Medicine and Health Sciences Commons^™

Directional Secretory Response Of Double Stranded Rna-Induced Thymic Stromal Lymphopoetin (Tslp) And Ccl11/Eotaxin-1 In Human Asthmatic Airways, Gustavo Nino, Shehlanoor Huseni, Geovanny F. Perez, Krishna Pancham, Humaira Mubeen, Aleeza Abeesi, Justin Wang, Stephen Eng, Anamaris M. Colberg-Poley, Mary C. Rose

Pediatrics Faculty Publications

Background

Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state.

Methods

Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) …

Integrative Therapy Use For Management Of Side Effects And Toxicities Experienced By Pediatric Oncology Patients, Shana Jacobs

Pediatrics Faculty Publications

Integrative Therapies (IT), otherwise known as Complementary and Alternative Medicine, are widely used among pediatric oncology patients, despite a paucity of available evidence. This review summarizes surveys that describe the prevalence of IT use by pediatric oncology patients, both during therapy and in survivorship, as well as the modalities being used. Additionally, the evidence that exists for specific treatments that appear to be efficacious in controlling specific symptoms is described. Finally, there are recommendations for practitioners on how to best counsel patients about IT use.

Utility Of Heidelberg Retinal Tomography As A Screening Tool For Analyzing Retinal Nerve Fiber Layer Defects, David A. Belyea, Rashed Alhabshan, Sankaranarayana P. Mahesh, Gregory S. Gertner, Mirsad M. Ibisevic, Abdullah S. Habib, Jacob A. Dan

Ophthalmology Faculty Publications

Context

Although Heidelberg retinal tomography (HRT)-generated topographic images have been studied extensively for the detection of retinal nerve fiber layer (RNFL) defects, little is known about the role of HRT-generated surface reflectivity images in the detection of RNFL defects in either patients with glaucoma or glaucoma suspects.

Aims

To evaluate the effectiveness of HRT version II (HRT II) optic nerve reflectivity images in uncovering RNFL defects in an outpatient population evaluated for glaucoma.

Study design/materials and methods

In 102 consecutive eyes from 60 patients evaluated for glaucoma in an academic-based practice, HRT II optic nerve images were prospectively imaged and …

Current Perspectives On Primary Care Workforce, Kathleen Klink

Health Workforce Speaker Series

No abstract provided.

Corticosteroids And Pediatric Septic Shock Outcomes: A Risk Stratified Analysis, Sarah J. Atkinson, Natalie Z. Cvijanovich, Neal J. Thomas, Geoffrey L. Allen, Nick Anas, Robert J. Freishtat, +17 Additional Authors

Pediatrics Faculty Publications

Background

The potential benefits of corticosteroids for septic shock may depend on initial mortality risk.

Objective

We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk.

Methods

We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression …

Antibiotic Prophylaxis And Reflux: Critical Review And Assessment, Bernarda Viteri Baquerizo, Craig A. Peters

Urology Faculty Publications

The use of continuous antibiotic prophylaxis (CAP) was critical in the evolution of vesicoureteral reflux (VUR) from a condition in which surgery was the standard of treatment to its becoming a medically managed condition. The efficacy of antibiotic prophylaxis in the management of VUR has been challenged in recent years, and significant confusion exists as to its clinical value. This review summarizes the critical factors in the history, use, and investigation of antibiotic prophylaxis in VUR. This review provides suggestions for assessing the potential clinical utility of prophylaxis.

The Translational Biology Of Remyelination: Past, Present, And Future, Robin J.M. Franklin, Vittorio Gallo

Pediatrics Faculty Publications

Amongst neurological diseases, multiple sclerosis (MS) presents an attractive target for regenerative medicine. This is because the primary pathology, the loss of myelin-forming oligodendrocytes, can be followed by a spontaneous and efficient regenerative process called remyelination. While cell transplantation approaches have been explored as a means of replacing lost oligodendrocytes, more recently therapeutic approaches that target the endogenous regenerative process have been favored. This is in large part due to our increasing understanding of (1) the cell types within the adult brain that are able to generate new oligodendrocytes, (2) the mechanisms and pathways by which this achieved, and (3) …

Vitamin A, Vitamin E, Iron And Zinc Status In A Cohort Of Hiv-Infected Mothers And Their Uninfected Infants, Jacqueline Pontes Monteiro, Maria Leticia Santos Cruz, Marisa Marcia Mussi-Pinhata, Roberta Garcia Salomao, Alceu Jordao Junior, Jennifer S. Read, Jose Henrique Da Silva Pilotto, Rachel Ann Cohen, Sonia Karolina Stoszek, George Kelly Siberry

Pediatrics Faculty Publications

Introduction

We hypothesized that nutritional deficiency would be common in a cohort of postpartum, human immunodeficiency virus (HIV)-infected women and their infants.

