Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons^™

Frequency Of Treatment Failure Of Utis In Children With Congenital Urinary Tract Anomalies, Catherine S Forster, Alexis C Wood, Stephanie Davis-Rodriguez, Pearl W Chang, Sanyukta Desai, Michael Tchou, John M Morrison, Jamie D Mudd, Brittany D Casey, Victor Trevisanut, Rana F Hamdy, Vijaya Vemulakonda, Patrick W Brady, Sowdhamini S Wallace, Uti In Children With Cakut Study Group

Faculty, Staff and Students Publications

OBJECTIVES: Children with certain congenital anomalies of the kidney and urinary tract and neurogenic bladder (CAKUT/NGB) are at higher risk of treatment failure for urinary tract infections (UTIs) than children with normal genitourinary anatomy, but the literature describing treatment and outcomes is limited. The objectives of this study were to describe the rate of treatment failure in children with CAKUT/NGB and compare duration of antibiotics between those with and without treatment failure.

METHODS: Multicenter retrospective cohort of children 0 to 17 years old with CAKUT/NGB who presented to the emergency department with fever or hypothermia and were diagnosed with UTI …

In Vivo Cardiac Electrophysiology In Mice: Determination Of Atrial And Ventricular Arrhythmic Substrates, Jose Alberto Navarro-Garcia, Florian Bruns, Oliver M Moore, Marcel A Tekook, Dobromir Dobrev, Christina Y Miyake, Xander H T Wehrens

Faculty, Staff and Students Publications

Cardiac arrhythmias are a common cardiac condition that might lead to fatal outcomes. A better understanding of the molecular and cellular basis of arrhythmia mechanisms is necessary for the development of better treatment modalities. To aid these efforts, various mouse models have been developed for studying cardiac arrhythmias. Both genetic and surgical mouse models are commonly used to assess the incidence and mechanisms of arrhythmias. Since spontaneous arrhythmias are uncommon in healthy young mice, intracardiac programmed electrical stimulation (PES) can be performed to assess the susceptibility to pacing-induced arrhythmias and uncover the possible presence of a proarrhythmogenic substrate. This procedure …

Cardiac Magnetic Resonance Imaging In Detection Of Progressive Graft Dysfunction In Pediatric Heart Transplantation, Kae Watanabe, Nicoleta C Arva, Joshua D Robinson, Cynthia Rigsby, Michael Markl, Melanie Sojka, Paul Tannous, Jennifer Arzu, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Chronic graft failure (CGF) in pediatric heart transplant (PHT) is multifactorial and may present with findings of fibrosis and microvessel disease (MVD) on endomyocardial biopsy (EMB). There is no optimal CGF surveillance method. We evaluated associations between cardiac magnetic resonance imaging (CMR) and historical/EMB correlates of CGF to assess CMR's utility as a surveillance method.

METHODS: Retrospective analysis of PHT undergoing comprehensive CMR between September 2015 and January 2022 was performed. EMB within 6 months was graded for fibrosis (scale 0-5) and MVD (number of capillaries with stenotic wall thickening per field of view). Correlation analysis and logistic regression …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

Macrocephaly And Digital Anomalies Expand The Phenotypic Spectrum Of Pgap2 Variants In Hyperphosphatasia With Impaired Intellectual Development Syndrome 3 (Hpmrs3), Seda Susgun, Afif Ben-Mahmoud, Franz Rüschendorf, Bonsu Ku, Syeda Iqra Hussain, Solveig Schulz, Oliver Puk, Saskia Biskup, Jonathan D.J. Labonne, Dilan Wellalage Don, Vijay Gupta, Tae Ik Choi, Saadullah Khan, Naveed Wasif, Yves Lacassie, Lawrence C. Layman, Sibel Aylin Ugur Iseri, Cheol Hee Kim, Hyung Goo Kim

School of Medicine Faculty Publications

Glycosylphosphatidylinositols (GPIs) anchor over 150 proteins as GPI-anchored proteins (GPI-APs) with crucial roles in diverse biological processes. The highly conserved biosynthesis of GPI-APs involves precise steps with at least 21 genes, categorized as PIG and PGAP genes. Pathogenic variants in these genes are linked to human diseases, highlighting the importance of each biosynthesis step. PGAP2 stands out among these genes due to its association with an expanded clinical spectrum of neurodevelopmental disorder (NDD) phenotypes with biallelic pathogenic variants. We present four patients from two families, one consanguineous and the other nonconsanguineous, each displaying distinct clinical presentations, including intellectual disability, hyperphosphatasia, …

