Medical Specialties Commons^™

Expanding The Phenotype Associated With Naa10-Related N-Terminal Acetylation Deficiency., Chloé Saunier, Svein Isungset Støve, Bernt Popp, Bénédicte Gérard, Marina Blenski, Nicholas Ahmew, +Several Additional Authors

Pediatrics Faculty Publications

N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ …

Cardiac Arrest In An Adolescent With Uhl’S Anomaly: Two Unusual Cardiac Arrhythmia Mechanisms, Jeffrey P. Moak, Gail D. Pearson, Bradley Clark, Charles I. Berul, Russell R. Cross, Dilip S. Nath

Pediatrics Faculty Publications

No abstract provided.

Improving Sickle Cell Transitions Of Care Through Health Information Technology., Jennifer R Frost, Rebecca K Cherry, Suzette O Oyeku, Elissa Z Faro, Lori E Crosby, Maria Britto, Lisa K. Tuchman, Ivor B. Horn, Charles J Homer, Anjali Jain

Pediatrics Faculty Publications

Introduction

Transitions between inpatient and outpatient care and pediatric to adult care are associated with increased mortality for sickle cell disease (SCD) patients. As accurate and timely sharing of health information is essential during transitions, a health information technology (HIT)-enabled tool holds promise to improve care transitions.

Methods

From 2012 through 2014, the team conducted and analyzed data from an environmental scan, key informant interviews, and focus groups to inform the development of an HIT-enabled tool for SCD patients’ use during care transitions. The scan included searches of peer-reviewed and gray literature to understand SCD patient needs, transition concerns, and …

Intracardiac Tumor Causing Left-Ventricular Outflow-Tract Obstruction In A Newborn, Christopher P. Jordan, John P. Costello, Kendal Endicott, Christine Reyes, Thomas Hougen, Susan Cummings, Dilip S. Nath

Pediatrics Faculty Publications

The following report describes the case of newborn girl with an asymptomatic systolic murmur, which on imaging revealed a nearly obstructive mass in the left-ventricular outflow tract. The mass was resected and found to be consistent with a rhabdomyoma. Here, we describe the pathologic and clinical characteristics of this tumor.

Neonatal Pain Management: Still In Search For The Holy Grail., Karel Allegaert, John N. Van Den Anker

Pediatrics Faculty Publications

Inadequate pain management but also inappropriate use of analgesics in early infancy has negative effects on neurodevelopmental outcome. As a consequence, neonatal pain management is still in search for the Holy Grail. At best, effective pain management is based on prevention, assessment, and treatment followed by a re-assessment of the pain to determine if additional treatment is still necessary. Unfortunately, epidemiological observations suggest that neonates are undergoing painful procedures very frequently, unveiling the need for effective preventive, non-pharmacological strategies. In addition, assessment is still based on validated, multimodal, but subjective pain assessment tools. Finally, in neonatal intensive care units, there …

Calls To A Teratogen Information Service Regarding Potential Exposures In Pregnancy And Breastfeeding, Sarah C. Campbell, Tyler T. Kast, Julia Robertson, Catherine M.T. Sherwin

Pediatrics Faculty Publications

Background

MotherToBaby Utah is a teratogen information service that provides support for pregnant and breastfeeding women and healthcare providers regarding risks of exposures to medications, infections, herbals, homeopathic and dietary medications, chemicals and other substances. Calls are anonymous and free of charge. This study was undertaken to examine the volume and classification of calls regarding exposures during pregnancy and breastfeeding.

Methods

Data were extracted from calls requesting information about medication use and other exposures to pregnant and breastfeeding women, between January 1 2009 and December 31 2012. Descriptive statistics were calculated.

Results

A total of 27,299 calls regarding 46,031 exposures …

Is Aerosalization A Problem With Carbapenem-Resistant Acinetobacter Baumannii In Thailand Hospital?, Anucha Apisarnthanarak, Ploenpit Tantajina, Pornpimol Laovachirasuwan, David J. Weber, Nalini Singh

Pediatrics Faculty Publications

We evaluated the presence of air contamination with carbapenem-resistant Acinetobacter baumannii (CRAB) in medical units where patients with CRAB pneumonia were hospitalized, and in Obstetrics and Gynecology units with open-air ventilation in-patient settings. There was no evidence of CRAB contamination in either of the units.

