Digestive System Diseases Commons^™

Investigating Corollaries Between Streptococcus Gallolyticus Subsp. Gallolyticus Virulence And Colorectal Cancer, Tyler G. Myers

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Streptococcus gallolyticus subsp. gallolyticus (Sgg) is a gram-positive, non-beta-hemolytic bacterium that belongs to the Lancefield group D of streptococcal pathogens. For the past several decades, associations between Sgg bacteremia and colorectal cancer (CRC) have been apparent, with gastroenterologists routinely recommending colonoscopies for positive cases of Sgg in either blood or stool samples. However, current research has not wholly established whether Sgg acts as a causative agent of CRC or if pre-existing cancers make the lumen of the colon more hospitable to its colonization. Regardless, Sgg has been implicated in the modulation of host inflammatory pathways and subsequent remodeling …

Post-Metabolites Of Two Commensal Bacteria Suppress Dna Damage In An Experimental Model Of Acid Reflux Disease, Maanya Pradeep

Honors Undergraduate Theses

Chronic heartburn or gastroesophageal reflux disease (GERD) affects approximately 25% of the US population [1]. Repeated bile acid exposure from the regurgitation of stomach contents leads to the production of reactive oxygen species (ROS), which can cause oxidative DNA damage and promote genomic instability [2]. Barrett’s esophagus (BE), which can develop as a response to chronic bile acid exposure, increases the risk of esophageal adenocarcinoma (EAC) by 30% to 125% [1].

There are more than 18,000 new cases of esophageal cancer in the United States each year, and while its incidence is relatively low compared to other cancers, its mortality …

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …

Aberrant Expression Of A Disintegrin And Metalloproteinase With Thrombospondin Motifs 13 (Adamts13) In Pancreatic Cancer Leads To Dichotomic Functions, Stephanie Allmang, Hagen R. Witzel, Anne Hausen, Simone Marquard, Christoph Eckert, Nicole Marnet, Nina Hörner, Philipp Mayer, Stefan Heinrich, Hien Dang, Wilfried Roth, Matthias M. Gaida

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers characterized by highly invasive growth into the surrounding peripancreatic fat tissue, where tumor cells can directly interact with adipocytes. Due to poor response to the currently available (radio)chemotherapies, there is an urgent need for advanced therapy concepts. The present study shows that ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13), a key factor in blood coagulation, is significantly overexpressed in human PDAC. Immunohistochemical analysis revealed that ADAMTS13 expression is associated with prolonged survival and negatively correlated with vascular density. In vitro and in vivo experiments demonstrate its partial …

Alcohol And Metabolic Stress Synergize To Dysregulate Mitochondrial Health And Lipid Metabolism; Evidence From A Hepatocyte Spheroid Model, Eden M. Gallegos, Kaitlin Couvillion, Drake Darden, Keishla Rodriguez-Graciani, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease frequently co-occur, manifesting as MetALD. Understanding the hepatocyte-specific effects of alcohol and metabolic stressors is critical to uncovering mechanisms of synergistic injury. This study evaluated the individual and combined effects of ethanol, sugars, and saturated/monounsaturated fats on hepatocyte lipid metabolism, oxidative stress, and mitochondrial function using a 3D human HepaRG spheroid model. HepaRG spheroids were treated with ethanol (50 mm), sugar (glucose and fructose), and fatty acids alone or in combination for 10 d. The combination of ethanol (E) and metabolic (sugar and fat, SF) stressors (ESF) synergistically increased triglyceride content …

Multimodal Reprogramming Of The Tumor Microenvironment By Mmr And Dual Checkpoint Blockade In Hepatocellular Carcinoma Models, Mulu Z. Tesfay, Aleksandra Cios, Khandoker Usran Ferdous, Randal S. Shelton, Bahaa Mustafa, Camila C. Simoes, Murat Gokden, Isabelle R. Miousse, Kimberly J. Krager, Marjan Boerma, Alicja Urbaniak, Anuradha Kunthur, Sri Obulareddy, Joshua M. Eichhorn, Steven R. Post, Jean Christopher Chamcheu, Omeed Moaven, Chiswili Y. Chabu, Dan G. Duda, Matteo Conti, Bruno Nardo, Rang Govindarajan, Martin E. Fernandez-Zapico, Lewis R. Roberts, Mitesh J. Borad, Martin J. Cannon, Alexei G. Basnakian, Bolni M. Nagalo

