Medical Specialties Commons^™

The Significance Of Macrocephaly Or Enlarging Head Circumference In Infants With The Triad: Further Evidence Of Mimics Of Shaken Baby Syndrome, David Miller, Patrick Barnes, Marvin E. Miller

Pediatrics Faculty Publications

Infants with the triad (neurologic dysfunction, subdural hematoma [SDH], and retinal hemorrhage) are often diagnosed as victims of shaken baby syndrome. Medical conditions/predisposing factors to developing the triad are often dismissed: short falls, birth-related SDH that enlarges, macrocephaly, sinus/cortical vein thrombosis, and others. Six infants with the triad are described in which child abuse was diagnosed, but parents denied wrongdoing. All 6 had either macrocephaly or enlarging head circumference, which suggested medical explanations. Three infants incurred short falls, 1 had a difficult delivery in which there was likely a rebleed of a birth-related SDH, 1 had a spontaneous SDH associated …

Emergence Of Multidrug Resistant Influenza A(H1n1)Pdm09 Virus Variants In An Immunocompromised Child Treated With Oseltamivir And Zanamivir., Daisuke Tamura, Roberta L. Debiasi, Margaret Okomo-Adhiambo, Vasiliy P. Mishin, Angela P. Campbell, Brett Loechelt, Bernhard L. Wiedermann, Alicia M. Fry, Larisa V. Gubareva

Pediatrics Faculty Publications

Prolonged treatment of an immunocompromised child with oseltamivir and zanamivir for A(H1N1)pdm09 virus infection led to the emergence of viruses carrying H275Y and/or E119G in the neuraminidase. When phenotypically evaluated by neuraminidase inhibition, the dual H275Y-E119G substitution caused highly reduced inhibition by four neuraminidase inhibitors including oseltamivir, zanamivir, peramivir and laninamivir.

Salud Mesoamérica 2015 Initiative: Design, Implementation, And Baseline Findings, Ali H. Mokdad, Katherine Elliott Colson, Paola Zuniga-Brenes, Diego Rios-Zertuche, Erin B. Palmisano, Catherine W. Gillespie, +27 Additional Authors

Pediatrics Faculty Publications

Background

Health has improved markedly in Mesoamerica, the region consisting of southern Mexico and Central America, over the past decade. Despite this progress, there remain substantial inequalities in health outcomes, access, and quality of medical care between and within countries. Poor, indigenous, and rural populations have considerably worse health indicators than national or regional averages. In an effort to address these health inequalities, the Salud Mesoamérica 2015 Initiative (SM2015), a results-based financing initiative, was established.

Methods

For each of the eight participating countries, health targets were set to measure the progress of improvements in maternal and child health produced by …

Open Letter On Shaken Baby Syndrome And Courts: A False And Flawed Premise, Bill Bache, Patrick Barnes, Beverly Beech, Flo Bellone, Thomas L. Bohan, Harry J. Bonnell, Marta Cohen, D. L. Contostavlos, Peter Dale, Lina Davidson, Steven Gabaeff, Horace Gardner, Margaret Gardner, Jean Golding, A. N. Guthkelch, Charles M. Harvey, Helen Hayward-Brown, John Hemming, John C. Hunsaker Iii, Charles Hyman, Jan Leestma, James Lefanu, John Lloyd, Marvin E. Miller, Catherine Mills, George R. Nichols Ii, Michael Nott, John Plunkett, Charles Pragnell, Jean Robinson, Robert K. Rothfeder, Irene Scheimberg, Ron Uscinski, Michael Weinraub, Ed Willey, R. K. Wright, Lynne Wrennall

Pediatrics Faculty Publications

The Open Letter on Shaken Baby Syndrome and Courts has been prepared under the auspices of the International Public Health Research Group [IPHRG]. It was developed from initial drafts by Bill Bache and Charles Pragnell. Final drafting and editing was by Dr Lynne Wrennall, Executive Director of the International Public Health Research Group and the Managing Editor of Argument & Critique. The process of writing the letter has relied on the published research in the field, much of it, published research by the signatories to the letter. The process has also drawn on the iterative contribution of insights by the …