Targeted Echocardiographic Screening For Latent Rheumatic Heart Disease In Northern Uganda: Evaluating Familial Risk Following Identification Of An Index Case., Twalib Aliku, Craig Sable, Amy Scheel, Alison Tompsett, Peter Lwabi, Emmy Okello, Robert Mccarter, Marshall Summar, Andrea Beaton

Pediatrics Faculty Publications

BACKGROUND: Echocardiographic screening for detection of latent RHD has shown potential as a strategy to decrease the burden of disease. However, further research is needed to determine optimal implementation strategies. RHD results from a complex interplay between environment and host susceptibility. Family members share both and relatives of children with latent RHD may represent a high-risk group. The objective of this study was to use echocardiographic family screening to determine the relative risk of RHD among first-degree relatives of children with latent RHD compared to the risk in first-degree relatives of healthy peers.

METHODOLOGY/PRINCIPAL FINDINGS: Previous school-based screening data were …

The Story Of Patrick’S: The First Center For Children With Autism In Nigeria, Dotun Akande, Alissa Briggs, Hatim A. Omar

Pediatrics Faculty Publications

Autism Spectrum Disorder (ASD) is one of the most common developmental disorders. However, there are still no epidemiological studies of ASD in African countries. In Nigeria, many children are diagnosed with ASD late or only if there are symptoms that severely inhibit their ability to function. Moreover, there are limited treatment options. This paper will describe the efforts of Patrick Speech and Languages Centre (Patrick’s), the first center in Nigeria specifically for children with ASD, which was set up to assess and treat autism.

Cardiac Remodeling And Dysfunction In Childhood Obesity: A Cardiovascular Magnetic Resonance Study, Linyuan Jing, Cassi M. Binkley, Jonathan D. Suever, Nivedita Umasankar, Christopher M. Haggerty, Jennifer Rich, Christopher D. Nevius, Gregory J. Wehner, Sean M. Hamlet, David K. Powell, Aurelia Radulescu, H. Lester Kirchner, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

Background: Obesity affects nearly one in five children and is associated with increased risk of premature death. Obesity-related heart disease contributes to premature death. We aimed to use cardiovascular magnetic resonance (CMR) to comprehensively characterize the changes in cardiac geometry and function in obese children.

Methods and results: Forty-one obese/overweight (age 12 ± 3 years, 56 % female) and 29 healthy weight children (age 14 ± 3 years, 41 % female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, LV mass index …

Fbxo30 Regulates Mammopoiesis By Targeting The Bipolar Mitotic Kinesin Eg5., Yan Liu, Yin Wang, Zhanwen Du, Xiaoli Yan, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Fbxo30 is an orphan member of the F-box protein family with no known substrate or function. Here we report that, while Fbxo30^−/− mice exhibit normal development, growth, lifespan, and fertility, the females fail to nurture their offspring as a result of defective mammopoiesis. Mass spectrometry analysis of Fbxo30-associated proteins revealed that Fbxo30 specifically interacts with the bipolar spindle kinesin EG5 (encoded byKif11). As a result, Fbxo30 targets Eg5 for ubiquitinylation and controls its oscillation during the cell cycle. Correlated with EG5 dysregulation, Fbxo30^−/− mammary epithelial cells exhibit multiple defects in centrosome homeostasis, mitotic spindle …

A Single Exercise Bout Enhances The Manufacture Of Viral-Specific T-Cells From Healthy Donors: Implications For Allogeneic Adoptive Transfer Immunotherapy, Guillaume Spielmann, Catherine Bollard, Hawley Kunz, Patrick J. Hanley, Richard J. Simpson

Pediatrics Faculty Publications

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and …

How Complicated Can It Be? The Link Between Apol1 Risk Variants And Lipoprotein Heterogeneity In Kidney And Cardiovascular Diseases., Chien-An A Hu, Patricio E Ray

Pediatrics Faculty Publications

The beginning of human apolipoprotein L1 study (gene: APOL1; protein: ApoL1) originated from the identification of circulating ApoL1 as an interacting protein of ApoA1 and a minor component of high-density lipoprotein subfraction 3 (HDL3) in 1997 [1]. In the past 18 years, ApoL1 has been investigated in the context of complex human diseases such as African sleeping sickness, schizophrenia, host innate immunity, cancer, hyperlipidemia, cardiovascular diseases, stroke and type 2 diabetes [2–10]. A major breakthrough, however, was the documentation of two haplotypes of APOL1, harboring three coding-sequence mutations as risk variants associated with non-diabetic …

