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Seventeenth Annual Child Health Research Day
Sponsored by The Jack and Lucy Clark Department of Pediatrics and
The Mindich Child Health and Development Institute
Program and Abstracts
Image Courtesy of Megan Horton, PhD, MPH (Department of Preventive Medicine):
“White matter fiber tracts of 4 year old brain as seen with Diffusion Tensor Imaging
(DTI).”
” (Division of Nephrology, Department of Pediatrics)
April 16, 2015
Hatch Auditorium & Guggenheim Pavilion
A Program of
The Jack and Lucy Clark Department of Pediatrics
and
The Mindich Child Health and Development Institute
Keynote Speaker:
Joel N. Hirschhorn, M.D., Ph.D.
Concordia Professor of Pediatrics and Professor of Genetics, Harvard Medical School
Director, Center for Basic and Translational Obesity Research, Boston Children’s Hospital
Senior Associate Member, Broad Institute
Child Health Research Day
Steering Committee:
M. Cecilia Berin, PhD, Chair
Supinda Bunyanavich, MD
Jaime Chu, MD
Nicole Dubois, PhD
David Dunkin, MD
Megan Horton, PhD, MPH
Hirofumi Morishita, MD, PhD
Perry Sheffield, MD
Annemarie Stroustrup, MD, MPH
Nita Vangeepuram, MD, MPH
Advisory Committee:
Bruce D. Gelb, MD
Lisa M. Satlin, MD
Robert Wright, MD, MPH
Rosalind Wright, MD, MPH
Administrator: Carla Monaco
Breakfast is courtesy of the
Dr. Howard Rappaport Memorial Lectureship Fund
ii
Icahn School of Medicine at Mount Sinai
Seventeenth Annual Child Health Research Day
Schedule of Events
April 16, 2015 – Hatch Auditorium
7:45-8:00 a.m.
Coffee and Tea
8:00-8:10 a.m.
Welcome and Introduction
Lisa M. Satlin, MD, Chair, The Jack and Lucy Clark Department of Pediatrics
Bruce D. Gelb, MD, Director, The Mindich Child Health and Development Institute
8:10-9:05 a.m.
Grand Rounds: The Dr. Howard Rappaport Memorial Lecture
“ Human Height and Weight: From Genetics to Biology ”
Joel N. Hirschhorn, MD, PhD
Concordia Professor of Pediatrics and Professor of Genetics, Harvard Medical School,
Director, Center for Basic and Translational Obesity Research, Boston Children’s Hospital, and
Senior Associate Member, Broad Institute
9:05-9:30 a.m.
Breakfast
9:30-11:30 a.m.
9:30-9:45 a.m.
9:45-10:00 a.m.
Plenary Presentations – Hatch Auditorium
Moderators: Megan Horton, PhD, MPH and Perry Sheffield, MD
Gender-Specific Associations between Placental Expression of Imprinted Genes
And Birth Weight
Maya Kappil, Jia Chen, Calvin Jara, Robert O. Wright, Rosalind J. Wright
Microbial Regulation of IgE Production in Early Life
Ana Belen Blazquez, Jeremiah Faith, Hugh Sampson, Cecilia Berin
10:00-10:15 a.m.
NICU-Based Phthalate Exposure and Neurodevelopmental Outcomes
Annemarie Stroustrup, Hilary Haimes, Jennifer Bragg, Ying Guo, Syam Andra,
Kurunthachalam Kannan, Chris Gennings
10:15-10:30 a.m.
Associations Between Telomere Length and Mitochondrial DNA Copy Number in Newborns
Thomas W. Church, Kelly J. Brunst, Calvin Jara, Andrea Baccarelli, Marco Sanchez Guerra,
Alexandra Dereix, Robert O. Wright, Rosalind J. Wright
10:30-10:45 a.m.
Epicutaneous Tolerance Induction for the Treatment of Colitis
David Dunkin, Zaruhi Hovhannisyan, Garabet Yeretssian, M. Cecilia Berin, Hugh Sampson
10:45-11:00 a.m.
Improving HPV Vaccination Rates through the Design and Implementation of a
Provider Education Module
Siri Sastry, Jennifer Chase, Maan Dela-Cruz, Elizabeth Garland, Kristin Oliver
11:00-11:15 a.m.
The Discrepancy in Classification of Obesity among Adolescents by Body Mass
Index vs. Body Composition
Meryam Shikara, Elizabeth Speidel, Margot Yopes, Izamar Gallardo, Christopher Ochner
11:15-11:30 a.m.
Cholesterol Affects Flow-Stimulated Cyclooxygenase-2 Expression and Prostanoid
Secretion in the Cortical Collecting Duct (CCD)
Yu Kevin Liu, Daniel Flores, Rolando Carrisoza-Gaytán, Rajeev Rohatgi
11:45 a.m.-12:45 p.m.
12:45-1:00 p.m.
Poster Session and Lunch
Guggenheim Pavilion Atrium
Poster Presentation Awards Ceremony
Presented by M. Cecilia Berin, PhD
iii
Icahn School of Medicine at Mount Sinai
Seventeenth Annual Child Health Research Day
Thursday, April 16, 2015
WELCOME
We welcome you to the 17th Annual Child Health Research Day at Mount Sinai! This event
aims to highlight the outstanding research activities of students, housestaff, clinical and
research post-doctoral fellows, research staff, social workers, nurses and junior faculty in the
Department of Pediatrics at Mount Sinai and our affiliates, as well as The Mindich Child
Health and Development Institute (MCHDI). The basic, translational, population-based and
clinical research, broadly related to the health and welfare of infants, children and
adolescents, presented in today’s plenary and poster sessions, exemplifies the commitment to
scientific discovery and scholarship central to our academic mission. The event provides a
unique opportunity for young investigators in the Department of Pediatrics and MCHDI to
share the results of their research with colleagues, and thereby discover new applications for
their work or identify potential future areas for collaboration. We thank you for attending and
congratulate all the participants on their accomplishments!
Lisa M. Satlin, MD
Chair, The Jack and Lucy Clark Department of Pediatrics
Bruce D. Gelb, MD
Director, The Mindich Child Health and Development Institute
iv
ORAL PRESENTATION INDEX
ABSTRACTS
PAGE #
Gender-Specific Associations between Placental Expression of Imprinted Genes And Birth
Weight - Maya Kappil, Jia Chen, Calvin Jara, Robert O. Wright, Rosalind J. Wright
1
Microbial Regulation of IgE Production in Early Life - Ana Belen Blazquez, Jeremiah Faith,
Hugh Sampson, Cecilia Berin
2
NICU-Based Phthalate Exposure and Neurodevelopmental Outcomes - Annemarie Stroustrup,
Hilary Haimes, Jennifer Bragg, Ying Guo, Syam Andra, Kurunthachalam Kannan, Chris Gennings
3
Associations Between Telomere Length and Mitochondrial DNA Copy Number in Newborns Thomas W. Church, Kelly J. Brunst, Calvin Jara, Andrea Baccarelli, Marco Sanchez Guerra,
Alexandra Dereix, Robert O. Wright, Rosalind J. Wright
4
Epicutaneous Tolerance Induction for the Treatment of Colitis - David Dunkin,
Zaruhi Hovhannisyan, Garabet Yeretssian, M. Cecilia Berin, Hugh Sampson
5
Improving HPV Vaccination Rates through the Design and Implementation of a
Provider Education Module - Siri Sastry, Jennifer Chase, Maan Dela-Cruz, Elizabeth Garland,
Kristin Oliver
6
The Discrepancy in Classification of Obesity among Adolescents by Body Mass Index vs.
Body Composition - Meryam Shikara, Elizabeth Speidel, Margot Yopes, Izamar Gallardo,
Christopher Ochner
7
Cholesterol Affects Flow-Stimulated Cyclooxygenase-2 Expression and Prostanoid
Secretion in the Cortical Collecting Duct (CCD) - Yu Kevin Liu, Daniel Flores,
Rolando Carrisoza-Gaytán, Rajeev Rohatgi
8
v
POSTER GUIDE & PRESENTATION INDEX
(To view all abstracts visit http://www.mssm.edu/departments-and-institutes/pediatrics)
ABSTRACTS
PAGE & POSTER #
(In alphabetical order)
Evaluation of Plasma Chemokines and Cytokines in the Setting of Egg Oral Immunotherapy (OIT) S. Albin, K. Fei, R.A. Wood, D.M. Fleischer, S.H. Sicherer, R.W. Lindblad, B.P. Vickery, A.H. Liu,
A.M. Scurlock, A.W. Burks, S.M. Jones, H. A. Sampson, M. C. Berin
9
Assessment of IgE Binding Profiles of Lentil Allergic Children; Similarity and Potential
Cross-Reactivity Between Dal Proteins - Doerthe A. Andreae, Galina Grishina, Cansin Sackesen,
Maria Dolores Ibáñez, Hugh A. Sampson
10
Swallowed Fluticasone is an effective and safe long-term maintenance therapy in Children with
Eosinophilic Esophagitis (EoE) - Doerthe A. Andreae, Matthew Hanna, Margret S. Magid,
Stefano Malerba, Emilia Bagiella, Mirna Chehade
11
Zinc Finger Protein 217 Regulates N6-methyladenosine Deposition in Embryonic Stem Cell Transcripts Francesca Aguilo, Fan Zhang, Ana Sancho, Serena Di Cecilia, Ajay Vashisht, Chih-Hung Chen,
Dung-Fang Lee, Farid Jahouh, Blanca Andino, Angel Roman, Sheryl R. Krig, Rong Wang,
Weijia Zhang, James A. Wohlschlegel, Martin J. Walsh
12
Arsenic and DNA Methylation: Using Zebrafish to Uncover the Mechanism of Arsenic Induced
Toxicity and Methylome Reprogramming - Kathryn Bambino, Jaime Chu, Kirsten Sadler
13
Functional Heterogeneity of Mast Cell Subsets Underlies Different Manifestations of Food Allergy Sara Benede, Cecilia Berin
14
The Relationship Between Self-Esteem and Intention of Contraception Use - Sari Bentsianov,
Angela Diaz, Anne Nucci-Sack, Christopher Ochner
15
The Role of the Kynurenine Pathway in Suicidality in Adolescent Major Depressive Disorder Kailyn A. L. Bradley, Julia A. C. Case, Omar Khan, Thomas Ricart, Amira Hanna, Carmen M. Alonso,
Vilma Gabbay
16
Evaluation of a Multidisciplinary Home Visiting Program for Children with Special Health Care Needs Maureen Braun, Elaine Lin, Susann Cortes, Sanite Theophile, Joseph Truglio
17
Prenatal Stress and Mitochondrial Function at the Maternal-Fetal Interface: Modification by Maternal
Antioxidant Status - Kelly J. Brunst, Calvin Jara, Chris Gennings, Andrea Baccarelli, Marco Sanchez Guerra,
Alexandra Dereix, Robert O. Wright, Rosalind J. Wright
18
Cell-Specific Regulation of BK Channel and WNK Kinases in Cortical Collecting Duct (CCD) by
Dietary K - Rolando Carrisoza, Arohan Subramanya, Marcelo Carattino, Thomas Kleyman, Lisa Satlin
19
Vision Screening Among Primary Care Clinic Patients - Lwbba Chait, Angeliki Makri, Gwen Raphan
20
Phenotypic Analysis of Peanut-Responsive T Cells at Baseline in Subjects Enrolled in CoFAR6, a
Randomized Placebo-Controlled Epicutaneous Immunotherapy (EPIT) Trial for the Treatment of Peanut
Allergy - David Chiang, A. Wesley Burks, Wendy Davidson, Peter Dawson, Alexander Grishin,
Alice Henning, Stacie M. Jones, Donald Y. M. Leung, Robert W. Lindblad, Andrew H. Liu,
Amy M. Scurlock, Scott H. Sicherer, Brian P. Vickery, Robert A. Wood, Hugh A. Sampson,
M. Cecilia Berin
21
vi
Associations Between Cumulative Maternal Stress During the Perinatal Period and Lung Function in
Children at Age 7 Years - Yueh-Hsiu Mathilda Chiu, Brent A. Coull, Harriet Fernandez, Sheldon Cohen,
Wayne J. Morgan, Robert O. Wright, Rosalind J. Wright
22
The Non-Diagnostic Ultrasound in Appendicitis: Is a Non-Visualized Appendix the Same As a Negative
Study? - Brian Cohen, Jordan Bowling, Peter Midulla, Edward Shlasko, Neil Lester, Henrietta Rosenberg,
Aaron Lipskar
23
Repurposing Small Molecule Drugs for Cytomegalovirus - Tobias Cohen, Thomas Gardner,
Domenico Tortorella
24
Factors Resulting in Deferral of Diagnostic Oral Food Challenges - Natalie Davis, Maureen Egan,
