaluation with endoscopic retrograde cholangiopancreatography (ERCP) was unremarkable. The antimitochondrial antibody (AMA) titers were elevated. She was discharged on ursodeoxycholic acid (UDCA) for Primary Biliary Cirrhosis (PBC) but was readmitted for worsening symptoms. The patient's liver biopsy results suggested Overlap syndrome (Primary Biliary Cirrhosis-Autoimmune hepatitis). She was then given corticosteroid therapy concurrently with UDCA after which she improved and remained asymptomatic. In conclusion, we would like to report this atypical presentation of overlap syndrome and hope the medical community learns …

In Utero Exposure To Antihistamines And Risk Of Hepatocellular Carcinoma In A Multigenerational Cohort, Caitlin C Murphy, Karim Seif El Dahan, Amit G Singal, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Growing evidence suggests that liver disease originates in early life. Antihistamines cross the placenta and are frequently prescribed to pregnant women to treat nausea and vomiting, as well as allergy and asthma symptoms. Exposure to antihistamines in utero may impact the developing liver by reprogramming or inducing epigenetic changes in fetal hepatocytes.

METHODS: We examined in utero exposure to antihistamines and the risk of HCC in the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in the East Bay, CA, between 1959 and 1966 (n=14,507 mothers and 18,751 liveborn offspring). We reviewed mothers' medical records …

Association Between Intravenous Fluids During Labor And Primary Postpartum Hemorrhage: A Retrospective Cohort Study, Belinda R Bruce, Heather L Shepherd, Saleem Ahmed Khan, Charlotte R Haunton, Julie Leask, Bradley S De Vries

Faculty, Staff and Student Publications

INTRODUCTION: There is a major research gap relating to the impact of intravenous (IV) fluids administration during labor on maternal and neonatal outcomes. It is biologically plausible that a relationship between volume of IV fluids and primary postpartum hemorrhage (PPH) exists. The primary objective of this study was to evaluate whether the administration of high-volume IV fluids during labor (≥ 2500 mL) increases the risk of primary PPH and other adverse outcomes for women with a term, singleton pregnancy, in comparison to low-volume IV fluids during labor (<2500 >mL).

MATERIAL AND METHODS: A retrospective cohort study was conducted at a …

Crohn's Disease-Associated Granulomatous Pancreatitis With Exocrine Pancreatic Insufficiency, Anthony A Xu, Sara Vincent, Samuel Ma, Vanessa Catania, Neda Zarrin-Khameh

Faculty, Staff and Students Publications

Extraintestinal manifestations of inflammatory bowel disease occur commonly and can lead to considerable morbidity. Pancreatic manifestations of inflammatory bowel disease have been reported to be more common in Crohn's disease (CD) than ulcerative colitis. We report a case of granulomatous inflammation in the body of the pancreas with exocrine pancreatic insufficiency, which prompted a diagnosis switch from ulcerative colitis to CD. This is of interest to readers to remind them that pancreatic manifestations can occur and are more common in CD.

Low Vitamin D Levels In Patients With Symptoms Of Gastroparesis: Relationships With Nausea And Vomiting, Gastric Emptying And Gastric Myoelectrical Activity, Kenneth L Koch, Henry P Parkman, Katherine P Yates, Mark L Van Natta, Madhusudan Grover, Gianrico Farrugia, Thomas L Abell, Richard W Mccallum, Irene Sarosiek, Braden Kuo, Robert J Shulman, Laura Miriel, James Tonascia, Pankaj J Pasricha

Faculty, Staff and Students Publications

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and …

Use Of Pancreatic Endotherapy In Patients With Chronic Pancreatitis: Results From A Multicenter Cohort Study In The United States, Samuel Han, Darwin L Conwell, Jeffrey J Easler, Yunlong Yang, Dana K Andersen, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Steven J Hughes, Liang Li, Stephen J Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Although pancreatic endotherapy (PET) is commonly used for treating adverse events of chronic pancreatitis, data on the frequency and factors associated with the use of PET are limited. Our aim was to define the use of and factors predictive for receiving PET in a well-characterized chronic pancreatitis cohort.

METHODS: This is a cross-sectional analysis of data from PROCEED, a multicenter U.S. cohort study of chronic pancreatitis. PET modalities primarily consisted of ERCP. A treatment course was defined as the number of sessions performed for a specific indication. A repeat course was defined as PET >1 year after …

Transcecal Endoscopic Appendectomy For Management Of Complex Appendiceal Polyps Extending Into The Appendiceal Orifice, Tara Keihanian, Mai A Khalaf, Fuad Zain Aloor, Dina Hani Zamil, Salmaan Jawaid, Mohamed O Othman

Faculty, Staff and Students Publications

Background and study aims Endoscopic resection of appendiceal orifice (AO) polyps extending inside the appendiceal lumen is challenging given the inability to determine polyp lateral margins and risk of appendicitis. Transcecal endoscopic appendectomy (TEA) ensures en bloc resection of these complex polyps.