Comparison Of Two Commercial Dna Extraction Kits For The Analysis Of Nasopharyngeal Bacterial Communities, Marcos Pérez-Losada, Keith Crandall, Robert J. Freishtat

Pediatrics Faculty Publications

Characterization of microbial communities via next-generation sequencing (NGS) requires an extraction ofmicrobial DNA. Methodological differences in DNA extraction protocols may bias results and complicate inter-study comparisons. Here we compare the effect of two commonly used commercial kits (Norgen and Qiagen)for the extraction of total DNA on estimatingnasopharyngeal microbiome diversity. The nasopharynxis a reservoir for pathogens associated with respiratory illnesses and a key player in understandingairway microbial dynamics.
Total DNA from nasal washes corresponding to 30 asthmatic children was extracted using theQiagenQIAamp DNA and NorgenRNA/DNA Purification kits and analyzed via IlluminaMiSeq16S rRNA V4 ampliconsequencing. The Norgen samples included more sequence reads …

Perspectives On Pediatric Pain, Donald E. Greydanus, Dilip R. Patel, Colleen Dodich, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Resident Training Curriculum In Adolescent Depression And Suicide Screening, Angela Stanley, Gayathri Chelvakumar, Paula Cody, Mandakini Sadhir, Melodee Nugent, Raymond Hoffmann, Pippa Simpson

Pediatrics Faculty Publications

Introduction: Routine screening of adolescents for depression and suicide risk is now considered best clinical practice. However, due to a lack of training, many physicians do not engage in screening. The goal of this curriculum is to improve learner knowledge of and comfort in adolescent depression and suicide risk assessment and management. Methods: The didactic session typically takes 60-90 minutes to complete. In addition to a teaching PowerPoint that provides instruction in both the assessment and management of adolescent depression and suicide risk, the curriculum also includes a suicide assessment and management protocol. This protocol outlines an algorithm that assists …

Hydroxycarbamide Versus Chronic Transfusion For Maintenance Of Transcranial Doppler Flow Velocities In Children With Sickle Cell Anaemia-Tcd With Transfusions Changing To Hydroxyurea (Twitch): A Multicentre, Open-Label, Phase 3, Non-Inferiority Trial., Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Lori Luchtman-Jones, +Several Additional Authors

Pediatrics Faculty Publications

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.

METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible …

Dnah6 And Its Interactions With Pcd Genes In Heterotaxy And Primary Ciliary Dyskinesia., You Li, Hisato Yagi, Ezenwa Obi Onuoha, Rama Rao Damerla, Richard Francis, Yoshiyuki Furutani, Iman Sami, Linda Leatherbury, +13 Additional Authors

Pediatrics Faculty Publications

Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and …

Unbalanced But Satisfied?, Asha N. Shenoi

Pediatrics Faculty Publications

No abstract provided.

Two Sampling Methods Yield Distinct Microbial Signatures In The Nasopharynges Of Asthmatic Children., Marcos Pérez-Losada, Keith A. Crandall, Robert J. Freishtat

Pediatrics Faculty Publications

Background

The nasopharynx is a reservoir for pathogens associated with respiratory illnesses, such as asthma. Next-generation sequencing (NGS) has been used to characterize the nasopharyngeal microbiome during health and disease. Most studies so far have surveyed the nasopharynx as a whole; however, less is known about spatial variation (biogeography) in nasal microenvironments and how sampling techniques may capture that microbial diversity.