Methods

Weight and height, as well as blood concentrations of retinol, α-tocopherol, ferritin, hemoglobin, and zinc, were measured in mothers after delivery and in their infants at birth and at 6-12 weeks and six months of age. Retinol and α-tocopherol levels were quantified by high performance liquid chromatography, and zinc levels were measured by atomic absorption spectrophotometry. The maternal body mass index during pregnancy was adjusted for gestational age (adjBMI).

Results

Among the 97 women 19.6% were underweight. …

Coagulopathy In Newborns With Hypoxic Ischemic Encephalopathy (Hie) Treated With Therapeutic Hypothermia: A Retrospective Case-Control Study, Katie R. Forman, Yaser A. Diab, Edward C.C. Wong, Stephen Baumgart, Naomi L. Luban, An Nguyen Massaro

Pediatrics Faculty Publications

Background

Newborns with hypoxic ischemic encephalopathy (HIE) are at risk for coagulopathy due to systemic oxygen deprivation. Additionally, therapeutic hypothermia (TH) slows enzymatic activity of the coagulation cascade, leading to constitutive prolongation of routinely assessed coagulation studies. The level of laboratory abnormality that predicts bleeding is unclear, leading to varying transfusion therapy practices.

Methods

HIE infants treated with TH between 2008–2012 were included in this retrospective study. Initial, minimum (min) and maximum (max) values of International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen (Fib) and platelet (PLT) count (measured twice daily during TH) were collected. Bleeding was defined …

Planning A Safe Exit: A Multidisciplinary Approach, Srijaya K. Reddy, Nina Deutsch

E-Learning Modules

This resource is a problem-based learning discussion (PBLD) case addressing the challenges and approach to planning and safely executing an EXIT procedure. It is primarily aimed at pediatric anesthesiologists but also applies to healthcare providers in fetal medicine and surgery.

The clinical scenario involves a fetus with a large cervical neck mass requiring an EXIT procedure for tracheal obstruction. This case highlights the challenges and implications of a procedure involving a multidisciplinary team. After presentation of the case stem, the instructor moderates a student-focused group discussion using a series of questions that build upon the case and a review of …

Efficacy Of Transoral Fundoplication For Treatment Of Chronic Gastroesophageal Reflux Disease Incompletely Controlled With High-Dose Proton-Pump Inhibitors Therapy: A Randomized, Multicenter, Open Label, Crossover Study., Karim S. Trad, Gilbert Simoni, William Edris Barnes, Ahmad Bassel Shughoury, Mamoon Raza, Jeffrey Alan Heise, Daniel Gilles Turgeon, Mark Alan Fox, Peter George Mavrelis

Surgery Faculty Publications

Background

The aim of this randomized, crossover study was to determine if transoral fundoplication (TF) could further improve clinical outcomes in partial responders to high-dose (HD) proton-pump inhibitor (PPI) therapy and to evaluate durability of TF.

Methods

In seven United States centers, patients with hiatal hernia ≤2 cm and abnormal esophageal acid exposure (EAE) were randomized to TF (n = 40) or HD PPIs (n = 23) group. At 6-month follow-up, PPI patients underwent crossover. We assessed clinical outcomes 6-month post TF in crossover patients (COP), as compared to 6-month of HD PPI therapy, and 12-month outcomes in patients initially …

Neonatal Nmda Receptor Blockade Disrupts Spike Timing And Glutamatergic Synapses In Fast Spiking Interneurons In A Nmda Receptor Hypofunction Model Of Schizophrenia, Kevin S. Jones, Joshua G. Corbin, Molly M. Huntsman

Pediatrics Faculty Publications

The dysfunction of parvalbumin-positive, fast-spiking interneurons (FSI) is considered a primary contributor to the pathophysiology of schizophrenia (SZ), but deficits in FSI physiology have not been explicitly characterized. We show for the first time, that a widely-employed model of schizophrenia minimizes first spike latency and increases GluN2B-mediated current in neocortical FSIs. The reduction in FSI first-spike latency coincides with reduced expression of the Kv1.1 potassium channel subunit which provides a biophysical explanation for the abnormal spiking behavior. Similarly, the increase in NMDA current coincides with enhanced expression of the GluN2B NMDA receptor subunit, specifically in FSIs. In this study mice …