Patients and methods This case series includes patients who underwent TEA by a single endoscopist in the United States. Technical success was defined as achieving complete removal of the appendix along with AO polyp in an en bloc fashion.

Results In total, nine patients were included (mean age 69.7 ± 9.6 years). The average appendix size was 4.07 …

Adaptation Of The Protein Misfolding Cyclic Amplification (Pmca) Technique For The Screening Of Anti-Prion Compounds, Katherine Do, Rebeca Benavente, Celso S G Catumbela, Uffaf Khan, Carlos Kramm, Claudio Soto, Rodrigo Morales

Faculty, Staff and Student Publications

Prion diseases result from the misfolding of the physiological prion protein (PrPC) to a pathogenic conformation (PrPSc). Compelling evidence indicates that prevention and/or reduction of PrPSc replication are promising therapeutic strategies against prion diseases. However, the existence of different PrPSc conformations (or strains) associated with disease represents a major problem when identifying anti-prion compounds. Efforts to identify strain-specific anti-prion molecules are limited by the lack of biologically relevant high-throughput screening platforms to interrogate compound libraries. Here, we describe adaptations to the protein misfolding cyclic amplification (PMCA) technology (able to faithfully replicate PrPSc strains) that increase its throughput to facilitate the …

Randomized, Double-Blind, Placebo-Controlled Study Of Anti-Mycobacterial Therapy (Rhb-104) In Active Crohn's Disease, David Y Graham, Saleh A Naser, Thomas Borody, Zbigniew Hebzda, Harry Sarles, Scott Levenson, Robert Hardi, Tomasz Arłukowicz, Petar Svorcan, Reza Fathi, Aida Bibliowicz, Patricia Anderson, Patrick Mclean, Clara Fehrmann, M Scott Harris, Shuhong Zhao, Ira N Kalfus

Faculty, Staff and Students Publications

This study, conducted between 4 October 2013, and 30 November 2018, tested the hypothesis that triple antimicrobial therapy, targeting Mycobacterium avium subspecies paratuberculosis (MAP), long considered a putative cause, would favorably affect Crohn’s disease. A double-blind multicenter study of adults with active Crohn’s disease, (i.e., Crohn’s Disease Activity Index [CDAI] 220–450 plus C-reactive protein ≥ 1.0 mg/dL, fecal calprotectin (FCP) >162.9 µg/g stool, or recent endoscopic or radiographic confirmation of active disease) receiving concomitant standard-of-care Crohn’s disease treatment (Clinicaltrials.gov: NCT01951326) were stratified by anti-tumor necrosis factor use and randomized (1:1) to anti-MAP RHB-104 (clarithromycin 95 mg, rifabutin 45 mg, …

Effect Of Resistance Training On Physical Function During Chemotherapy In Colon Cancer, Justin C. Brown, Shengping Yang, Stephanie L.E. Compton, Kristin L. Campbell, Elizabeth M. Cespedes Feliciano, Sara Quinney, Barbara Sternfeld, Bette J. Caan, Jeffrey A. Meyerhardt, Kathryn H. Schmitz

School of Medicine Faculty Publications

Background: The decline of physical function during chemotherapy predicts poor quality of life and premature death. It is unknown if resistance training prevents physical function decline during chemotherapy in colon cancer survivors. Methods: This multicenter trial randomly assigned 181 colon cancer survivors receiving postoperative chemotherapy to home-based resistance training or usual care control. Physical function outcomes included the short physical performance battery, isometric handgrip strength, and the physical function subscale of the Medical Outcomes Short-Form 36-item questionnaire. Mixed models for repeated measures quantified estimated treatment differences. Results: At baseline, participants had a mean (SD) age of 55.2 (12.8) years; 67 …

Dietary Acculturation Is Associated With Altered Gut Microbiome, Circulating Metabolites, And Cardiovascular Disease Risk In Us Hispanics And Latinos: Results From Hchs/Sol, Yi Wang, Guo-Chong Chen, Zheng Wang, Kai Luo, Yanbo Zhang, Yang Li, Amanda C Mcclain, Marta M Jankowska, Krista M Perreira, Josiemer Mattei, Carmen R Isasi, Maria M Llabre, Bharat Thyagarajan, Martha L Daviglus, Linda Van Horn, David Goldsztajn Farelo, Luis E Maldonado, Steven R Levine, Bing Yu, Eric Boerwinkle, Rob Knight, Robert D Burk, Robert C Kaplan, Qibin Qi, Brandilyn A Peters

Faculty, Staff and Student Publications

Background: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults.