Findings

We used targeted 16S rRNA MiSeq sequencing and two different sampling strategies [nasal washes (NW) and nasal brushes (NB)] to characterize the nasopharyngeal microbiota in 30 asthmatic children. Nasal brushing is more abrasive than nasal washing and targeted …

Different Vancomycin Immunoassays Contribute To The Variability In Vancomycin Trough Measurements In Neonates, Janko Samardzic, Anne Smits, Isabel Spriet, Ivan Soldatovic, Andrew Atkinson, Milica Bajcetic, John N. Van Den Anker, Karel Allegaert

Pediatrics Faculty Publications

Substantial interassay variability (up to 20%) has been described for vancomycin immunoassays in adults, but the impact of neonatal matrix is difficult to quantify because of blood volume constraints in neonates. However, we provide circumstantial evidence for a similar extent of variability. Using the same vancomycin dosing regimens and confirming similarity in clinical characteristics, vancomycin trough concentrations measured by PETINIA (2011-2012, n = 400) were 20% lower and the mean difference was 1.93 mg/L compared to COBAS (2012–2014, n =352 ) measurements. The impact of vancomycin immunoassays in neonatal matrix was hereby suggested, supporting a switch to more advanced techniques …

Human Metapneumovirus Infection Is Associated With Severe Respiratory Disease In Preschool Children With History Of Prematurity., Krishna Pancham, Iman Sami, Geovanny F. Perez, Shehlanoor Huseni, Bassem Kurdi, Mary C. Rose, Carlos E. Rodriguez-Martinez, Gustavo Nino

Pediatrics Faculty Publications

Background

Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same family as that of respiratory syncytial virus (RSV). Premature children are at high risk of severe RSV infections, however, it is unclear whether HMPV infection is more severe in hospitalized children with a history of severe prematurity.

Methods

We conducted a retrospective analysis of the clinical respiratory presentation of all polymerase chain reaction-confirmed HMPV infections in preschool-age children (≤5 years) with and without history of severe prematurity (<32 weeks gestation). Respiratory distress scores were developed to examine the clinical severity of HMPV infections. Demographic and clinical variables were obtained from reviewing electronic medical records.

Results

A total of 571 preschool children were identified using polymerase chain reaction-confirmed viral respiratory tract …

Dyslipidemia And Food Security In Low-Income Us Adolescents: National Health And Nutrition Examination Survey, 2003-2010., June M Tester, Barbara A Laraia, Cindy W Leung, Michele L. Mietus-Snyder

Pediatrics Faculty Publications

INTRODUCTION: Low levels of food security are associated with dyslipidemia and chronic disease in adults, particularly in women. There is a gap in knowledge about the relationship between food security among youth and dyslipidemia and chronic disease. We investigated the relationship between food security status and dyslipidemia among low-income adolescents.

METHODS: We analyzed data from adolescents aged 12 to 18 years (N = 1,072) from households with incomes at or below 200% of the federal poverty level from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. We used logistic regression to examine the relationship between household food security status …

Improved Workflow For Quantification Of Left Ventricular Volumes And Mass Using Free-Breathing Motion Corrected Cine Imaging., Russell Cross, Laura Olivieri, Kendall O'Brien, Peter Kellman, Hui Xue, Michael Hansen

Pediatrics Faculty Publications

BACKGROUND: Traditional cine imaging for cardiac functional assessment requires breath-holding, which can be problematic in some situations. Free-breathing techniques have relied on multiple averages or real-time imaging, producing images that can be spatially and/or temporally blurred. To overcome this, methods have been developed to acquire real-time images over multiple cardiac cycles, which are subsequently motion corrected and reformatted to yield a single image series displaying one cardiac cycle with high temporal and spatial resolution. Application of these algorithms has required significant additional reconstruction time. The use of distributed computing was recently proposed as a way to improve clinical workflow with …

Virtual Reality For Pediatric Sedation: A Randomized Controlled Trial Using Simulation., Pavan P. Zaveri, Aisha B. Davis, Karen J O'Connell, Emily Willner, Dana A Aronson Schinasi, Mary Ottolini

Pediatrics Faculty Publications

INTRODUCTION: Team training for procedural sedation for pediatric residents has traditionally consisted of didactic presentations and simulated scenarios using high-fidelity mannequins. We assessed the effectiveness of a virtual reality module in teaching preparation for and management of sedation for procedures.