Novel Techniques In Imaging Congenital Heart Disease: Jacc Scientific Statement, Ritu Sachdeva, Aimee K Armstrong, Rima Arnaout, Lars Grosse-Wortmann, B Kelly Han, Luc Mertens, Ryan A Moore, Laura J Olivieri, Anitha Parthiban, Andrew J Powell

Faculty, Staff and Students Publications

Recent years have witnessed exponential growth in cardiac imaging technologies, allowing better visualization of complex cardiac anatomy and improved assessment of physiology. These advances have become increasingly important as more complex surgical and catheter-based procedures are evolving to address the needs of a growing congenital heart disease population. This state-of-the-art review presents advances in echocardiography, cardiac magnetic resonance, cardiac computed tomography, invasive angiography, 3-dimensional modeling, and digital twin technology. The paper also highlights the integration of artificial intelligence with imaging technology. While some techniques are in their infancy and need further refinement, others have found their way into clinical workflow …

Reliable Detection Of Wnt7a Protein In Transfected Human Embryonic Kidney 293 Cells, Henry Okonkwo

Honors Undergraduate Theses

Fetal Alcohol Spectrum Disorders (FASDs) refer to a set of development abnormalities affecting a fetus that can result from prenatal alcohol exposure (PAE). Studies performed by the National Institute of Health estimate that the pervasiveness of FASDs may number as high as 1 to 5 per 100 school children. Congenital heart defects (CHDs) are a subset of these abnormalities and have been observed to occur in 38% of children with FASDs. While there is an association between PAE and CHDs, the exact molecular mechanism as to how it occurs remains unclear. A 2022 RNA sequencing study points to the Wnt7a …

Factors Leading To Osteoporosis In Turner Syndrome, Daniella O. Aleshinloye

Honors Undergraduate Theses

Turner Syndrome (TS) is a chromosomal disorder from conception characterized by the partial or complete absence of the second X chromosome in females. Chromosomal abnormalities, both numerical and structural, contribute to a significantly higher prevalence of fractures (30.5-32.2%) compared to non-TS postmenopausal women (14.9%). This highlights the intrinsic bone abnormalities associated with TS and increased fracture risk. Peripheral quantitative computed tomography (pQCT) is commonly used to assess bone mineral density (BMD). However, its accuracy in individuals with TS is limited due to the partial volume effect, highlighting the need for further clinical research to understand bone density changes compared to …

Wall Motion Assessment By Feature Tracking In Pediatric Patients With Coronary Anomalies Undergoing Dobutamine Stress Cmr, Shagun Sachdeva, Silvana Molossi, Dana Reaves-O'Neal, Prakash Masand, Tam T Doan

Faculty, Staff and Students Publications

BACKGROUND: Left ventricular (LV) wall motion assessment is an important adjunct in addition to perfusion defects in assessing ischemic changes. This study aims to investigate the feasibility and utility of performing feature tracking (FT) in pediatric patients with coronary anomalies undergoing dobutamine stress CMR to assess wall motion abnormalities (WMA) and perfusion defects.

METHOD: This is a retrospective study where 10 patients with an inducible first-pass perfusion (FPP) defect and 10 without were selected. Global LV circumferential strain/strain rate (GCS/GCSR) was measured at rest and at peak stress (systole and diastole) using a commercially available feature tracking software. Peak GCS …

Long-Term Efficacy And Safety Of Cardiac Genome Editing For Catecholaminergic Polymorphic Ventricular Tachycardia, Oliver M Moore, Yuriana Aguilar-Sanchez, Satadru K Lahiri, Mohit M Hulsurkar, J Alberto Navarro-Garcia, Tarah A Word, Joshua A Keefe, Dean Barazi, Elda M Munivez, Charles T Moore, Vaidya Parthasarathy, Jaysón Davidson, William R Lagor, So Hyun Park, Gang Bao, Christina Y Miyake, Xander H T Wehrens

Faculty, Staff and Students Publications

INTRODUCTION: Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model.

AIM: The purpose of this study was to assess whether adeno-associated virus type-9 (AAV9)-mediated somatic genome editing could prevent ventricular arrhythmias by removal of the mutant allele in mice that are heterozygous for

METHODS …

Prevalence Of Congenital Anomalies According To Maternal Race And Ethnicity, Texas, 1999–2018, Jeremy M Schraw, Elwin Jaime, Charles J Shumate, Mark A Canfield, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups.

