Digestive System Diseases Commons^™

Physical Activity And Diet Quality In Relation To Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study In A Representative Sample Of Us Adults Using Nhanes 2017–2018, Natalia I Heredia, Xiaotao Zhang, Maya Balakrishnan, Carrie R Daniel, Jessica P Hwang, Lorna H Mcneill, Aaron P Thrift

Faculty, Staff and Students Publications

The association of physical activity (PA) and diet quality with non-alcoholic fatty liver disease (NAFLD) and NAFLD-related fibrosis have never been examined in a representative sample of U.S. adults using a more precise form of measuring NAFLD. The purpose of this study was to assess the associations of PA and diet quality (Healthy Eating Index [HEI]-2015) with NAFLD and a subset with advanced fibrosis (F3-4) as assessed by vibration-controlled transient elastography with controlled attenuation parameter in a representative sample of U.S. adults. This cross-sectional analysis uses data from 2017-2018 National Health and Nutrition Examination Survey. NAFLD was defined as controlled …

Why Test Results Are Still Getting "Lost" To Follow-Up: A Qualitative Study Of Implementation Gaps, Andrew J Zimolzak, Umber Shahid, Traber D Giardina, Sahar A Memon, Umair Mushtaq, Lisa Zubkoff, Daniel R Murphy, Andrea Bradford, Hardeep Singh

Faculty, Staff and Students Publications

BACKGROUND: Lack of timely follow-up of abnormal test results is common and has been implicated in missed or delayed diagnosis, resulting in potential for patient harm.

OBJECTIVE: As part of a larger project to implement change strategies to improve follow-up of diagnostic test results, this study sought to identify specifically where implementation gaps exist, as well as possible solutions identified by front-line staff.

DESIGN: We used a semi-structured interview guide to collect qualitative data from Veterans Affairs (VA) facility staff who had experience with test results management and patient safety.

SETTING: Twelve VA facilities across the USA.

PARTICIPANTS: Facility staff …

Fourteen-Day Vonoprazan And Low- Or High-Dose Amoxicillin Dual Therapy For Eradicating Helicobacter Pylori Infection: A Prospective, Open-Labeled, Randomized Non-Inferiority Clinical Study, Yi Hu, Xin Xu, Xiao-Shun Liu, Cong He, Yao-Bin Ouyang, Nian-Shuang Li, Chuan Xie, Chao Peng, Zhen-Hua Zhu, Yong Xie, Xu Shu, Yin Zhu, David Y Graham, Nong-Hua Lu

Faculty, Staff and Students Publications

BACKGROUND AND AIM: We previously reported that vonoprazan-amoxicillin (VA) dual therapy for 7 or 10 days is not satisfactorily efficacious for

METHODS: This was a single center, prospective, open-labeled, randomized non-inferiority clinical study conducted in China. Treatment naïve

RESULTS: A total of 154 patients were assessed and 110 subjects were randomized. The eradication rate of VPZ with b.i.d. amoxicillin or t.i.d. amoxicillin for 14 days was 89.1% and 87.3% by intention-to-treat analysis, respectively, and 94.1% and 95.9% by per-protocol analysis, respectively. The eradication rate and incidence of adverse events were not different between the two groups.

CONCLUSION: VPZ with b.i.d. …

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 …

Severe Inflammatory Colitis Related To Encorafenib And Binimetinib Following Immune Checkpoint Inhibitor Therapy, Aaron G Issac, David Szafron, Dongguang Wei, Jennifer L Mcquade, Yinghong Wang

Faculty, Staff and Students Publications

Encorafenib, a BRAF kinase inhibitor, in combination with binimetinib, a selective MEK inhibitor have known gastrointestinal adverse events; however, adverse colitis events have not been well studied. We report a case series of 4 patients with melanoma who developed inflammatory colitis after BRAF and MEK inhibition with encorafenib and binimetinib, respectively. In the setting of immune checkpoint inhibitor use, BRAF and MEK inhibitors can cause significant inflammatory colitis with endoscopic patterns of predominant right colon ulcerations. It can lead to significant morbidity and frequent interruption of cancer treatment. Early recognition and prompt intervention are critical to improving patient outcomes.