Pregnant, Even When You Did Not Want To Be Pregnant, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Imitation By Combination: Preschool Age Children Evidence Summative Imitation In A Novel Problem-Solving Task., Francys Subiaul, Edward Krajkowski, Elizabeth E Price, Alexander Etz

Pediatrics Faculty Publications

Children are exceptional, even 'super,' imitators but comparatively poor independent problem-solvers or innovators. Yet, imitation and innovation are both necessary components of cumulative cultural evolution. Here, we explored the relationship between imitation and innovation by assessing children's ability to generate a solution to a novel problem by imitating two different action sequences demonstrated by two different models, an example of imitation by combination, which we refer to as "summative imitation." Children (N = 181) from 3 to 5 years of age and across three experiments were tested in a baseline condition or in one of six demonstration conditions, varying in …

Treatment Planning And Patient Positioning For Mr-Guided High Intensity Focused Ultrasound Treatment: A Systematic Approach, David Kinnaird, Doug Wackerle, Daniel Yang, Matthew E. Oetgen, Avinash Eranki, Aerang Kim, +5 Additional Authors

Pediatrics Faculty Publications

No abstract provided.

Improving Newborn Care Practices Through Home Visits: Lessons From Malawi, Nepal, Bangladesh, And Uganda., Deborah Sitrin, Tanya Guenther, Peter Waiswa, Sarah Namutamba, Gertrude Namazzi, Srijana Sharma, K. C. Ashish, Sayed Rubayet, Subrata Bhadra, Reuben Ligowe, Emmanuel Chimbalanga, Elizabeth Sewell, Kate Kerber, Allisyn Moran

Pediatrics Faculty Publications

Background: Nearly all newborn deaths occur in low- or middle-income countries. Many of these deaths could be prevented through promotion and provision of newborn care practices such as thermal care, early and exclusive breastfeeding, and hygienic cord care. Home visit programmes promoting these practices were piloted in Malawi, Nepal, Bangladesh, and Uganda.

Objective: This study assessed changes in selected newborn care practices over time in pilot programme areas in four countries and evaluated whether women who received home visits during pregnancy were more likely to report use of three key practices.

Design: Using data from cross-sectional surveys …

Percutaneous Mr Guided Direct Left Atrial Access To Deliver Large Interventional Devices, Toby Rogers, William Schenke, Jonathan R. Mazal, Merdim Sonmez, Ozgur Kocaturk, Kanishka Ratnayaka, Michael Hansen, Anthony Z. Faranesh, Robert J. Lederman

Pediatrics Faculty Publications

No abstract provided.

The Oral Bacterial Communities Of Children With Well-Controlled Hiv Infection And Without Hiv Infection., Brittany E. Goldberg, Emmanuel F. Mongodin, Cheron E. Jones, Michelle Chung, Claire M. Fraser, Anupama R. Tate, Steven L. Zeichner

Pediatrics Faculty Publications

The oral microbial community (microbiota) plays a critical role in human health and disease. Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi's sarcoma, oral warts and other diseases. Here, we used 454 pyrosequencing of bacterial 16S rRNA genes to examine the oral microbiome of saliva, mucosal and tooth samples from HIV-positive and negative children. Patient demographics and clinical characteristics were collected from a cross-section …

Temporal Order Of Rnase Iiib And Loss-Of-Function Mutations During Development Determines Phenotype In Dicer1 Syndrome: A Unique Variant Of The Two-Hit Tumor Suppression Model [V1; Ref Status: Approved With Reservations 1, Http://F1000r.Es/5l9], Mark Brenneman, Amanda Field, Jiandong Yang, Gretchen Williams, Leslie A. Doros, Christopher T. Rossi, Heather A. Gordish-Dressman, D. Ashley Hill, Et Al.