Scott H. Sicherer
25
Trends in Repeat Cow Milk sIgE Levels - Maureen Egan, Manish Ramesh, Tricia Lee, Jacob Kattan,
Julie Wang
26
Serum IgE Response to Itraconazole in Children with Severe Asthma with Fungal Sensitization:
A Pilot Study - Leah I. Elizondo, Angela J. Tsuang, David L. Goldman, Alfin G. Vicencio
27
A Novel Protocol for Characterizing Long Non-Coding RNAs in Autism Spectrum Disorders Nancy J. Francoeur, Robert Sebra, Dalila Pinto
28
Comparison of IgE Epitope Mapping by Peptide Microarray and a Novel Luminex-based Peptide
Assay - Gustavo Gimenez, Cansin Sackesen, Stephanie Schmidt, Robert C. Getts, Jing Lin,
George N. Konstantinou, Ebru Arik Yilmaz, Ozlem Cavkaytar, Ozge Soyer, Galina Grishina,
Hugh Sampson
29
Hyperosmolar Hyperglycemic State in a Pediatric Renal Transplant Patient with Medication-Induced
Diabetes - Marina Goldis, Elizabeth Burtman, Lindsey Waldman, Dennis Chia, Elizabeth Wallach,
Laura Castellanos Reyes, Hilary Hotchkiss, Robert Rapaport, Molly Regelmann
30
Mild Congenital Hypothyroidism: Persistence Beyond 3 Years - Marina Goldis, Molly Regelmann,
Elizabeth Burtman, Lindsey Waldman, Elizabeth Wallach, Robert Rapaport
31
How Does Age of Overweight & Obese Weight Status Onset Influence the Adolescent Dating Market? Lonna Gordon, Angela Diaz, Christopher Ochner
32
Oral Health Practices of an Inner City Cohort of Girls in East Harlem, New York - Loy Hagan,
Nancy Mervish, Susan L. Teitelbaum, Mary S. Wolff, the Breast Cancer and Environmental Research
Program
33
Screening for Anxiety and Distress in Children with Food Allergy and their Parents – Does Streamlined
Care Impact Utilization? - Jacqueline Helcer, Brianna Lewis, Melissa Rubes, Evan Wiley, Caitlin Shneider,
Scott H. Sicherer, Eyal Shemesh, Rachel A. Annunziato
34
Prenatal Exposure to a Mixture of Metals and Associations with Executive Function and Cognitive
Development - Megan K. Horton, Anny L. Bonilla, Katherine Svensson, Chris Gennings,
Deborah A. Cory-Slechta, Robert Wright
35
Gold-Standard Autism Assessment in an Ethnically and Racially Diverse Population - J. M. Jamison,
E. S. Fourie, M. Oliphant, P. M. Weinger, J. Krata, E. Holl, J. Shaoul, B. Hernandez, J.D. Buxbaum,
A. Kolevzon
36
Expression Profiles of Genes that Regulates the Cellular Respiration Are Associated with Intrauterine
Growth Restriction - Richard Jones, Elana Mystal, Juan Peña, Luca Lambertini
37
vii
Disruption in Placental Expression of Imprinted Genes is Associated with Birth Weight - Maya Kappil,
Luca Lambertini, Dylan Guerin, Benjamin Green, Carmen Marsit, Jia Chen
38
Soy Reactivity May be Better Identified by Component Testing with Gly m 8 than Traditional Testing
Methods - Jacob D. Kattan, Hugh A. Sampson
39
Parental Survey Study: Opinions of Informed Consent in Newborn Screening and Dried Blood Spot
Retention - Nicole R. Kelly, Dalia Chehayeb Makarem, Melissa P. Wasserstein
40
Changing Trends in Indications for Fetal Echocardiography: Impact on Referral Volume and Prenatal
Detection Rates of Congenital Heart Disease - Jonathan Komisar, Miwa Geiger, Shubhika Srivastava,
John Doucette, H. Helen Ko, Jay Shenoy, Rajesh Shenoy
41
Preseason Pediatrics: A Preclinical Hands-on Experience for Medical Students - Benjamin M. Laitman,
Scott Moerdler, Suzanne Friedman, Blair Hammond, Alefiyah Malbari, Kathleen Gibbs
42
Uncovering the Genetic Architecture of Congenital Heart Disease: Ebstein’s Anomaly - Kathryn B. Landy,
Bruce D. Gelb
43
Relationship Between Living Situation and Substance Use in an Urban Adolescent Population - Janet Lee,
Angela Diaz, Christopher Ochner
44
Variability of Repeat Egg sIgE Levels - Tricia D. Lee, Manish Ramesh, Jacob Kattan, Julie Wang
45
Discovering Thyroid Stimulating Hormone Receptor (TSHR) T-cell Epitopes in Autoimmune Thyroiditis Cheuk Wun Li, Francesca Menconi, Roman Osman, Chella David, Erlinda Concepcion, Yaron Tomer
46
Exploring the Associations Between microRNA Expression Profiles and Environmental Pollutants in
Human Placenta from the National Children’s Study (NCS) - Qian Li, Maya Kappil, An Li, PS Dassanyake,
Tom Darrah, Alan E. Friedman, Michelle R. Friedman, Luca Lambertini, Philip Landrigan, Chris J. Stodgell,
Kjersti M. Aagaard, Eric Schadt, Jeffrey Murray, Edward B. Clark, Nancy Dole, Jennifer Culhane,
James Swanson, Michael Varner, Jack Moye, Carol Kasten, Richard K. Miller, Jia Chen,
National Children’s Study Consortium
47
The Flavonoid 7, 4'- Dihydroxyflavone Inhibits MUC5AC Gene Expression, Production, and Secretion Via
Regulation of NF-κB, STAT6 and HDAC2 - Changda Liu, David Weir, Paula Busse, Nan Yang,
Zhenwen Zhou, Charles Emala, Xiu-Min Li
48
Visual Evoked Potentials in Autism Spectrum Disorder - Stacey Lurie, Paige M. Siper, Vance Zemon,
James Gordon, Joseph D. Buxbaum, Alexander Kolevzon
49
Surgical Treatment of Pediatric Craniofacial Fractures: A National Perspective - Benjamin B. Massenburg,
Paymon Sanati-Mehrizy, Peter J. Taub
50
Learning by Educating: Mastering Pediatric Core Competencies Through Simulation Case Development
and Implementation - Sheera Minkowitz, Keila Veiga, Sheemon Zackai
51
Remission Induction in Mixed Lineage T/Myeloid Leukemia with Clofarabine in Patients who Fail
ALL-type Therapy Followed by Hematopoietic Stem Cell Transplantation - Sheera Minkowitz,
Jaclyn Davis, Bruce Petersen, Birte Wistinghausen
52
A Longitudinal Approach to Developing Educators in Medicine: The Pediatric Resident Teaching Group Scott Moerdler, Suzanne Friedman, Benjamin Laitman, Alefiyah Malbari, Kathleen Gibbs, Blair Hammond
53
Mutants and Morphants: Can’t We All Just Get Along? - Shikha Nayar, Nataly Shtraizent, Jaime Chu
54
viii
Impact of Pasteurization on the Oligosaccharide Concentration of Human Breast Milk - Sarah A Nitka,
Aimee R Herdt, Javier Pacheco-Quinto, Caryn Peters, Nancy Mejias-Cepeda, Annemarie Stroustrup,
Robert D. Voyksner, Denise C Hassinger
55
Bacterial Culture Result in Pediatrics at Elmhurst Hospital Center in 2014 - Chikara Ogimi, Shanna Kowalsky,
David Rhee
56
Genetic and Allele-Specific Expression Analysis of Congenital Heart Disease - Neil Patel, Andrew J. Sharp,
Bruce D. Gelb
57
Dilated Intercellular Spaces and Increased Esophageal Permeability in Eosinophilic Esophagitis Mary Ellen Riffle, Ronald E. Gordon, Mirna Chehade
58
Esophageal Granular Cell Tumor and Eosinophilic Esophagitis: More than a Coincidence? Mary Ellen Riffle, Alexandros D. Polydorides, Jessica Niakan, Mirna Chehade
59
Modeling Multifocal Atrial Tachycardia and Hypertrophic Cardiomyopathy in Costello Syndrome
Using Patient-Derived iPSCs - Nelson A. Rodriguez, Rebecca Josowitz, Salomeh M. Salari,
Bruce D. Gelb
60
Transition of IBD Care: Assessment of Transition Readiness Factors and Disease Outcomes
in a Young Adult Population - Danya Rosen, Rachel Annunziato, Eyal Shemesh, Aaron Lipskar,
Jean Fred Colombel, Marla Dubinsky, Keith Benkov
61
Prenatal Arsenic Exposure and Childhood Blood Pressure at 4-6 Years of Age - Alison P. Sanders,
Katherine Svensson, Chitra Amarasiriwardena, Priyanka Basnet, Adriana Mercado-García,
Lourdes Schnaas, Andrea A. Baccarelli, Martha M. Tellez-Rojo, Chris Gennings, Lisa M. Satlin,
Robert O. Wright
62
Trends in Soy sIgE Levels in Food Allergic Patients - Edith Schussler, Manish Ramesh, Jacob Kattan,
Julie Wang
63
Follow-Up After a Mental Health Hospital Discharge - Sandeep Sharma, Barbara Rabin Fastman,
Eyal Shemesh, Amy Balbierz, Lawrence C. Kleinman
64
The Relationship between Anxiety and Tic Severity Revisited: Beyond DSM Classification Zoey A. Shaw, Julia A. C. Case, Laura Ibanez Gomez, Amira Hanna, Barbara J. Coffey, Vilma Gabbay
65
Ambient Ozone Exposure and Children’s Acute Asthma in New York City: A Case-Crossover Analysis Perry E. Sheffield, Jiang Zhou, Jessie Loving-Carr Shmool, Jane E. Clougherty
66
Parent / Child Perceptions of Children’s Readiness to Self-Inject Epinephrine - Caitlin Shneider,
Evan Wiley, Brianna Lewis, Melissa Rubes, Eyal Shemesh, Rachel A. Annunziato, Scott H. Sicherer
67
A Novel Negative Feedback Loop of p53 and Mannose Phosphoisomerase (Mpi) is Essential in
Development and Cancer - Nataly Shtraizent, Shikha Nayar, Jaime Chu
68
Sophora Flavescens Alkaloid-Rich Fraction Induction of IL-10 Production and Prevention of
Dexamethasone Suppression of Asthma Patient PBMC IL-10 Production is Associated with Altered
DNA Methylation at foxp3 Gene Promoter - Ying Song, Li Xin Wang, Changda Liu, Lauren Lisann,
David Weir, Ching-feng Huang, Paula J. Busse, Xiu-Min Li
69
ASHMI, But Not Corticosteroid Treatment Restores Maternal Allergen Long-Term Tolerance and
Prevents Offspring Asthma Risk via Epigenetic Modulation - Kamal D. Srivastava, Ying Song,
Jia Chen, Xiu-Min Li
70
ix
Use of Pediatric Fundamental Critical Care Support (PFCCS) to Improve Pediatric Resident Confidence
in Acute Care - Sheemon Zackai, Cecilia Thompson
71
Epicutaneous but not Oral Immunotherapy Induces Antigen-Specific Gastrointestinal Tregs and Protects
against Food-Induced Anaphylaxis - Leticia Tordesillas, Lucie Mondoulet, Pierre-Henri Benhamou,
Hugh Sampson, Cecilia Berin
72
Early Liquid Protein Supplementation of Human Milk in Very Low Birth Weight Infants - Megan Tracy,
Robert Green, Ian Holzman, Andrea Weintraub
73
Comparison of Baseline Characteristics between Adolescents Recruited in Community Versus Clinical
Sites in a Pilot Diabetes Prevention Study - Nita Vangeepuram, Kenya Townsend, LaTanya Phelps-Waldropt,
Guedy Arniella, Carol R. Horowitz
74
Title: Quality Assurance: Streamlining Chemotherapy Admissions from Clinic - Keila Veiga, Victoria Shakhin,
Rose Morales, Christine Angrisani, Jaclyn Davis, Birte Wistinghausen
75
Recipe for a Healthy Lifestyle: An Obesity Prevention Program for Hispanic Families in East Harlem Lindsey Waldman, Marilyn Figueroa, Heather Mitchell, Robert Fallar, Leora Mogilner
76
Fetoplacental Environment and the Origin of the Infant Gut Microbiome: A Twin Study - Ryan W. Walker,
Ruth J.F. Loos
77
Feature Tracking-Derived Longitudinal and Circumferential Peak Systolic Strain vs. Late Gadolinium
Enhancement in Troponin-Positive Myocarditis: a Cardiac Magnetic Resonance Case- Control Study Justin Weigand, James C. Nielsen, Partho P. Sengupta, Javier Sanz, Shubhika Srivastava, Santosh Uppu
78
Approach to Food Allergy by Non-Specialty Providers - Kate Welch, Julie Wang
79
Early Life Housing Stress and Urban Childhood Asthma - Lauren Zajac, Rosalind Wright,
Marina Jacobson Canner, Harriet Fernandez
80
