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Virtualized Clinical Studies To Assess The Natural History And Impact Of Gut Microbiome Modulation In Non-Hospitalized Patients With Mild To Moderate Covid-19 A Randomized, Open-Label, Prospective Study With A Parallel Group Study Evaluating The Physiologic Effects Of Kb109 On Gut Microbiota Structure And Function: A Structured Summary Of A Study Protocol For A Randomized Controlled Study, John P. Haran, Jose C. Pinero, Yan Zheng, Norma Alonzo Palma, Mark Wingertzahn 2021 University of Massachusetts Medical School

Virtualized Clinical Studies To Assess The Natural History And Impact Of Gut Microbiome Modulation In Non-Hospitalized Patients With Mild To Moderate Covid-19 A Randomized, Open-Label, Prospective Study With A Parallel Group Study Evaluating The Physiologic Effects Of Kb109 On Gut Microbiota Structure And Function: A Structured Summary Of A Study Protocol For A Randomized Controlled Study, John P. Haran, Jose C. Pinero, Yan Zheng, Norma Alonzo Palma, Mark Wingertzahn

University of Massachusetts Medical School Faculty Publications

OBJECTIVES: These 2 parallel studies (K031 and K032) aim to evaluate the safety of KB109 in addition to supportive self-care (SSC) compared with SSC alone in outpatients with mild to moderate coronavirus disease 2019 (COVID-19). KB109 is a novel synthetic glycan that was formulated to modulate the gut microbiome composition and metabolic output in order to increase beneficial short-chain fatty acid (SCFA) production in the gut. The K031 study is designed to evaluate the safety of KB109 and characterize its impact on the natural progression of COVID-19 in patients with mild to moderate disease. The K032 study is evaluating the ...


The High Prevalence Of Clostridioides Difficile Among Nursing Home Elders Associates With A Dysbiotic Microbiome, John P. Haran, Doyle V. Ward, Shakti K. Bhattarai, Ethan Loew, Protiva Dutta, Amanda Higgins, Beth A. McCormick, Vanni Bucci 2021 University of Massachusetts Medical School

The High Prevalence Of Clostridioides Difficile Among Nursing Home Elders Associates With A Dysbiotic Microbiome, John P. Haran, Doyle V. Ward, Shakti K. Bhattarai, Ethan Loew, Protiva Dutta, Amanda Higgins, Beth A. Mccormick, Vanni Bucci

University of Massachusetts Medical School Faculty Publications

Clostridioides difficile disproportionally affects the elderly living in nursing homes (NHs). Our objective was to explore the prevalence of C. difficile in NH elders, over time and to determine whether the microbiome or other clinical factors are associated with C. difficile colonization. We collected serial stool samples from NH residents. C. difficile prevalence was determined by quantitative polymerase-chain reaction detection of Toxin genes tcdA and tcdB; microbiome composition was determined by shotgun metagenomic sequencing. We used mixed-effect random forest modeling machine to determine bacterial taxa whose abundance is associated with C. difficile prevalence while controlling for clinical covariates including demographics ...


Abdominal Ultrasound - Gallbladder And Biliary Tree, Brian Loe 2020 RAD-AID

Abdominal Ultrasound - Gallbladder And Biliary Tree, Brian Loe

PEER Liberia Project

This presentation is part of the PEER Liberia Radiology Lecture Series. The presentation provides an overview of how to perform an abdominal ultrasound of the gallbladder and biliary tree.


