Pediatrics Commons^™

Disruption Of Neonatal Cardiomyocyte Physiology Following Exposure To Bisphenol-A., Manelle Ramadan, Meredith Sherman, Rafael Jaimes, Ashika Chaluvadi, Luther Swift, Nikki Gillum Posnack

Pediatrics Faculty Publications

Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate, beat …

Amygdala Corticofugal Input Shapes Mitral Cell Responses In The Accessory Olfactory Bulb, Livio Oboti, Eleonora Russo, Tuyen Tran, Daniel Durstewitz, Joshua G. Corbin

Pediatrics Faculty Publications

Interconnections between the olfactory bulb and the amygdala are a major pathway for triggering strong behavioral responses to a variety of odorants. However, while this broad mapping has been established, the patterns of amygdala feedback connectivity and the influence on olfactory circuitry remain unknown. Here, using a combination of neuronal tracing approaches, we dissect the connectivity of a cortical amygdala [posteromedial cortical nucleus (PmCo)] feedback circuit innervating the mouse accessory olfactory bulb. Optogenetic activation of PmCo feedback mainly results in feedforward mitral cell (MC) inhibition through direct excitation of GABAergic granule cells. In addition, LED-driven activity of corticofugal afferents increases …

A Global Health Research Checklist For Clinicians., Rasha D Sawaya, Kristen A Breslin, Eiman Abdulrahman, Jennifer I Chapman, Dafina M Good, Lili Moran, Paul C Mullan, Oluwakemi Badaki-Makun

Pediatrics Faculty Publications

Global health research has become a priority in most international medical projects. However, it is a difficult endeavor, especially for a busy clinician. Navigating the ethics, methods, and local partnerships is essential yet daunting.To date, there are no guidelines published to help clinicians initiate and complete successful global health research projects. This Global Health Research Checklist was developed to be used by clinicians or other health professionals for developing, implementing, and completing a successful research project in an international and often low-resource setting. It consists of five sections: Objective, Methodology, Institutional Review Board and Ethics, Culture and partnerships, and Logistics. …

Characterization Of Sex-Based Dna Methylation Signatures In The Airways During Early Life., Cesar L Nino, Geovanny F Perez, Natalia Isaza, Maria J Gutierrez, Jose L Gomez, Gustavo Nino

Pediatrics Faculty Publications

Human respiratory conditions are largely influenced by the individual's sex resulting in overall higher risk for males. Sex-based respiratory differences are present at birth suggesting a strong genetic component. Our objective was to characterize early life sex-based genomic signatures determined by variable X-chromosome methylation in the airways. We compared male versus female genome-wide DNA methylation in nasal airway samples from newborns and infants aged 1-6 months (N = 12). We analyzed methylation signals across CpG sites mapped to each X-linked gene using an unsupervised classifier (principal components) followed by an internal evaluation and an exhaustive cross-validation. Results were validated in …

Pupillometric Assessment Of Small Doses Of Opioid In A Pediatric Population, David Strum, Elizabeth Malphrus, Kevin Jackson, Julia Finkel

GW Research Days 2016 - 2020

According to the CDC, opioid prescriptions in the United States have more than tripled from 1999-2014, which has correlated with the staggering increase in opioid-involved drug overdose deaths. This pattern of prescription is thought to be a major contributory factor to the increase in drug overdose in America, as four out of five new heroin users started by misusing prescription painkillers. Providers need the means to objectively monitor analgesic efficacy of treatment in patients with pain to mitigate unnecessary analgesic prescribing.

It is well established that mu opioid agonists like morphine cause miosis, an effect to which tolerance does not …

Characteristics Of Correctly Identified Pediatric Obesity And Overweight Status And Management In An Academic General Pediatric Clinic, Ana Morais, Joseph Kelly, James E. Bost, Susma Vaidya

GW Research Days 2016 - 2020

Objective: The goals of this study were to identify and characterize the rates of documentation and guideline-based management of overweight and obese children within an academic pediatric clinic.

Population/Methods: Overweight, obese, and severely obese children were identified from 7,422 well child visits in 2016 within a primary care clinic that cares for a primarily urban, minority (80% African American), and Medicaid (85%) population until the age of 12. During this 1-year study, there were 79 pediatric residents, 19 attending pediatricians, and 5 nurse practitioners who treated patients. Through a retrospective electronic medical record review, diagnosis and treatment including counseling, …

Parental Compliance For Two Stage Fowler-Stephens Laparoscopic Orchiopexy: Is Everyone Following Up For The Second Stage And, If Not, Who Is At Risk?, Campbell Grant, H. Gil Rushton, Tanya D. Davis

GW Research Days 2016 - 2020

Purpose: Patients undergoing a two-stage Fowler-Stephens laparoscopic orchiopexy for intra-abdominal testes are typically recommended to undergo the second stage 4-6 months after the first stage. . As part of a quality care initiative, our studied examined if patients were in fact following up within this window and, if not, why patients were lost to follow up.