Food Allergies in a Pediatric Clinic – Interventions to Improve Management - Ari Zelig,
Ilana Harwayne-Gidansky, Allison Gault, Julie Wang
81
The Chinese Herbal Formula Seasonal Tea Alleviated Rhinitis and Conjunctivitis Symptoms in a
murine Ragweed Allergy Model - Lianzhu Zhang, Ying Song, Banghao Liang, Xiu-Min Li
82
x
POSTER GUIDE & PRESENTATION INDEX
(To view all abstracts visit http://www.mssm.edu/departments-and-institutes/pediatrics)
ABSTRACTS
PAGE & POSTER #
(In order by affiliation)
Adolescent Medicine
7, 15, 32, 44
Allergy & Immunology
2, 9, 10, 11, 14, 21, 25, 26, 29, 39, 45, 48, 58,
59, 63, 69, 70, 71, 72, 79, 81, 82
Behavioral & Developmental
34, 67
Cardiology
41, 43, 57, 60, 78
Child & Adolescent Psychiatry
36, 49
Critical Care
51
Endocrinology
30, 31, 46
Gastroenterology & Hepatology
5, 12, 13, 54, 61, 68
General Pediatrics
17, 20, 42, 53, 56, 76
Genetics
28, 40
Health Evidence & Policy
64, 74
Hematology Oncology
52, 75
Microbiology
24
The Mindich Child Health & Development Institute
2, 9, 10, 11, 14, 16, 18, 19, 21, 22, 25, 26, 28,
29, 34, 35, 37, 38, 39, 43, 45, 46, 47, 48, 54,
57, 60, 62, 63, 64, 65, 67, 68, 69, 70, 71, 72,
77, 79, 80, 81, 82
Nephrology
8, 19
Newborn Medicine
3, 55, 73
Preventive Medicine
1, 4, 6, 18, 22, 33, 35, 37, 38, 47, 62, 66, 77,
80
Pulmonology
27
Surgery
23, 50
xi
Gender-Specific Associations between Placental Expression of
Imprinted Genes and Birth Weight
Author Name(s): Maya Kappil, Jia Chen, Calvin Jara, Robert O. Wright, Rosalind J. Wright
Department: Preventive Medicine
Division: Environmental Health
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: The necessity of the carefully-regulated balance in the expression of imprinted genes for fetal-placental
development has been long established. Yet, few human studies have assessed associations between imprinted gene
expression in placenta and fetal growth outcomes. Evolving data also show differential placental gene expression
based on fetal sex.
Hypothesis: We hypothesized that placental imprinted gene expression will be associated with birth weight in a sexdependent manner.
Methods: Placental samples were obtained from newborns (n=68 girls, n=82 boys) from the PRogramming of
Intergenerational Stress Mechanisms (PRISM) study. The expression profile was generated using a custom-designed
code-set of 150 established and putative imprinted genes (Nanostring technologies, Seattle, WA). Differential
expression of genes across birth-weight z-score categories (≤10%, 11-89%, ≥90%) were determined based on an FDRcorrected ANOVA. Linear regression models were adjusted for batch, gestational age, maternal age, maternal race,
maternal education, maternal BMI, and maternal smoking status.
Results: The sample was ethnically mixed (33% African American, 8% Latino), and mean maternal age was 31.4 +
5.1 years. The expression level of DDC, MAGEL2, and PRIM2 were observed to be significantly associated with birth
weight z-score in a sex-specific manner (pinteraction<0.10). A decrease in birth weight z-score was observed relative to
an increase in DDC expression levels among girls (p=0.03), while an increase in birth weight z-score relative to an
increase in expression levels of MAGEL2 (p=0.03) and PRIM2 (p=0.01) was observed among boys.
Conclusion: We found 3 imprinted loci associated with birth weight in a sex-specific manner.
1
Microbial Regulation of IgE Production in Early Life
Author Name(s): Ana Belen Blazquez1, Jeremiah Faith2, Hugh Sampson1, Cecilia Berin1
Department(s): 1 Pediatrics, 2 Genetics and Genomic Sciences
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Changes in gastrointestinal microbiota have been suggested to drive the increasing prevalence of
food allergy.
Hypothesis: Our aim was to determine the impact of intestinal microbiota on peanut allergy using adjuvant-free
sensitization and mice with humanized microbiota.
Methods: Mice were treated with antibiotics (ABX) for 4 weeks. Germ-free (GF) mice were colonized with fecal
microbiota from a healthy pediatric donor. IgE was measured by ELISA, blood eosinophils and basophils by flow
cytometry, and cytokine expression in Peyer’s patches (PP) by qPCR. Mice received 100 mg of ground peanut
orally once per week for 6 weeks.
Results: ABX treatment immediately after weaning induced a significant increase in total serum IgE, and surface
IgE on basophils. Circulating eosinophils were also significantly increased. IL-4 was significantly upregulated in
the PP after ABX-treatment of young mice. Susceptibility of IgE and eosinophils to modulation by ABX was not
observed in 5 week old mice. Despite this increase in non-specific parameters of allergy, ABX-treated mice were
less susceptible to anaphylaxis after high dose peanut feeding and challenge (drop in body temperature -1.98 ±1.58
(control) vs -0.32 ± 0.96 (ABX), p<0.005). GF-mice had progressively increasing levels of IgE with age, which
were significantly suppressed by human intestinal microbiota transplant. GF mice were resistant to peanut induced
anaphylaxis (0 of 8), while a subset of mice with a humanized microbiota developed anaphylaxis (3 of 5).
Conclusions: ABX-treatment in early-life leads to a Th2-milieu in the PP and elevated IgE and circulating eosinophils.
However, we found that microbiota is required for sensitization and anaphylaxis to peanut. This finding was replicated
in GF mice with ‘humanized’ microbiota, and suggests that there are microbial factors that promote peanut allergy.
2
NICU-Based Phthalate Exposure and Neurodevelopmental Outcomes
Author Names: Annemarie Stroustrup, Hilary Haimes, Jennifer Bragg, Ying Guo, Syam Andra,
Kurunthachalam Kannan, Chris Gennings
Department(s): Pediatrics, Preventive Medicine
Division: Newborn Medicine
Institution Affiliation(s): Icahn School of Medicine at Mount Sinai, Stamford Hospital, Stamford, CT,
Wadsworth Center, NY State Department of Health and SUNY at Albany
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Each year in the United States, over 300,000 newborns are cared for in a neonatal intensive care unit
(NICU) where they are exposed to a chemical-intensive hospital environment. In utero phthalate exposure at this point
in development can alter behavior and motor outcomes in healthy fetuses. Neurodevelopmental disorders among NICU
grads are incompletely predicted by degree of prematurity or neonatal illness. The relationship between NICU-based
phthalate exposure and neurodevelopmental outcomes has not previously been explored.
Hypothesis: (1) Exposure to medical materials used in NICU care is associated with phthalate exposure. (2) Phthalate
exposure during the NICU hospitalization impacts neurodevelopment at NICU discharge.
Methods: We conducted a prospective cohort study of 81 preterm infants from birth until NICU discharge. Exposure
to specific medical materials was recorded daily, serial urine specimens were collected, and the NICU Network
Neurobehavioral Scale (NNNS) was performed at discharge. We used weighted quartile sum regression to evaluate the
association between exposure to medical equipment and urinary biomarker levels, as well as between exposure to
phthalate mixtures and NNNS performance. Preliminary analysis of data from 20 infants and 1 NNNS subscale is
currently available, but data from all 81 infants will be available for final presentation.
Results:
Association between WQS Index of 10
phthalate monoesters and the NNNS
Quality of Movement subscale adjusted
for covariates (n=15, p=0.126)
Exposure sources for preliminary
analyses of source scores correlated
with the WQS index (n=20)
Source category
Respiratory support
Feeding supplies
IV Tubing
Medications
Crib / Isolette
Phototherapy
Blood transfusion
R (P value)
0.40 (p=0.079)
0.10 (p=0.664)
0.24 (p=0.318)
0.20 (p=0.403)
0.34 (p=0.141)
0.32 (p=0.164)
0.49 (p=0.029)
Conclusions: Preliminary analysis confirms the known association between blood transfusion and phthalate exposure.
We also identify respiratory support equipment as a probable novel source of phthalate exposure. NICU-based
exposure to phthalates may be associated with poorer performance on the NNNS Quality of Movement subscale at
NICU discharge.
3
Associations Between Telomere Length and Mitochondrial
DNA Copy Number in Newborns
Author Name(s): Thomas W. Church1, Kelly J. Brunst1, Calvin Jara1, Andrea Baccarelli3, Marco Sanchez Guerra3,
Alexandra Dereix3, Robert O. Wright1,2,6, Rosalind J. Wright1,2,6
Department(s): 1Pediatrics; 2Preventive Medicine
Division: Pulmonary
Institution Affiliation(s): Icahn School of Medicine at Mount Sinai, 3Department of Environmental Health, Harvard
T. H. Chan School of Public Health, Boston MA
Institute Affiliation: 6The Mindich Child Health and Development Institute
Introduction: Accelerated biological aging may begin at conception due to feedback between oxidative stress (OS),
telomere dysfunction and mitochondrial decline, with a central role of mitochondria as an integrator of the oxidative
stress response. Associations among telomere length (TL) and mitochondrial decline, biomarkers of aging, have not
been examined at the maternal-fetal interface in human studies.
Hypothesis: Telomere length and mitochondrial DNA copy number (mtDNAcn) will be positively correlated in cord
blood.
Methods: Analyses included 130 newborns from a racially diverse population (47% white, 32% black, 9% Hispanic,
and 12% other) with lower socioeconomic status (52% mothers with < high school education). Mean maternal age was
31.4 + 5.1 years. Cord blood biomarkers included log transformed mtDNAcn assessed by quantitative polymerase
chain reaction (Q-PCR) and leukocyte TL assayed using real-time PCR. Associations were examined using Pearson
correlations and multivariable linear regression models adjusting for confounders.
Preliminary results: Cord blood mtDNAcn was positively associated with TL (r=0.21, p=0.008). In multivariable
linear regression models, increased TL was associated with higher mtDNAcn (β=0.31, p=0.02) adjusting for maternal
age, race, and education level.
Conclusion: This is the first human study linking increased leukocyte TL with higher mtDNA copy number in cord
blood. These findings are consistent with an evolving understanding of the links between DNA damage, telomere
biology, and mitochondrial biogenesis that may begin in utero and influence disease development. Future research
will investigate the role that environmentally-induced oxidative stress plays in this relationship.
