Digital Commons Network^™

Convergence Of Wnt/Beta-Catenin And Mtor Signaling In Liver Physiology And Hepatocellular Carcinoma, Adeola O. Adebayo Michael, Junyan Tao, Satdarshan P. Monga

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Ureterovaginal Fistula Secondary To Retained Vaginal Foreign Body In A Young Girl, Anjum Bandarkar, Adebunmi O. Adeyiga, Eglal Shalaby-Rana

Radiology Faculty Publications

We present the case of a 13-year-old girl with a recurrent urinary tract infection, malodorous vaginal discharge, and urinary incontinence caused by a retained vaginal foreign body. The foreign body, an aerosol cap retained for over 2 years, resulted in the formation of a ureterovaginal fistula, an extremely rare complication. The critical value of ultrasound and magnetic resonance urography in delineating the foreign body, the fistulous tract, and the intraperitoneal urine leak is described. Through this unique diagnostic dilemma, we wish to highlight that the evaluation of persistent unusual urinary symptoms and vaginal discharge in a young girl must include …

The Role Of Osteopontin And Its Gene On Glucocorticoid Response In Myasthenia Gravis., Yanchen Xie, Hai-Feng Li, Liang Sun, Linda L Kusner, Shuhui Wang, Yunxiao Meng, Xu Zhang, Yu Hong, Xiang Gao, Yao Li, Henry J Kaminski

Neurology Faculty Publications

Biomarkers that assess treatment response for patients with the autoimmune disorder, myasthenia gravis (MG), have not been evaluated to a significant extent. We hypothesized the pro-inflammatory cytokine, osteopontin (OPN), may be associated with variability of response to glucocorticoids (GCs) in patients with MG. A cohort of 250 MG patients treated with standardized protocol of GCs was recruited, and plasma OPN and polymorphisms of its gene, secreted phosphoprotein 1 (SPP1), were evaluated. Mean OPN levels were higher in patients compared to healthy controls. Carriers of rs11728697*T allele (allele definition: one of two or more alternative forms of a gene) were more …

Febrile Rhinovirus Illness During Pregnancy Is Associated With Low Birth Weight In Nepal., Erin K Philpott, Janet A Englund, Joanne Katz, James Tielsch, Subarna Khatry, Stephen C Leclerq, Laxman Shrestha, Jane Kuypers, Amalia S Magaret, Mark C Steinhoff, Helen Y Chu

Global Health Faculty Publications

BACKGROUND: Adverse birth outcomes, including low birth weight (LBW), defined as <2500 >grams, small-for-gestational-age (SGA), and prematurity, contribute to 60%-80% of infant mortality worldwide and may be related to infections during pregnancy. The aim of this study was to assess whether febrile human rhinovirus (HRV) illness is associated with adverse birth outcomes.

METHODS: Active household-based weekly surveillance was performed for respiratory illness episodes in pregnant women as part of a community-based, prospective, randomized trial of maternal influenza immunization in rural Nepal. Rhinovirus (HRV) febrile illness episodes were defined as fever plus cough, sore throat, runny nose, and/or myalgia with HRV detected …

Life Of A Child With Hypotonia, Shannon Valedta

School of Human Sciences Research Showcase

The disorder is found in infants, and not many people heard of this disability. People need to be informed about Hypotonia so that it will benefit research to develop a cause and cure to Hypotonia. Also, in our field we are able to educate parents and therapists about what is Hypotonia, and develop techniques for the child to be able to develop properly.

What is Benign Congenital Hypotonia

Benign Congenital Hypotonia, also known as "Floppy Baby Syndrome", is the medical term for low muscle tone.

Studying The Optimal Scheduling For Controlling Prostate Cancer Under Intermittent Androgen Suppression, Sunil K. Dhar, Hans R. Chaudhry, Bruce G. Bukiet, Zhiming Ji, Nan Gao, Thomas W. Findley

Harvard University Biostatistics Working Paper Series

This retrospective study shows that the majority of patients’ correlations between PSA and Testosterone during the on-treatment period is at least 0.90. Model-based duration calculations to control PSA levels during off-treatment are provided. There are two pairs of models. In one pair, the Generalized Linear Model and Mixed Model are both used to analyze the variability of PSA at the individual patient level by using the variable “Patient ID” as a repeated measure. In the second pair, Patient ID is not used as a repeated measure but additional baseline variables are included to analyze the variability of PSA.