Tps Mutational Status Is A Potential Marker For Risk Stratification In Wilms Tumour With Diffuse Anaplasia, Mariana Maschietto, Richard D. Williams, Tasnim Chagtai, Sergey D. Popov, Neil J. Sebire, Gordan Vujanic, Elizabeth Perlman, James R. Anderson, Paul Grundy, Jeffrey S. Dome, Kathy Pritchard-Jones

Pediatrics Faculty Publications

Purpose

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whetherTP53 mutational status confers additional prognostic information.

Patients and Methods

We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. …

The Association Of Meningococcal Disease With Influenza In The United States, 1989-2009, Jessica Hartman Jacobs, Cecile Viboud, Eric Tchetgen Tchetgen, Joel Schwartz, Claudia Steiner, Lone Simonsen, Marc Lipsitch

Global Health Faculty Publications

Importance and Objective

Prior influenza infection is a risk factor for invasive meningococcal disease. Quantifying the fraction of meningococcal disease attributable to influenza could improve understanding of viral-bacterial interaction and indicate additional health benefits to influenza immunization.

Design, Setting and Participants

A time series analysis of the association of influenza and meningococcal disease using hospitalizations in 9 states from 1989–2009 included in the State Inpatient Databases from the Agency for Healthcare Research and Quality and the proportion of positive influenza tests by subtype reported to the Centers for Disease Control. The model accounts for the autocorrelation of meningococcal disease and …

Abnormal White Matter Integrity Related To Head Impact Exposure In A Season Of High School Varsity Football, Elizabeth M. Davenport, Christopher T. Whitlow, Jillian E. Urban, Mark A. Espeland, Jung Youngkyoo, Daryl A. Rosenbaum, Gerard A. Gioia, Alexander K. Powers, Joel D. Stitzel, Joseph A. Maldjian

Psychiatry and Behavioral Sciences Faculty Publications

The aim of this study was to determine whether the cumulative effects of head impacts from a season of high school football produce magnetic resonance imaging (MRI) measureable changes in the brain in the absence of clinically diagnosed concussion. Players from a local high school football team were instrumented with the Head Impact Telemetry System (HITS™) during all practices and games. All players received pre- and postseason MRI, including diffusion tensor imaging (DTI). Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) was also conducted. Total impacts and risk-weighted cumulative exposure (RWE), including linear (RWE_Linear), rotational (RWE_Rotational), and …

A Delphi Process To Optimize Quality And Performance Of Drug Evaluation In Neonates, Frederic Legrand, Rym Boulkedid, Valery Elie, Stephanie Leroux, Elizabeth Valls, Adolfo Valls-I-Soler, John N. Van Den Anker

Pediatrics Faculty Publications

Background

Neonatal trials remain difficult to conduct for several reasons: in particular the need for study sites to have an existing infrastructure in place, with trained investigators and validated quality procedures to ensure good clinical, laboratory practices and a respect for high ethical standards. The objective of this work was to identify the major criteria considered necessary for selecting neonatal intensive care units that are able to perform drug evaluations competently.

Methodology and Main Findings

This Delphi process was conducted with an international multidisciplinary panel of 25 experts from 13 countries, selected to be part of two committees (a scientific …

Lin28a Expression Reduces Sickling Of Cultured Human Erythrocytes, Jaira F. De Vasconcellos, Ross M. Fasano, Y. Terry Lee, Megha Kaushal, Colleen Burns, Emily Riehm Meier, Molly Anderson, Antoinette Rabel, Raul Braylan, David F. Stroncek, Jeffery L. Miller

Pediatrics Faculty Publications

Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocytes cultured from peripheral blood progenitor cells of pediatric subjects with SCD. Transgenic expression of LIN28A was accomplished by lentiviral transduction in CD34(+) sickle cells cultivated ex vivo in serum-free medium. LIN28A over-expression (LIN28A-OE) increased HbF, reduced beta (sickle)-globin, and strongly suppressed …

Psychiatry And Efforts To Build Community In Iraq., Amir A Afkhami

Psychiatry and Behavioral Sciences Faculty Publications

No abstract provided.