Methods: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US …

Rare Causes Of Gastrointestinal Hemorrhage: A Case Series Of Adult Duodenal And Jejunal Gastric Heterotopia, Venkata Vinod Matli, John Kirkikis, Gregory Wellman, Dustin Hadley, Ross M. Dies, David F. Dies

School of Medicine Faculty Publications

Gastric heterotopia (GH) is a rare cause of gastrointestinal bleeding. GH of the small bowel is rare, and the duodenum is more commonly involved than the jejunum. Here, we present five cases of GH involving the duodenum and jejunum, with presentations including gastrointestinal bleeding, symptomatic anemia, and no symptoms. A 63-year-old man presented with melenic stools but could not identify an obvious bleeding source during endoscopy. He was ultimately diagnosed with jejunal GH. A 70-year-old woman with melena and severe anemia had a duodenal bulb mass detected during endoscopy, which was histopathologically diagnosed as GH. A 54-year-old woman experienced nausea, …

A Presentation Of Acute On Chronic Pancreatitis Complicated By Pancreaticopleural Fistula Leading To Bilateral Exudative Pleural Effusions And Empyema, Ashruta Patel, Do, Ms

The Journal of Integrated Primary Care

This case report highlights a rare but serious complication of acute pancreatitis, where pancreatic juice drains into the pleural space, causing bilateral exudative pleural effusions and potentially leading to empyema. The patient's history of alcohol abuse and splenic vein thrombosis likely contributed to the development of this complication. The clinical presentation, including progressive shortness of breath and pleuritic chest pain, along with findings on examination and imaging, prompted further investigation. The MRI findings of a pancreaticopleural fistula, along with a pseudocyst, were significant in diagnosing the condition. Treatment involved a multidisciplinary approach, including antibiotic therapy, chest tube placement to drain …

Histopathology Imaging And Clinical Data Including Remission Status In Pediatric Inflammatory Bowel Disease, Chloe Martin-King, Ali Nael, Louis Ehwerhemuepha, Blake Calvo, Quinn Gates, Jamie Janchoi, Elisa Ornelas, Melissa Perez, Andrea Venderby, John Miklavcic, Peter Chang, Aaron Sassoon, Kenneth Grant

Food Science Faculty Articles and Research

The incidence of inflammatory bowel disease (IBD) is increasing annually. Children with IBD often suffer significant morbidity due to physical and emotional effects of the disease and treatment. Corticosteroids, often a component of therapy, carry undesirable side effects with long term use. Steroid-free remission has become a standard for care-quality improvement. Anticipating therapeutic outcomes is difficult, with treatments often leveraged in a trial-and-error fashion. Artificial intelligence (AI) has demonstrated success in medical imaging classification tasks. Predicting patients who will attain remission will help inform treatment decisions. The provided dataset comprises 951 tissue section scans (167 whole-slides) obtained from 18 pediatric …

Disappearing Dysphagia And The Spontaneous Intraesophageal Hematoma, A Wayne Wheeler, Stephen Landreneau

School of Medicine Faculty Publications

No abstract provided.

Developing The Openflexure Microscope Towards Medical Use: Technical And Social Challenges Of Developing Globally Accessible Hardware For Healthcare, Joe Knapper, Freya Whiteford, Daniel Rosen, William Wadsworth, Julian Stirling, Catherine Mkindi, Joram Mduda, Valerian L Sanga, Paul T Nyakyi, Thomas Hervé Mboa Nkoudou, Elisée Jafsia, Stephane Fadanka, Kelsey Hummel, Sharmila Anandasabapathy, Richard Bowman

Faculty, Staff and Students Publications

The OpenFlexure Microscope is an accessible, three-dimensional-printed robotic microscope, with sufficient image quality to resolve diagnostic features including parasites and cancerous cells. As access to lab-grade microscopes is a major challenge in global healthcare, the OpenFlexure Microscope has been developed to be manufactured, maintained and used in remote environments, supporting point-of-care diagnosis. The steps taken in transforming the hardware and software from an academic prototype towards an accepted medical device include addressing technical and social challenges, and are key for any innovation targeting improved effectiveness in low-resource healthcare. This article is part of the Theo Murphy meeting issue 'Open, reproducible …