Epigenetic Silencing Of Socs3 Expression Contributes To Fibrosis In Crohn’S Disease, Emily T. Marshall, Chao Li, John K. Kuemmerle

MD Student Summer Research Fellowship Program Posters

Identified risk polymorphisms affecting the Jak-STAT3 pathway in patients with Crohn’s disease could affect TGF-β1 and collagen I expression and in the pathway’s negative regulator, SOCS3. Genetic factors, however, account for only ~25% of disease. Epigenetic events also shape gene expression. Recent experiments showed that autocrine IL-6 production in mesenchymal cells, subepithelial myofibroblasts (SEMF) and muscle cells, of patients with fibrostenotic Crohn’s disease causes sustained Jak-STAT3 activity, excess TGF-β1 and Collagen I production and fibrosis. SOCS3 paradoxically decreased in these cells. We now identify epigenetic mechanisms that silence SOCS3 expression in SEMF of patients with fibrostenotic Crohn’s disease. In a …

Metabolic Reprogramming Of Triple-Negative Breast Cancer: The Role Of Mirnas, Amal Qattan

Biochemistry and Molecular Medicine Faculty Publications

MicroRNAs (miRNAs) are well known to influence the expression of the genes that regulate critical cellular functions. Various reports have suggested that they play critical roles in breast cancer metabolism through the regulation of various metabolic pathways, including the metabolism of glucose, lipids, glycolysis and the mitochondrial tricarboxylic acid cycle (TCA). miRNAs regulate the metabolic process by targeting key molecules (enzymes, kinases transporters) or by modifying the expression of key transcription molecules. In addition, miRNAs can indirectly regulate mRNA translation by targeting chromatin-remodeling enzymes. Furthermore, miRNAs influence the expression of both oncogenes and tumor suppressors and have a major impact …

Genomes Of Fasciola Hepatica From The Americas Reveal Colonization With Neorickettsia Endobacteria Related To The Agents Of Potomac Horse And Human Sennetsu Fevers., Samantha N Mcnulty, Jose F Tort, Gabriel Rinaldi, Bruce A Rosa, Victoria H. Mann, Patricia S. Latham, Paul J. Brindley, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Food borne trematodes (FBTs) are an assemblage of platyhelminth parasites transmitted through the food chain, four of which are recognized as neglected tropical diseases (NTDs). Fascioliasis stands out among the other NTDs due to its broad and significant impact on both human and animal health, as Fasciola sp., are also considered major pathogens of domesticated ruminants. Here we present a reference genome sequence of the common liver fluke, Fasciola hepatica isolated from sheep, complementing previously reported isolate from cattle. A total of 14,642 genes were predicted from the 1.14 GB genome of the liver fluke. Comparative genomics indicated that F. …

Mait Cells Are Reduced In Frequency And Functionally Impaired In Human T Lymphotropic Virus Type 1 Infection: Potential Clinical Implications., Dominic Paquin-Proulx, Benjamin C Greenspun, Emanuela A S Costa, Aluisio C Segurado, Esper G Kallas, Douglas F Nixon, Fabio E Leal

Microbiology, Immunology, and Tropical Medicine Faculty Publications

HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection. Evidence suggests an important role for Mucosal-associated invariant T (MAIT) cells in the early control of Mtb infection. Chronic viral infections like HIV and HCV have …

Schistosoma Mansoni Reinfection: Analysis Of Risk Factors By Classification And Regression Tree (Cart) Modeling., Andréa Gazzinelli, Roberta Oliveira-Prado, Leonardo Ferreira Matoso, Bráulio M Veloso, Gisele Andrade, Helmut Kloos, Jeffrey M Bethony, Renato M Assunção, Rodrigo Correa-Oliveira

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Praziquantel (PZQ) is an effective chemotherapy for schistosomiasis mansoni and a mainstay for its control and potential elimination. However, it does not prevent against reinfection, which can occur rapidly in areas with active transmission. A guide to ranking the risk factors for Schistosoma mansoni reinfection would greatly contribute to prioritizing resources and focusing prevention and control measures to prevent rapid reinfection. The objective of the current study was to explore the relationship among the socioeconomic, demographic, and epidemiological factors that can influence reinfection by S. mansoni one year after successful treatment with PZQ in school-aged children in Northeastern Minas …

Ancylostoma Ceylanicum Infective Third-Stage Larvae Are Activated By Co-Culture With Ht-29-Mtx Intestinal Epithelial Cells, Caitlin Feather, John M. Hawdon, John March

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human hookworm larvae arrest development until they enter an appropriate host. This makes it difficult to access the larvae for studying larval development or host-parasite interactions. While there are in vivo and in vitro animal models of human hookworm infection, there is currently no human, in vitro model. While animal models have provided much insight into hookworm biology, there are limitations to how closely this can replicate human infection. Therefore, we have developed a human, in vitro model of the initial phase of hookworm infection using intestinal epithelial cell culture.