Iga As A Potential Candidate For Enteric Monoclonal Antibody Therapeutics With Improved Gastrointestinal Stability, Aaron L. Wallace, Matthew I. Schneider, Jacqueline R. Toomey, Ryan M. Schneider, Mark S. Klempner, Yang Wang, Lisa A. Cavacini 2020 University of Massachusetts Medical School

Iga As A Potential Candidate For Enteric Monoclonal Antibody Therapeutics With Improved Gastrointestinal Stability, Aaron L. Wallace, Matthew I. Schneider, Jacqueline R. Toomey, Ryan M. Schneider, Mark S. Klempner, Yang Wang, Lisa A. Cavacini

Open Access Publications by UMMS Authors

Mucosal surfaces of the gastrointestinal tract play an important role in immune homeostasis and defense and may be compromised by enteric disorders or infection. Therapeutic intervention using monoclonal antibody (mAb) offers the potential for treatment with minimal off-target effects as well as the possibility of limited systemic exposure when administered orally. Critically, to achieve efficacy at luminal surfaces, mAb must remain stable and functionally active in the gastrointestinal environment. To better understand the impact of isotype, class, and molecular structure on the intestinal stability of recombinant antibodies, we used an in vitro simulated intestinal fluid (SIF) assay to evaluate a ...


Hepatic Lipocalin 2 Promotes Liver Fibrosis And Portal Hypertension, Jiegen Chen, Josepmaria Argemi, Gemma Odena, Ming-Jiang Xu, Yan Cai, Veronica Massey, Austin Parrish, Rajanikanth Vadigepalli, Jose Altamirano, Joaquin Cabezas, Pere Gines, Juan Caballeria, Natasha Snider, Pau Sancho-Bru, Shizuo Akira, Ivan Rusyn, Bin Gao, Ramon Bataller 2020 University of North Carolina at Chapel Hill

Hepatic Lipocalin 2 Promotes Liver Fibrosis And Portal Hypertension, Jiegen Chen, Josepmaria Argemi, Gemma Odena, Ming-Jiang Xu, Yan Cai, Veronica Massey, Austin Parrish, Rajanikanth Vadigepalli, Jose Altamirano, Joaquin Cabezas, Pere Gines, Juan Caballeria, Natasha Snider, Pau Sancho-Bru, Shizuo Akira, Ivan Rusyn, Bin Gao, Ramon Bataller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Advanced fibrosis and portal hypertension influence short-term mortality. Lipocalin 2 (LCN2) regulates infection response and increases in liver injury. We explored the role of intrahepatic LCN2 in human alcoholic hepatitis (AH) with advanced fibrosis and portal hypertension and in experimental mouse fibrosis. We found hepatic LCN2 expression and serum LCN2 level markedly increased and correlated with disease severity and portal hypertension in patients with AH. In control human livers, LCN2 expressed exclusively in mononuclear cells, while its expression was markedly induced in AH livers, not only in mononuclear cells but also notably in hepatocytes. Lcn2−/− mice were protected from liver ...


Dietary Suppression Of Mhc-Ii Expression In Intestinal Stem Cells Enhances Intestinal Tumorigenesis [Preprint], Semir Beyaz, Deniz M. Ozata, Alper Kucukural, Stuart H. Orkin, Omer H. Yilmaz 2020 Harvard Medical School

Dietary Suppression Of Mhc-Ii Expression In Intestinal Stem Cells Enhances Intestinal Tumorigenesis [Preprint], Semir Beyaz, Deniz M. Ozata, Alper Kucukural, Stuart H. Orkin, Omer H. Yilmaz

University of Massachusetts Medical School Faculty Publications

Little is known about how interactions between diet, immune recognition, and intestinal stem cells (ISCs) impact the early steps of intestinal tumorigenesis. Here, we show that a high fat diet (HFD) reduces the expression of the major histocompatibility complex II (MHC-II) genes in ISCs. This decline in ISC MHC-II expression in a HFD correlates with an altered intestinal microbiome composition and is recapitulated in antibiotic treated and germ-free mice on a control diet. Mechanistically, pattern recognition receptor and IFNg signaling regulate MHC-II expression in ISCs. Although MHC-II expression on ISCs is dispensable for stem cell function in organoid cultures in ...