Materials and Methods: We retrospectively reviewed a cohort of 105 patients who underwent the first stage of a 2-stage Fowler-Stephens orchidopexy at our institution between 1/2005 to 1/2015. Bivariate and multivariate analyses were performed to compare clinical, surgical, and socioeconomic factors. Patients identified as …

Resilience Of Children With Chronic Health Conditions: The Impact Of Neuropsychiatric Comorbidities, Sarah Bernstein, Sandra Cushner-Weinstein

GW Research Days 2016 - 2020

BACKGROUND: Resilience, the ability to overcome adversity and effectively recover from stressful experiences, is a complex theory with many contributing factors. Previous studies have shown that condition-specific summer camps for children with chronic health conditions increase resilience and adaptive coping skills, change attitudes toward the illness, and improve quality of life. The aim of this study was to determine how neuropsychiatric comorbid diagnoses such as attention deficit hyperactivity disorder (ADHD), learning disability, and anxiety disorder influence the resilience of children with chronic health conditions.

METHODS: Children with chronic health conditions including autism, epilepsy, cerebral palsy, Tourette’s syndrome, sickle cell anemia, …

Communicating Effectively In Pediatric Cancer Care: Translating Evidence Into Practice., Lindsay J Blazin, Cherilyn Cecchini, Catherine Habashy, Erica C Kaye, Justin N Baker

Pediatrics Faculty Publications

Effective communication is essential to the practice of pediatric oncology. Clear and empathic delivery of diagnostic and prognostic information positively impacts the ways in which patients and families cope. Honest, compassionate discussions regarding goals of care and hopes for patients approaching end of life can provide healing when other therapies have failed. Effective communication and the positive relationships it fosters also can provide comfort to families grieving the loss of a child. A robust body of evidence demonstrates the benefits of optimal communication for patients, families, and healthcare providers. This review aims to identify key communication skills that healthcare providers …

Risk Factors For Major Early Adverse Events Related To Cardiac Catheterization In Children And Young Adults With Pulmonary Hypertension: An Analysis Of Data From The Impact (Improving Adult And Congenital Treatment) Registry., Michael L O'Byrne, Kevin F Kennedy, Joshua P Kanter, John T Berger, Andrew C Glatz

Pediatrics Faculty Publications

BACKGROUND: Cardiac catheterization is the gold standard for assessment and follow-up of patients with pulmonary hypertension (PH). To date, there are limited data about the factors that influence the risk of catastrophic adverse events after catheterization in this population.

METHODS AND RESULTS: A retrospective multicenter cohort study was performed to measure risk of catastrophic adverse outcomes after catheterization in children and young adults with PH and identify risk factors for these outcomes. All catheterizations in children and young adults, aged 0 to 21 years, with PH at hospitals submitting data to the IMPACT (Improving Adult and Congenital Treatment) registry between …

Impaired Type I Interferon Regulation In The Blood Transcriptome Of Recurrent Asthma Exacerbations., Jose L Gomez, Maria P Diaz, Gustavo Nino, Clemente J Britto

Pediatrics Faculty Publications

BACKGROUND: Asthma exacerbations are an important cause of morbidity in asthma. Respiratory infections are often involved in asthma exacerbations in both children and adults. Some individuals with asthma have increased susceptibility to viral infections and as a result increased rates of asthma exacerbations. We sought to identify a transcriptomic signature in the blood associated with asthma exacerbations triggered by respiratory infections (AETRI) and determine its association with increased risk for asthma exacerbations.

METHODS: We conducted a two-step study using publicly available, previously generated transcriptomic signatures in peripheral blood mononuclear cells (PBMCs) from asthmatics to identify novel markers of increased risk …

Predicting Cyp3a-Mediated Midazolam Metabolism In Critically Ill Neonates, Infants, Children And Adults With Inflammation And Organ Failure., Janneke M Brussee, Nienke J Vet, Elke H J Krekels, Abraham J Valkenburg, Evelyne Jacqz-Aigrain, Joop M A Van Gerven, Eleonora L Swart, Johannes N Van Den Anker, Dick Tibboel, Matthijs De Hoog, Saskia N De Wildt, Catherijne A J Knibbe

Pediatrics Faculty Publications

No abstract provided.

