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

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.

Analyzing Prominent Genes In Acute Lymphocytic Leukemia (All), Shima Z. Omar

Honors College Theses

Acute lymphocytic leukemia (ALL) is the most common type of childhood cancer. Leukemia is a type of cancer that involves the bone marrow and blood. This research study examined prominent genes in the disease. Two groups of genes, tumor suppressor and cell differentiation, were compared using statistical analysis to compare their binding potential and epigenetic potential. It is most likely that I failed to detect significant differences either because these genes’ function in the disease etiology is not strongly contexed to changes in expression, or that the magnitude of the differences were too slight to be detected with these methods. …

Stigma And Patient-Controlled Analgesia: Trust Is The Essential Ingredient Of Successful Patient Education In The Patient-Doctor Relationship, Trey D. Vanaken

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Van Beers EJ, Van Tuijn CFJ, Nieuwkerk PT, et al. Patient-controlled analgesia versus continuous infusion of morphine during vaso-occlusive crisis in sickle cell disease, a randomized controlled trial. Am J Hematol. 2007;82(11):955-960. https://doi.org/10.1002/ajh.20944.

for a patient with recurrent vaso-occlusive crisis secondary to Sickle Cell Disease.

A Rare Case Of Tricuspid Atresia Absent Pulmonary Valve Diagnosed On Fetal Echocardiography, Wesam Sourour, Shannon K. Powell

School of Medicine Faculty Publications

• TA absent PV is a rare congenital heart anomaly. • TA absent PV is associated with a poor prognosis. • TA absent PV can be successfully diagnosed on fetal echocardiography.

A Novel, Minimally Invasive, Paper-Based Biomarker Assay For Molecular Diagnosis Of Preeclampsia, Tomi Taiwo

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Preeclampsia is a severe pregnancy condition marked by high blood pressure and proteinuria that can strike at any point throughout pregnancy or immediately after birth. Although the exact cause of this disease is unknown, there are several symptoms associated. The goal of this study is focused on the evaluation of biomarker-based assays for molecular diagnosis of the condition in a sensitive and timely manner. This project involved the use of an immunoassay, fabricated serum samples, and a paper-based assay to assess the strength of the presence of the placental growth factor (PlGF). This was done to facilitate a proof-of-concept mechanism …

Trio-Based Gwas Identifies Novel Associations And Subtype-Specific Risk Factors For Cleft Palate, Kelsey Robinson, Trenell J Mosley, Kenneth S Rivera-González, Christopher R Jabbarpour, Sarah W Curtis, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, David J Cutler, Michael P Epstein, Lord J J Gowans, Jacqueline T Hecht, Jeffrey C Murray, Gary M Shaw, Lina Moreno Uribe, Seth M Weinberg, Harrison Brand, Mary L Marazita, Robert J Lipinski, Elizabeth J Leslie

Faculty, Staff and Student Publications

Cleft palate (CP) is one of the most common craniofacial birth defects; however, there are relatively few established genetic risk factors associated with its occurrence despite high heritability. Historically, CP has been studied as a single phenotype, although it manifests across a spectrum of defects involving the hard and/or soft palate. We performed a genome-wide association study using transmission disequilibrium tests of 435 case-parent trios to evaluate broad risks for any cleft palate (ACP) (n = 435), and subtype-specific risks for any cleft soft palate (CSP), (n = 259) and any cleft hard palate (CHP) (n = 125). We identified …

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 …

Repurposing Normal Chromosomal Microarray Data To Harbor Genetic Insights Into Congenital Heart Disease, Nephi Walton, Hoang Nguyen, Sara Procknow, Darren Johnson, Alexander Anzelmi, Patrick Jay

Department of Medicine Faculty Papers

About 15% of congenital heart disease (CHD) patients have a known pathogenic copy number variant. The majority of their chromosomal microarray (CMA) tests are deemed normal. Diagnostic interpretation typically ignores microdeletions smaller than 100 kb. We hypothesized that unreported microdeletions are enriched for CHD genes. We analyzed "normal" CMAs of 1762 patients who were evaluated at a pediatric referral center, of which 319 (18%) had CHD. Using CMAs from monozygotic twins or replicates from the same individual, we established a size threshold based on probe count for the reproducible detection of small microdeletions. Genes in the microdeletions were sequentially filtered …