School of Graduate Studies Faculty Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, thus, there is an urgent need to develop more effective therapeutic options for this dismal condition. Tumor-infiltrating lymphocytes (TILs) are associated with improved response to immune checkpoint blockade in HCC, but their low abundance in most cases limits their therapeutic efficacy. Here, we demonstrate, in mice, that low-dose intratumoral immunovirotherapy with the trivalent measles, mumps, and rubella vaccine (MMR) induces superior tumor-growth delay and extended host survival compared to individually administered vaccines for measles, mumps, or rubella viruses. Further, our results show that MMR therapy synergizes with PD-1 and …

The Brescia International Multidisciplinary Consensus Guidelines On The Optimal Pathology Assessment And Multidisciplinary Pathways Of Non-Pancreatic Neoplasms In And Around The Ampulla Of Vater (Peripan), Mohammad Abu Hilal, Bas A Uijterwijk, Daniël H L Lemmers, Boris V Janssen, Marc G Besselink, Denise Bianchi, Arantza Fariña, Noriyoshi Fukushima, Anthony J Gill, Seung-Mo Hong, Alyssa Krasinskas, Claudio Luchini, Laura Melocchi, Giulio Rossi, Aldo Scarpa, Olca Basturk, Deyali Chatterjee, Angela Chou, Irene Esposito, Roger Feakins, Bas Groot Koerkamp, Ralph H Hruban, Stefano La Rosa, Chanjuan Shi, Aatur Singhi, Joanne Verheij, Huamin Wang, Sergio Alfieri, Fabio Ausania, Adnan Alseidi, Marco J Bruno, Ugo Boggi, Claudio Bnà, Christos Dervenis, Massimo Falconi, Michele Ghidini, Jakob W Kist, Giovanni Marchegiani, Michele Milella, Roberto Salvia, Ajith Siriwardena, Hanneke Wilmink, Alberto Zaniboni, Shaimaa Al-Janabi, Maia Blomhoff Holm, Eva Roos, Naoki Sano, In Hye Song, Zeynep Tarcan, Gianpaolo Balzano, Isabella Frigerio, Alfredo Guglielmi, Giuseppe Malleo, Horacio Asbun, Volkan Adsay, Caroline Verbeke

Faculty, Staff and Student Publications

IMPORTANCE: The lack of multidisciplinary workflow guidelines and clear definitions and classifications for neoplasms in and around the ampulla of Vater results in inconsistencies affecting patient care and research.

OBJECTIVE: The PERIPAN international multidisciplinary consensus group aimed to standardize the multidisciplinary diagnostic workflow and achieve consensus on definitions and classifications in order to ensure proper classification and optimal diagnostic assessment and consequently to improve patient care and future research.

DESIGN: An international team of 43 experts (pathologists, surgeons, radiologists, gastroenterologists, oncologists) from 12 countries identified knowledge gaps, reviewed 37061 articles, and proposed recommendations using the Scottish Intercollegiate Guidelines Network methodology …

Risk Factors Of Acute Gastroenteritis And The Implementation Of Community-Based Total Sanitation In Banyuwangi, Indonesia: A Cross-Sectional Study, Citra Al Karina, Juniastuti Juniastuti, Budi Utomo, I Made Dwi Mertha Adnyana

Makara Journal of Health Research

Background: In Banyuwangi Regency, Indonesia, diarrhea remains a major health problem, even though the community-based total sanitation (CBTS) program has been implemented for ten years. This household survey study aimed to identify the risk factors of acute gastroenteritis (AGE) and to evaluate the implementation of CBTS in Banyuwangi Regency.

Methods: A cross-sectional study was conducted in Banyuwangi Regency. Characteristic data from patients with AGE were collected from the two primary healthcare working areas, followed by collecting data of their family members and CBTS in their houses. Data were obtained through interviews and direct observation. The CBTS evaluation results …

A Hard Problem: Managing Constipation In The Geriatric Population, William G. Jones, Veeraen Jonnalagadda, Alexandra E. Thomson, Victoria Grumbles, Chase Cottle, Christian Robertson, Maulikkumar Patel

HCA Healthcare Journal of Medicine

Constipation is a common condition among geriatric patients with different presenting symptoms and potential serious complications. Additionally, the condition causes a significant burden on our healthcare system. Here, we summarized recommendations from several societies, including the American College of Gastroenterology, American Geriatrics Society, and American Academy of Family Physicians to provide guidance on managing constipation with geriatric patients. Our aim was to emphasize the importance of prevention of constipation in this population and methods to do so. We also give recommendations on how to manage constipation when it does develop and how to manage it across different healthcare settings. These …