Mir-638 Mediated Regulation Of Brca1 Affects Dna Repair And Sensitivity To Uv And Cisplatin In Triple Negative Breast Cancer, Xiaohui Tan, Jin Peng, Yebo Fu, Shejuan An, M. Katayoon Rezaei, Sana Tabbara, Christine B. Teal, Yan-Gao Man, Rachel F. Brem, Sidney W. Fu

Pathology Faculty Publications

Introduction

Triple-negative breast cancer (TNBC) represents 15 to 20% of all types of breast cancer; however, it accounts for a large number of metastatic cases and deaths, and there is still no effective treatment. The deregulation of microRNAs (miRNAs) in breast cancer has been widely reported. We previously identified that miR-638 was one of the most deregulated miRNAs in breast cancer progression. Bioinformatics analysis revealed that miR-638 directly targets BRCA1. The aim of this study was to investigate the role of miR-638 in breast cancer prognosis and treatment.

Methods

Formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were microdissected into normal …

Epidemiology Of Patients Presenting To The Emergency Centre Of Princess Marina Hospital In Gaborone, Botswana, Amit Chandra, Paul C. Mullan, Ari Ho-Foster, Antanoid Langeveldt, Ngaire Caruso, Joseph Motsumi, Andrew Kestler

Pediatrics Faculty Publications

No abstract provided.

Double Trouble: A Rare Case Of Bilateral Upper Pole Ureteropelvic Junction Obstruction, Craig A. Peters, Nirmal Pathak

Urology Faculty Publications

A 16-year-old girl presented with bilateral back pain caused by bilateral upper pole ureteropelvic junction obstructions; an extremely rare phenomenon. Bilateral robotically assisted upper pole pyeloplasties were preformed at the same setting with an excellent clinical response. Although rare, upper pole ureteropelvic junction obstruction is a defined entity that urologists should be aware of.

Somatic Intronic Microsatellite Loci Differentiate Glioblastoma From Lower-Grade Gliomas, Enusha Karunasena, Lauren J. Mciver, Brian R. Rood, Xiaowei Wu, Hongxiao Zhu, Jasmin H. Bavarva, Harold R. Garner

Pediatrics Faculty Publications

Genomic studies of glioma sub-types have amassed new disease specific mutations, yet these only partially explain how mutations are linked to predisposition or progression. We hypothesized that microsatellite variation could expand the understanding of glioma etiology. Furthermore, germline markers for gliomas are typically undetectable; therefore we also hypothesize that the predictability of cancer-associated microsatellite loci in germline DNA may support the current hypothesis of a glioma cell of origin.

In this study, “normal” germline exome sequenced DNA from the 1000 Genomes Project (n=390) were compared with exome sequences from germlines of subjects with WHO grade II and III lower-grade glioma …

Sleep Disturbance, Depression And Pain In Adults With Sickle Cell Disease, Gwenyth R. Wallen, Caterina P. Minniti, Michael Krumlauf, Ellen Eckes, Darlene Allen, Anna Oguhebe, Cassie Seamon, Deepika Darbari

Pediatrics Faculty Publications

Background

Sleep disturbance and depression are commonly encountered in primary care. In sickle cell disease, depression is associated with pain, poor treatment compliance, and lower quality of life. The prevalence of sleep disturbance and its effect upon quality of life in adults with sickle cell disease is unknown. The goal of this study was to determine the prevalence of sleep disturbance and if it is associated with pain and depression in sickle cell disease.

Methods

Three hundred twenty eight adults with sickle cell disease enrolled on the Bethesda Sickle Cell Cohort Study were assessed using the Pittsburgh Sleep Quality Index …

Serum Metabolomic Response Of Myasthenia Gravis Patients To Chronic Prednisone Treatment, Manjistha Sengupta, Amrita Cheema, Henry J. Kaminski, Linda Louise Kusner

Neurology Faculty Publications

Prednisone is often used for the treatment of autoimmune and inflammatory diseases but they suffer from variable therapeutic responses and significant adverse effects. Serum biological markers that are modulated by chronic corticosteroid use have not been identified. Myasthenia gravis is an autoimmune neuromuscular disorder caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction resulting in weakness. The patients with myasthenia gravis are primarily treated with prednisone. We analyzed the metabolomic profile of serum collected from patients prior to and after 12 weeks of prednisone treatment during a clinical trial. Our aim was to identify metabolites …