Anatomy And Function Of Autonomic Innervation Of The Liver, Kennan Negrete 2020 University of Central Florida

Anatomy And Function Of Autonomic Innervation Of The Liver, Kennan Negrete

The Pegasus Review: UCF Undergraduate Research Journal

The liver is one of the most important regulatory organs, and its extensive influence upon homeostatic balance is well-documented. However, the role of autonomic innervation in the control and regulation of hepatic function is poorly understood relative to the other organs of the digestive system. Furthermore, the neuroanatomical layout of the liver remains an incomplete puzzle with various missing pieces. The scarcity of information concerning such a critical organ presents an interesting conundrum for the scientific and biomedical communities alike, especially given the prevalence of liver degeneracy and disease in the modern clinical setting. A more complete understanding of the ...


The Snakeskin-Mesh Complex Of Smooth Septate Junction Restricts Yorkie To Regulate Intestinal Homeostasis In Drosophila, Hsi-Ju Chen, Qi Li, Niraj K. Nirala, Y. Tony Ip 2020 University of Massachusetts Medical School

The Snakeskin-Mesh Complex Of Smooth Septate Junction Restricts Yorkie To Regulate Intestinal Homeostasis In Drosophila, Hsi-Ju Chen, Qi Li, Niraj K. Nirala, Y. Tony Ip

Open Access Publications by UMMS Authors

Tight junctions in mammals and septate junctions in insects are essential for epithelial integrity. We show here that, in the Drosophila intestine, smooth septate junction proteins provide barrier and signaling functions. During an RNAi screen for genes that regulate adult midgut tissue growth, we found that loss of two smooth septate junction components, Snakeskin and Mesh, caused a hyperproliferation phenotype. By examining epitope-tagged endogenous Snakeskin and Mesh, we demonstrate that the two proteins are present in the cytoplasm of differentiating enteroblasts and in cytoplasm and septate junctions of mature enterocytes. In both enteroblasts and enterocytes, loss of Snakeskin and Mesh ...


Ctrp3 And Alcoholic Liver Disease In Female Mice, Callie Root 2020 East Tennessee State University

Ctrp3 And Alcoholic Liver Disease In Female Mice, Callie Root

Undergraduate Honors Theses

C1q TNF Related Protein 3 (CTRP3), is a cytokine that is primarily secreted from adipose tissue, which classifies it as an adipokine. Our previous research has shown that CTRP3 prevents alcoholic fatty liver disease (ALD) in male mice. However, even when accounting for confounding factors such as absolute and relative alcohol intake, females are more sensitive to the effects of consumption compared to male mice. Therefore, the goal of this project was to determine whether CTRP3 prevented ALD in female mice. Methods: Female wild type (WT) and female CTRP3 transgenic over expressing (Tg) mice were fed an ethanol containing liquid ...


269— Age Of Colon Cancer Screening - A Retrospective Review, Christopher Cook 2020 SUNY Geneseo

269— Age Of Colon Cancer Screening - A Retrospective Review, Christopher Cook

GREAT Day

Colon cancer is the third most common cause of cancer-related death in the U.S. In 2019, the American Cancer Society predicted that 101,420 people in the U.S. would receive a new diagnosis of colon cancer. Due to this high prevalence, there has been a recent debate about the appropriate age to start colon cancer screening. Currently, the American Society of Gastroenterology recommends that screening start for average risk individuals at the age of 50. Conversely, the American Cancer Society has recently recommended that colon cancer screening for average risk individuals begin at the age of 45. The ...