Results

Co-culture of the human hookworm Ancylostoma ceylanicum with …

Review Of Applications Of Microneedling In Dermatology., Christopher Iriarte, Olabola Awosika, Monica Rengifo-Pardo, Alison Ehrlich

Dermatology Faculty Publications

Microneedling (MN) is a novel therapeutic modality in dermatology. Through physical trauma from needle penetration, MN induces a wound healing cascade with minimal damage to the epidermis. This allows for enhancement in the absorption of mainstay topical therapies across the thick stratum corneum. MN has become increasingly utilized over the last several years as it is a relatively simple procedure that is cost-effective, well tolerated, and offers both cosmetic and therapeutic benefits. The ability to treat localized areas of disease has led to numerous studies gauging its potential in focal diseases of inflammation, dyschromia, and photodamage. This review discusses the …

Human Ipsc-Derived Cerebellar Neurons From A Patient With Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks, Sam Nayler, Joseph Powell, Darya Vanichkina, Othmar Korn, Christine Wells, Ryan J. Taft, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Ataxia-telangiectasia (A-T) is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and …

Distinct Neural Bases Of Disruptive Behavior And Autism Symptom Severity In Boys With Autism Spectrum Disorder., Y.J. Daniel Yang, Denis G Sukhodolsky, Jiedi Lei, Eran Dayan, Kevin A. Pelphrey, Pamela Ventola

Pediatrics Faculty Publications

BACKGROUND: Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings of disruptive behavior in ASD, while addressing whether the neural basis is shared with or separable from that of core ASD symptoms.

METHODS: Participants consisted of 48 male children and adolescents: 31 ASD (7 had high disruptive behavior) and 17 typically developing (TD) controls, well-matched on sex, age, and IQ. For ASD participants, autism symptom severity, disruptive behavior, anxiety symptoms, and ADHD symptoms were measured. All participants were scanned while …

Pediatric Cardiovascular Care In Uganda: Current Status, Challenges, And Opportunities For The Future., Twalib Olega Aliku, Sulaiman Lubega, Judith Namuyonga, Tom Mwambu, Michael Oketcho, John O Omagino, Craig Sable, Peter Lwabi

Pediatrics Faculty Publications

In many developing countries, concerted action against common childhood infectious diseases has resulted in remarkable reduction in infant and under-five mortality. As a result, pediatric cardiovascular diseases are emerging as a major contributor to childhood morbidity and mortality. Pediatric cardiac surgery and cardiac catheterization interventions are available in only a few of Sub-Saharan African countries. In Uganda, open heart surgeries (OHSs) and interventional procedures for pediatric cardiovascular disease are only possible at the Uganda Heart Institute (UHI), having been started with the help of expatriate teams from the years 2007 and 2012, respectively. Thereafter, independent OHS and cardiac catheterization have …

"It Makes You Feel Like Someone Cares" Acceptability Of A Financial Incentive Intervention For Hiv Viral Suppression In The Hptn 065 (Tlc-Plus) Study., Elizabeth Greene, Allison Pack, Jill Stanton, Victoria Shelus, Elizabeth E Tolley, Jamilah Taylor, Wafaa M El Sadr, Bernard M Branson, Jason Leider, Natella Rakhmanina, Theresa Gamble

Pediatrics Faculty Publications

BACKGROUND: HPTN 065 (TLC-Plus) evaluated the feasibility and effectiveness of providing quarterly $70 gift card financial incentives to HIV-infected patients on antiretroviral therapy (ART) to encourage ART adherence and viral suppression, and represents the largest study to-date of a financial incentive intervention for HIV viral suppression. A post-trial qualitative substudy was undertaken to examine acceptability of the financial incentives among those receiving and implementing the intervention.