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 …

Pathologic Inflammation In Malnutrition Is Driven By Proinflammatory Intestinal Microbiota, Large Intestine Barrier Dysfunction, And Translocation Of Bacterial Lipopolysaccharide, Grace T Patterson, Elvia Y Osorio, Alex Peniche, Sara M Dann, Erika Cordova, Geoffrey A Preidis, Ji Ho Suh, Ichiaki Ito, Omar A Saldarriaga, Michael Loeffelholz, Nadim J Ajami, Bruno L Travi, Peter C Melby

Faculty, Staff and Students Publications

Acute malnutrition, or wasting, is implicated in over half of all deaths in children under five and increases risk of infectious disease. Studies in humans and preclinical models have demonstrated that malnutrition is linked to an immature intestinal microbiota characterized by increased prevalence of Enterobacteriaceae. Observational studies in children with moderate acute malnutrition (MAM) have also observed heightened systemic inflammation and increased circulating bacterial lipopolysaccharides (LPS; endotoxin). However, the mechanisms that underpin the systemic inflammatory state and endotoxemia, and their pathophysiological consequences, remain uncertain. Understanding these pathophysiological mechanisms is necessary to design targeted treatments that will improve the unacceptable rate …

Hepatic Pparα Is Destabilized By Sirt1 Deacetylase In Undernourished Male Mice, Ji Ho Suh, Kang Ho Kim, Margaret E Conner, David D Moore, Geoffrey A Preidis

Faculty, Staff and Students Publications

The nutrient sensing nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) regulates the host response to short-term fasting by inducing hepatic transcriptional programming of ketogenesis, fatty acid oxidation and transport, and autophagy. This adaptation is ineffective in chronically undernourished individuals, among whom dyslipidemia and hepatic steatosis are common. We recently reported that hepatic PPARα protein is profoundly depleted in male mice undernourished by a low-protein, low-fat diet. Here, we identify PPARα as a deacetylation target of the NAD-dependent deacetylase sirtuin-1 (SIRT1) and link this to the decrease in PPARα protein levels in undernourished liver. Livers from undernourished male mice expressed high levels …

The Texas Collaborative Center For Hepatocellular Cancer: Reducing Liver Cancer Mortality In Texas Through Coordination, Collaboration And Advocacy, Ariel C Harrison, Fasiha Kanwal, Sumeet K Asrani, Aaron P Thrift, Chris I Amos, Maria L Jibaja-Weiss, Jane R Montealegre, Jessica P Hwang, Amit G Singal, Hashem B El-Serag

Faculty, Staff and Students Publications

Texas has the highest age-adjusted incidence rate of hepatocellular carcinoma (HCC) in the United States. To address cancer prevention and early detection through research, Cancer Prevention and Research Institute of Texas (CPRIT) has funded the Texas Collaborative Center for Hepatocellular Cancer (TeCH) to facilitate liver cancer research, education and advocacy activities. This paper describes the organizational structure, program measures, the actions completed and future plans of TeCH. This center is comprised of several cores and committees including the Administrative Core, Steering Committee, Data and Biospecimen Core, Scientific Committee, Clinical Network Committee, and the Community Outreach Committee. Each core and committee …

Cytomegalovirus Infection Among Patients With Cancer Receiving Immune Checkpoint Inhibitors, Kavea Panneerselvam, David Szafron, Rajan N Amin, Dongguang Wei, Dongfeng Tan, Mehmet Altan, Pablo C Okhuysen, Malek Shatila, Gottumukkala Subba Raju, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Students Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs), used for the treatment of solid and hematologic malignancies, come with the risk of immune-related adverse events (irAEs). Opportunistic infections (e.g., cytomegalovirus [CMV]) mimic irAE symptoms and are understudied in this population. We aimed to describe the incidence, characteristics, treatment and outcomes of CMV infection in ICI-treated patients.

METHODS: We conducted a single-center retrospective review of all adult patients who were CMV-positive after ICI therapy between 06/2011 and 05/2020. A CMV-positive non-ICI cohort was matched to the ICI group based on age, sex and cancer type. Variables of interest were collected through electronic medical records. …

Foxo1 Is Present In Stomach Epithelium And Determines Gastric Cell Distribution, Wendy M Mckimpson, Taiyi Kuo, Takumi Kitamoto, Sei Higuchi, Jason C Mills, Rebecca A Haeusler, Domenico Accili

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.

METHODS: Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.

