Medical Specialties Commons^™

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 …

Rate Control Of Atrial Arrhythmias Can Be Achieved By Selective Cardiac Neurostimulation, Mark Marchitto, Aditya C. Sharma, Jeffrey P. Moak, Dingchao He, Conor Hynes, Gregory Trachiotis, Andy Blichard, Erin Montague, Xiyan Li, Gene Bornzin, Charles I. Berul, Richard A. Jonas, Marco A. Mercader

GW Research Days 2015

Introduction: Atrial arrhythmias (AA) occur in up to 40% of patients recovering from open-heart surgery (OHS). Pharmacologic treatment has been the main strategy used for the control of post-operative AA, but is associated with hypotension, pro-arrhythmia and myocardial dysfunction. There is a need for a reversible, modulated solution to rate control. We demonstrated the efficacy of vagal stimulation at inferior right fat pad (FP) to slow the ventricular response (VR) of atrial fibrillation (AF) and junctional ectopic tachycardia (JET). We hypothesized that the VR response to AA could be improved by alterations in 1) the site of stimulation (anterior right …

Minimal Increase In Contrast Enhancement After Chemo-Radiotherapy (Crt) For Glioblastoma Predicts Worse Survival And Progression-Free Survival, Sameer Aggarwal, Jason Molitoris, Cecelia Gzell, Minesh Mehta

GW Research Days 2015

No abstract provided.

Default Mode Network Segregation And Social Deficits In Autism Spectrum Disorder: Evidence From Non-Medicated Children., Benjamin E Yerys, Evan M Gordon, Danielle N Abrams, Theodore D Satterthwaite, Rachel Weinblatt, Kathryn F Jankowski, John Strang, Lauren Kenworthy, William D. Gaillard, Chandan J Vaidya

Psychiatry and Behavioral Sciences Faculty Publications

Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8-13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within …

Lateralization Of Mesial Temporal Lobe Epilepsy With Chronic Ambulatory Electrocorticography, David King-Stephens, Emily Mirro, Peter B. Weber, Kenneth D. Laxer, Paul C. Van Ness, Donald C. Shields, +24 Additional Authors

Neurological Surgery Faculty Publications

Objective

Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video–electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.

Methods

Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were …

Epidural Steroid Injections Compared With Gabapentin For Lumbosacral Radicular Pain: Multicenter Randomized Double Blind Comparative Efficacy Study, Steven P. Cohen, Steven Hanling, Mark C. Bicket, Ronald L. White, Elias Velzi, Connie Kurihara, Zirong Zhao, Salim Hayek, Kevin B. Guthmiller, Scott R. Griffith, Vitaly Gordin, Mirinda Anderson White, Yakov Vorobeychik, Paul F. Pasquina

Neurology Faculty Publications

Objective To evaluate whether an epidural steroid injection or gabapentin is a better treatment for lumbosacral radiculopathy.

Design A multicenter randomized study conducted between 2011 and 2014. Computer generated randomization was stratified by site. Patients and evaluating physicians were blinded to treatment outcomes.

Settings Eight military, Veterans Administration, and civilian hospitals.

Participants 145 people with lumbosacral radicular pain secondary to herniated disc or spinal stenosis for less than four years in duration and in whom leg pain is as severe or more severe than back pain.

Interventions Participants received either epidural steroid injection plus placebo pills or sham injection plus …

Association Between Respiratory Syncytial Virus Activity And Pneumococcal Disease In Infants: A Time Series Analysis Of Us Hospitalization Data., Daniel M. Weinberger, Keith P. Klugman, Claudia A. Steiner, Lone Simonsen, Cécile Viboud

Epidemiology Faculty Publications

BACKGROUND:

The importance of bacterial infections following respiratory syncytial virus (RSV) remains unclear. We evaluated whether variations in RSV epidemic timing and magnitude are associated with variations in pneumococcal disease epidemics and whether changes in pneumococcal disease following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) were associated with changes in the rate of hospitalizations coded as RSV.

METHODS AND FINDINGS:

We used data from the State Inpatient Databases (Agency for Healthcare Research and Quality), including >700,000 RSV hospitalizations and >16,000 pneumococcal pneumonia hospitalizations in 36 states (1992/1993-2008/2009). Harmonic regression was used to estimate the timing of the average seasonal …

Anesthesia For Deep Brain Stimulation In Traumatic Brain Injury-Induced Hemidystonia, Jill M. Jani, Chima O. Oluigbo, Srijaya K. Reddy

Neurological Surgery Faculty Publications

Deep brain stimulation in an awake patient presents several unique challenges to the anesthesiologist. It is important to understand the various stages of the procedure and the complexities of anesthetic management in order to have a successful surgical outcome and provide a safe environment for the patient.