4
Epicutaneous Tolerance Induction for the Treatment of Colitis
Author Name(s): David Dunkin, Zaruhi Hovhannisyan, Garabet Yeretssian, M. Cecilia Berin,
Hugh Sampson
Department: Pediatrics
Division: Gastroenterology and Hepatology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Crohn’s disease patients have a defect in inducing T-regulatory cells(Treg) via the gut. When Tregs are
generated externally in response to food antigen and infused into patients, they suppress inflammation in Crohn’s via
bystander suppression.
Hypothesis: We hypothesized that Tregs could be induced by applying antigen to the skin, and after migration to the
gut could block inflammation via bystander suppression.
Methods: Mice were exposed epicutaneously daily for 5 days to ovalbumin(OVA). To determine if exposure blocked
T-effector responses, mice were immunized with OVA, and cytokine production by draining lymph nodes (LN) was
assessed by ELISA. Treg development in the MLN, spleen and intestines were determined. Tregs from skin draining
LN were checked for suppression of colitis in the T-cell transfer model. To determine if epicutaneous tolerance
induction abrogated colitis, mice were epicutaneously exposed to OVA, gavage fed OVA to induce Treg homing to the
gut, and colitis was induced with dextran sodium sulfate (DSS) or S. typhimurium. Weight loss and colonic
inflammatory cytokine production were assessed.
Results: Epicutaneous exposure to OVA induced tolerance with suppression of OVA-specific IFN-γ. OVA exposure
induced proliferation of OVA-specific Tregs in the spleen, MLN, and intestines. Tregs from skin draining LNs
suppressed the development of colitis. In both colitis models, prior epicutaneous OVA exposure followed by oral OVA
decreased colonic IFN-γ and TNF-α production (p<0.05).
Conclusions: Epicutaneous exposure induces Tregs, which migrate to the gut and suppress inflammation.
Epicutaneous tolerance induction has potential as a treatment for Crohn’s disease and warrants further study.
5
Improving HPV Vaccination Rates through the
Design and Implementation of a Provider Education Module
Author Name(s): Siri Shastry, Jennifer Chase, Maan Dela-Cruz, Elizabeth Garland, Kristin Oliver
Department(s): Pediatrics, Preventive Medicine
Division(s): General Pediatrics, General Preventive Medicine
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: HPV vaccination rates have lagged behind other adolescent vaccination rates in New York City and
nationwide. Previous studies have shown that deficiencies in provider knowledge and provider attitudes/practices may
cause lower HPV vaccination uptake.
Hypothesis: An educational module about HPV vaccination targeted toward providers will improve provider
knowledge, practices and attitudes as well as vaccination rates.
Methods: HPV vaccination rates from 2008-2012 and 2009-2013 at Mount Sinai clinics/practices that serve children
and adolescents were determined via analysis of Epic and the Citywide Immunization Registry. Literature review was
used to formulate: (1) a 30-minute Power Point educational module and (2) a 14-question survey of knowledge,
attitudes and practices. This survey was administered to General Pediatrics and Triple Board residents a week before
module presentation. 3 months after module presentation, the survey was re-administered.
Results: On the pre-module survey, residents reported increased comfort initiating discussions about HPV vaccination
with parents of older patients (9-10 vs. 11 vs. 14 year olds p < .001) and with parents of female versus male patients
ages 11 and older (p = .025). At 3-month follow-up, residents were significantly more likely to report taking further
steps to discuss concerns when parents initially refused vaccination (p < .05). Overall, adolescent vaccination rates
showed statistically significant increases, but there was no unique significant increase in vaccination rates attributable
to the educational module.
Conclusions: A provider education module significantly increased provider likelihood to address parental concerns
after initial vaccine refusal, but did not significantly impact HPV vaccination rates.
6
The Discrepancy in Classification of Obesity among Adolescents by Body Mass
Index vs. Body Composition
Author Name(s): Meryam Shikara, Elizabeth Speidel, Margot Yopes, Izamar Gallardo,
Christopher Ochner
Department: Pediatrics
Division: Adolescent Health
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Criticism has been raised about the classification of obesity via body mass index (BMI). This study
tested the discrepancy between the classification of obesity via BMI or percentile, as appropriate by age, vs. body
composition.
Hypothesis: The prevalence of obesity will differ when classified using BMI vs % body fat.
Methods: Data was collected from 577 adolescent & young adult (88% female) patients at the MSAHC. Ss age
ranged from 13-24 (M = 19.7 ± 2.4) y. and 97% were Hispanic and/or African American. Chi square analyses were
used to test classification differences using BMI [percentile] vs. % body fat measured via bioelectric impedance
analysis.
Results: For males, mean % body fat was 16.5 ± 8.0 (range = 6.0 to 46.4), with a mean age of 20.2 ± 2.8 y. For
females, mean % body fat was 30.4 ± 9.2 (range = 6.4 to 56.6), with a mean age of 19.6 ± 2.3 y. Classification using
BMI, or BMI percentile as appropriate by age, vs. body fat % resulted in significant differences in the number of
adolescents with obesity (19.1 vs. 22.3% respectively; chi square = 65.8, p <
0.0005). For adolescents (<20y), the underestimation of obesity was even greater using BMI percentile vs. body fat
% (19.5 vs. 25%; chi square = 200.8, p < 0.0005).
Conclusion: The current classification system may underestimate the prevalence of obesity, particularly in
adolescents, which may have important clinical implications.
7
Cholesterol Affects Flow-Stimulated Cyclooxygenase-2 Expression and Prostanoid
Secretion in the Cortical Collecting Duct (CCD)
Author Name(s): Yu Kevin Liu, Daniel Flores, Rolando Carrisoza-Gaytán, Rajeev Rohatgi
Department(s): Pediatrics, Medicine
Division(s): Pediatric Nephrology, Adult Nephrology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Hypertension (HTN) is associated with hypercholesterolemia, but how cholesterol contributes to HTN
is unknown. Recent evidence demonstrates that short-term dietary cholesterol ingestion induces ENaC-dependent Na
absorption with a subsequent rise in blood pressure (BP), implicating cholesterol in salt-sensitive eHTN. Prostaglandin
E2 (PGE2), an autocrine/paracrine molecule, is induced by flow in endothelia to vasodilate the vasculature and inhibit
ENaC-dependent Na absorption in the renal collecting duct (CD), which reduce BP.
Hypothesis: We hypothesize that cholesterol suppresses flow-mediated cyclooxygenase-2 (COX-2) expression and
PGE2 release in the CD which affects Na absorption.
Methods: PGE2 and COX-2 are measured in CD cells and dissected CDs after manipulating cholesterol.
Results: Cortical CDs (CCDs) were microperfused at 0, 1, and 5 nL/min.mm and PGE2 release measured. Secreted
PGE2 was similar between no and low flow CCDs; but, PGE2 was ~4 fold greater in high flow (p<0.05) CCDs. Next,
mice were fed either a 0% or 1% cholesterol diet, injected with saline to generate high urine flow rates, and CCDs
microdissected for PGE2 secretion. CCDs isolated from cholesterol fed mice secreted less PGE2 and had a lower
PGE2 generating capacity than CCDs isolated from control fed mice, implying cholesterol repressed flow induced
PGE2 synthesis. Cholesterol extraction in a CD cell line induced COX-2 expression and PGE2 release while
cholesterol incorporation, conversely suppressed their expression. Moreover, FSS and cholesterol extraction induced
COX-2 protein abundance via p38 dependent activation.
Conclusion: Thus, cellular cholesterol composition affects biomechanical signaling which, in turn, affects FSSmediated COX-2 expression and PGE2 release via a p38 dependent mechanism.
8
Evaluation of Plasma Chemokines and Cytokines in the Setting
of Egg Oral Immunotherapy (OIT)
Author Name(s): S. Albin, K. Fei, R.A. Wood, D.M. Fleischer, S.H. Sicherer, R.W. Lindblad, B.P. Vickery, A.H. Liu,
A.M. Scurlock, A.W. Burks, S.M. Jones, H. A. Sampson, M. C. Berin
Department: Pediatrics
Division: Allergy and Immunology
Institution Affiliation(s): Icahn School of Medicine at Mount Sinai, Johns Hopkins University School of Medicine,
National Jewish Health, University of North Carolina, University of Arkansas, EMMES
Corporation
Institute Affiliation: The Mindich Child and Health Development Institute
Introduction: Plasma cytokine markers have not been evaluated in the setting of oral immunotherapy (OIT) for food
allergy.
Hypothesis: We hypothesized that those who achieve sustained unresponsiveness through OIT will have decreased
Th2-associated and increased Th-1 associated chemokines compared to baseline, as well as compared to those who do
not achieve sustained unresponsiveness.
Methods: Plasma samples were obtained from subjects who participated in CoFAR3, an OIT trial for egg allergy.
Chemoattractants of Th1 cells (CXCL9, 10, 11) and Th2 cells (CCL1, 17, 22) as well as Th2-promoting cytokines
(TSLP, IL-33) were measured by multiplex assay at baseline and after 22 months of treatment.
Results: Plasma was available for 55 subjects (15 placebo, 40 OIT) at baseline and 51 subjects at 22 months (12
placebo, 39 OIT). CCL1, 17, 22 and CXCL9, 10, and 11 were detectable in all samples at baseline, while TSLP and
IL-33 were detectable in a subset of samples. Spearman rank correlation showed significant positive correlation
between cytokines and chemokines with overlapping or related function (CCL17 and 22 (rs=0.427, p=4.8x10-6), TSLP
and IL-33 (rs=0.72, p=6.4x10-18), CXCL10 and CXCL11 (rs=0.51, p=2.7x10-8)). There were no significant differences
between 0 and 22 months in any of the chemokines/cytokines in either placebo or OIT group, and no significant
association of any of these measures with clinical outcome of desensitization or tolerance.
Conclusions: In this study, chemokines and cytokines show significant correlation according to functional groupings
(Th1, Th2, and Th2-promoting), suggesting common regulation, but are not significantly altered by OIT.
9
Assessment of IgE Binding Profiles of Lentil Allergic Children; Similarity and
Potential Cross-Reactivity Between Dal Proteins
Author Name(s): Doerthe A Andreae¹, Galina Grishina¹, Cansin Sackesen¹،², Maria Dolores Ibáñez³,
Hugh A Sampson¹
Department(s): ¹Pediatrics, ³Allergy
Division: ¹Allergy and Immunology
Institution Affiliation(s): ¹Icahn School of Medicine at Mount Sinai ²Hacettepe University School of Medicine,
Department of Pediatric Allergy, Ankara, Turkey;
³Department of Allergy, Niño Jesús University Hospital, Madrid, Spain
Institute Affiliation(s): The Mindich Child Health and Development Institute, Jaffe Food Allergy Institute
Introduction: Lentils and dal proteins, seeds of edible legumes, are a major protein source in Mediterranean and Asian
countries and are increasingly being consumed in the westernized world. Tolerance and sensitization varies among
allergic individuals.
Hypothesis: IgE binding profiles, similarity and potential cross-reactivity between dal proteins, lentil, chick pea and
peanut and clinical reactivity help assess clinical implications and guide recommendations.
Methods: Green lentil, toor dal, mung dal, urad dal, chana dal, mooth dal, masoor dal, chickpea, and peanut extracts
were prepared and evaluated by immunoblotting. Sera from lentil allergic children (IgE >0.35 kUA/L) and a negative
control were used. Clinical data, IgE levels and binding patterns were compared among patients. Sequence similarity
and consensus was compared between lentil (Lenc1), chickpea provicilin and peanut (Arah1); and lentil (Lenc3) and
peanut (Arah9).
Results: Banding patterns and IgE binding patterns of lentil allergic patients showed similarity among taxonomically
and phenotypically similar dal proteins (Mong Dal (Vigna aconitifolia) and Mooth Dal (Vigna mungo/ radiata); Urad
Dal and Toor Dal; Chana Dal and Chickpea).
Sequence comparison between Lenc1 and Chickpea provicilin revealed Identity 47.3 % and Consensus 57.1% with
>90% identity at Lenc1 IgE binding epitopes. Lenc1 and Arah1 showed Identity 33.4 % Consensus 42.4 %. Lenc3 and
Arah9 (LTP) showed Identity 52.5 % and Consensus 61.9%.
