Medicine and Health Sciences Commons^™

Obesity Reduces Left Ventricular Strains, Torsion, And Synchrony In Mouse Models: A Cine Displacement Encoding With Stimulated Echoes (Dense) Cardiovascular Magnetic Resonance Study, Sage P. Kramer, David K. Powell, Christopher M. Haggerty, Cassi M. Binkley, Andrea C. Mattingly, Lisa A. Cassis, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

BACKGROUND: Obesity affects a third of adults in the US and results in an increased risk of cardiovascular mortality. While the mechanisms underlying this increased risk are not well understood, animal models of obesity have shown direct effects on the heart such as steatosis and fibrosis, which may affect cardiac function. However, the effect of obesity on cardiac function in animal models is not well-defined. We hypothesized that diet-induced obesity in mice reduces strain, torsion, and synchrony in the left ventricle (LV).

METHODS: Ten 12-week-old C57BL/6 J mice were randomized to a high-fat or low-fat diet. After 5 months on …

The Ciliary Protein Cystin Forms A Regulatory Complex With Necdin To Modulate Myc Expression, Maoqing Wu, Chaozhe Yang, Binli Tao, Su Bu, Lisa Guay-Woodford

Pediatrics Faculty Publications

Cystin is a novel cilia-associated protein that is disrupted in the cpk mouse, a well-characterized mouse model of autosomal recessive polycystic kidney disease (ARPKD). Interestingly, overexpression of the Myc gene is evident in animal models of ARPKD and is thought to contribute to the renal cystic phenotype. Using a yeast two-hybrid approach, the growth suppressor protein necdin, known to modulate Myc expression, was found as an interacting partner of cystin. Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, …

Self-Reported Juvenile Firesetting: Results From Two National Survey Datasets, Carrie Howell Bowling, Joav Merrick, Hatim A. Omar

Pediatrics Faculty Publications

The main purpose of this study was to address gaps in existing research by examining the relationship between academic performance and attention problems with juvenile firesetting. Two datasets from the Achenbach System for Empirically Based Assessment (ASEBA) were used. The Factor Analysis Dataset (N = 975) was utilized and results indicated that adolescents who report lower academic performance are more likely to set fires. Additionally, adolescents who report a poor attitude toward school are even more likely to set fires. Results also indicated that attention problems are predictive of self-reported firesetting. The National Survey Dataset (N = 1158) …

Examining The Claim That 80-90% Of Suicide Cases Had Depression, Said Shahtahmasebi

Pediatrics Faculty Publications

No abstract provided.

Severe Painful Vaso-Occlusive Crises And Mortality In A Contemporary Adult Sickle Cell Anemia Cohort Study., Deepika S. Darbari, Zhengyuan Wang, Minjung Kwak, Mariana Hildesheim, James Nichols, Darlene Allen, Catherine Seamon, Marlene Peters-Lawrence, Anna Conrey, Mary K. Hall, Gregory J. Kato, James G. Taylor Vi

Pediatrics Faculty Publications

BACKGROUND: Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.

METHODS: Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations …

A Profile Of Children With Complex Chronic Conditions At End Of Life Among Medicaid Beneficiaries: Implications For Health Care Reform, Lisa C. Lindley, Maureen E. Lyon

Pediatrics Faculty Publications

Background: As the United States braces for full implementation of health care reform, the eyes of the nation are on Medicaid. The large number of newly eligible Medicaid beneficiaries may challenge health care resources and ultimately impact quality of care. This is a special concern among current Medicaid beneficiaries such as children with complex chronic conditions (CCCs) who have significant health care needs, especially at end of life (EOL). Yet, a comprehensive profile of these children is lacking.

Objective: To understand the demographic and health characteristics, health care utilization, and expenditures among Medicaid children with CCCs at EOL.