RESULTS: FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, …

Clinical Outcome And Gut Development After Insulin-Like Growth Factor-1 Supplementation To Preterm Pigs, Kristine Holgersen, Martin Bo Rasmussen, Galen Carey, Douglas G Burrin, Thomas Thymann, Per Torp Sangild

Faculty, Staff and Students Publications

BACKGROUND: Elevation of circulating insulin-like growth factor-1 (IGF-1) within normal physiological levels may alleviate several morbidities in preterm infants but safety and efficacy remain unclear. We hypothesized that IGF-1 supplementation during the first 1-2 weeks after preterm birth improves clinical outcomes and gut development, using preterm pigs as a model for infants.

METHODS: Preterm pigs were given vehicle or recombinant human IGF-1/binding protein-3 (rhIGF-1, 2.25 mg/kg/d) by subcutaneous injections for 8 days (Experiment 1, n = 34), or by systemic infusion for 4 days (Experiment 2, n = 19), before collection of blood and organs for analyses.

RESULTS: In both …

De Novo Glycine Synthesis Is Reduced In Adults With Morbid Obesity And Increases Following Bariatric Surgery, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Chun Fan Lee, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance.

OBJECTIVE: Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m

METHODS: [1,2-

RESULTS: Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced

CONCLUSION: Hypoglycinemia …

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., …

Interaction Between Alcohol Consumption And Pnpla3 Variant In The Prevalence Of Hepatic Steatosis In The Us Population, Mariana Lazo, Usama Bilal, Mack C Mitchell, James Potter, Ruben Hernaez, Jeanne M Clark

Faculty, Staff and Students Publications

BACKGROUND & AIMS: To our knowledge, the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis has not been explored in a representative sample. To examine the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis in the US adult population.

METHODS: Cross-sectional study of 4,674 adult participants of the Third National Health and Nutrition Examination Survey, Phase 2 (1991-1994) with data on PNPLA3 genotype, self-reported alcohol consumption, ultrasound-defined hepatic steatosis and socio-demographic characteristics.

RESULTS: In 1991-1994 in the U.S. population, the weighted allele frequency of the G (risk) allele of the rs738409 at PNPLA3 was 25.4%. We …

Predicted Vitamin D Status And Colorectal Cancer Incidence In The Black Women's Health Study, Lauren E Barber, Kimberly A Bertrand, Jessica L Petrick, Hanna Gerlovin, Laura F White, Lucile L Adams-Campbell, Lynn Rosenberg, Hemant K Roy, Julie R Palmer

Faculty, Staff and Students Publications

BACKGROUND: Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations.

METHODS: We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of …

A Community-Based Management Of Covid-19 In A Mobile Container Unit, Elena Petrova, Timothy Farinholt, Tejas P Joshi, Hannah Moreno, Mayar Al Mohajer, Shital M Patel, Joseph Petrosino, Sharmila Anandasabapathy

Faculty, Staff and Students Publications

Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved regions. Mobile clinics hold the promise of ameliorating such inequities, although there is a paucity of studies that validate environmental infection in such facilities. Here, we describe community-based management of COVID-19 through a Smart Pod mobile clinic deployed in an underserved community area in the United States (Aldine, Harris County, TX, USA). In particular, we validate infection …

Mapk6-Akt Signaling Promotes Tumor Growth And Resistance To Mtor Kinase Blockade, Qinbo Cai, Wolong Zhou, Wei Wang, Bingning Dong, Dong Han, Tao Shen, Chad J Creighton, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Mitogen-activated protein kinase 6 (MAPK6) is an atypical MAPK. Its function in regulating cancer growth remains elusive. Here, we reported that MAPK6 directly activated AKT and induced oncogenic outcomes. MAPK6 interacted with AKT through its C34 region and the C-terminal tail and phosphorylated AKT at S473 independent of mTORC2, the major S473 kinase. mTOR kinase inhibitors have not made notable progress in the clinic. Our identified MAPK6-AKT axis may provide a major resistance pathway. Besides repressing growth, inhibiting MAPK6 sensitized cancer cells to mTOR kinase inhibitors. MAPK6 overexpression is associated with decreased overall survival and the survival of patients with …