Conclusions: Similar binding patterns among selected dal proteins point to high identity at the protein level making
evaluation of IgE binding to discriminate clinical reactivity difficult. Clinical cross-reactivity is likely and has to be
evaluated in more detail.
10
Swallowed Fluticasone is an Effective and Safe Long-Term Maintenance Therapy in
Children with Eosinophilic Esophagitis (EoE)
Author Names: Doerthe A Andreae1, Matthew Hanna2, Margret S Magid2, Stefano Malerba3, Emilia Bagiella3,
Mirna Chehade1
Departments: 1Pediatrics, ²Pathology, ³Population Health Science and Policy
Division: 1 Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Swallowed topical corticosteroids are effective in the treatment of EoE in children. Chronic use of
swallowed fluticasone has not been studied.
Hypothesis: Long-term use of swallowed fluticasone leads to sustained reduction in esophageal eosinophils and
endoscopic and clinical improvement in children with EoE.
Methods: This is an open-label, prospective, single-center study of long-term swallowed fluticasone. Pediatric
patients with active EoE (esophageal symptoms+esophageal eosinophils 15/HPF despite PPI therapy) seen June
2006-August 2012 were offered fluticasone. Clinical, endoscopic and histological assessments were performed at
baseline then at 2-12 months. If histological remission was seen, fluticasone was continued with clinical follow-ups
every 4 months, and endoscopic and histological follow-ups yearly. Clinical scores (from 9 symptoms), endoscopic
scores (6 features), and histological scores (6 features) were derived. Median scores were compared over 4 time
intervals: <4 months, 2 months-1 year, 1-2 years, and >2 years. Growth and adverse effects were monitored.
Results: 54 children were enrolled. Mean follow-up was 20.4 months, longest was 5.7 years. Esophageal eosinophils
significantly dropped at follow-up time intervals compared to baseline (p <0.01). Histological and endoscopic scores
significantly improved at all follow-ups (p<0.01-0.03). Symptoms also improved (all p<0.05 except at >2 years:
p=0.05). Asymptomatic esophageal candidiasis, seen in 3 children, resolved with anti-fungal therapy. Height and
weight Z-scores followed expected growth curves.
Conclusion: To our knowledge, this is the first pediatric study to demonstrate that swallowed fluticasone is effective
as a long-term maintenance therapy of EoE for up to 5.7 years, without growth impediment or serious side effects.
11
Zinc Finger Protein 217 Regulates N6-methyladenosine Deposition in
Embryonic Stem Cell Transcripts
Author Name(s): Francesca Aguilo, Fan Zhang, Ana Sancho, Serena Di Cecilia, Ajay Vashisht,
Chih-Hung Chen, Dung-Fang Lee, Farid Jahouh, Blanca Andino, Angel Roman,
Sheryl R. Krig, Rong Wang, Weijia Zhang, James A. Wohlschlegel &
Martin J. Walsh
Department(s): Pediatrics, Structural and Chemical Biology, Genetics and Genomic Sciences
Institution: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Embryonic stem cell (ESC) maintenance and somatic cell reprogramming require the wellcoordinated integration of epigenomic and epitranscriptomic networks to function. Zinc finger protein 217
(ZNF217) is a chromatin organizer that has been associated with several cancers. However, the role for this
transcription factor in normal cellular processes remains unknown.
Hypothesis: We hypothesize that Zfp217 is fundamental for instructing pluripotency through epigenetic
and epitranscriptomic regulation of pluripotency factors such as Nanog, Klf4, Myc and Sox2.
Results: We identified an unexpected and novel developmental function for murine Zfp217 in directly
activating the transcription of Nanog, Sox2, Klf4, Myc. Furthermore, Zfp217 directs N6- methyladenosine (m6A)
deposition at these transcripts through m6A methyltransferase-like 3 (Mettl3) interaction. Loss of Zfp217
decreases pluripotency factors expression accompanied with a global increase of m6A RNA methylation
that compromise self-renewal and somatic cell reprogramming, leading to spontaneous differentiation.
Conclusions: Collectively, these novel aspects of Zfp217 fundamentally shift our view of how a transcription
factor can tightly couple gene transcription to m6A epigenetic modification of RNA to insure the execution of
the pluripotency program during early embryonic development.
12
Arsenic and DNA Methylation: Using Zebrafish to Uncover the Mechanism
of Arsenic Induced Toxicity and Methylome Reprogramming
Author Name(s): Kathryn Bambino, Jaime Chu, Kirsten Sadler
Department(s): Preventive Medicine, Pediatrics, Developmental & Regenerative Biology
Division: Gastroenterology and Hepatology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Exposure to inorganic arsenic is a major public health concern with far reaching effects: prenatal and
childhood exposure elevates the risk of mortality and cancer in childhood, and the risk of adverse health outcomes after
exposure persists throughout life. Despite its rank as the #1 toxin on the ATSDR watch list, the mechanism underlying
the effects of arsenic remains virtually unknown. While some studies report that arsenic exposure can result in loss of
DNA methylation, no studies have examined specific biochemical and epigenetic changes and outcomes associated
with arsenic exposure in a whole animal system.
Hypothesis: Arsenic toxicity in zebrafish embryos is caused by DNA hypomethylation.
Methods: We analyzed global DNA methylation levels by slot blot and immunofluorescence staining and will assess
changes in methylation at specific loci by methylation-specific PCR and reduced representation bisulfite sequencing
(RRBS).
Results: We have established a zebrafish model to investigate the mechanism of arsenic toxicity. Zebrafish embryos
express trivalent arsenic specific methyltransferase (As3mt) and are susceptible to arsenic toxicity. Early exposure to
inorganic arsenic caused specific phenotypes beginning at 4 days post-fertilization, including reduced liver size. We
also observed lower levels of global DNA methylation in arsenic-exposed embryos at 24 hours post-fertilization by slot
blot and immunofluorescence staining using an antibody that recognizes 5-methylcytosine.
Conclusions: Preliminary results suggest reduced levels of methylation in arsenic treated zebrafish embryos compared
to control. Further studies will enable us to identify functional links between arsenic metabolism, alterations to the
methylome, and arsenic toxicity.
13
Functional Heterogeneity of Mast Cell Subsets Underlies
Different Manifestations of Food Allergy
Author Name(s): Sara Benede, Cecilia Berin
Department: Pediatrics
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Mast cells are key effector cells of allergic reactions that release pre-formed and rapidly synthesized
mediators after cross-linking of surface IgE by allergen. Mast cells are classified into mucosal (MMC) and connective
tissue (CTMC) mast cells, showing different profiles of protease expression. The function of these different mast cell
subsets in food allergy remains unknown.
Hypothesis: We hypothesized that MMC and CTMC could contribute to different clinical manifestations of food
allergy.
Methods: We evaluated MMC activation by release of the protease MMCP-1, and CTMC by MMCP-7, using two
different mouse models of food allergy with gastrointestinal or anaphylaxis symptoms after oral ovalbumin (OVA)
challenge. Anaphylaxis severity was measured by drop in body temperature, gastrointestinal symptoms (diarrhea) were
marked as present or absent. Mice with anaphylaxis underwent an oral desensitization protocol by feeding antigen for 2
weeks. Serum IgE and proteases were measured by ELISA.
Results: Tissue restriction of MMCP1 and MMCP7 in gut and skin, respectively, was confirmed by
immunohistochemistry. Increased levels of the MMC marker MMCP-1 were observed after oral OVA challenge in
sensitized but not naïve mice. MMCP-1 positively correlated with diarrhea but not anaphylaxis. On the other hand, the
CTMC marker MMCP-7 positively correlated with both diarrhea and anaphylaxis. OVA-specific IgE positively
correlated with diarrhea, but not anaphylaxis. We observed that oral immunotherapy protected mice from anaphylaxis
and was associated with a decrease in CTMC, but not MMC, activation.
Conclusions: Despite a shared oral route of allergen exposure, different manifestations of food allergy were associated
with different activation patterns of mast cell subsets. Only CTMC were desensitized by oral immunotherapy,
suggesting that other treatment approaches are needed to address gastrointestinal symptoms of food allergy.
14
The Relationship Between Self-Esteem and Intention of Contraception Use
Author Name(s): Sari Bentsianov, Angela Diaz, Anne Nucci-Sack, Christopher Ochner
Department: Pediatrics
Division: Adolescent Medicine
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: The relationship between self-esteem and safe sex practices (e.g. contraception use) is well established;
however, studies that have examined the relationship between self-esteem and motivation for contraception use are
lacking. The purpose of this study was to evaluate the relationship between self-esteem and use of contraception for
protection against pregnancy vs. protection against sexually transmitted infections (STIs).
Hypothesis: Self-esteem will be positively related to contraception use for the protection against both STIs and
pregnancy.
Methods: Data was collected from an evaluation survey of The Mount Sinai Adolescent Health Center (MSAHC), a
large freestanding comprehensive-care adolescent health center in New York City. We performed a cross sectional
analysis of data from the baseline report of 1402 adolescents (age range 12-21 years old, 81% female, 54% African
American). A multinomial logistic regression was done to examine the relationship between the statement, “I have a
lot of good qualities” (as a marker of self-esteem) to use of protection against pregnancy and use of protection against
STIs. We controlled for age, sex, socioeconomic status, and race/ethnicity.
Results: There is a significant positive relationship between thinking one has good qualities and use of protection
against pregnancy (p<0.0005). Interestingly, however, there is no relationship between thinking one has good qualities
and use of protection against STIs (p>0.2).
Conclusions: Adolescents with higher self-esteem are more likely to use protection against pregnancy but not STIs.
Clinical implications suggest physicians should pay close attention to the sex practices of patients with low selfesteem.
15
The Role of the Kynurenine Pathway in Suicidality in Adolescent
Major Depressive Disorder
Author Names: Kailyn A. L. Bradley, Julia A. C. Case, Omar Khan, Thomas Ricart, Amira Hanna,
Carmen M. Alonso, Vilma Gabbay
Department: Psychiatry
Division(s): Pediatric Mood and Anxiety Disorders Program
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: The neuroimmunological kynurenine pathway (KP) has been implicated in major depressive disorder
(MDD) in adults and adolescents. The KP is initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), which
degrades tryptophan (TRP) into kynurenine (KYN) en route to neurotoxins. Here, we sought to specifically examine
the KP in relation to suicidality in depressed adolescents.
Hypothesis: We hypothesized that depressed adolescents at high risk for suicide would exhibit increased KP
activation, indexed by elevated IDO, KYN and 3-hydroxyanthranilic acid (3-HAA), and decreased TRP.
Methods: Plasma levels of TRP, KYN, 3-HAA, and IDO (indexed by KYN/TRP) were assessed in 20 adolescents
with MDD at high risk for suicide—composed of past attempters and those who expressed active suicidal intent—30
non-suicidal depressed youth, and 22 healthy controls (HC).
Results: Adolescents with MDD at high risk for suicide showed decreased TRP and elevated KYN/TRP compared to
both non-suicidal depressed adolescents and HC. Findings became more significantly pronounced when excluding
medicated participants, wherein there was also a positive correlation between KYN/TRP and suicidality. Finally,
depressed adolescents with a history of suicide attempt differed from acutely suicidal adolescents with respect to
disease severity, anhedonia, and suicidality, but not KP activation.
Conclusions: Our findings suggest a possible specific role of the KP in suicidality in depressed adolescents, while
illustrating the clinical phenomenon that depressed adolescents with a history of suicide attempt are similar with
respect to KP activation to acutely suicidal youth and are at increased risk for completion of suicide.
16
Evaluation of a Multidisciplinary Home Visiting Program for Children
with Special Health Care Needs
Author Names: Maureen Braun, Elaine Lin, Susann Cortes, Sanite Theophile, and Joseph Truglio
Department: Pediatrics
Division: General Pediatrics
Institute Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Children with special health care needs (CSHCN) often have unmet medical and social needs and
receive fragmented care. Evidence suggests that home visitation and care coordination can improve health outcomes
for CSHCN, however, few studies exist that examine a physician-led multidisciplinary team delivering comprehensive
home-based care to CSHCN.