Methods: Our …

Autonomic Nervous System Function Following Prenatal Opiate Exposure, Matthew Todd Hambleton, Eric W. Reynolds, Thitinart Sithisarn, Stuart J. Traxel, Abhijit R. Patwardhan, Timothy N. Crawford, Marta S. Mendiondo, Henrietta S. Bada

Pediatrics Faculty Publications

In utero exposure to opiates may affect autonomic functioning of the fetus and newborn. We investigated heart rate variability (HRV) as a measure of autonomic stability in prenatal opiate-exposed neonates (n = 14) and in control term infants (n = 10). Electrocardiographic data during both non-nutritive and nutritive sucking were evaluated for RR intervals, heart rate (HR), standard deviation of the consecutive RR intervals (SDRR), standard deviation of the differences of consecutive RR intervals (SDDRR), and the power spectral densities in low and high frequency bands. In controls, mean HR increased significantly, 143-161 per min (p = …

Marijuana: Current Concepts, Donald E. Greydanus, Elizabeth K. Hawver, Megan M. Greydanus, Joav Merrick

Pediatrics Faculty Publications

Marijuana (cannabis) remains a controversial drug in the twenty-first century. This paper considers current research on use of Cannabis sativa and its constituents such as the cannabinoids. Topics reviewed include prevalence of cannabis (pot) use, other drugs consumed with pot, the endocannabinoid system, use of medicinal marijuana, medical adverse effects of cannabis, and psychiatric adverse effects of cannabis use. Treatment of cannabis withdrawal and dependence is difficult and remains mainly based on psychological therapy; current research on pharmacologic management of problems related to cannabis consumption is also considered. The potential role of specific cannabinoids for medical benefit will be revealed …

Firesetting In Childhood And Adolescence, Joav Merrick, Carrie Howell Bowling, Hatim A. Omar

Pediatrics Faculty Publications

Fire is the rapid oxidation of a material in the exothermic chemical process of combustion, releasing heat, light, and various reaction products. Fire is intriguing and therefore something that will attract a curious child from an early age.

In 2010, the United States fire department responded to 44,900 fires started by someone, usually a child, playing with fire. These fires caused 90 civilian deaths, 890 civilian injuries, and $210 million in direct property damage. Preschoolers and kindergartners are most likely to start these fires, while playing with matches or lighters and most likely to die in these fires. Most fire-play …

Human Sexuality And Adolescence, Joav Merrick, Ariel Tenenbaum, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

An Assessment Of Hepatitis E Virus (Hev) In Us Blood Donors And Recipients: No Detectable Hev Rna In 1939 Donors Tested And No Evidence For Hev Transmission To 362 Prospectively Followed Recipients., Chenyu Xu, Richard Y. Wang, Cathy A. Schechterly, Shengxiang Ge, James W. Shih, Ning-Shao Xia, Naomi L. Luban, Harvey J. Alter

Pediatrics Faculty Publications

BACKGROUND:

Hepatitis E virus (HEV) infection has become relevant to blood transfusion practice because isolated cases of blood transmission have been reported and because HEV has been found to cause chronic infection and severe liver disease in immunocompromised patients.

STUDY DESIGN AND METHODS:

We tested for immunoglobulin (Ig)G and IgM antibodies to the HEV and for HEV RNA in 1939 unselected volunteer US blood donors. Subsequently, we tested the same variables in pre- and serial posttransfusion samples from 362 prospectively followed blood recipients to assess transfusion risk.

RESULTS:

IgG anti-HEV seroprevalence in the total 1939 donations was 18.8%: 916 of …

Incidence Of Methicillin-Resistant Staphylococcus Aureus Infection In A Children's Hospital In The Washington Metropolitan Area Of The United States, 2003-2010, Xiaoyan Song, Joanthan Cogen, Nalini Singh

Pediatrics Faculty Publications

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major public health threat. In this retrospective cohort study, we included patients with laboratory-confirmed MRSA infections treated at Children’s National Medical Center in Washington, District of Columbia between July 2003 and December 2010. The secular trends in the incidence rates of skin/soft tissue and invasive MRSA infections were assessed. Molecular analyses were performed on a subset of patients with invasive infections whose MRSA isolates were available for genotyping. The study identified 3750 patients with MRSA infections. The incidence of MRSA infections peaked in 2007 (incidence rate: 5.34 per 1000 patient-visits) and subsequently …

National Trends In C. Difficileinfections In Hospitalized Children And Young Adults With Inflammatory Bowel Disease, 2001 –2010, Kelly C. Sandberg, Matthew M. Davis, Achamyeleh Gebremariam, Jeremy Adler, Child Health Evaluation And Research Unit, University Of Michigan, C.S. Mott Children's Hospital, Pediatric Gastroenterology, University Of Michigan

Pediatrics Faculty Publications

Clostridium difficile infection complicates inflammatory bowel disease in children and adults. Increased hospitalizations have been reported due to recent hypervirulent c. difficile strains. National trends of c. difficile infections in hospitalized children and young adults with inflammatory bowel disease (IBD) are currently incomplete.