METHODS: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for …

Diagnostic Value Of Soluble Urokinase-Type Plasminogen Activator Receptor In Patients With Acute Coronary Syndrome: A Systematic Review And Meta-Analysis, Michal Pruc, Iwona Jannasz, Damian Swieczkowski, Grzegorz Procyk, Aleksandra Gasecka, Zubaid Rafique, Francesco Chirico, Nicola Luigi Bragazzi, Milosz J Jaguszewski, Jaroslaw Wysocki, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS.

METHODS: A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used …

Meta-Analysis Of Postoperative Myocardial Injury As A Predictor Of Mortality After Living Donor Liver Transplantation, Krzysztof Jankowski, Frank W Peacock, Michal Pruc, Teresa Malecka-Massalska, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: The purpose of this study was to perform a systematic review and meta-analysis to investigate postoperative myocardial injury, as expressed by the postoperative concentration of high-sensitivity cardiac troponin I (hs-cTnI) as a predictor of mortality among living donor liver transplantation (LDLT) patients.

METHODS: PubMed, Scopus, Embase and the Cochrane Library were searched through to September 1st 2022. The primary endpoint included in-hospital mortality. Secondary endpoints were 1-year mortality and re-transplantation occurrence. Estimates are expressed as risk ratios (RRs) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with the I² test.

RESULTS: During the search, 2 studies were found …

A Phenotypically Robust Model Of Spinal And Bulbar Muscular Atrophy In Drosophila, Kristin Richardson, Medha Sengupta, Alyson Sujkowski, Kozeta Libohova, Autumn C. Harris, Robert Wessells, Diane E. Merry, Sokol V. Todi

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is an X-linked disorder that affects males who inherit the androgen receptor (AR) gene with an abnormal CAG triplet repeat expansion. The resulting protein contains an elongated polyglutamine (polyQ) tract and causes motor neuron degeneration in an androgen-dependent manner. The precise molecular sequelae of SBMA are unclear. To assist with its investigation and the identification of therapeutic options, we report here a new model of SBMA in Drosophila melanogaster. We generated transgenic flies that express the full-length, human AR with a wild-type or pathogenic polyQ repeat. Each transgene is inserted into the same safe …

The Role Of Noncoding Rnas In Pancreatic Birth Defects, Ziyue Zoey Yang, Ronald J Parchem

Faculty, Staff and Students Publications

Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes …

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

Retrieval Of Large Balloon Fragments During Transcatheter Pulmonary Valve Implantation Using A Novel Retrieval System, Anne C Taylor, Mohamed Ali H Ghandour, Asra Khan, Srinath T Gowda, Flora Nunez-Gallegos, Lynn F Peng, Jamil A Aboulhosn, Daniel S Levi, Doff B Mcelhinney, Athar M Qureshi

Faculty, Staff and Students Publications

The removal of balloon fragments from the pulmonary artery without damaging the pulmonary and tricuspid valves can be difficult. Four cases during transcatheter pulmonary valve replacement are described in which a novel retrieval system was used to facilitate safe removal. (Level of Difficulty: Advanced.)

Late-Gadolinium Enhancement Is Common In Older Pediatric Heart Transplant Recipients And Is Associated With Lower Ejection Fraction, Andrew A Lawson, Kae Watanabe, Lindsay Griffin, Christina Laternser, Michael Markl, Cynthia K Rigsby, Melanie Sojka, Joshua D Robinson, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Chronic graft failure and cumulative rejection history in pediatric heart transplant recipients (PHTR) are associated with myocardial fibrosis on endomyocardial biopsy (EMB). Cardiovascular magnetic resonance imaging (CMR) is a validated, non-invasive method to detect myocardial fibrosis via the presence of late gadolinium enhancement (LGE). In adult heart transplant recipients, LGE is associated with increased risk of future adverse clinical events including hospitalization and death. We describe the prevalence, pattern, and extent of LGE on CMR in a cohort of PHTR and its associations with recipient and graft characteristics.

METHODS: This was a retrospective study of consecutive PHTR who underwent …

Improving Outcomes For Infants After Cardiopulmonary Bypass Surgery For Congenital Heart Disease: A Commentary On Recent Randomized Controlled Trials, Luregn J Schlapbach, Kristen S Gibbons, Warwick Butt, Prince J Kannankeril, Jennifer S Li, Kevin D Hill

Faculty, Staff and Students Publications

The recent NITRIC and STRESS trials demonstrate opportunities to perform pragmatic large randomized trials in congenital heart disease. We discuss lessons learnt from these trials which can inform future trial design and conduct in the field of pediatric heart surgery.