Hypothesis: Development of a physician-led home visiting program for CSHCN if feasible and will improve patient
outcomes.
Methods: Children with poorly controlled asthma, children with medical complexity, and infants discharged from the
neonatal intensive care unit who live in East and Central Harlem are being recruited from the outpatient clinic at an
urban academic medical center. A team of 2 pediatricians, 1 social worker and 1 patient navigator provides medical
and psychosocial care at home as well as care coordination, including collaboration with ancillary services, community
agencies, and subspecialty providers. Infants are enrolled for 6 months, asthma patients for 1 year, and medically
complex children are followed until transition to adult care. Healthcare utilization rates were reviewed for children who
have been enrolled in the program for at least 3 months and received more than 1 home visit. Equal pre and post
enrollment periods were compared and data were analyzed with a paired t test.
Results: Since July 2013, a total of 92 patients have been enrolled including 45 patients with poorly controlled asthma,
17 children with medical complexity and 30 infants discharged from the NICU. A 46% reduction in asthma ED visits
(65 vs 35, p<0.001, n=35) and a 67% reduction in asthma hospitalizations (21 vs 7, p <0.02, n=35) were observed in
asthma patients. A 43% reduction in total ED visits (14 vs 8, p=0.21, n =12) and a 63% reduction in total
hospitalizations (8 vs 3, p=0.16, n=12) were noted in children with medical complexity. Amongst infants discharged
from the NICU, the 30-day readmission rate was 4.5% (n=22).
Conclusions: We found that it is feasible to develop a multidisciplinary pediatric home visiting program for CSHCN.
Our pilot data show a decrease in ED visits and hospitalizations across multiple medical conditions, suggesting an
improvement in health outcomes. Further study is warranted including comparison to a control group, assessment of
other patient-centered outcomes and cost-effectiveness of the program.
17
Prenatal Stress and Mitochondrial Function at the Maternal-Fetal Interface:
Modification by Maternal Antioxidant Status
Author Name(s): Kelly J. Brunst1, Calvin Jara1, Chris Gennings2, Andrea Baccarelli3,
Marco Sanchez Guerra3, Alexandra Dereix3, Robert O. Wright1,2,6,
Rosalind J. Wright1,2,6
Department(s): Pediatrics1;2 Preventive Medicine2;
Institution Affiliation(s): 1Icahn School of Medicine at Mount Sinai; 3Department of Environmental Health,
Harvard T. H. Chan School of Public Health, Boston MA
Institute Affiliation: 6The Mindich Child Health and Development Institute
Introduction: Prenatal stress may disrupt fetal antioxidant/oxidant balance and mitochondrial homeostasis to impact
fetal health, although this has not been examined in humans. Micronutrients that reduce fetal vulnerability to oxidative
stress may modify this relationship.
Hypothesis: Increased prenatal stress is associated with decreased mitochondrial DNA copy number (mtDNAcn),
reflecting cumulative oxidative stress over gestation at the maternal-fetal interface. Effects are enhanced by low
maternal antioxidant intakes.
Methods: Analyses included 148 mother-infant dyads from a prospective cohort. A prenatal stress index was
calculated by averaging percentiled values of lifetime trauma, prenatal life events, depressive symptoms, and hair
cortisol. Antioxidant intakes were estimated from a validated food frequency questionnaire. Higher values indicate
greater stress and intakes. Relative placental and cord blood (CB) mtDNAcn, assessed by Q-PCR, was log
transformed. Independent relationships between stress and antioxidant status on mtDNAcn were examined using
multivariable linear regression adjusting for maternal age, race, education, smoking and child sex. Modification by
antioxidant status was examined by including a product term in the model and stratification.
Results: Higher stress was associated with decreased placental (βP=-0.34, p<0.0001) and CB (βCB= -0.27, p=0.07)
mtDNAcn. Higher antioxidant intakes were associated with increased placental mtDNAcn (βP = 0.31, p=0.03, βCB = 0.04, p=0.78). A steeper decrease in CB mtDNAcn was observed as stress increased among mothers whose
antioxidant intakes were in the 25th percentile compared to those in the 50th and 75th percentiles (pinteraction= 0.04).
Conclusions: Among infants born to mothers experiencing increased prenatal stress, optimal antioxidant intakes may
protect the fetus by regulating mitochondrial homeostasis.
18
Cell-Specific Regulation of BK Channel and WNK Kinases in Cortical Collecting
Duct (CCD) by Dietary K
Authors Names: Rolando Carrisoza1, Arohan Subramanya2, Marcelo Carattino2, Thomas Kleyman,2 Lisa Satlin1
Department(s): 1Pediatrics, 2 Medicine
Division(s): 1Pediatric Nephrology, 2Renal-Electrolyte
Institution Affiliation(s): 1Icahn School of Medicine at Mount Sinai, 2University of Pittsburgh School of Medicine
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Total body K balance is regulated primarily by renal K secretion in the aldosterone sensitive distal
nephron (ASDN), which includes the CCD. The ASDN is comprised of (i) principal cells (PCs), which mediate Na
absorption via ENaC and basal K secretion via ROMK channels, and (ii) intercalated cells (ICs), which transport acidbase. With-no-lysine (WNK) kinases regulate ENaC and ROMK in the ASDN in response to dietary K intake;
mutations in WNK1, WNK4, or their cognate E3 ubiquitin ligase complex Kelch-like 3/Cullin 3 cause familial
hyperkalemic hypertension (Fhht, or pseudohyopaldosteronism type II). Evidence now suggests that WNK kinases also
regulate expression of apical BK channels, which contribute to adaptation to a high K (HK) diet in the ASDN.
Specifically, WNK4 inhibits BKα by targeting the channel for degradation through an ubiquitin-dependent pathway.
Although WNK1 and WNK4 show distinct subcellular distribution patterns in the ASDN, cell-specific regulation by
dietary K has not been studied.
Hypothesis: WNK kinases are regulated by dietary K in a cell-specific fashion in the ASDN.
Methods: CCDs from NZW rabbits fed a HK or low K (LK) diet x 10 d were fixed, perfused initially with antibodies
(Abs) directed against BKα, L-WNK1 (exon 1) or WNK4, followed by fluorescent 2o Abs or rhodamine-peanut lectin
(PNA), which binds to apical surfaces of ICs but not PCs, and examined by confocal microscopy.
Results: In LK CCDs, BKα localized predominantly to cilia with minimal detection along the apical membranes of
ciliated > non-ciliated cells. In HK CCDs, apical BKα was enhanced in non-ciliated > ciliated cells. WNK1 was not
detected in LK CCDs (2) but was observed in HK CCDs (4) in a basolateral (BL) distribution in all cells and robustly
along the apical membrane of PNA+ cells. In contrast, cytoplasmic and BL WNK4 was observed in all cells in LK
CCDs (2) but was minimally expressed in a BL distribution in non-ciliated cells in HK CCDs (2).
Conclusions: Adaptation to a HK diet includes an increase in apical BKα and L-WNK1 and reduction in WNK4
expression in ICs, suggesting that increased L-WNK1 and reduced WNK4 contribute to enhanced BK channelmediated K secretion in HK animals. In PCs, HK diet increases apical but not cilia BKα, a response associated with BL
WNK1 but absent WNK4. These results are consistent with cell-specific regulation of BKα and WNK kinase
expression by dietary K in the ASDN.
19
Vision Screening Among Primary Care Clinic Patients
Author Name(s): Lwbba Chait, Angeliki Makri, Gwen Raphan
Department: Pediatrics
Division: General Pediatrics
Institution Affiliation: Icahn School of Medicine, Elmhurst Hospital Center
Introduction: In the United States, an estimated 1 in 20 children is at risk of permanent vision loss.[1] Amblyopia is
the most common cause of vision loss.[2] One of the most important screenings a primary care provider needs to
perform is assessment of the child’s vision at age appropriate well-child visits. The AAP recommends vision screening
to begin at 3 years of age.[3]
Hypothesis: We hypothesized that vision screening at an early age will improve the rates of Ophthalmology referral
after 2 unsuccessful vision screening attempts.
Methods: This was a retrospective study involving a single primary care pediatric practice, Elmhurst Hospital Center.
During a six-month period (November 2014 to January 2015), 90 charts of health maintenance visits between 3 and
4yo were randomly reviewed to gather baseline data.
Results: 63% (n=57) children were unable to complete vision screening at 3 years. Out of these, 53% (n=30) did not
complete by 3 ½ years. And only 20% (n=6) were referred to Ophthalmology.
Conclusions: If a three year old is unable to complete standard vision screening, repeat exam or referral to
Ophthalmology is crucial in detecting and preventing amblyopia.
Low number of timely referrals to Ophthalmology or repeat exams suggests a need for physician education in our
clinic to increase adherence to AAP guidelines. Going forward our QI project will incorporate an educational
component for providers with increased signage and discussions at regular clinic conferences etc.
References:
[1, 2, 3] Nye, C; A Child’s Vision
Pediatric Clin N American, 2014;61;493-503
Committee on Practice and Ambulatory Medicine, Section on Ophthalmology. American Association of Certified Orthoptists; American Association for
Pediatric Ophthalmology and Strabismus; American Academy of Ophthalmology
Pediatrics, 2003;111 (4 Pt 1): 902-7.
20
Phenotypic Analysis of Peanut-Responsive T Cells at Baseline in Subjects Enrolled in CoFAR6,
a Randomized Placebo-Controlled Epicutaneous Immunotherapy (EPIT) Trial
for the Treatment of Peanut Allergy
Author Name(s): David Chiang1, A. Wesley Burks2, Wendy Davidson3, Peter Dawson4, Alexander Grishin1,
Alice Henning4, Stacie M. Jones5, Donald Y. M. Leung6, Robert W. Lindblad4, Andrew H. Liu6,
Amy M. Scurlock5, Scott H. Sicherer1, Brian P. Vickery2, Robert A. Wood7, Hugh A. Sampson1,
M. Cecilia Berin1
Department: Pediatrics
Division: Allergy and Immunology
Institution Affiliation(s): 1Icahn School of Medicine at Mount Sinai, 2University of North Carolina School of
Medicine, 3National Institutes of Health, 4EMMES, 5 University of Arkansas for Medical
Sciences and Arkansas Children’s Hospital, 6National Jewish Health,
7
Johns Hopkins University Medical Center
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: The role of allergen-specific T cells in the pathogenesis of food allergy is poorly understood.
Hypothesis: Food allergy is associated with a unique Th2-biased signature and a defect in allergen-specific regulatory
T cells.
Methods: Baseline blood samples were obtained from challenge-confirmed peanut-allergic subjects (4-25 years)
enrolled in CoFAR6 (n=75), and from healthy controls (n=8). PBMCs were stimulated with peanut extract and
analyzed by flow cytometry. Peanut-responsive CD4+ and CD4+Treg (CD25+CD127-Foxp3+) cells were identified by
CD154 expression at 6h and 18h of stimulation, respectively.
Results: PBMCs from peanut-allergic subjects had increased Th2+CD154+ cells after 6h stimulation. Median
(lower/upper quartile) values/106 CD4+ cells for peanut- vs. unstimulated were 140 (66/327) vs. 11 (4/20) for
IL4+CD154+, 131 (45/295) vs. 4 (1/7) for IL13+C
(2/8) for IL10+CD154+. Controls had no response to peanut. Peanut-responsive cells at 6h expressed skin, mucosal, or
follicle homing molecules at low frequency (CCR4-16% (10/27), CCR6-5.6% (3/12), CXCR5-7.2% (5/9)). At 18h,
CD154+ Tregs were increased from peanut-allergic subjects (441(208/686) stimulated vs. 31(20/49) unstimulated) but
not from controls. CD154+Tregs expressed CCR4 (52.6% (35/64)) and CCR6 (29.8% (16/42)), but little IL10 (1.8%
-specific IgE (median 78.6 kUA/L), but not IgG4) correlated with
CD154+IL4+ cells (rs=0.68, p<0.001) and CD154+IL13+ cells (rs=0.69, p<0.001), but not CD154+ Tregs.
Conclusions: Peanut-allergic individuals have circulating peanut-responsive Th2 cells that correlate with specific IgE
levels. Peanut-responsive Tregs expressing skin and mucosal homing markers are detectable, but do not correlate with
IgE or IgG4.