Pediatrics Faculty Publications

Pleuropulmonary blastoma (PPB) is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific “hotspot” codons within the RNase IIIb domain of DICER 1, combined with complete loss of function (LOF) in the other allele. We analyzed a cohort of 124 PPB children for predisposing DICER1 mutations and sought correlations with clinical phenotypes. Over …

Β2-Adrenergic Receptor Promoter Haplotype Influences The Severity Of Acute Viral Respiratory Tract Infection During Infancy: A Prospective Cohort Study., Pingsheng Wu, Emma K. Larkin, Sara S Reiss, Kecia N Carroll, Marshall L. Summar, Patricia A Minton, +6 Additional Authors

Pediatrics Faculty Publications

BACKGROUND: Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections.

METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of …

Differential Expression Of The Nrf2-Linked Genes In Pediatric Septic Shock., Jocelyn R Grunwell, Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, +10 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock.

METHODS: We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated …

Beyond Cd19: Opportunities For Future Development Of Targeted Immunotherapy In Pediatric Relapsed-Refractory Acute Leukemia., Haneen Shalabi, Anne Angiolillo, Terry J Fry

Pediatrics Faculty Publications

Chimeric antigen receptor (CAR) T cell therapy has been used as a targeted approach in cancer therapy. Relapsed and refractory acute leukemia in pediatrics has been difficult to treat with conventional therapy due to dose-limiting toxicities. With the recent success of CD 19 CAR in pediatric patients with B cell acute lymphoblastic leukemia (ALL), this mode of therapy has become a very attractive option for these patients with high-risk disease. In this review, we will discuss current treatment paradigms of pediatric acute leukemia and potential therapeutic targets for additional high-risk populations, including T cell ALL, AML, and infant ALL.

Intracellular Cd24 Disrupts The Arf-Npm Interaction And Enables Mutational And Viral Oncogene-Mediated P53 Inactivation., Lizhong Wang, Runhua Liu, Peiying Ye, Chunshu Wong, Guo-Yun Chen, Penghui Zhou, +11 Additional Authors

Pediatrics Faculty Publications

CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the …

Acute Glomerular Diseases In Children, Kanwal Kher

Pediatrics Faculty Publications

Glomerulonephritis [GN] is one of the common acquired pediatric renal disorders encountered in clinical practice. The clinical manifestations include gross or microscopic hematuria, proteinuria, and nephrotic syndrome. Renal dysfunction and hypertension may also be present in many patients. Etiopathogenesis of GN can be idiopathic in a large majority, while some may result from infections or known immune disorders. Several of these disorders are now believed to arise from dysfunctions of podocytes and are grouped under the heading of “podocytopathies”. This review focuses on the clinical manifestations and management of the common forms of acute GN encountered in children.

Genetic And Informatic Analyses Implicate Kif12 As A Candidate Gene Within The Mpkd2 Locus That Modulates Renal Cystic Disease Severity In The Cys1cpk Mouse., Michal Mrug, Juling Zhou, Chaozhe Yang, Bruce J Aronow, Xiangqin Cui, Trenton R Schoeb, Gene P Siegal, Bradley K Yoder, Lisa M. Guay-Woodford

Pediatrics Faculty Publications

We have previously mapped the interval on Chromosome 4 for a major polycystic kidney disease modifier (Mpkd) of the B6(Cg)-Cys1cpk/J mouse model of recessive polycystic kidney disease (PKD). Informatic analyses predicted that this interval contains at least three individual renal cystic disease severity-modulating loci (Mpkd1-3). In the current study, we provide further validation of these predicted effects using a congenic mouse line carrying the entire CAST/EiJ (CAST)-derived Mpkd1-3 interval on the C57BL/6J background. We have also generated a derivative congenic line with a refined CAST-derived Mpkd1-2 interval and demonstrated its dominantly-acting disease-modulating effects (e.g., 4.2-fold increase in total cyst area; …

Extraordinary Diversity Of Immune Response Proteins Among Sea Urchins: Nickel-Isolated Sp185/333 Proteins Show Broad Variations In Size And Charge., Lauren S. Sherman, Catherine S. Schrankel, Kristy J. Brown, L. Courtney Smith