Food Insecurity, Diet And Health Outcomes In Pediatric Inflammatory Bowel Disease: A Pilot Study, Nicole Zeky, Alysse Baudier, Colleen Leblanc, Elizabeth Mcdonough, Sarah A. Dumas, Dedrick Moulton

School of Medicine Faculty Publications

Background/Objectives: Food insecurity (FI) is a well-defined factor in pediatric health outcomes and has been associated with lower diet quality. While poor diet quality has been linked to the rising prevalence of inflammatory bowel disease (IBD), little is known about the impact of FI on pediatric IBD. This pilot study explores the feasibility and potential impact of FI on dietary intake and clinical outcomes in children with newly diagnosed IBD. Methods: This pilot study included newly diagnosed IBD patients aged 5 to 18. FI screening was completed using the USDA 6-item and AAP 2-item screeners at diagnosis and 6 months. …

Single Balloon Enteroscopy In The Elderly, Marc J Zuckerman, Majd Michael, Mohammad Bashashati, Alok K Dwivedi, Nancy A Casner, Mohamed O Othman, Sherif E Elhanafi

Faculty, Staff and Students Publications

Background: Single-balloon enteroscopy (SBE) is a minimally invasive procedure to assess and treat small bowel pathologies. The most common use is to detect suspected small bowel bleeding: Insignificant gastrointestinal (GI) bleeding or iron deficiency anaemia (IDA). The safety and feasibility of SBE in the elderly has not been adequately studied.

Aim: To assess the safety and feasibility of both antegrade and retrograde SBE in elderly patients.

Methods: We performed a retrospective cohort study of all antegrade and retrograde SBE done at our center from March 2011 through May 2020. We collected patient's data including demographics, indications, findings, therapeutic interventions, and …

Dietary Nitrogen And Its Role In The Gut Microbiome And Inflammatory Bowel Disease: A Narrative Review, Matthew Herrera, Lauri O. Byerley

School of Medicine Faculty Publications

In recent years, gut microbiota has emerged as a critical regulator of gastrointestinal health and disease, with its role in inflammatory bowel disease (IBD)—including Crohn’s disease and ulcerative colitis—being particularly significant. Among the many factors influencing the gut microbiota, dietary components such as fibers, fats, and polyphenols have received substantial attention. However, nitrogen-containing compounds, such as amino acids, nitrates, urea, and even nucleic acids, such as purines, remain underexplored despite their integral role in shaping microbial ecology, host metabolism, and immune responses. Some of these compounds are metabolized by gut bacteria into bioactive molecules such as short-chain fatty acids, ammonia, …

An Integrative Genomics Approach For The Discovery Of Potential Clinically Actionable Diagnostic And Prognostic Biomarkers In Colorectal Cancer, Mark Fertel, Duaa Mohammad Alawad, Chindo Hicks

School of Graduate Studies Faculty Publications

Background: Despite remarkable progress in clinical management of patients and intensified screening, colorectal cancer remains the second most common cause of cancer-related death in the United States. The recent surge of next generation sequencing has enabled genomic analysis of colorectal cancer genomes. However, to date, there is little information about leveraging gene expression data and integrating it with somatic mutation information to discover potential biomarkers and therapeutic targets. Here, we integrated gene expression data with somatic mutation information to discover potential diagnostic and prognostic biomarkers and molecular drivers of colorectal cancer. Methods: We used publicly available gene expression and somatic …

Hydration Status And Acute Kidney Injury Biomarkers In Ncaa Female Soccer Athletes During Preseason Conditioning, Daniel E Newmire, Erica M Filep, Jordan B Wainwright, Heather E Webb, Darryn S Willoughby

Faculty, Staff and Students Publications

Exercise training in extreme temperatures concurrent with hypohydration status may potentiate the development of acute kidney injury (AKI) in young, healthy persons.

Background/Objectives: It is unknown how repeated training bouts in ambient higher temperatures and humidity may influence measures of AKI. The purpose of this study was to investigate hydration status and renal biomarkers related to AKI in NCAA Division I female soccer athletes during preseason conditioning.