METHODS: Between July and October 2013, semi-structured interviews were conducted with 72 patients and 12 investigators from 14 sites; three focus groups were conducted with 12 staff from 10 sites. Qualitative data collection elicited …

Uhl’S Anomaly: A One And A Half Ventricular Repair In A Patient Presenting With Cardiac Arrest, Reginald Chonoune, Adam Lowry, Karthik Ramakrishnan, Gail D. Pearson, Jeffrey P. Moak, Dilip S. Nath

Pediatrics Faculty Publications

Uhl’s anomaly, first reported in 1952, is an extremely rare congenital cardiac defect characterized by partial or complete loss of the right ventricular myocardium and unknown etiology. Fewer than 100 cases have been described. The response to medical management is poor and there is no known ideal surgical approach or timing for treatment. We report the case of a previously active adolescent male presenting with cardiac arrest, who underwent successful bidirectional cavopulmonary anastomosis (“Glenn” anastomosis) with right atrial reduction and right ventricular free wall plication.

Endotypes Of Difficult-To-Control Asthma In Inner-City African American Children., K R Brown, R Z Krouse, A Calatroni, C M Visness, U Sivaprasad, C M Kercsmar, E C Matsui, J B West, M M Makhija, M A Gill, H Kim, M Kattan, D Pillai, J E Gern, W W Busse, A Togias, A H Liu, G K Khurana Hershey

Pediatrics Faculty Publications

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6-17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or …

Transvenous Nonfluoroscopic Pacemaker Implantation During Pregnancy Guided By 3-Dimensional Electroanatomic Mapping, Jacob Hartz, Bradley C. Clark, Seiji Ito, Elizabeth D Sherwin, Charles I Berul

Pediatrics Faculty Publications

Patients with congenital heart disease are at ongoing risk of developing both bradyarrhythmias and tachyarrhythmias decades after surgical repair. Rarely, arrhythmias can be exacerbated during pregnancy and require emergent intervention. Here, we report unique experience with nonfluoroscopic pacemaker implantation during pregnancy. Ionizing radiation, even in low doses, is associated with an increased risk of malignancy, and a fetus may be at particularly increased risk.1, 2 Over the past 2 decades, the use of fluoroscopy in cardiac ablation procedures has become nearly obsolete with the development of 3-dimensional (3D) electroanatomic mapping software such as CARTO (Biosense-Webster, Diamond Bar, CA) …

Mycn Amplification Is Associated With Repressed Cellular Immunity In Neuroblastoma: An In Silico Immunological Analysis Of Target Database, Peng Zhang, Xiaofang Wu, Moushumi Basu, Chen Dong, Pan Zhang, Yang Liu, Anthony D. Sandler

Pediatrics Faculty Publications

Purpose: RNA and DNA sequencing data are traditionally used to discern intrinsic cellular pathways in cancer pathogenesis, their utility for investigating the tumor microenvironment (TME) has not been fully explored. This study explores the use of sequencing data to investigate immunity within the TME.

Experimental design: Here, we use immune cell fraction estimation analysis to determine the immune profiles in the microenvironment of neuroblastoma (NB) based on RNA-seq data in the TARGET database. The correlation between immune cell transcripts and prognosis in pediatric NB is also investigated.

Results: In silico analysis revealed a strong inverse correlation between MYCNamplification and …

Disorders Of Metal Metabolism, Carlos Ferreira, William A. Gahl

Pediatrics Faculty Publications

Trace elements are chemical elements needed in minute amounts for normal physiology. Some of the physiologically relevant trace elements include iodine, copper, iron, manganese, zinc, selenium, cobalt and molybdenum. Of these, some are metals, and in particular, transition metals. The different electron shells of an atom carry different energy levels, with those closest to the nucleus being lowest in energy. The number of electrons in the outermost shell determines the reactivity of such an atom. The electron shells are divided in sub-shells, and in particular the third shell has s, p and d sub-shells. Transition metals are strictly defined as …

H-Ipse Is A Pathogen-Secreted Host Nucleus Infiltrating Protein (Infiltrin) 3 Expressed Exclusively By The Schistosoma Haematobium Egg Stage, Luke Pennington, Abdulaziz Alouffi, Evaristus Mbanefo, Debalina Ray, David Heery, Theodore Jardetzky, Michael Hsieh, Franco Falcone

Urology Faculty Publications

Urogenital schistosomiasis, caused by the parasitic trematode Schistosoma haematobium, affects over 112 million people worldwide. As with S. mansoniinfections, the pathology in urogenital schistosomiasis is mainly related to the egg stage, which induces granulomatous inflammation of affected tissues. Schistosoma eggs and their secretions have been studied extensively for the related S. mansoniorganism which is more amenable to laboratory studies. Indeed, we have shown that IPSE/alpha-1 (M-IPSE herein), a major protein secreted from S .mansoni eggs, can infiltrate host cells. Although M-IPSE function is unknown, its ability to translocate to their nucleus and bind DNA suggests a possible …

Antibiotic Prophylaxis In Orbital Fractures., Benjamin Reiss, Lamise Rajjoub, Tamer Mansour, Tony Chen, Aisha Mumtaz

Ophthalmology Faculty Publications

Purpose:

To determine whether prophylactic antibiotic use in patients with orbital fracture prevent orbital infection.