Quantitative Ultrasound: Measurement Considerations For The Assessment Of Muscular Dystrophy And Sarcopenia, Michael O. Harris-Love, Reza Monfaredi, Catheeja Ismail, Marc R. Blackman, Kevin Cleary

Exercise and Nutrition Sciences Faculty Publications

Diagnostic musculoskeletal ultrasound has potential clinical utility in characterizing pathological muscle tissue. Sonography has been long proposed as method of assessing muscle damage due to neuromuscular diseases such as muscular dystrophy, and more recently, changes in body and tissue composition associated with muscle wasting disorders such as sarcopenia. The use of quantitative ultrasound as an adjunct diagnostic procedure has different technical challenges than the traditional use of ultrasound in clinical medicine. Operator-dependent technique and variation are critical considerations when obtaining measures of echointensity (i.e., tissue composition estimates) and tissue dimensions (i.e., muscle thickness) – key elements of the ultrasound assessment …

Metastatic Renal Cell Carconima To The Thyroid 23 Years After Nephrectomy, Carrie Valdez, M. Katayoon Rezaei, Frederick Hendricks, Stanley M. Knoll

Pathology Faculty Publications

Thyroid carcinoma is an uncommon form of human cancer, with an outstanding overall cure rate. This excellent prognosis is based on the fact that well over 99% of thyroid cancers are primary tumors. Metastatic cancer to the thyroid remains very rare. We report a case of clear cell renal carcinoma metastatic to the thyroid gland 23 years after nephrectomy.

Safety Of Celecoxib And Nonselective Nonsteroidal Anti-Inflammatory Drugs In Juvenile Idiopathic Arthritis: Results Of The Phase 4 Registry, Rachel E. Sobel, Daniel J. Lovell, Hermine I. Brunner, Jennifer E. Weiss, Paula W. Morris, Beth S. Gottlieb, Elizabeth C. Chalom, Lawrence K. Jung, Karen B. Onel, Lisa Petiniot, Donald P. Goldsmith

Pediatrics Faculty Publications

Background

This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs).

Methods

Children aged ≥2 to <18 years with rheumatoid-factor–positive or –negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database.

Results

A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently …

Treatment Preferences Among Problem Drinkers In Primary Care., Daniel Z Lieberman, Anne Cioletti, Suena H Massey, Rochelle S Collantes, Brad B Moore

Psychiatry and Behavioral Sciences Faculty Publications

OBJECTIVE: Alcohol misuse is common among primary care patients, yet many do not receive treatment because doctors believe problem drinkers are "in denial," or are unwilling to change their drinking habits. The real problem, however, may be that patients are being offered treatment modalities that do not meet their needs. This study was designed to measure the acceptability of various treatment options among drinkers who were currently not receiving treatment.

METHOD: Patients in a primary care clinic were given a self-report questionnaire that included: (1) the Alcohol Use Disorders Questionnaire, (2) a measure of readiness to change drinking behavior, and …

Vulnerability Of The Ventral Language Network In Children With Focal Epilepsy, Louise J. Croft, Torsten Baldeweg, Leigh Sepeta, Lauren Zimmaro, Madison M. Berl, William D. Gaillard

Neurology Faculty Publications

Children with focal epilepsy are at increased risk of language impairment, yet the neural substrate of this dysfunction is not yet known. Using functional magnetic resonance imaging we investigated the impact of focal epilepsy on the developing language system using measures of network topology (spatial organization of activation) and synchrony (functional connectivity). We studied healthy children (n = 48, 4–12 years, 24 females) and children with focal epilepsy (n = 21, 5–12 years, nine females) with left hemisphere language dominance. Participants performed an age-adjusted auditory description decision task during functional magnetic resonance imaging, to identify perisylvian language regions. …

Psychiatric Boarding In U.S. Eds: A Multifactorial Problem That Requires Multidisicplinary Solutions, Zaynah Abid, Andrew C. Meltzer, Danielle Lazar, Jesse M. Pines

Center for Health Care Quality

ED visits for psychiatric conditions make up an ever-increasing share of all ED visits. Patients with psychiatric complaints have a significantly greater length-of-stay in the ED than patients with non-psychiatric complaints. Prolonged boarding in the ED for psychiatric patients is associated with lower quality care for psychiatric patients and further contributes to overall ED crowding.