Early Antibiotic Exposure Is Not Detrimental To Therapeutic Effect From Immunotherapy In Hepatocellular Carcinoma, Petros Fessas, Muntaha Naeem, Matthias Pinter, Thomas U Marron, David Szafron, Lorenz Balcar, Anwaar Saeed, Tomi Jun, Sirish Dharmapuri, Anuhya Gampa, Yinghong Wang, Uqba Khan, Mahvish Muzaffar, Musharraf Navaid, Pei-Chang Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I Abugabal, Tiziana Pressiani, Nicola Personeni, Naoshi Nishida, Masatoshi Kudo, Ahmed Kaseb, Yi-Hsiang Huang, Celina Ang, Anjana Pillai, Lorenza Rimassa, Abdul Rafeh Naqash, Elad Sharon, Alessio Cortellini, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND AND RATIONALE: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC.

METHODS: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within -30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. …

Early Antibiotic Exposure Is Not Detrimental To Therapeutic Effect From Immunotherapy In Hepatocellular Carcinoma, Petros Fessas, Muntaha Naeem, Matthias Pinter, Thomas U Marron, David Szafron, Lorenz Balcar, Anwaar Saeed, Tomi Jun, Sirish Dharmapuri, Anuhya Gampa, Yinghong Wang, Uqba Khan, Mahvish Muzaffar, Musharraf Navaid, Pei-Chang Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I Abugabal, Tiziana Pressiani, Nicola Personeni, Naoshi Nishida, Masatoshi Kudo, Ahmed Kaseb, Yi-Hsiang Huang, Celina Ang, Anjana Pillai, Lorenza Rimassa, Abdul Rafeh Naqash, Elad Sharon, Alessio Cortellini, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND AND RATIONALE: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC.

METHODS: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within -30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. …

Comparison Of Culture With Antibiogram To Next-Generation Sequencing Using Bacterial Isolates And Formalin-Fixed, Paraffin-Embedded Gastric Biopsies, Kristina G Hulten, Robert M Genta, Ira N Kalfus, Yi Zhou, Hongjun Zhang, David Y Graham

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The decline in Helicobacter pylori cure rates emphasizes the need for readily available methods to determine antimicrobial susceptibility. Our aim was to compare targeted next-generation sequencing (NGS) and culture-based H pylori susceptibility testing using clinical isolates and paired formalin-fixed, paraffin-embedded (FFPE) gastric biopsies.

METHODS: H pylori isolates and FFPE tissues were tested for susceptibility to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin using agar dilution and NGS targeted to 23S rRNA, gyrA, 16S rRNA, pbp1, rpoB and rdxA. Agreement was quantified using κ statistics.

RESULTS: Paired comparisons included 170 isolates and FFPE tissue for amoxicillin, clarithromycin, metronidazole, …

Drivers Of Transcriptional Variance In Human Intestinal Epithelial Organoids, Zachary K Criss, Nobel Bhasin, Sara C Di Rienzi, Anubama Rajan, Kali Deans-Fielder, Ganesh Swaminathan, Nabiollah Kamyabi, Xi-Lei Zeng, Harsha Doddapaneni, Vipin K Menon, Deepavali Chakravarti, Clarissa Estrella, Xiaomin Yu, Ketki Patil, Joseph F Petrosino, James C Fleet, Michael P Verzi, Sylvia Christakos, Michael A Helmrath, Sumimasa Arimura, Ronald A Depinho, Robert A Britton, Anthony W Maresso, K Jane Grande-Allen, Sarah E Blutt, Sue E Crawford, Mary K Estes, Sasirekha Ramani, Noah F Shroyer

Faculty, Staff and Students Publications

Human intestinal epithelial organoids (enteroids and colonoids) are tissue cultures used for understanding the physiology of the human intestinal epithelium. Here, we explored the effect on the transcriptome of common variations in culture methods, including extracellular matrix substrate, format, tissue segment, differentiation status, and patient heterogeneity. RNA-sequencing datasets from 276 experiments performed on 37 human enteroid and colonoid lines from 29 patients were aggregated from several groups in the Texas Medical Center. DESeq2 and gene set enrichment analysis (GSEA) were used to identify differentially expressed genes and enriched pathways. PERMANOVA, Pearson's correlation, and dendrogram analysis of the data originally indicated …

Advances In Optical Gastrointestinal Endoscopy: A Technical Review, Yubo Tang, Sharmila Anandasabapathy, Rebecca Richards-Kortum