Adolescence, Violence, And Public Health, Joav Merrick, Isack Kandel, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

Neonatal Neurobehavioral Abnormalities And Mri Brain Injury In Encephalopathic Newborns Treated With Hypothermia, Maya B. Coleman, Penny Glass, Judy Brown, Nadja Kadom, Tammy Tsuchida, Joseph Scafidi, Taeun Chang, Gilbert Vezina, An Nguyen Massaro

Pediatrics Faculty Publications

Background

Neonatal Encephalopathy (NE) is a prominent cause of infant mortality and neurodevelopmental disability. Hypothermia is an effective neuroprotective therapy for newborns with encephalopathy. Post-hypothermia functional–anatomical correlation between neonatal neurobehavioral abnormalities and brain injury findings on MRI in encephalopathic newborns has not been previously described.

Aim

To evaluate the relationship between neonatal neurobehavioral abnormalities and brain injury on magnetic resonance imaging (MRI) in encephalopathic newborns treated with therapeutic hypothermia.

Study design

Neonates with hypoxic ischemic encephalopathy (HIE) referred for therapeutic hypothermia were prospectively enrolled in this observational study. Neurobehavioral functioning was assessed with the NICU network neurobehavioral scale (NNNS) performed …

Reproducibility Of Cine Displacement Encoding With Stimulated Echoes (Dense) Cardiovascular Magnetic Resonance For Measuring Left Ventricular Strains, Torsion, And Synchrony In Mice, Christopher M. Haggerty, Sage P. Kramer, Cassi M. Binkley, David K. Powell, Andrea C. Mattingly, Richard Charnigo, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

BACKGROUND: Advanced measures of cardiac function are increasingly important to clinical assessment due to their superior diagnostic and predictive capabilities. Cine DENSE cardiovascular magnetic resonance (CMR) is ideal for quantifying advanced measures of cardiac function based on its high spatial resolution and streamlined post-processing. While many studies have utilized cine DENSE in both humans and small-animal models, the inter-test and inter-observer reproducibility for quantification of advanced cardiac function in mice has not been evaluated. This represents a critical knowledge gap for both understanding the capabilities of this technique and for the design of future experiments. We hypothesized that cine DENSE …

Positive Youth Development, Life Satisfaction, And Problem Behaviors Of Adolescents In Intact And Non-Intact Families In Hong Kong, Daniel T. L. Shek, Hildie Leung

Pediatrics Faculty Publications

This study investigated whether Chinese adolescents living in intact and non-intact families differed in their positive development, life satisfaction, and risk behavior. A total of 3,328 Secondary 1 students responded to measures of positive youth development (such as resilience and psychosocial competencies), life satisfaction, and risk behavior (substance abuse, delinquency, Internet addiction, consumption of pornographic materials, self-harm, and behavioral intention to engage in problem behavior). Findings revealed that adolescents growing up in intact families reported higher levels of positive developmental outcomes and life satisfaction as compared with adolescents from non-intact families. Adolescents in non-intact families also reported higher levels of …

Increased Reticulocytosis During Infancy Is Associated With Increased Hospitalizations In Sickle Cell Anemia Patients During The First Three Years Of Life, Emily Riehm Meier, Colleen Byrnes, Y. Terry Lee, Elizabeth C. Wright, Alan N. Schechter, Naomi L. Luban, Jeffrey L. Miller

Pediatrics Faculty Publications

Objective

Among older children with sickle cell anemia, leukocyte counts, hemoglobin, and reticulocytosis have previously been suggested as disease severity markers. Here we explored whether these blood parameters may be useful to predict early childhood disease severity when tested in early infancy, defined as postnatal ages 60–180 days.

Study Design

Data from fifty-nine subjects who were followed at Children’s National Medical Center’s Sickle Cell Program for at least three years was retrospectively analyzed. Comparisons were made between white blood cell counts, hemoglobin and reticulocyte levels measured at ages 60–180 days and the clinical course of sickle cell anemia during infancy …

Ereply. Re: Balancing The Pulmonary Circulation In Tricuspid Atresia With An Aortopulmonary Window, Pranava Sinha, Syed Murfad Peer, Mary T. Donofrio

Pediatrics Faculty Publications

No abstract provided.