21
Associations Between Cumulative Maternal Stress During the Perinatal Period and
Lung Function in Children at Age 7 Years
Author Name(s): Yueh-Hsiu Mathilda Chiu1,2, Brent A. Coull3, Harriet Fernandez4, Sheldon Cohen5,
Wayne J. Morgan6, Robert O. Wright2,7, Rosalind J. Wright1,7
Department(s): 1Pediatrics,2 Preventive Medicine
Division(s): 1Pulmonology, 2Environmental Health
Institution Affiliations (other than ISMMS): 3Department of Biostatistics, Harvard School of Public Health;
4
Channing Laboratory, Brigham and Women's Hospital & Harvard
Medical School; 5Department of Psychology, Carnegie Mellon
University; 6Department of Pediatrics, University of Arizona
Institute Affiliation: 7Mindich Child Health and Development Institute
Introduction: Evidence suggests that perinatal stress may influence lung development through disrupted maturation of
the immune, neural, and endocrine systems although this has not been studied in humans.
Hypothesis: Higher perinatal stress will be associated with lower lung function at age 7 years.
Methods: We prospectively examined associations between pre/postnatal stress and child lung function in 150 motherchild pairs. Maternal stress was indexed by a negative life events (NLEs) score on the Crisis in Family SystemsRevised survey (higher scores indicate increased stress) assessed prenatally, when children were ~2 years old (early
postnatal), and at lung function testing (7.0±0.9 years) (late postnatal). Stress was categorized based on the median
split (0-2 vs. ≥3) and exposure was considered across developmental windows.
Results: Mothers were primarily Hispanic (60%) and black (27%) with ≤12 years of education (60%). Median (IQR)
of lung function were 1.4 (1.25-1.63) L for forced expiratory volume in 1 second (FEV1) and 1.53 (1.38-1.77) L for
forced vital capacity (FVC). In linear regression models adjusting for child (age, height, gender, season of birth,
asthma), maternal (race, atopy, smoking), and environmental (prenatal traffic-related black carbon, cockroach allergen,
neighborhood disadvantage) factors, children exposed to high stress in both pre- and early postnatal periods had
decreased percent predicted FEV1 (β=-0.09, p=0.04) and FVC (β=-0.08, p=0.05) compared to children exposed to low
stress in both periods; the FEV1/FVC ratio was preserved.
Conclusions: Cumulative stress in pregnancy and early childhood was associated with a symmetric reduction in FEV1
and FVC suggesting compromised lung growth.
22
The Non-Diagnostic Ultrasound in Appendicitis: Is a Non-Visualized Appendix
the Same As a Negative Study?
Author Name(s): Brian Cohen1, Jordan Bowling2, Peter Midulla1, Edward Shlasko1, Neil Lester3,
Henrietta Rosenberg3, Aaron Lipskar1
Department(s): 1 & 2 Surgery, 3Radiology
Division: 1 Pediatric General and Thoracic Surgery
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: The purpose of this retrospective study was to investigate outcomes in children who underwent a nondiagnostic ultrasound (US) evaluating for appendicitis and to identify predictors of a negative diagnosis.
Hypothesis: We hypothesized that a non-diagnostic US, especially in conjunction with specific clinical parameters
such as the absence of leukocytosis, the absence of obesity, and the study being performed between normal work/fully
staffed hours (9am and 5pm), are highly predictive of a truly negative appendicitis diagnosis.
Methods: An IRB-approved retrospective chart review was performed on patients, age 0-18, who underwent an
abdominal US evaluating for acute appendicitis from 2004 through 2013. Clinical data and specified outcomes were
recorded, and exams were categorized into non-diagnostic studies and further separated into studies where the
appendix was non-visualized.
Results: Of the 1,383 studies included for analysis, 876 were non-diagnostic for acute appendicitis (63.34%) with 777
specifically because the appendix was non-visualized. 740 of the 876 non-diagnostic studies and 671 of the 777 studies
with a non-visualized appendix were ultimately considered true negatives, corresponding to a negative predictive value
(NPV) of 84.47% and 86.36%, respectively. In patients with WBC < 7.5 x 109/L, the NPV of non-diagnostic and nonvisualized studies increased to 97.12% and 98.86%, respectively. Patients with WBC < 11.0 x 109/L have similarly
high NPVs of 95.59% and 96.99% (non-diagnostic and non-visualized).
Conclusions: Based on the high NPV of a non-diagnostic US in children without leukocytosis, these patients may
safely avoid further diagnostic imaging for the workup of suspected appendicitis.
23
Repurposing Small Molecule Drugs for Cytomegalovirus
Author Names: Tobias Cohen, Thomas Gardner, Domenico Tortorella
Department: Microbiology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Cytomegalovirus (CMV) infection is a major source of morbidity and mortality in the pediatric
transplant population and congenital infection is the leading cause of congenital mental retardation in the USA. There
are no FDA approved therapeutics for use in pregnant women, and the four currently approved for pediatric patients
mainly target a single step in the infection and are incredibly toxic. We have previously identified small molecule
drugs that inhibit CMV infection in vitro and in this study we further elucidate their exact mechanism of action against
CMV.
Hypothesis: Currently existing small molecule drugs can be repurposed as CMV therapeutics and/or as research tools
to guide future drug development.
Methods: We employed mutant CMV reporter viruses to quantify viral infection in vitro. This system allowed us to
measure various parameters of the drugs such as dose-response, time of addition, reversibility, and cell/virus
specificity. Additionally we employed qRT-PCR, qRT-RT-PCR and lipid fusion assays to determine the mechanism of
action of multiple novel CMV inhibitors.
Results: We found that the microtubule inhibitor, podofilox, is a potent CMV entry inhibitor that prevents complete
viral fusion with the cell surface unlike other microtubule inhibitors and that several cardiac glycosides inhibit CMV at
a post entry step in the viral life cycle.
Conclusions: Certain microtubule inhibitors and cardiac glycosides represent potential new therapeutic candidates for
CMV infection. Additionally, our knowledge about the anti-CMV activity of these compounds introduces novel drug
targets for future CMV therapies to expand the treatment options for pediatric patients suffering from CMV.
24
Factors Resulting in Deferral of Diagnostic Oral Food Challenges
Author Names: Natalie Davis, Maureen Egan, Scott H. Sicherer
Department: Pediatrics
Division: Allergy and Immunology
Institution: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Physician-supervised oral food challenges (OFC) are recommended diagnostic tests and improve
quality of life, but patient/family motivating factors leading to deferral of the test have not been extensively explored.
Methods: Participants were parents of children with food allergy consecutively attending the Jaffe Food Allergy
Institute who were offered an OFC but had not undertaken one within 24 months. Subjects completed a questionnaire
listing 27 possible deferral reasons, marking all factors that applied, with the option to indicate “other”, and identify
most important factors.
Hypothesis: Patients and their families defer OFCs due to addressable issues (e.g., fear).
Results: A total of 102 surveys were completed (participation rate 92.7%) for 183OFC invitations encompassing 30
different foods. The children were 38% female, mean age 8.4 years, 31.4% had been treated with epinephrine. Among
total invitations, categorical responses were: scheduling issues (56.3%), not interested/not important/impractical for
diet (36.7%), fear/emotional issues (25.7%), doubted passing (18.6%), tried on own (10.9%), and others
(13.1%). Considering the most important factors (selected for 156 OFC offers, 85%) responses were: scheduling
issues (47.4%), not interested/not important/impractical for diet (20.5%), fear/emotional issues (14.1%), doubted
passing (4.5%), tried on own (5.8%) and others (7.7%). Other reasons included economic factors and fear of making
the allergy worse.
Conclusions: Excluding scheduling issues, OFCs were deferred primarily for reasons of lack of interest in the food
and concern for emotional impact or fear of reactions; these factors could be anticipated and addressed to reduce
deferral rates.
25
Trends in Repeat Cow Milk sIgE Levels
Author Name(s): Maureen Egan1, Manish Ramesh2 , Tricia Lee1, Jacob Kattan1, Julie Wang 1
Department(s): Pediatrics, Medicine
Division: Allergy and Immunology
Institution Affiliation(s): Icahn School of Medicine at Mount Sinai;
Albert Einstein College of Medicine/Montefiore, New York, NY
Institute Affiliation(s): The Mindich Child Health and Development Institute;
Jaffe Food Allergy Institute
Introduction: Cows milk (CM) allergy is the most common food allergy in children. Approximately 50% of children
will outgrow the allergy by age 5yo with a low initial CM serum IgE (sIgE) being positively correlated with resolution.
Hypothesis: We hypothesized that initial CM sIgE levels may help predict future progression.
Methods: This retrospective review included all patients at a teaching institution who had CM sIgE drawn on two or
more occasions between January 1, 2003 and January 1, 2013.
Results: 822 patients had two or more CM sIgE levels drawn in the study time frame that had a median age of 4.3
years and a median initial sIgE of 10.7 kUA/L. 364 patients (44%) had initial levels ≥15 kUA/L. Of those patients only
7 individuals (1.9%) had repeat sIgE levels ≤ 2 kUA/L over a median of 1.7 years and 15 patients (4.1%) had repeat
sIgE levels ≤5 kUA/L over a median of 1.9 years. Additionally, 142 patients (17.3%) had initial milk sIgE levels >5-15
kUA/L. Of these patients 19 (13%) had subsequent levels of ≤2 kUA/L over a median of 1.9 years while 56 patients
(39%) had subsequent levels ≤5 kUA/L over a median of 1.5 years.
Conclusions: Lower initial CM sIgE levels were correlated with the progression toward a sIgE level at which one
could expect a clinical resolution of symptoms. Further analysis is needed to identify the optimal frequency for reassessing CM sIgE levels.
26
Serum IgE Response to Itraconazole in Children with Severe Asthma
with Fungal Sensitization: A Pilot Study
Author Names: Leah I. Elizondo1, Angela J. Tsuang1, David L. Goldman3,4, Alfin G. Vicencio1,2
Department: Pediatrics1
Division(s): Pulmonology2; Microbiology and Immunology3
Institution Affiliation(s): Icahn School of Medicine at Mount Sinai1;
Children’s Hospital at Montefiore at Albert Einstein College of Medicine4
Introduction: Prior studies suggest that some patients with severe asthma with fungal sensitization (SAFS) may
benefit from itraconazole therapy, though reports of its use in children are limited. We review initial data of an
ongoing pilot study characterizing IgE response to itraconazole in childhood SAFS.
Hypothesis: Total IgE levels in children with moderate to severe asthma with fungal sensitization will decrease after
treatment with itraconazole.
Methods: SAFS was diagnosed when patients met the following criteria: severe persistent asthma, serum IgE >100
IU/mL, and fungal sensitization by mold-specific IgE or skin prick testing. Patients had the option of standard of care
or an off-label trial of oral itraconazole. Total IgE levels were measured before and after 6 months of treatment with
itraconazole.
Results: Twelve pediatric patients with SAFS have been enrolled into the study. Three patients were candidates for
omalizumab based on serum and allergen-specific IgE, though none initially agreed to therapy. Nine patients elected
to undergo treatment with itraconazole. Eight patients were considered responders, defined as >50% reduction in
rescue and/or maintenance therapy and >25% decrease in serum IgE level. Itraconazole was discontinued in one
patient due to asymptomatic mildly elevated liver function tests. The mean IgE level for all treated patients postitraconazole was statistically lower than the mean IgE level pre-itraconazole (p=0.0156).
Conclusions: Initial data suggest that IgE levels decrease in response to itraconazole. However, given the small
number of patients recruited thus far, larger studies are required to determine the role of itraconazole in childhood
SAFS.
27
A Novel Protocol for Characterizing Long Non-Coding RNAs
in Autism Spectrum Disorders
Author Name(s): Nancy J. Francoeur1-4, Robert Sebra2, Dalila Pinto1-4
Department(s): Psychiatry1, and Genetics and Genomic Sciences2
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliations(s): The Mindich Child Health and Development Institute3, Seaver Autism Center4
Introduction: Long non-coding RNAs (lncRNAs) are key components of gene regulatory networks and may play a
role in autism spectrum disorders (ASD) and other neurodevelopmental disorders. Making use of a list of lncRNA
genes curated from multiple resources including GENCODEv19, we are developing a novel protocol to sequence fulllength lncRNAs in postmortem brains of ASD cases and controls as a first step towards incorporating lncRNA
expression profiles into the analysis of gene regulatory networks underlying these disorders.