METHODS: After developing a virtual reality environment in Second Life® (Linden Lab, San Francisco, CA) where providers perform and recover patients from procedural sedation, we conducted a randomized controlled trial to assess the effectiveness of the virtual reality module versus a traditional web-based educational module. A 20 question pre- and post-test was administered to assess knowledge change. All subjects participated …

Discovery Of Metabolic Biomarkers For Duchenne Muscular Dystrophy Within A Natural History Study., Simina M. Boca, Maki Nishida, Michael Harris, Shruti Rao, Amrita Cheema, Kirandeep Gill, Haeri Seol, Lauren P. Morgenroth, Erik Henricson, Craig M. Mcdonald, Jean K. Mah, Paula R. Clemens, Eric P. Hoffman, Yetrib Hathout, Subha Madhavan

Pediatrics Faculty Publications

Serum metabolite profiling in Duchenne muscular dystrophy (DMD) may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS) for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate) in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown …

Examination Of Reticulocytosis Among Chronically Transfused Children With Sickle Cell Anemia., Megha Kaushal, Colleen Byrnes, Zarir Khademian, Natalie Duncan, Naomi L. Luban, Jeffery L Miller, Ross Fasano, Emily R. Meier

Pediatrics Faculty Publications

Sickle cell anemia (SCA) is an inherited hemolytic anemia with compensatory reticulocytosis. Recent studies have shown that increased levels of reticulocytosis during infancy are associated with increased hospitalizations for SCA sequelae as well as cerebrovascular pathologies. In this study, absolute reticulocyte counts (ARC) measured prior to transfusion were analysed among a cohort of 29 pediatric SCA patients receiving chronic transfusion therapy (CTT) for primary and secondary stroke prevention. A cross-sectional flow cytometric analysis of the reticulocyte phenotype was also performed. Mean duration of CTT was 3.1 ± 2.6 years. Fifteen subjects with magnetic resonance angiography (MRA) -vasculopathy had significantly higher …

Proteomic Characterization Of Middle Ear Fluid Confirms Neutrophil Extracellular Traps As A Predominant Innate Immune Response In Chronic Otitis Media., Stephanie Val, Marian Poley, Kristy Brown, Rachel Choi, Stephanie Jeong, Annie Colberg-Poley, Mary C. Rose, Karuna C Panchapakesan, Joseph C. Devaney, Marcos Perez-Losada, Diego Preciado

Pediatrics Faculty Publications

BACKGROUND: Chronic Otitis Media (COM) is characterized by middle ear effusion (MEE) and conductive hearing loss. MEE reflect mucus hypersecretion, but global proteomic profiling of the mucosal components are limited.

OBJECTIVE: This study aimed at characterizing the proteome of MEEs from children with COM with the goal of elucidating important innate immune responses.

METHOD: MEEs were collected from children (n = 49) with COM undergoing myringotomy. Mass spectrometry was employed for proteomic profiling in nine samples. Independent samples were further analyzed by cytokine multiplex assay, immunoblotting, neutrophil elastase activity, next generation DNA sequencing, and/or immunofluorescence analysis.

RESULTS: 109 unique and …

Circulating Fibroblast Growth Factor-2, Hiv-Tat, And Vascular Endothelial Cell Growth Factor-A In Hiv-Infected Children With Renal Disease Activate Rho-A And Src In Cultured Renal Endothelial Cells., Jharna R Das, J Silvio Gutkind, Patricio E. Ray

Pediatrics Faculty Publications

Renal endothelial cells (REc) are the first target of HIV-1 in the kidney. The integrity of REc is maintained at least partially by heparin binding growth factors that bind to heparan sulfate proteoglycans located on their cell surface. However, previous studies showed that the accumulation of two heparin-binding growth factors, Vascular Endothelial Cell Growth Factor-A (VEGF-A) and Fibroblast Growth Factor-2 (FGF-2), in combination with the viral protein Tat, can precipitate the progression of HIV-renal diseases. Nonetheless, very little is known about how these factors affect the behavior of REc in HIV+ children. We carried out this study to determine how …

Do 6-8 Year Old Girls With Central Precocious Puberty Need Routine Brain Imaging?, Paul B. Kaplowitz

Pediatrics Faculty Publications

BACKGROUND: The subject of whether all girls with central precocious puberty (CPP) require brain imaging is controversial.

FINDINGS: A review of the major papers concerning this topic published since 1994 was conducted looking primarily at the frequency of occult intracranial lesions, particularly brain tumors, in girls with CPP. While CNS abnormalities are frequently noted (8-15 %), the proportion of previously unknown findings requiring intervention in 6-8 year old girls is very small, in the range of 0-2 %.

CONCLUSION: While MRI should still be done in boys and in girls with onset of puberty younger than age 6 and in …