Innate Immunity In The C. Elegans Intestine Is Programmed By A Neuronal Regulator Of Awc Olfactory Neuron Development, Kyle J. Foster, Hilary K. Cheesman, Pengpeng Liu, Nicholas D. Peterson, Sarah M. Anderson, Read Pukkila-Worley 2020 University of Massachusetts Medical School

Innate Immunity In The C. Elegans Intestine Is Programmed By A Neuronal Regulator Of Awc Olfactory Neuron Development, Kyle J. Foster, Hilary K. Cheesman, Pengpeng Liu, Nicholas D. Peterson, Sarah M. Anderson, Read Pukkila-Worley

Open Access Publications by UMMS Authors

Olfactory neurons allow animals to discriminate nutritious food sources from potential pathogens. From a forward genetic screen, we uncovered a surprising requirement for the olfactory neuron gene olrn-1 in the regulation of intestinal epithelial immunity in Caenorhabditis elegans. During nematode development, olrn-1 is required to program the expression of odorant receptors in the AWC olfactory neuron pair. Here, we show that olrn-1 also functions in AWC neurons in the cell non-autonomous suppression of the canonical p38 MAPK PMK-1 immune pathway in the intestine. Low activity of OLRN-1, which activates the p38 MAPK signaling cassette in AWC neurons during larval development ...


Anal Fistulotomy (Seton Placement), James M. Nottingham, Rebecca M. Rentea 2020 Children's Mercy Hospital

Anal Fistulotomy (Seton Placement), James M. Nottingham, Rebecca M. Rentea

Manuscripts, Articles, Book Chapters and Other Papers

An anal fistula (anorectal fistula) is one of the most common colorectal issues in the U.S. An anal or anorectal fistula is an inflammatory tract or connection between the anal canal and the perianal skin. Classic anal fistulas are the result of a perineal infection and abscess formation. These infections arise from the anal glands, which form a cryptoglandular abscess at the dentate line and then communicate outward to the perianal skin. The abscess or infections can spontaneously drain externally or be drained by a surgical incision and drainage procedure. After the drainage, a chronic tract can form that ...


The Effects Of Modifiable And Non-Modifiable Risk Factors On The Severity Of Gastroparesis-Like Symptoms, Jonathon B. Nelson 2020 University of Central Florida

The Effects Of Modifiable And Non-Modifiable Risk Factors On The Severity Of Gastroparesis-Like Symptoms, Jonathon B. Nelson

Honors Undergraduate Theses

Gastroparesis (GP) is a clinical disorder recognized by measured delayed gastric emptying without mechanical obstruction, in addition to symptoms such as nausea, vomiting, chronic abdominal pain, heartburn, early satiety upon eating a regular-sized meal, and exaggerated postprandial fullness. While GP is considered a clinically rare disorder, there is much suspicion that a much larger number of patients experience GP-like symptoms without an official diagnosis. Furthermore, little work has been done to identify the causes and exacerbations of this gastrointestinal (GI) distress in the young adult population. This study's primary goal was to establish a relationship between modifiable and non-modifiable ...


Associations Between Sleep And In-Race Gastrointestinal Symptoms: An Observational Study Of Running And Triathlon Race Competitors, Patrick Benjamin Wilson 2020 Old Dominion University

Associations Between Sleep And In-Race Gastrointestinal Symptoms: An Observational Study Of Running And Triathlon Race Competitors, Patrick Benjamin Wilson

Human Movement Sciences Faculty Publications

OBJECTIVE: It remains unstudied whether poor sleep is involved in the etiology of gastrointestinal (GI) problems in athletes.

METHODS: Eighty-seven running and triathlon/duathlon race (>60 minutes) participants completed questionnaires to quantify the Sleep Problems Index-(SPI)-I and sleep parameters from the night before races. For GI symptoms, participants reported the severity (0-10 scale) of four upper and three lower symptoms during races. Spearman's correlations examined whether sleep measures were associated with in-race GI symptoms. Partial correlations were calculated to control for age, resting GI symptoms, and anxiety.

RESULTS: SPI-I scores correlated with in-race upper GI symptoms (rho ...