Design:

Retrospective cohort study.

Participants:

All patients diagnosed with orbital fracture between January 1, 2008 and March 1, 2014 at The George Washington University Hospital and Clinics.

Main Outcome Measures:

Development of orbital infection.

Results:

One hundred seventy-two patients with orbital fracture met our inclusion and exclusion criteria. No orbital infections were documented. Twenty subjects (12%) received no prophylactic antibiotic, and two (1%) received only one dose of antibiotics pre-operatively for surgery. For primary antibiotic, 136 subjects (79%) received oral antibiotics, and 14 (8%) received …

Diabetes Mellitus: Concerns, Treatment Options, And The Future, Ryan Curry

Biology: Student Scholarship & Creative Works

Diabetes is a serious disease that is becoming very serious worldwide. This review will discuss some of the treatment options that are available for type two diabetes with a comparison to insulin management. It will discuss the history, genetics, economics, and also the future of diabetes management.

Trinidad & Tobago : Hiv Epidemic, Madison Caldwell

Global Public Health

Trinidad and Tobago are twin islands located in the Caribbean off the coast of Venezuela. In the recent years since about 1990, citizens of this country have been greatly affected by the HIV epidemic. HIV stands for human immunodeficiency virus and is spread through infected seman, blood, or vaginal fluids usually through sexual intercourse. As this virus continues to progress in the body, it will eventually turn into AIDS, which stands for acquired immunodeficiency syndrome. Once HIV progresses to AIDS, the outcome is ultimately fatal, hence why there is a dire need to promote awareness and methods of intervention to …

Singapore : Severe Acute Respiratory Syndrome (Sars), Dexter Lipps

Global Public Health

Singapore ranks as one of the healthiest countries in the world and its healthcare system has been regarded as one of the most efficient. While a minority of the population experience any chronic diseases such as diabetes or asthma, one illness, severe acute respiratory syndrome or SARS has been prevalent in the country since the global outbreak in 2003. SARS is a virus causing disease that is easily transmitted through the air. In 2003, Singapore, along with much of the world, saw a high rate of infection for the disease. An in depth look revealed that three women traveling home …

New Zealand : Mumps Outbreak, Kathryn Evans

Global Public Health

The purpose of this Health Brief is to discuss the outbreak of mumps in New Zealand during the summer of 2017. The year saw more cases than the past sixteen years combined. The reason that New Zealand, a high-income country that generally does not struggle with communicable diseases, may be experiencing this outbreak is low vaccination rates in the 1990’s. It appears that there was a decline in coverage for the MMR immunization at this time due to several factors. These include a transition in the timing of the second dose of MMR, a change from four years to eleven …

Nepal : Healthcare And Sanitation Issues Resulting From Frequent Natural Disasters In Nepal, Jake Lauderdale

Global Public Health

This Public Health Brief calls to attention the issues plaguing Nepal as a result of both frequent natural disasters and poor healthcare infrastructure. The geographic characteristics of Nepal are shown to be a major factor in the damage and aftermath of natural disasters such as earthquakes. Due to its status as a poor and economically weakened country, Nepal must rely heavily on outside aid in order to alleviate the pressure of frequently occurring natural disasters. Despite work being done by several Non-Governmental Organizations, Nepal has a long way to go before they are able to independently manage the outcomes of …

Peru : Zika Virus, Benjamin Martin

Global Public Health

This document covers zika virus as a public health issue in Peru. Peru is a coastal country in South America. It has a population of 31,777,000 and faces many problems in the years to come. Some of those problems are a largely informal economy, the melting of glaciers, and lots of the population are impoverish and under-educated. These challenges the country is facing makes zika virus more dangerous. Zika virus is a disease that is spreading across the world and is most dangerous to pregnant women because it can cause birth defects for the child, such as microcephaly. In this …