Cardiac Magnetic Resonance Imaging To Determine Single Ventricle Function In A Pediatric Population Is Feasible In A Large Trial Setting: Experience From The Single Ventricle Reconstruction Trial Longitudinal Follow Up, Jon Detterich, Michael D Taylor, Timothy C Slesnick, Michael Dilorenzo, Anthony Hlavacek, Christopher Z Lam, Shagun Sachdeva, Sean M Lang, M Jay Campbell, Jennifer Gerardin, Kevin K Whitehead, Rahul H Rathod, Mark Cartoski, Shaji Menon, Felicia Trachtenberg, Russell Gongwer, Jane Newburger, Caren Goldberg, Adam L Dorfman, The Pediatric Heart Network Investigators

Faculty, Staff and Students Publications

The Single Ventricle Reconstruction (SVR) Trial was a randomized prospective trial designed to determine survival advantage of the modified Blalock-Taussig-Thomas shunt (BTTS) vs the right ventricle to pulmonary artery conduit (RVPAS) for patients with hypoplastic left heart syndrome. The primary aim of the long-term follow-up (SVRIII) was to determine the impact of shunt type on RV function. In this work, we describe the use of CMR in a large cohort follow up from the SVR Trial as a focused study of single ventricle function. The SVRIII protocol included short axis steady-state free precession imaging to assess single ventricle systolic function …

An Assessment Of Fetal Rhd Screening In Non-Invasive Prenatal Testing (Nipt) And Implementation Of Targeted Routine Antenatal Anti-D Prophylaxis (Traadp) In Enhancing Management Of Rhd-Negative Women At Risk Of Haemolytic Disease Of The Fetus/Newborn (Hdfn) In University Hospital Limerick Group (Uhlg), Anna Pohrebyannyk

International Undergraduate Journal of Health Sciences

Alloimmunisation, formerly isoimmunisation, or sensitisation can occur in pregnancy when a Rhesus D (RhD)-negative woman carries an RhD-positive fetus. Incompatibility of Rh status causes development of allo anti-D antibodies in response to antigen exposure from foreign fetal red cells in fetomaternal haemorrhages (FMHs) or potential sensitising events (PSEs) i.e., iatrogenic interventions (medical or surgical treatment), silent or spontaneous transplacental haemorrhages (STHs) in pregnancy, at birth or other traumas. Anti-D antibodies are immune-mediated and can cross the placenta and attach to fetal cells causing destruction and haemolysis. Offspring of primigravida women are unaffected usually and it is later pregnancies that may …

Automated Prediction Of Cardiorespiratory Deterioration In Patients With Single-Ventricle Parallel Circulation: A Multicenter Validation Study, Craig G Rusin, Sebastian I Acosta, Kennith M Brady, Eric Vu, Carly Scahill, Brian Fonseca, Cindy Barrett, Janet Simsic, Andrew R Yates, Brenna Klepczynski, William J Gaynor, Daniel J Penny

Faculty, Staff and Students Publications

OBJECTIVES: Patients with single-ventricle physiology have a significant risk of cardiorespiratory deterioration between their first- and second-stage palliation surgeries. Detection of deterioration episodes may allow for early intervention and improved outcomes.

METHODS: A prospective study was executed at Nationwide Children's Hospital, Children's Hospital of Philadelphia, and Children's Hospital Colorado to collect physiologic data of subjects with single ventricle physiology during all hospitalizations between neonatal palliation and II surgeries using the Sickbay software platform (Medical Informatics Corp). Timing of cardiorespiratory deterioration events was captured via chart review. The predictive algorithm previously developed and validated at Texas Children's Hospital was applied to …

A Cryptic Microdeletion Del(12)(P11.21p11.23) Within An Unbalanced Translocation T(7;12)(Q21.13;Q23.1) Implicates New Candidate Loci For Intellectual Disability And Kallmann Syndrome, Afif Ben-Mahmoud, Shotaro Kishikawa, Vijay Gupta, Natalia T. Leach, Yiping Shen, Oana Moldovan, Himanshu Goel, Bruce Hopper, Kara Ranguin, Nicolas Gruchy, Saskia M. Maas, Yves Lacassie, Soo Hyun Kim, Woo Yang Kim, Bradley J. Quade, Cynthia C. Morton, Cheol Hee Kim, Lawrence C. Layman, Hyung Goo Kim