Cardiovascular Effects Of Metabolic Syndrome After Transplantation: Convergence Of Obesity And Transplant-Related Factors., Kristen Sgambat, Sarah Clauss, Asha Moudgil

Pediatrics Faculty Publications

Children are at increased risk of developing metabolic syndrome (MS) after kidney transplantation, which contributes to long-term cardiovascular (CV) morbidities and decline in allograft function. While MS in the general population occurs due to excess caloric intake and physical inactivity, additional chronic kidney disease and transplant-related factors contribute to the development of MS in transplant recipients. Despite its significant health consequences, the interplay of the individual components in CV morbidity in pediatric transplant recipients is not well understood. Additionally, the optimal methods to detect early CV dysfunction are not well defined in this unique population. The quest to establish clear …

Teenage Exercise Is Associated With Earlier Symptom Onset In Dysferlinopathy: A Retrospective Cohort Study., Ursula R Moore, Marni Jacobs, Roberto Fernandez-Torron, Jiji Jang, Meredith K James, Diana X Bharucha-Goebel, +Several Additional Authors

Pediatrics Faculty Publications

No abstract provided.

Genotype-Phenotype Correlation In Nf1: Evidence For A More Severe Phenotype Associated With Missense Mutations Affecting Nf1 Codons 844-848, M Koczkowska, Y Chen, T Callens, A Gomes, A Sharp, Rhonda Schonberg, +Several Additional Authors

Pediatrics Faculty Publications

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons—Leu844, Cys845, Ala846, Leu847, and Gly848—located in the cysteine-serine-rich domain (CSRD). …

Genetic Programming Of Hypertension, Sun-Young Ahn, Charu Gupta

Pediatrics Faculty Publications

The heritability of hypertension (HTN) is widely recognized and as a result, extensive studies ranging from genetic linkage analyses to genome-wide association studies are actively ongoing to elucidate the etiology of both monogenic and polygenic forms of HTN. Due to the complex nature of essential HTN, however, single genes affecting blood pressure (BP) variability remain difficult to isolate and identify and have rendered the development of single-gene targeted therapies challenging. The roles of other causative factors in modulating BP, such as gene–environment interactions and epigenetic factors, are increasingly being brought to the forefront. In this review, we discuss the various …

The Effects Of An Acute Exercise Bout On Gh And Igf-1 In Prediabetic And Healthy African Americans: A Pilot Study Investigating Gene Expression, N. Berry, Monica J. Hubal, L. Wideman

Pediatrics Faculty Publications

The incidence of pre-diabetes (PD) and Type-2 Diabetes Mellitus (T2D) is a worldwide epidemic. African American (AA) individuals are disproportionately more likely to become diabetic than other ethnic groups. Over the long-term, metabolic complications related to diabetes result in significant alterations in growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Considering the limited exercise-related studies in the area of gene expression changes with disease progression, the objective of this study was to examine differences in exercise-induced gene expression related to the GH and IGF-1 pathways in peripheral blood mononuclear cells (PBMCs) of healthy (CON) and PD AA individuals. Design: Ten …

Real-Time, Label-Free, Intraoperative Visualization Of Peripheral Nerves And Microvasculatures Using Multimodal Optical Imaging Techniques, Jaepyong Cha, A Broch, S Mudge, K Kim, J Namgoong, E Oh, P Kim

Pediatrics Faculty Publications

Accurate, real-time identification and display of critical anatomic structures, such as the nerve and vasculature structures, are critical for reducing complications and improving surgical outcomes. Human vision is frequently limited in clearly distinguishing and contrasting these structures. We present a novel imaging system, which enables noninvasive visualization of critical anatomic structures during surgical dissection. Peripheral nerves are visualized by a snapshot polarimetry that calculates the anisotropic optical properties. Vascular structures, both venous and arterial, are identified and monitored in real-time using a near-infrared laser-speckle-contrast imaging. We evaluate the system by performing in vivo animal studies with qualitative comparison by contrast-agent-aided …

Adoptive T Cell Therapy For Epstein-Barr Virus Complications In Patients With Primary Immunodeficiency Disorders, L Mclaughlin, Catherine Bollard, Michael D. Keller