Pediatrics Faculty Publications

Effective protection against pathogens requires the host to produce a wide range of immune effector proteins. The Sp185/333 gene family, which is expressed by the California purple sea urchin Strongylocentrotus purpuratus in response to bacterial infection, encodes a highly diverse repertoire of anti-pathogen proteins. A subset of these proteins can be isolated by affinity to metal ions based on multiple histidines, resulting in one to four bands of unique molecular weight on standard Western blots, which vary depending on the individual sea urchin. Two dimensional gel electrophoresis (2DE) of nickel-isolated protein samples followed by Western blot was employed to detect …

Mllt1 Yeats Domain Mutations In Clinically Distinctive Favourable Histology Wilms Tumours., Elizabeth J Perlman, Samantha Gadd, Stefan T Arold, Anand Radhakrishnan, Daniela S Gerhard, Jeffrey S. Dome, +19 Additional Authors

Pediatrics Faculty Publications

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar …

Work-Life Balance Is An Illusion: Replace Guilt With Acceptance., Tessie W. October

Pediatrics Faculty Publications

No abstract provided.

Educational Neuroscience, Constructivism, And The Mediation Of Learning And Creativity In The 21st Century., M. Layne Kalbfleisch

Pediatrics Faculty Publications

No abstract provided.

Absolute Reticulocyte Count Acts As A Surrogate For Fetal Hemoglobin In Infants And Children With Sickle Cell Anemia., Emily Riehm Meier, Colleen Byrnes, Maxine Weissman, Y Terry Lee, Jeffery L Miller

Pediatrics Faculty Publications

Hemoglobin switching is largely complete in humans by six months of age. Among infants with sickle cell anemia (HbSS, SCA), reticulocytosis begins early in life as fetal hemoglobin (HbF) is replaced by sickle hemoglobin (HbS). The objective of this study was to determine if absolute reticulocyte count (ARC) is related to HbF levels in a cohort of pediatric SCA patients. A convenience sample of 106 children with SCA between the ages of 1 month and 20 years who were not receiving hydroxyurea or monthly blood transfusions were enrolled in this observational study. Hematologic data, including ARC and HbF levels, were …

Characterizing The Propagation Of Uterine Electrophysiological Signals Recorded With A Multi-Sensor Abdominal Array In Term Pregnancies., Diana Escalona-Vargas, Rathinaswamy B. Govindan, Adrian Furdea, Pam Murphy, Curtis L Lowery, Hari Eswaran

Pediatrics Faculty Publications

The objective of this study was to quantify the number of segments that have contractile activity and determine the propagation speed from uterine electrophysiological signals recorded over the abdomen. The uterine magnetomyographic (MMG) signals were recorded with a 151 channel SARA (SQUID Array for Reproductive Assessment) system from 36 pregnant women between 37 and 40 weeks of gestational age. The MMG signals were scored and segments were classified based on presence of uterine contractile burst activity. The sensor space was then split into four quadrants and in each quadrant signal strength at each sample was calculated using center-of-gravity (COG). To …

Making The Leap From Research Laboratory To Clinic: Challenges And Opportunities For Next-Generation Sequencing In Infectious Disease Diagnostics., Brittany Goldberg, Heike Sichtig, Chelsie Geyer, Nathan Ledeboer, George M Weinstock

Pediatrics Faculty Publications

Next-generation DNA sequencing (NGS) has progressed enormously over the past decade, transforming genomic analysis and opening up many new opportunities for applications in clinical microbiology laboratories. The impact of NGS on microbiology has been revolutionary, with new microbial genomic sequences being generated daily, leading to the development of large databases of genomes and gene sequences. The ability to analyze microbial communities without culturing organisms has created the ever-growing field of metagenomics and microbiome analysis and has generated significant new insights into the relation between host and microbe. The medical literature contains many examples of how this new technology can be …

Impact Of Prenatal Environmental Stress On Cortical Development, Seiji Ishii, Kazue Hashimoto-Torii