Methods: A convenience sample of n = 21 athletes were recruited (mean ± SEM; age: 19.3 ± 0.25 y; height: 169.6 ± 1.36 cm; mass: 68.43 ± 2.46 kg; lean body …

Unraveling The Mystery: A Case Study On Eosinophilic Esophagitis, Echo Kopplin

Lynchburg Journal of Medical Science

The incidence of Eosinophilic Esophagitis (EoE) has dramatically increased in the last two decades. This article reviews the presentation, diagnosis, and treatment of EoE, enhancing clinician awareness and recognition of the condition.

Association Of Estimated Plasma Volume Status With Invasive Hemodynamics And All-Cause Mortality In Patients With Liver Cirrhosis, Esteban Kosak Lopez, Phuuwadith Wattanachayakul, Jose Manuel Martinez Manzano, Andrew Geller, Simone Jarrett, John Malin, Raul Leguizamon, Tara John, Rasha Khan, Ian Mclaren, Alexander Prendergast, Kevin Lo, Zurab Azmaiparashvili

Einstein Health Papers

BACKGROUND: Estimated plasma volume status (ePVS) correlates with intravascular congestion and prognosis in patients with heart failure. The ePVS relationship with invasive hemodynamic profiling and clinical outcomes in patients with liver cirrhosis (LC) remains unclear.

METHODS: This single-center retrospective cohort study included LC patients who underwent right heart catheterization (RHC) between 2018 and 2023. Estimated plasma volume status (ePVS) was calculated using the Strauss-derived Duarte formula, with patients classified into high (> 5.5%) and low-ePVS (≤ 5.5%) groups. Cox-multivariable analysis was used to determine if ePVS was associated with all-cause mortality within 1 year post-RHC among transplant-free patients.

RESULTS: Of …

A Cluster Randomized Trial Of A Multicomponent Clinical Care Pathway (Mccp) To Improve Masld Diagnosis And Management In Primary Care: Study Protocol, Kyler M Godwin, Larissa Grigoryan, Aaron P Thrift, Hao Duong, Fasiha Kanwal, Traber Giardina, Himabindu Kadiyala, Andrew Zimolzak, Kavish R Patidar, Hashem B El-Serag

Faculty, Staff and Students Publications

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common chronic liver disorder in the world. Most patients with MASLD are undiagnosed, untreated and unreferred. Treatment depends on diagnosis and accurate staging of fibrosis risk, and therefore screening at the primary care setting coupled with consistent, timely, evidence-based, widely accessible, and testable management processes is critical. Randomized controlled trials of methods for screening, diagnosis, severity stratification, and referral are lacking. We previously validated the MASLD clinical care pathway (MCCP), a multistep algorithmic process geared to support primary care settings in screening, diagnosis, risk stratification, and suggested referral and …

Efficacy And Safety Of Larotrectinib In Patients With Trk Fusion Gastrointestinal Cancer, Changsong Qi, Lin Shen, Thierry Andre, Hyun Cheol Chung, Timothy L Cannon, Elena Garralda, Antoine Italiano, Damian T Rieke, Tianshu Liu, Domnita-Ileana Burcoveanu, Natascha Neu, Chiara E Mussi, Rui-Hua Xu, David S Hong, Alexander Drilon, Jordan Berlin

Faculty, Staff and Student Publications

Background: Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.

Methods: Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.

Results: As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients …

Low Dose Aspirin Is Associated With Improved 30-And 92-Day Outcomes In Patients With Acute Pancreatitis: A Multinational Multicenter Analysis, Do Han Kim Md, Donghyun Ko Md, Pedro Palacios Argueta Md, Wilhelm S. Basegoda Md, Jose A. Porres, Frank J. Lukens Md, Paul T. Kroner Md

Posters

Currently, no medications are known to formally treat or prevent acute pancreatitis (AP). Significant attention has been devoted to aspirin (ASA), with rodent models showing that it is associated with decreased inflammatory cytokine levels and protects against acinar cell necrosis. Current human studies, which are limited to retrospective inpatient outcomes only on the index hospitalization for AP, do suggest that patients on ASA have improved outcomes. The aim of our study was to explore de 30- and 90- day outcomes of patients with AP on long-term ASA use.