Pediatrics Faculty Publications

Patients with primary immunodeficiency disorders (PID) have an increased risk from acute and chronic Epstein-Barr Virus (EBV) viral infections and EBV-associated malignancies. Hematopoietic stem cell transplantation (HSCT) is a curative strategy for many patients with PID, but EBV-related complications are common in the immediate post-transplant period due to delayed reconstitution of T cell immunity. Adoptive T cell therapy with EBV-specific T cells is a promising therapeutic strategy for patients with PID both before and after HSCT. Here we review the methods used to manufacture EBV-specific T cells, the clinical outcomes, and the ongoing challenges for future development of the strategy. …

Evaluation Of Performance, Acceptance, And Compliance Of An Auto-Injector In Healthy And Rheumatoid Arthritic Subjects Measured By A Motion Capture System., Xiao Xiao, Wei Li, Corbin Clawson, David Karvani, Perceval Sondag, James K Hahn

Pediatrics Faculty Publications

Purpose: The study aimed to develop a motion capture system that can track, visualize, and analyze the entire performance of self-injection with the auto-injector.

Methods: Each of nine healthy subjects and 29 rheumatoid arthritic (RA) patients with different degrees of hand disability performed two simulated injections into an injection pad while six degrees of freedom (DOF) motions of the auto-injector and the injection pad were captured. We quantitatively measured the performance of the injection by calculating needle displacement from the motion trajectories. The max, mean, and SD of needle displacement were analyzed. Assessments of device acceptance and usability were evaluated …

Improving Outcomes After Pediatric Cardiac Arrest – The Icu-Resuscitation Project: Study Protocol For A Randomized Controlled Trial, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Collaborative Pediatric Critical Care Research Network (Cpccrn), Murray M. Pollack

Pediatrics Faculty Publications

Background

Quality of cardiopulmonary resuscitation (CPR) is associated with survival, but recommended guidelines are often not met, and less than half the children with an in-hospital arrest will survive to discharge. A single-center before-and-after study demonstrated that outcomes may be improved with a novel training program in which all pediatric intensive care unit staff are encouraged to participate in frequent CPR refresher training and regular, structured resuscitation debriefings focused on patient-centric physiology.

Methods/design

This ongoing trial will assess whether a program of structured debriefings and point-of-care bedside practice that emphasizes physiologic resuscitation targets improves the rate of survival to hospital …

Regional Microstructural Organization Of The Cerebral Cortex Is Affected By Preterm Birth., Marine Bouyssi-Kobar, Marie Brossard-Racine, Marni Jacobs, Jonathan Murnick, Taeun Chang, Catherine Limperopoulos

Pediatrics Faculty Publications

Objectives: To compare regional cerebral cortical microstructural organization between preterm infants at term-equivalent age (TEA) and healthy full-term newborns, and to examine the impact of clinical risk factors on cerebral cortical micro-organization in the preterm cohort.

Study design: We prospectively enrolled very preterm infants (gestational age (GA) at birth<32 >weeks; birthweight<1500 >g) and healthy full-term controls. Using non-invasive 3T diffusion tensor imaging (DTI) metrics, we quantified regional micro-organization in ten cerebral cortical areas: medial/dorsolateral prefrontal cortex, anterior/posterior cingulate cortex, insula, posterior parietal cortex, motor/somatosensory/auditory/visual cortex. ANCOVA analyses were performed controlling for sex and postmenstrual age at MRI.

Results: We studied …

Genetic Variation In Acid Ceramidase Predicts Non-Completion Of An Exercise Intervention., Lauren S Lewis, Kim M Huffman, Ira J Smith, Mark P Donahue, Cris A Slentz, Joseph A Houmard, Monica J Hubal, Eric P Hoffman, Elizabeth R Hauser, Ilene C Siegler, William E Kraus

Pediatrics Faculty Publications

Genetic variation is associated with a number of lifestyle behaviours; it may be associated with adherence and individual responses to exercise training. We tested single nucleotide polymorphisms (SNPs) in the acid ceramidase gene (ASAH1) for association with subject adherence and physiologic benefit with exercise training in two well-characterised randomised, controlled 8-month exercise interventions: STRRIDE I (n = 239) and STRRIDE II (n = 246). Three ASAH1 non-coding SNPs in a linkage disequilibrium block were associated with non-completion: rs2898458(G/T), rs7508(A/G), and rs3810(A/G) were associated with non-completion in both additive (OR = 1.8, 1.8, 2.0; P < 0.05 all) and dominant (OR = 2.5, 2.6, 3.5; P < 0.05 all) models; with less skeletal muscle ASAH …