Intestinal Neurod1 Expression Impairs Paneth Cell Differentiation And Promotes Enteroendocrine Lineage Specification, Joyce H. Li, Subir Ray, Ning Pan, Jody Haigh, Bernd Fritzsch, Andrew B. Leiter 2019 University of Massachusetts Medical School

Intestinal Neurod1 Expression Impairs Paneth Cell Differentiation And Promotes Enteroendocrine Lineage Specification, Joyce H. Li, Subir Ray, Ning Pan, Jody Haigh, Bernd Fritzsch, Andrew B. Leiter

Open Access Publications by UMMS Authors

Transcription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether Neurod1 can similarly switch cell fates in the intestine. We generated a mouse line that would enable us to conditionally express Neurod1 in intestinal epithelial cells at different stages of differentiation. Forced expression of Neurod1 throughout intestinal epithelium increased the number of EECs as well as the expression of EE specific transcription ...


Comparative Pangenomics Of The Mammalian Gut Commensal Bifidobacterium Longum, Korin Albert, Asha Rani, David Sela 2019 University of Massachusetts Amherst

Comparative Pangenomics Of The Mammalian Gut Commensal Bifidobacterium Longum, Korin Albert, Asha Rani, David Sela

Open Access Publications by UMMS Authors

Bifidobacterium longum colonizes mammalian gastrointestinal tracts where it could metabolize host-indigestible oligosaccharides. Although B. longum strains are currently segregated into three subspecies that reflect common metabolic capacities and genetic similarity, heterogeneity within subspecies suggests that these taxonomic boundaries may not be completely resolved. To address this, the B. longum pangenome was analyzed from representative strains isolated from a diverse set of sources. As a result, the B. longum pangenome is open and contains almost 17,000 genes, with over 85% of genes found in < /=28 of 191 strains. B. longum genomes share a small core gene set of only ~500 genes, or ~3% of the total pangenome. Although the individual B. longum subspecies pangenomes share similar relative abundances of clusters of orthologous groups, strains show inter- and intrasubspecies differences with respect to carbohydrate utilization gene content and growth phenotypes.


Single Cell Transcriptomic Profiling Of Large Intestinal Enteroendocrine Cells In Mice - Identification Of Selective Stimuli For Insulin-Like Peptide-5 And Glucagon-Like Peptide-1 Co-Expressing Cells, Lawrence J. Billing, Pierre Larraufie, Jo Lewis, Andrew B. Leiter, Joyce H. Li, Brian Lam, Giles Sh. Yeo, Deborah A. Goldspink, Richard G. Kay, Fiona M. Gribble, Frank Reimann 2019 University of Cambridge

Single Cell Transcriptomic Profiling Of Large Intestinal Enteroendocrine Cells In Mice - Identification Of Selective Stimuli For Insulin-Like Peptide-5 And Glucagon-Like Peptide-1 Co-Expressing Cells, Lawrence J. Billing, Pierre Larraufie, Jo Lewis, Andrew B. Leiter, Joyce H. Li, Brian Lam, Giles Sh. Yeo, Deborah A. Goldspink, Richard G. Kay, Fiona M. Gribble, Frank Reimann

Open Access Publications by UMMS Authors

OBJECTIVE: Enteroendocrine cells (EECs) of the large intestine, found scattered in the epithelial layer, are known to express different hormones, with at least partial co-expression of different hormones in the same cell. Here we aimed to categorize colonic EECs and to identify possible targets for selective recruitment of hormones.

METHODS: Single cell RNA-sequencing of sorted enteroendocrine cells, using NeuroD1-Cre x Rosa26-EYFP mice, was used to cluster EECs from the colon and rectum according to their transcriptome. G-protein coupled receptors differentially expressed across clusters were identified, and, as a proof of principle, agonists of Agtr1a and Avpr1b were tested as candidate ...