School of Medicine Faculty Publications

In a patient diagnosed with both Kallmann syndrome (KS) and intellectual disability (ID), who carried an apparently balanced translocation t(7;12)(q22;q24)dn, array comparative genomic hybridization (aCGH) disclosed a cryptic heterozygous 4.7 Mb deletion del(12)(p11.21p11.23), unrelated to the translocation breakpoint. This novel discovery prompted us to consider the possibility that the combination of KS and neurological disorder in this patient could be attributed to gene(s) within this specific deletion at 12p11.21-12p11.23, rather than disrupted or dysregulated genes at the translocation breakpoints. To further support this hypothesis, we expanded our study by screening five candidate genes at both breakpoints of the chromosomal translocation …

The Effect Of Genetic Taste Status On Swallowing: A Literature Review, Theresa S. Lee, Angela M. Dietsch, Rana H. Damra, Rachel W. Mulheren

Department of Special Education and Communication Disorders: Faculty Publications

Purpose

Swallowing and taste share innervation pathways and are crucial to nutritive intake. Individuals vary in their perception of taste due to factors such as genetics; however, it is unclear to what extent genetic taste status influences swallowing physiology and function. The purpose of this review article is to provide background on genetic taste status, review the evidence on the association between genetic taste status and swallowing, and discuss research and clinical implications.

Method

A comprehensive literature review was conducted using search terms related to swallowing and genetic taste status. Studies were included if they investigated the main effect of …

Mid-Life Leukocyte Telomere Length And Dementia Risk: An Observational And Mendelian Randomization Study Of 435,046 Uk Biobank Participants, Rui Liu, Luke C. Pilling, David Melzer, Lihong Wang, Kevin J. Manning, David C. Steffens, Jack Bowden, Richard H. Fortinsky, George A. Kuchel, Taeho G. Rhee, Breno S. Diniz, Chia-Ling Kuo

Health Science Faculty Publications

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data ( …

Esophageal Lesion Reveals An Aortic Pseudoaneurysm In The Setting Of Actinomyces Odontolyticus Bacteremia, Anneliese Grewing, Harsha Jujjavarapu, Cameron Price, Lindsay F Eilers, Sloane Zimmerman, Nahid Hiermandi, Athar M Qureshi, Richard Kellermayer, Jolie J Britt

Faculty, Staff and Students Publications

A toddler presented with hematemesis a few weeks after ingesting a penny. Workup revealed an esophageal lesion communicating with an aortic pseudoaneurysm in the setting of Actinomyces odontolyticus bacteremia. A. odontolytica is an oropharyngeal bacteria known to cause fistulas when introduced into tissue planes. (Level of Difficulty: Intermediate.)

Genome Editing For Cystic Fibrosis, Guoshun Wang

School of Medicine Faculty Publications

Cystic fibrosis (CF) is a monogenic recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator gene (CFTR). Remarkable progress in basic research has led to the discovery of highly effective CFTR modulators. Now ~90% of CF patients are treatable. However, these modulator therapies are not curative and do not cover the full spectrum of CFTR mutations. Thus, there is a continued need to develop a complete and durable therapy that can treat all CF patients once and for all. As CF is a genetic disease, the ultimate therapy would be in-situ repair of the genetic lesions in the …

Clinical Spectrum And Genetic Causes Of Mitochondrial Hepatopathy Phenotype In Children, James E Squires, Alexander G Miethke, C Alexander Valencia, Kieran Hawthorne, Lisa Henn, Johan L K Van Hove, Robert H Squires, Kevin Bove, Simon Horslen, Rohit Kohli, Jean P Molleston, Rene Romero, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Evelyn Hsu, Saul J Karpen, Kathleen M Loomes, Vicky L Ng, Philip Rosenthal, Krupa Mysore, Kasper S Wang, Marisa W Friederich, John C Magee, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH.

METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes.

RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

Molecular Diagnosis Of Non X-Linked Ectodermal Dysplasias Using Next Generation Sequencing, Eman Abdelalim Rabie

Theses and Dissertations

Ectodermal Dysplasias (EDs) are rare heterogenous monogenic developmental disorders sharing the impairment of at least two surface ectoderm-derived organs. Symptoms characteristically manifest developmental abnormalities of the teeth, and three skin derivatives: hair follicles, nails, and sweat glands. The disease-causing gene was identified for only fewer than half of 160 characterized ED phenotypes. Expectedly, ED-causing genes regulate or function in ectodermal-developmental processes. The most common phenotype is hypohidrotic ED featuring teeth agenesis, and diminished or complete absence of hair and sweat production. Disease-causing variants of EDA, EDAR, EDARADD and WNT10A genes were identified in 60-90% of ED patients in …