Pediatrics Faculty Publications

Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS) cells to demonstrate: 1. molecular mechanisms shared by various types of environmental stressors, 2. the mechanisms by which the affected extracortical tissues indirectly impact the cortical development …

Dual Transcriptomic Profiling Of Host And Microbiota During Health And Disease In Pediatric Asthma., Marcos Pérez-Losada, Eduardo Castro-Nallar, Matthew L. Bendall, Robert J. Freishtat, Keith A. Crandall

Pediatrics Faculty Publications

BACKGROUND: High-throughput sequencing (HTS) analysis of microbial communities from the respiratory airways has heavily relied on the 16S rRNA gene. Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. Consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota and even less to explore the microbe-host interactions. Here we present a simultaneous assessment of microbiome and host functional diversity and host-microbe interactions from the same RNA-seq experiment, while accounting for …

Integrating Microbial And Host Transcriptomics To Characterize Asthma-Associated Microbial Communities., Eduardo Castro-Nallar, Ying Shen, Robert J. Freishtat, Marcos Pérez-Losada, Solaiappan Manimaran, Et Al.

Pediatrics Faculty Publications

BACKGROUND: The relationships between infections in early life and asthma are not completely understood. Likewise, the clinical relevance of microbial communities present in the respiratory tract is only partially known. A number of microbiome studies analyzing respiratory tract samples have found increased proportions of gamma-Proteobacteria including Haemophilus influenzae, Moraxella catarrhalis, and Firmicutes such as Streptococcus pneumoniae. The aim of this study was to present a new approach that combines RNA microbial identification with host gene expression to characterize and validate metagenomic taxonomic profiling in individuals with asthma.

METHODS: Using whole metagenomic shotgun RNA sequencing, we characterized and compared the microbial …

Pharmacologically-Induced Mitotic Synchrony In Airway Epithelial Cells As A Mechanism Of Action Of Anti-Inflammatory Drugs, Robert J. Freishtat, Gustavo Nino, Y. Tsegaye, Sarah E. Alcala, Angela S. Benton, Alan M. Watson, E.K.M. Reeves, S. K. Haider, Jesse M. Damsker

Pediatrics Faculty Publications

Background

Mitotic synchrony is the synchronous progression of a population of cells through the cell cycle and is characteristic of non-diseased airway epithelial cells. However, we previously showed that asthmatic airway epithelial cells are characterized by mitotic asynchrony and are pro-inflammatory as a result. Glucocorticoids can induce mitotic synchrony that in turn suppresses the pro-inflammatory state of diseased cells, suggesting a novel anti-inflammatory mechanism of action. Herein, we benchmarked traditional glucocorticoids against the ability of a new clinical-stage dissociative steroidal drug, VBP15, for mitotic resynchronization and associated anti-inflammatory activity in asthmatic airway epithelial cells.

Methods

Primary airway epithelial cells differentiated …

Are Immune Modulating Single Nucleotide Polymorphisms Associated With Necrotizing Enterocolitis?, Ashanti L Franklin, Mariam Said, Clint D Cappiello, Heather Gordish-Dressman, Zohreh Tatari-Calderone, Stanislav Vukmanovic, Khodayar Rais-Bahrami, Naomi L.C. Luban, Joseph M. Devaney, Anthony D. Sandler

Pediatrics Faculty Publications

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over …

St Segment Depression After Norwood/Systemic-Pulmonary Artery Shunt, Ashraf Harahsheh, Craig A. Sable, Pranava Sinha, Richard A. Jonas

Pediatrics Faculty Publications

A three-month-old girl with double inlet left ventricle (S;D;D), hypoplastic outlet ventricle, restrictive bulboventricular foramen, d-transposition of great arteries and interrupted aortic arch underwent Norwood stage 1 operation, systemic to pulmonary artery (PA) shunt and atrial septectomy, and developed ectopic atrial tachycardia that responded to digoxin therapy. She developed fussiness lasting two hours, not associated with cyanosis, and not relieved by feeding. Her pulse oximetry was 88% while breathing room air, and she had no differential blood pressure gradient.