Safe And Effective Use Of A Hands-Free Intracorporeal Retractor For Suture-Based Liver Retraction During Minimally Invasive Bariatric Procedures: Results Of A Large Case Series, Roger De la Torre, Matthew Sappington, Tom Smith, Jeremy Bryner, David Mantilla, J Stephen Scott 2019 HCA Healthcare

Safe And Effective Use Of A Hands-Free Intracorporeal Retractor For Suture-Based Liver Retraction During Minimally Invasive Bariatric Procedures: Results Of A Large Case Series, Roger De La Torre, Matthew Sappington, Tom Smith, Jeremy Bryner, David Mantilla, J Stephen Scott

General Surgery

Background

Laparoscopic bariatric surgery requires retraction of the left lobe of the liver to provide adequate operative view and working space. Conventional approaches utilize a mechanical retractor that requires a dedicated incision, may cause liver damage, and often requires an assistant. This study evaluated the safety and efficacy of hands-free intracorporeal retractors in a large series of subjects undergoing laparoscopic bariatric surgery. This method eliminates the need for a subxiphoid incision, enables full surgeon autonomy, and allows for adjustments throughout the procedure.

Methods

Retrospective chart review identified all subjects at a single hospital undergoing bariatric surgery between September 2017-March 2019 ...


Extracapsular Hepatocellular Adenoma: A Diagnostic Dilemma, iIsin Y. Comba, Richard Henriquez, Sundeep Kumar, Ruthvik Srinvasa-Murthy, Maria Wallis-Crespo, Olga Karasik, Lakhinder Bhatia, Dong Xu 2019 HCA Healthcare

Extracapsular Hepatocellular Adenoma: A Diagnostic Dilemma, Iisin Y. Comba, Richard Henriquez, Sundeep Kumar, Ruthvik Srinvasa-Murthy, Maria Wallis-Crespo, Olga Karasik, Lakhinder Bhatia, Dong Xu

Gastroenterology

Introduction: Hepatocellular adenoma (HCA) is a benign tumor of the liver and almost always located intracapsular. Bleeding (25%), and malignant transformation (5%) can complicate the disease course if left untreated. Herein, we present a case of extracapsular HCA of ectopic liver in the omentum complicated with intraperitoneal hemorrhage.

Case Description/Methods: A 43-year-old lady with no past medical history presented to emergency department with two-day history of left shoulder pain and epigastric discomfort. Her only medication was an oral contraceptive pill (OCP). On physical exam, the patient had persistent sinus tachycardia, and epigastric tenderness. Initial labs were unremarkable except for ...


Expression Of Mitochondrial Membrane-Linked Sab Determines Severity Of Sex-Dependent Acute Liver Injury, Sanda Win, Robert W. M. Min, Christopher Q. Chen, Jun Zhang, Yibu Chen, Meng Li, Ayako Suzuki, Manal F. Abdelmalek, Ying Wang, Mariam Aghajan, Filbert W. M. Aung, Anna Mae Diehl, Roger J. Davis, Tin A. Than, Neil Kaplowitz 2019 University of Southern California

Expression Of Mitochondrial Membrane-Linked Sab Determines Severity Of Sex-Dependent Acute Liver Injury, Sanda Win, Robert W. M. Min, Christopher Q. Chen, Jun Zhang, Yibu Chen, Meng Li, Ayako Suzuki, Manal F. Abdelmalek, Ying Wang, Mariam Aghajan, Filbert W. M. Aung, Anna Mae Diehl, Roger J. Davis, Tin A. Than, Neil Kaplowitz

University of Massachusetts Medical School Faculty Publications

SAB is an outer membrane docking protein for JNK mediated impaired mitochondrial function. Deletion of Sab in hepatocytes inhibits sustained JNK activation and cell death. Current work demonstrated that increasing SAB enhanced the severity of APAP liver injury. Female mice were resistant to liver injury and exhibited markedly decreased hepatic SAB protein expression versus males. The mechanism of SAB repression involved a pathway from ERalpha to p53 expression which induced miR34a-5p. miR34a-5p targeted the Sab mRNA coding region, repressing SAB expression. Fulvestrant or p53 knockdown decreased miR34a-5p and increased SAB in females leading to increased injury from APAP and TNF ...


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