Pediatrics Commons^™

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.

Final Thoughts, Hatim A. Omar

Pediatrics Faculty Publications

The work to establish the "Stop Youth Suicide Campaign (SYS)" has resulted in contact with many young adults. We realized that the most important thing for the kids was finding a caring person they can trust and talk to. This project has been a learning process for all involved. I learned that I can help and so can everyone else. This community and grassroots approach showed tangible results. It needs caring and dedication and most importantly desire to make a difference. It is hard work, but well worth it. Many people, including myself, are afraid of failure. I suffered every …

Growing Up With Chronic Kidney Disease: What Parents And Children Really Want To Know, Uptal D. Patel, Debbie S. Gipson, Abiodun Aderogba Omoloja, Caitlin Wise Carter

Pediatrics Faculty Publications

Adolescents with chronic kidney disease have specific questions about how their disease will affect their quality of life, but they may not always bring this up with their nephrologist. This session is designed to provide pediatricians and pediatric nephrologists with practical information to provide to adolescents with chronic kidney disease and their families. All providers who care for adolescents with renal disease need to be equipped to educate this high risk population and help them navigate through this vulnerable period. This session is designed to explore issues related to athletic participation, academic performance, substance use and abuse and sexual and …

Factors Facilitating Constructive Coping With Stress, Kamilla Bargiel-Matusiewicz, Hatim A. Omar

Pediatrics Faculty Publications

This review focuses on coping with stress, with particular emphasis on mechanisms facilitating constructive coping with stress. An important area of contemporary research is the attempt to identify factors that make it possible to stay mentally healthy or preventing the weakening of the cognitive and social functioning. The currently prevailing approach to stress is the relational approach. According to this approach, the criterion for the occurrence of stress is the cognitive assessment of the situation made by an individual. This review presents the most recent proposals concerning the analysis of specific methods of coping with stress, in particular from the …

Revisiting Menstrual Bleeding Patterns In Adolescents Using Etonogestrel (Eng) Implant, Anna Iddings, Hatim A. Omar

Pediatrics Faculty Publications

Etonogestrel (ENG) implant is an effective method of contraception. The implant is designed to provide contraceptive efficacy for three years with a relatively quick return of fertility upon its removal. Dysfunctional uterine bleeding (DUB) is a common side effect of long acting progestins and is often the reason patients state for removal or discontinuation. A retrospective chart analysis was completed on 292 patients who chose to be on the ENG implant. Age of patients ranged from 10-29 years of age with the average age at implant being 17 years +/- 3 years. Patients retained implant for 1-68 months with the …

Cyberbullying In Adolescents: The Prevalence Of Mental Disorders And Suicidal Behavior, Elizabeth L. Mirsky, Hatim A. Omar

Pediatrics Faculty Publications

This paper defines the phenomena of cyberbullying in relation to traditional bullying, along with its negative consequences on adolescents in modern society. The reasons for the highly destructive effects of cyberbullying are given along with information about psychological instability resulting from the occurrence of cyberbullying. The correlation of cyberbullying with suicidal thoughts and behaviors is also discussed. Finally, some prevention techniques are listed in an attempt to lower the prevalence of cyberbullying.

Syphilis: The Forgotten Sexually Transmitted Disease. A Brief Case Report, Amy Burnett, Hatim A. Omar

Pediatrics Faculty Publications

Syphilis has declined significantly over the last 30 years. Due to that success, many physicians no longer have the skills to recognize its symptoms. We present a case of syphilis as a demonstration of this fact.

Hiv And Minority Youth, Mandakini Sadhir, Hatim A. Omar

Pediatrics Faculty Publications

Human Immunodeficiency virus (HIV) infection is a major public health problem with the burden of disease increasing in adolescents and young adults particularly among black males and males who have sex with males (MSM).

Paper I: Stress In Adolescents, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

It is well known that adolescents experience stress. In this article, sources of adolescent stress will be discussed as well as the physiological effects of stress on the body. Stress disorders will also be briefly reviewed. Mainly, research on stress management strategies that have been evaluated in adolescents will be presented. Many studies have a small number of participants and lack control groups. Therefore, there is a need for ongoing research in this important area.

Part Ii - Stress And Stress Management Strategies In Adolescents, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

It is well known that adolescents experience stress. In this article, sources of adolescent stress will be discussed as well as the physiological effects of stress on the body. Stress disorders will also be briefly reviewed. Mainly, research on stress management strategies that have been evaluated in adolescents will be presented. Many studies have a small number of participants and lack control groups. Therefore, there is a need for ongoing research in this important area.

The Importance Of Comprehensive Sexuality Education In Adolescents, Sarah Lebrun, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

Female Athlete Triad Review, Hannah Harrison, Hatim A. Omar

Pediatrics Faculty Publications

This article defines the female athlete triad and discusses long-term consequences for adolescents and women symptoms related to the triad. The pillars of the female athlete triad consist of menstruation disruption, decreased bone mineral density, and disordered eating (energy availability). We will discuss the problems that can arise from each of the three pillars of the female athlete triad and the relationships among them. There are different treatments for the triad based on the needs of the individual and new treatments are being researched. Finally, the need for more informed coaches, parents, and medical professionals is discussed.

Effective Youth Suicide Prevention: Evidence From Kentucky, Dessi Slavova, Hatim A. Omar

Pediatrics Faculty Publications

In 2013, Suicide was the second leading cause of death among U.S. young adolescents (15-19 years of age), accounting for 18.4% of all deaths in this age group. According to a nationally representative study on the lifetime prevalence of adolescent suicidal behaviors, 12.1% of U.S. adolescents experience suicidal ideation, 4.0% develop a plan, and 4.1% attempt suicide. The same study estimated that approximately 60% of young people with a suicide plan will attempt suicide, and most of the adolescents who subsequently make an attempt do so within the first year after the onset of ideation.

These findings support the importance …

Children With Asthma: What About The Quality Of Life Of Their Parents?, Anna Trzcieniecka-Green, Kamilla Bargiel-Matusiewicz, Agnieszka Wilczyńska, Hatim A. Omar

Pediatrics Faculty Publications

An increased frequency of asthma in children has been lately observed. The course of asthma depends not only on treatment. but also on the actions taken by the parents of a sick child. Design: A non-experimental cross-sectional design. Methods: In this study the Pediatric Asthma Quality of Life Questionnaire (PACQLQ) and Satisfaction with Life Scale (SWLS) were administered to 60 parents of children with :asthma. Two groups of parents were compared. The first group consisted of parents of children who had been diagnosed with asthma less than three months before the beginning of the study. The second group consisted of …

Starting Off, Hatim A. Omar

Pediatrics Faculty Publications

This book is really a reflection of the past 15 years of work with teens and suicide prevention in the state of Kentucky. The work to establish the "Stop Youth Suicide Campaign (SYS)" has resulted in contact with many young adults and we have found that the most important thing for all of them, was finding a caring person they trust and can talk to. Because of the constant need, the SYS went from a goal of one year awareness campaign to a major community resource, to work with the state and local governments and state legislators to add as …