Appendicitis Is Like A Box Of Chocolates, Clint D. Cappiello, Phillip C. Guzzetta, Faisal G. Qureshi

Pediatrics Faculty Publications

Appendicitis is the most commonly encountered abdominal emergency in pediatric surgery. However, the presentation of acute appendicitis is as diverse as the patient population. We present here a case of appendicitis presenting as an intra-abdominal mass consistent with lymphoma. Our patient is a 3 year old male with an atypical presentation of acute appendicitis. Additionally, he was found to have malrotation at the time of surgery. A delayed presentation, coupled with anomalous laboratory findings and aberrant anatomy made for a difficult diagnosis and overall interesting case of appendicitis.

Pediatric Palliative Care For Youth With Hiv/Aids: Systematic Review Of The Literature, Megan L. Wilkins, Ronald H. Dallas, Kathleen E. Fanone, Maureen E. Lyon

Pediatrics Faculty Publications

Improvement in treatment has led to decreased death in youth with human immunodeficiency virus (HIV) in developed countries. Despite this, youth with HIV are still at risk for increased mortality and morbidity compared with their uninfected counterparts. In developing countries, high numbers of youth die from acquired immune deficiency syndrome (AIDS)-related illnesses due to lack of access to consistent antiretroviral treatment. As a result, pediatric palliative care is a relevant topic for those providing care to youth with HIV. A systematic review was conducted to gather information regarding the status of the literature related to pediatric palliative care and medical …

Crystal Structure Of The N-Acetyltransferase Domain Of Human N-Acetyl-L-Glutamate Synthase In Complex With N-Acetyl-L-Glutamate Provides Insights Into Its Catalytic And Regulatory Mechanisms, Gengxiang Zhao, Zhongmin Jin, Norma M. Allewell, Mendel Tuchman, Dashuang Shi

Pediatrics Faculty Publications

N-acetylglutamate synthase (NAGS) catalyzes the conversion of AcCoA and L-glutamate to CoA and N-acetyl-L-glutamate (NAG), an obligate cofactor for carbamyl phosphate synthetase I (CPSI) in the urea cycle. NAGS deficiency results in elevated levels of plasma ammonia which is neurotoxic. We report herein the first crystal structure of human NAGS, that of the catalyticN-acetyltransferase (hNAT) domain with N-acetyl-L-glutamate bound at 2.1 Å resolution. Functional studies indicate that the hNAT domain retains catalytic activity in the absence of the amino acid kinase (AAK) domain. Instead, the major functions of the AAK domain appear to be providing …

A Synthetic Model Of Human Beta-Thalassemia Erythropoiesis Using Cd34+ Cells From Healthy Adult Donors, Y. Terry Lee, Ki-Soon Kim, Colleen Byrnes, Jaira F. De Vasconcellos, Seung-Jae Noh, Antoinette Rabel, Emily Riehm Meier, Jeffrey L. Meier

Pediatrics Faculty Publications

Based upon the lack of clinical samples available for research in many laboratories worldwide, a significant gap exists between basic and clinical studies of beta-thalassemia major. To bridge this gap, we developed an artificially engineered model for human beta thalassemia by knocking down beta-globin gene and protein expression in cultured CD34+ cells obtained from healthy adults. Lentiviral-mediated transduction of beta-globin shRNA (beta-KD) caused imbalanced globin chain production. Beta-globin mRNA was reduced by 90% compared to controls, while alpha-globin mRNA levels were maintained. HPLC analyses revealed a 96% reduction in HbA with only a minor increase in HbF. During the terminal …

Is Adrenalectomy Necessary During Unilateral Nephrectomy For Wilms Tumor? A Report From The Children's Oncology Group., Kathleen Kieran, James R Anderson, Jeffrey S Dome, Peter F Ehrlich, Michael L Ritchey, Robert C Shamberger, Elizabeth J Perlman, Daniel M Green, Andrew M Davidoff

Pediatrics Faculty Publications

PURPOSE: To determine whether performing adrenalectomy at the time of nephrectomy for unilateral Wilms tumor impacts clinical outcome.