Clinical Implications Of Mismatch Repair Deficiency In Pancreatic Ductal Adenocarcinoma, Zachary Kaplan, Elizabeth Prezioso, Aditi Jain, Harish Lavu, Charles Yeo, Wilbur Bowne, Avinoam Nevler

Kimmel Cancer Center Faculty Papers

BACKGROUND: Pancreatic cancer is a highly aggressive and lethal disease, characterized by a limited response to chemotherapy and overall poor prognosis. Pancreatic cancers with a distinct mismatch repair deficiency, although relatively rare, have been shown to be associated with markedly better outcomes in comparison. Furthermore, whereas pancreatic cancers are generally unresponsive to current immunotherapy, this specific group of tumors has been shown to have a notable susceptibility to immune checkpoint inhibitors.

AIMS: In this review, we aim to summarize the relevant literature regarding mismatch-repair associated pancreatic cancers, the impacted biological mechanisms, and the resulting vulnerabilities for potential opportunistic immunotherapeutic treatment …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

Characterization Of Hepatic Pathology During Azoxymethane-Induced Acute Liver Failure, Shadikchhya Maya Bhattarai, Ashwin Jhawer, Gabriel Frampton, Eleonora Troyanovskaya, Sharon Demorrow, Matthew Mcmillin

Faculty, Staff and Students Publications

Background: Acute liver failure (ALF) is a loss of liver function due to a severe hepatic insult. Studies utilizing the azoxymethane (AOM) mouse model of ALF, which also generates hepatic encephalopathy, have primarily focused on development of neurological deficits. However, the molecular processes that generate liver damage have not been fully characterized. Therefore, a more comprehensive characterization of the hepatic consequences of AOM toxicity is needed to better understand this disease model.

Aim: To identify molecular pathology contributing to hepatic injury during the progression of AOM-induced ALF.

Methods: C57BL/6 mice were injected with AOM to produce ALF and hepatic encephalopathy. …

Cracking The Code Of Hbv Persistence: Cutting-Edge Approaches To Targeting Cccdna In Chronic Hepatitis B With Or Without Pyogenic Liver Abscesses, Umar Saeed, Zahra Zahid Piracha, Mahmood Khan, Muhammad Nouman Tariq, Syed Shahan Gilani, Muhammad Raza, Rakshana Munuswamy, Naveen Bose, Dilber Uzun Ozsahin, Ilker Özşahin, Surya M. Nauli

Pharmacy Faculty Articles and Research

Chronic Hepatitis B Virus (HBV) infection remains a formidable global health challenge, driving severe liver complications such as hepatocellular carcinoma (HCC) and pyogenic liver abscesses (PLA). At the core of HBV persistence lies covalently closed circular DNA (cccDNA), a viral reservoir that fuels ongoing infection despite antiviral treatments. This review highlights molecular mechanisms governing cccDNA formation, maintenance, and clearance, spotlighting innovative therapeutic strategies to disrupt this key viral element. We explore cutting-edge approaches, including epigenetic modulation to silence cccDNA, RNA interference (RNAi) for viral RNA degradation, and CRISPR/Cas genome editing to excise cccDNA directly. Additionally, emerging antiviral therapies and immunotherapies, …

A Case Of Turmeric-Induced Hepatotoxicity With Hyperferritinemia, Nina R. Spitofsky, Albert A. Huang, Aria Jalalian, Stefanie Gallagher, Scott Fink

Department of Medicine Faculty Papers

Introduction: We present the first published case of turmeric-associated drug-induced liver injury (DILI) accompanied by significant ferritin elevation. Case Presentation: Our patient, a 59-year-old female with DILI caused by long-term ingestion of oral turmeric supplements, presented with painless jaundice on an annual exam. The patient’s liver function tests exhibited a hepatocellular pattern and hyperferritinemia (>2,000 ng/dL). Additional testing was negative except for heterozygosity for the H63D allele associated with hemochromatosis. A liver biopsy indicated acute hepatitis without fibrosis or stainable iron. Conclusion: Upon discontinuation of the supplement, liver enzymes normalized within a month. This case highlights the potential for …

Factors Driving Adolescent Tuberculosis Incidence By Age And Sex In 30 High-Tuberculosis Burden Countries: A Mathematical Modelling Study, Silvia S Chiang, Megan B Murray, Alexander W Kay, Peter J Dodd

Faculty, Staff and Students Publications

INTRODUCTION: During adolescence, tuberculosis incidence rises, with a greater increase in males compared with females. Tuberculosis notifications and estimates infrequently disaggregate adolescent age groups. Moreover, the factors that drive the increases in overall incidence and the male-to-female (MF) ratio remain unclear.