Protein S Antibody As An Adjunct Therapy For Hemophilia B, Hope P. Wilson, Aliyah Pierre, Ashley L. Paysse, Narender Kumar, Brian C. Cooley, Pratyadipta Rudra, Adrianne W. Dorsey, Diana Polania-Villanueva, Sabyasachi Chatterjee, Maissaa Janbain, Maria C. Velez, Rinku Majumder

School of Medicine Faculty Publications

ABSTRACT: Hemophilia B (HB) is caused by an inherited deficiency of plasma coagulation factor IX (FIX). Approximately 60% of pediatric patients with HB possess a severe form of FIX deficiency (< 1% FIX activity). Treatment typically requires replacement therapy through the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant protein S (PS) inhibits activated FIX (FIXa). PS ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercially obtained plasma and plasma from pediatric patients with HB. We included 11 pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of the FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Furthermore, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.

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 …

Improving Maternal, Neonatal And Child Health Outcomes In Low-Resource Settings: Translating Research Evidence To Practice - Report From The Third International Conference On Maternal, Newborn And Child Health, Robert L. Goldenberg, Shivaprasad S. Goudar, Nancy F. Krebs, Richard Derman, Sarah Saleem, Elizabeth M. Mcclure

Community Health Sciences

No abstract provided.

Incorporating Poi As A Therapeutic Modality For Preschool Aged Children In The Care Clinic, Danielle Zirkle

Department of Occupational Therapy Entry-Level Capstone Projects

No abstract provided.

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 ( …

Lifelong Fitness In Ambulatory Children And Adolescents With Cerebral Palsy I: Key Ingredients For Bone And Muscle Health, Noelle G. Moreau, Kathleen M. Friel, Robyn K. Fuchs, Sudarshan Dayanidhi, Theresa Sukal-Moulton, Marybeth Grant-Beuttler, Mark D. Peterson, Richard D. Stevenson, Susan V. Duff

Physical Therapy Faculty Articles and Research

Physical activity of a sufficient amount and intensity is essential to health and the prevention of a sedentary lifestyle in all children as they transition into adolescence and adulthood. While fostering a fit lifestyle in all children can be challenging, it may be even more so for those with cerebral palsy (CP). Evidence suggests that bone and muscle health can improve with targeted exercise programs for children with CP. Yet, it is not clear how musculoskeletal improvements are sustained into adulthood. In this perspective, we introduce key ingredients and guidelines to promote bone and muscle health in ambulatory children with …

Evaluation Of The Orally Bioavailable 4-Phenylbutyrate-Tethered Trichostatin A Analogue Ar42 In Models Of Spinal Muscular Atrophy, Casey J. Lumpkin, Ashlee W. Harris, Andrew J. Connell, Ryan W. Kirk, Joshua A. Whiting, Luciano Saieva, Livio Pellizzoni, Arthur H.M. Burghes, Matthew E.R. Butchbach

Department of Pediatrics Faculty Papers

Proximal spinal muscular atrophy (SMA) is a leading genetic cause for infant death in the world and results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of SMN protein and small molecules that can increase SMN expression are of considerable interest as potential therapeutics. Previous studies have shown that both 4-phenylbutyrate (4PBA) and trichostatin A (TSA) increase SMN expression in dermal fibroblasts derived from SMA patients. AR42 is a 4PBA-tethered TSA derivative that is a very potent histone deacetylase inhibitor. SMA patient fibroblasts were treated with either AR42, AR19 (a …

Lifelong Fitness In Ambulatory Children And Adolescents With Cerebral Palsy Ii: Influencing The Trajectory, Susan V. Duff, Justine D. Kimbel, Marybeth Grant-Beuttler, Theresa Sukal-Moulton, Noelle G. Moreau, Kathleen M. Friel

Physical Therapy Faculty Articles and Research

Physical activity of at least moderate intensity in all children contributes to higher levels of physical and psychological health. While essential, children with cerebral palsy (CP) often lack the physical capacity, resources, and knowledge to engage in physical activity at a sufficient intensity to optimize health and well-being. Low levels of physical activity place them at risk for declining fitness and health, contributing to a sedentary lifestyle. From this perspective, we describe a framework to foster a lifelong trajectory of fitness in ambulatory children with CP (GMFCS I–III) as they progress into adolescence and adulthood, implemented in conjunction with a …

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.)