Faculty, Staff and Students Publications

Optical endoscopy is the primary diagnostic and therapeutic tool for management of gastrointestinal (GI) malignancies. Most GI neoplasms arise from precancerous lesions; thus, technical innovations to improve detection and diagnosis of precancerous lesions and early cancers play a pivotal role in improving outcomes. Over the last few decades, the field of GI endoscopy has witnessed enormous and focused efforts to develop and translate accurate, user-friendly, and minimally invasive optical imaging modalities. From a technical point of view, a wide range of novel optical techniques is now available to probe different aspects of light-tissue interaction at macroscopic and microscopic scales, complementing …

Use Of Human Tissue Stem Cell-Derived Organoid Cultures To Model Enterohepatic Circulation, Sarah E Blutt, Sue E Crawford, Carolyn Bomidi, Xi-Lei Zeng, James R Broughman, Matthew Robertson, Cristian Coarfa, Mary Elizabeth M Tessier, Tor Savidge, F Blaine Hollinger, Steven A Curley, Mark Donowitz, Mary K Estes

Faculty, Staff and Students Publications

The use of human tissue stem cell-derived organoids has advanced our knowledge of human physiological and pathophysiological processes that are unable to be studied using other model systems. Increased understanding of human epithelial tissues including intestine, stomach, liver, pancreas, lung, and brain have been achieved using organoids. However, it is not yet clear whether these cultures recapitulate in vivo organ-to-organ signaling or communication. In this work, we demonstrate that mature stem cell-derived intestinal and liver organoid cultures each express functional molecules that modulate bile acid uptake and recycling. These organoid cultures can be physically coupled in a Transwell system and …

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 …

Habitual Sleep Duration And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Pilot Study, Ritwick Agrawal, Nadim J Ajami, Sonal Malhotra, Liang Chen, Donna L White, Amir Sharafkhaneh, Kristi L Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

We examined the association between the colonic adherent microbiota and nocturnal sleep duration in humans. In a cross-sectional study, 63 polyp-free adults underwent a colonoscopy and donated 206 mucosal biopsies. The gut microbiota was profiled using the 16S rRNA gene sequencing targeting the V4 region. The sequence reads were processed using UPARSE and DADA2, respectively. Lifestyle factors, including sleep habits, were obtained using an interviewer-administered questionnaire. We categorized the participants into short sleepers (<6 h per night; n = 16) and normal sleepers (6–8 h per night; n = 47) based on self-reported data. Differences in bacterial biodiversity and the taxonomic relative abundance …

Microbial Science Research In The Post-Covid Environment, Nguyen K Nguyen, Carey-Ann D Burnham, Arturo Casadevall, Mary K Estes, Rebecca V Ferrell, Suzanne M J Fleiszig, Speakers, Moderators, And Panelists Of The Asm Virtual Symposium: Microbial Science Research In The Post-Covid Environment

Faculty, Staff and Students Publications

Since early 2020, the world has witnessed the unprecedented accomplishments of the scientific community in the fight against the coronavirus disease 2019 (COVID-19) pandemic. In the meantime, we also learned valuable lessons and recognized the challenges that hindered our successes. In this article, we synthesize the ideas discussed at the ASM Virtual Symposium: Microbial Science Research in the Post-COVID Environment on 10 November 2020. We propose three new approaches that microbiology researchers can embrace to overcome these challenges. Moreover, we suggest broad systematic changes to focus on social impacts, teamwork, and diversity, equity, and inclusion. We believe these values are …

Patients' And Providers' Needs And Preferences When Considering Fertility Preservation Before Cancer Treatment: Decision-Making Needs Assessment, Aubri Hoffman, Laura Crocker, Aakrati Mathur, Deborah Holman, June Weston, Sukhkamal Campbell, Ashley Housten, Andrea Bradford, Shilpi Agrawala, Terri L Woodard

Faculty, Staff and Students Publications

BACKGROUND: As cancer treatments continue to improve, it is increasingly important that women of reproductive age have an opportunity to decide whether they want to undergo fertility preservation treatments to try to protect their ability to have a child after cancer. Clinical practice guidelines recommend that providers offer fertility counseling to all young women with cancer; however, as few as 12% of women recall discussing fertility preservation. The long-term goal of this program is to develop an interactive web-based patient decision aid to improve awareness, access, knowledge, and decision making for all young women with cancer. The International Patient Decision …

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 …