METHODS: We constructed a mechanistic model to estimate cumulative Mycobacterium tuberculosis infection and tuberculosis disease incidence in the WHO’s 30 high-tuberculosis burden countries (HBCs), which represent 86%–90% of global tuberculosis incidence. We derived infection risk from tuberculosis prevalence and assortative social mixing based on sex and age (10–14 years vs 15–19 years old). We adjusted age subgroup-specific risks of …

Tuberculosis In Adult Migrants In Europe: A Tbnet Consensus Statement, Heinke Kunst, Berit Lange, Olga Hovardovska, Annabelle Bockey, Dominik Zenner, Aase B Andersen, Sally Hargreaves, Manish Pareek, Jon S Friedland, Christian Wejse, Graham Bothamley, Lorenzo Guglielmetti, Dumitru Chesov, Simon Tiberi, Alberto Matteelli, Anna M Mandalakas, Jan Heyckendorf, Johannes Eimer, Akanksha Malhotra, Javier Zamora, Anca Vasiliu, Christoph Lange, Tbnet

Faculty, Staff and Students Publications

INTRODUCTION: Global migration has increased in recent decades owing to war, conflict, persecution and natural disasters, but also secondary to increased opportunities related to work or study. Migrants' risk of tuberculosis (TB) differs depending on migration, socioeconomic status, mode of travel and TB risk in transit, TB incidence and healthcare provision in country of origin. Despite advances in TB care for migrants and new treatment strategies, decisions for managing migrants at risk of TB often rely on expert opinions, rather than clinical evidence.

METHODS: A systematic literature search was conducted, studies were mapped to different recommendation groups and included studies …

Loss Of Mucin 2 And Mhc Ii Molecules Causes Rare Resistance To Murine Rv Infection, Carolyn Bomidi, Faith M Sawyer, Noah Shroyer, Margaret Conner, Mary K Estes, Sarah E Blutt

Faculty, Staff and Students Publications

Enteric pathogen rotavirus (RV) primarily infects mature enterocytes at the tips of the intestinal villi; however, the role of secretory Paneth and goblet cells in RV pathogenesis remains unappreciated. Atoh1 knockout mice (Atoh1cKO) were used to conditionally delete Paneth, goblet, and enteroendocrine cells in the epithelium to investigate the role of secretory cells in RV infection. Unexpectedly, the number of infected enterocytes and the amount of RV shedding in the stool were greatly decreased following secretory cell deletion. Resistance to RV infection persisted for 7 days after virus inoculation, and Atoh1 knockout mice co-housed with infected wild-type mice were uninfected, …

2′-Fucosyllactose Inhibits Human Norovirus Replication In Human Intestinal Enteroids, Ketki Patil, B Vijayalakshmi Ayyar, Nicole M Hayes, Frederick H Neill, Lars Bode, Mary K Estes, Robert L Atmar, Sasirekha Ramani

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection. Histo-blood group antigens (HBGAs) on the intestinal epithelium are cellular attachment factors for HuNoVs; molecules that block the binding of HuNoVs to HBGAs thus have the potential to be developed as antivirals. Human milk oligosaccharides (HMOs) are glycans in human milk with structures analogous to HBGAs. HMOs have been shown to act as decoy receptors to prevent the attachment of multiple enteric pathogens to host cells. Previous X-ray crystallography studies have demonstrated the binding of HMO 2′-fucosyllactose …

Silencing Faf2 Mitigates Alcohol-Induced Hepatic Steatosis By Modulating Lipolysis And Pcsk9 Pathway, Nazmul Huda, Praveen Kusumanchi, Yanchao Jiang, Hui Gao, Themis Thoudam, Ge Zeng, Nicholas J. Skill, Zhaoli Sun, Suthat Liangpunsakul, Jing Ma, Zhihong Yang

School of Medicine Faculty Publications

BACKGROUND: Chronic alcohol consumption leads to lipid accumulation, oxidative stress, cellular damage, and inflammation in the liver, collectively referred to as alcohol-associated liver disease (ALD). FAF2/UBXD8/ETEA (Fas-associated factor 2) is a ubiquitin ligase adaptor protein that plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. A recent genome-wide association study indicated an association between FAF2 and ALD; however, the exact contribution of FAF2 to ALD pathogenesis remains unclear. METHODS: FAF2 was knocked down using AAV-delivered shRNA in C57/BL6 mice. Mice were subjected to a chronic-plus-single binge ethanol feeding (NIAAA) model. Nine hours after gavage, …