Controversial Neuroendoscopic Monro Foraminoplasty In The Management Of Isolated Lateral Ventricle In An Adult, Max O. Krucoff, Moshe Chinn, Parker Babington, Zachary N. Litvack

Neurological Surgery Faculty Publications

This report describes the clinical presentation, differential diagnosis, imaging characteristics, and current literature regarding the minimally invasive neuroendoscopic treatment of a rare condition: idiopathic unilateral hydrocephalus presenting late in adulthood. This paper also addresses the current controversy regarding septum pellucidotomy and/or Monro foraminoplasty as mono- or dual therapies for UH. A 63 year old African American female presented with headaches, blurry vision, and gait instability for six months. She was referred for neurosurgical consultation after an MRI demonstrated enlargement of the right lateral ventricle with left septal deviation. The patient underwent endoscopic transventricular fenestration of an idiopathic membrane occluding the …

Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu

Medicine Faculty Publications

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal …

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

Pediatrics Faculty Publications

No abstract provided.

A Dietary Intervention For Chronic Diabetic Neuropathy Pain: A Randomized Controlled Pilot Study, A. E. Bunner, C. L. Wells, J. Gonzales, U. Agarwal, Elham Bayat, Neal D. Barnard

Neurology Faculty Publications

Background:

Diabetic neuropathy is a common and often debilitating condition for which available treatments are limited. Because a low-fat plant-based diet has been shown to improve glycemic control in individuals with type 2 diabetes, we hypothesized that such a diet would reduce painful symptoms of diabetic neuropathy.

Methods:

In this 20-week pilot study, individuals with type 2 diabetes and painful diabetic neuropathy were randomly assigned to two groups. The intervention group was asked to follow a low-fat, plant-based diet, with weekly classes for support in following the prescribed diet, and to take a vitamin B12 supplement. The control group was …

Effect Of Cold Plasma On Glial Cell Morphology Studied By Atomic Force Microscopy., Nina Recek, Xiaoqian Cheng, Michael Keidar, Uros Cvelbar, Alenka Vesel, Miran Mozetic, Jonathan Sherman

Neurological Surgery Faculty Publications

The atomic force microscope (AFM) is broadly used to study the morphology of cells. The morphological characteristics and differences of the cell membrane between normal human astrocytes and glial tumor cells are not well explored. Following treatment with cold atmospheric plasma, evaluation of the selective effect of plasma on cell viability of tumor cells is poorly understood and requires further evaluation. Using AFM we imaged morphology of glial cells before and after cold atmospheric plasma treatment. To look more closely at the effect of plasma on cell membrane, high resolution imaging was used. We report the differences between normal human …

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 …

Integrating Spirituality As A Key Component Of Patient Care, Suzette Bremault-Phillips, Joanne Olson, Pamela Brett-Maclean, Doreen Oneschuk, Shane Sinclair, Ralph Magnus, Jeanne Weis, Marjan Abbasi, Jasneet Parmar, Christina M. Puchalski

Medicine Faculty Publications

Patient care frequently focuses on physical aspects of disease management, with variable attention given to spiritual needs. And yet, patients indicate that spiritual suffering adds to distress associated with illness. Spirituality, broadly defined as that which gives meaning and purpose to a person’s life and connectedness to the significant or sacred, often becomes a central issue for patients. Growing evidence demonstrates that spirituality is important in patient care. Yet healthcare professionals (HCPs) do not always feel prepared to engage with patients about spiritual issues. In this project, HCPs attended an educational session focused on using the FICA Spiritual History Tool …

Isolation Of Leclercia Adecarboxylata From A Patient With A Subungual Splinter., Rina Allawh, Brendan J Camp

Medicine Faculty Publications

Leclercia adecarboxylata is a rarely described motile, aerobic, gram-negative bacillus reported to cause clinically significant solitary infections in immunocompromised patients and polymicrobial wound infections in immunocompetent patients [1-5]. We present a case of a polymicrobial infection including L. adecarboxylata in a healthy female patient with a subungual splinter, to increase awareness and aid in the diagnosis and treatment of cutaneous L. adecarboxylata infections. To our knowledge, this is the first reported case of trauma-related subungual L. adecarboxylata infection reported in the dermatology literature.

Meeting The Challenge Of Abortion As A Topic In Medical Education, Julia B. Frank, Seema Kakar, Gisela Butera, Maria Jarkowiec, Suzanne Gouda

Medicine Faculty Posters and Presentations

Abortions typically occur outside of academic medical centers, in a highly politicized context. As adult learners. students may have well formed beliefs about abortion. Few schools address the subject in the clinical years and even fewer in the pre-clinical years. Fulfilling the APGO mandate to provide abortion education requires the development of innovative approaches.

Genetic Modifiers Of Duchenne Muscular Dystrophy And Dilated Cardiomyopathy., Andrea Barp, Luca Bello, Luisa Politano, Paola Melacini, Chiara Calore, Eric P. Hoffman, +16 Additional Authors

Genomics and Precision Medicine Faculty Publications

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m2 as …