METHODS: We reviewed information on all patients enrolled on National Wilms Tumor Study-4 and -5. Data were abstracted on patient demographics, tumor characteristics, surgical and pathologic status of the adrenal gland, and patient outcomes. The primary endpoints were intraoperative spill and five-year event-free survival (EFS) in patients who did or did not undergo adrenalectomy.

RESULTS: Of 3825 patients with complete evaluable data, the adrenal was left in situ in 2264 (57.9%) patients, and was removed completely in 1367 patients (36.7%) or partially …

From Qualitative Work To Intervention Development In Pediatric Oncology Palliative Care Research, Terrah Foster Akard, Mary Jo Gilmer, Debra L. Friedman, Barbara Given, Verna L. Hendricks-Ferguson, Pamela S. Hinds

Pediatrics Faculty Publications

Qualitative methods can be particularly useful approaches to use with individuals who are experiencing a rare disease and thus who comprise a small sample (such as children with cancer) and are at points in care that few experience (such as end of life). This data-based methods article describes how findings from a qualitative study were used to guide and shape a pediatric oncology palliative care intervention. Qualitative data can lay a strong foundation for subsequent pilot intervention work by facilitating the development of an underlying study conceptualization, providing recruitment feasibility estimates, helping establish clinically meaningful inclusion criteria, establishing staff acceptability …

Characteristics Of Children With The Best And Poorest First- And Second-Year Growth During Rhgh Therapy: Data From 25 Years Of The Genentech National Cooperative Growth Study (Ncgs), Paul B. Kaplowitz, Dorothy I. Shulman, James W. Frane, Joan Jacobs, Barbara Lippe

Pediatrics Faculty Publications

Background

Models assessing characteristics contributing to response to recombinant human growth hormone (rhGH) response rarely address growth extremes in both years 1 and 2 or examine how children track from year to year. Using National Cooperative Growth Study (NCGS) data, we determined characteristics contributing to responsiveness to rhGH and the pattern of change from years 1 to 2.

Patients and methods

Height velocity standard deviation score (HV SDS) for 2 years for prepubertal children with idiopathic GH deficiency (IGHD) (n = 1899) and idiopathic short stature (ISS) (n = 1186) treated with similar doses for two years were computed. Group …

Effects Of Perinatal Oxycodone Exposure On The Cardiovascular Response To Acute Stress In Male Rats At Weaning And In Young Adulthood, Thitinart Sithisarn, Henrietta S. Bada, Richard J. Charnigo, Sandra J. Legan, David C. Randall

Pediatrics Faculty Publications

Oxycodone (OXY) is one of the most commonly abused opiates during pregnancy. Perinatal opiate exposure (POE) is associated with neurobehavioral and hormone changes. Little is known about the effects of perinatal OXY on the cardiovascular (CV) responses to stress.

Objectives: to determine the effects of POE on: (1) CV responses to acute stress and ability to discriminate using a classical conditioning paradigm; (2) changes in CV response to the paradigm and retention of the ability to discriminate from postnatal day (PD) 40 to young adulthood.

Methods: Pregnant rats were given i.v. OXY or vehicle (CON) daily. OXY and CON males …

Caveolar Fatty Acids And Acylation Of Caveolin-1, Qian Cai, Ling Guo, Haiqing Gao, Xiang-An Li

Pediatrics Faculty Publications

PURPOSE: Caveolae are cholesterol and sphingolipids rich subcellular domains on plasma membrane. Caveolae contain a variety of signaling proteins which provide platforms for signaling transduction. In addition to enriched with cholesterol and sphingolipids, caveolae also contain a variety of fatty acids. It has been well-established that acylation of protein plays a pivotal role in subcellular location including targeting to caveolae. However, the fatty acid compositions of caveolae and the type of acylation of caveolar proteins remain largely unknown. In this study, we investigated the fatty acids in caveolae and caveolin-1 bound fatty acids.

METHODS: Caveolae were isolated from Chinese hamster …

The Young And Suicide, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Age-Related Accumulation Of T Cells With Markers Of Relatively Stronger Autoreactivity Leads To Functional Erosion Of T Cells., Zohreh Tatari-Calderone, Milica Stojakovic, Ramita Dewan, Gama L. Bouder, Dragana Jankovic, Stanislav Vukmanovic

Pediatrics Faculty Publications

Background

Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases.

Results

The phenotype of T cells …