Hypothesis: We have designed a lncRNA-Seq capture protocol for the purpose of uncovering gene structure details,
sequencing of full-length isoforms, and identification of splice variants and novel isoforms of lncRNAs, particularly
those in the vicinity of protein-coding genes implicated in, or candidates of, ASD, intellectual disability or epilepsy.
Methods: As proof-of-principle, we are generating full-length cDNA libraries using total RNA extracted from a
neuroblastoma cell line and sequencing entire transcripts within single reads on the PacBio RS II platform. We will
also hybridize full-length cDNA libraries to lncRNA capture probes to enrich for lncRNA transcripts present in our
samples.
Results: Our multi-library sequencing strategy to profile full-length transcripts at different size ranges has been
successfully applied in a SH-SY5Y cell line, which is allowing us to refine our SeqCap protocol and tools for the
discovery and characterization of lncRNAs genome-wide or around any genes of interest.
Conclusions: Our strategy and tools developed for profiling lncRNA expression in ASD brain tissues will be widely
applicable to other neurodevelopmental disorders.
28
Comparison of IgE Epitope Mapping by Peptide Microarray and a
Novel Luminex-based Peptide Assay
Author Name(s): Gustavo Gimenez, Cansin Sackesen, Stephanie Schmidt, Robert C Getts, Jing Lin,
George N Konstantinou, Ebru Arik Yilmaz, Ozlem Cavkaytar, Ozge Soyer, Galina Grishina,
Hugh Sampson
Department: Pediatrics
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Peptide microarray-based immunoassays (MIA) identify food protein allergenic epitopes. The diversity
of epitope-specific IgE binding and affinity correlate with different clinical phenotypes of cow’s milk (CM) allergy.
Here we compare IgE binding of milk-allergic subjects utilizing MIA and a novel, high throughput Luminex-based
peptide assay (LPA).
Methods: 80 subjects with different degrees of tolerance to milk products were categorized into 4 groups: A, reactive
to baked-milk (BM, n=20, median CM-sIgE=38.7), B, reactive to yogurt-cheese/BM-tolerant (n=17, CM-sIgE=10.5),
C, reactive to pasteurized milk/tolerant to BM and yogurt-cheese (n=23, CM-sIgE=7.7), and D, outgrown milk allergy
(n=20, CM-sIgE=2.9). Serum samples were tested in both assays, and inter-assay variability, sensitivity, and IgE
binding to various epitopes of milk proteins were compared.
Results: Correlations between replicate peptides within the same experiment in MIA were good (R>0.91), while LPA
replicates were highly correlated (R>0.99). The identified epitopes with significant differences between groups were
similar between the two systems, and overall binding diversity detected was higher in Group A in both assays
(p=0.002, Mann-Whitney). LPA, however, showed more pronounced epitope-recognition patterns for high-binding
allergic subjects. Non-binding subjects in group A were consistent in both assays, but subjects with undetectable
binding in the other groups using MIA showed some positive recognition patterns on LPA due to higher sensitivity.
Conclusions: The agreement between allergenic epitopes identified is excellent. However, LPA has several advantages
including lower serum volume requirement, lower inter-assay variability, increased sensitivity and ease of automation,
making the assay more practical as a diagnostic tool for clinical practice.
29
Hyperosmolar Hyperglycemic State in a Pediatric Renal Transplant Patient
with Medication-Induced Diabetes
Author Name(s): Marina Goldis, Elizabeth Burtman, Lindsey Waldman, Dennis Chia,
Elizabeth Wallach, Laura Castellanos Reyes, Hilary Hotchkiss, Robert Rapaport,
Molly Regelmann
Department: Pediatrics
Division: Endocrinology and Diabetes
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Hyperosmolar hyperglycemic state (HHS) is serious and potentially life threatening. Osmotic diuresis
results in profound dehydration and severe electrolyte imbalance.
Objective: Describe the occurrence of unsuspected HHS in a pediatric patient with RTx
Methods: Retrospective chart review
Results: 18 yo AA female with RTx at 16 yo with focal segmental glomerulosclerosis related renal failure.
Immunosuppression was primarily with tacrolimus and mycophenolate mofetil; she had 4 days of glucocorticoids
immediately after RTx. Diagnosis of new onset diabetes after transplant (NODAT) was made 4 mo after RTx. At
diagnosis, hemoglobin A1c (HbA1c) 9.1%, diabetes-related autoantibodies negative. She was initially treated with
insulin glargine and diet modification; HbA1c 6.5-7.9% 3-11 mo after NODAT diagnosis.
At 13 mo after diagnosis, she presented with 8.6 kg weight loss in 6 wks, polyuria and polydipsia x1 mo, vomiting x2
days and altered mental status x1 day. Her serum glucose was 625 mg/dL, corrected sodium corrected 155.4 mEq/L,
HbA1c 14.6%. Initially treated with subcutaneous insulin, lispro and glargine, and IV fluids (20 mL/kg of 0.9%NS,
then maintenance). HHS diagnosed and more aggressive IV fluid management instituted with subsequent resolution of
electrolyte abnormalities, return to baseline mental status.
Conclusions: The pathophysiology of NODAT is complicated; tacrolimus induces hyperglycemia likely by a
combination of decreased insulin secretion, b-cell necrosis, and increased insulin resistance. Mortality rates are as high
as 10-20%. It is unclear whether the underlying mild renal disease predisposed to HHS. Prompt recognition and
treatment of HHS in a critical care setting is important to prevent mortality.
30
Mild Congenital Hypothyroidism: Persistence Beyond 3 Years
Author Name(s): Marina Goldis, Molly Regelmann, Elizabeth Burtman, Lindsey Waldman,
Elizabeth Wallach, Robert Rapaport
Department: Pediatrics
Division: Endocrinology and Diabetes
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: The apparent increased incidence of congenital hypothyroidism (CH) is likely multifactorial, and in part
related to demographic changes, rise in premature births and an increased detection of mild CH (MCH), defined as an
elevated TSH <25 uIU/mL and normal thyroxine (T4). There is no consensus about diagnosis, management or long
term consequences of MCH. Previous reports have suggested a degree of persistent CH in some diagnosed with MCH.
We recommend treatment of MCH in infancy and re-evaluation after the age of 3 years.
Hypothesis: Report the persistence of MCH after the age of 3 years
Methods: Retrospective chart review of patients with CH evaluated at Mount Sinai Medical Center from 2008-2014.
Results: 12 of the 25 patients re-evaluated at >3 years had persistently elevated TSH values when levothyroxine was
withdrawn.
Conclusions: In the population presented, one third of the patients with MCH had evidence of persistent thyroid
dysfunction after 3 years. Previous reports of genetic abnormalities in patients with MCH and transient CH, coupled
with our results, suggest MCH should be recognized as part of the spectrum of CH and likely deserve treatment with
LT4 even if transiently. The value of diagnostic imaging in the MCH population remains to be determined.
31
How Does Age of Overweight & Obese Weight Status Onset Influence
the Adolescent Dating Market?
Author Name(s): Lonna Gordon, Angela Diaz, Christopher Ochner
Department: Pediatrics
Division: Adolescent Medicine
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Adolescence can be divided into three distinct phases of early (11-13 years old), middle (14-16 years
old) and late (17-21 years old) with each phases have developmental tasks that relate to establishing positive body
image and appropriate peer and romantic relationship formation. The works of social epidemiologists and health
economists have worked to outline an adolescent dating market where various physical, social, and psychological
attributes increase an adolescent’s desirability as a date. They have identified obesity as a physical attribute that
decreases desirability but have not explored how the time frame during which obesity is acquired may mediate this
relationship and how it affects future relationship formation and sexual practices. This study seeks to explore these
relationships.
Hypothesis: We hypothesize that non-lean weight status acquired during any developmental phase of adolescence will
decrease desirability on the adolescent dating market resulting in poorer relationship formation in comparison to lean
peers.
Methods: Using a nationally representative longitudinal database (Add Health) we will compare the longitudinal
relationship outcomes of adolescents who become overweight or obese during early vs middle vs late adolescence. We
will compare the responses of overweight and obese adolescents to their healthy weight counterparts stratified by
adolescent developmental phase for age first primary romantic relationship was identified; and number of nonromantic sexual partners. We will then compare reproductive health outcomes of STI acquisition, and number of
pregnancies prior to age 20
Results: Pending
Conclusions: Pending
32
Oral Health Practices of an Inner City Cohort of Girls in East Harlem, New York
Author Name(s): Loy Hagan, ¹ Nancy Mervish, ² Susan L. Teitelbaum, ² Mary S. Wolff, ²
and the Breast Cancer and Environmental Research Program 3
Department(s): ¹Dentistry, ²Preventive Medicine, ³ Breast Cancer and Environment Research Program,
http:www.bcerp.org/index.htm
Institution Affiliation: ¹²Icahn School of Medicine at Mount Sinai
Introduction: According to the CDC/NCHS 2012 report, dramatic disparities in caries prevalence and access to
sealants were reported in children living in poverty and born to ethnic minorities.
Objective: To describe dental practices, access to examination, and sealant prevalence in an inner city cohort of
adolescent girls in East Harlem, NY.
Methods: Study participants are girls from the MSSM site Breast Cancer and Environment Research Program
(BCERP), a longitudinal cohort examining environmental risk factors on pubertal development. Dental habits and
practices, including frequency of dental visits, brushing, flossing, sealant placement data were obtained from girls aged
12-18 and their mothers through a standardized questionnaire.
Results: Participant’s average age (n=219) was 15.4 yrs, 62% Hispanic and 38% Black. Reported dental practices
were as follows: routine checkups more than once/year (53%); brushed teeth daily or more often (79%); flossed
<once/day (75%); and sealant placement (34%). The prevalence of sealants is lower than reported among similar
age/race/ethnicity adolescents from NHANES (2009-2013). Socioeconomic status, indicated by insurance, maternal
education or US-born mother was not associated with differences in frequency of dental examinations, flossing or
dental sealants.
Conclusions: Dental sealants in adolescents are effective in preventing caries. The lower prevalence of sealant
placement among East Harlem adolescents may put them at greater risk for caries. Children with poor oral health are
three times more likely to miss school due to dental pain; therefore community-based interventions to increase the use
of dental sealants may have public health impacts beyond just improvement of oral health.
33
Screening for Anxiety and Distress in Children with Food Allergy and their
Parents – Does Streamlined Care Impact Utilization?
Authors Name (s): Jacqueline Helcer, Brianna Lewis, Melissa Rubes, Evan Wiley, Caitlin Shneider,
Scott H. Sicherer, Eyal Shemesh, Rachel A. Annunziato
Department (s): Pediatrics, Kravis Children’s Hospital
Division: The EMPOWER program at the Jaffe Food Allergy Institute
Institution Affiliation (s): Icahn School of Medicine at Mount Sinai;
Fordham University’s Department of Psychology
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Mental health screening in medical care settings has been recommended, but it is unclear whether
receipt of enhanced care is associated with a higher symptom level.
Hypothesis: We hypothesized that higher anxiety is associated with receipt of enhanced care in the context of a
screening program in a pediatric food allergy clinic.
Methods: We analyzed screening and referral results from a consecutive sample of 695 families. Referrals to a free
mental health consultation were based on screen results and clinicians’ assessments. Measures included the
SCARED© for children and the IES-6 for caretakers. Independent-samples t-tests were used to compare measure
scores.
Results: Referred families reported greater anxiety. The referred group’s (n=74) average SCARED© score was 5.50
(SD=3.81) vs. non-referred, 2.66 (SD=3.42), t(269) = -4.12, p < .001; parent IES-6 average score, referred: 14.27
(SD=7.01) vs. non-referred: 6.74 (SD=6.39), t(629) = -9.02, p < .001. Among referred families, we found no
significant differences between those who opted to receive the consultation vs. those who did not: SCARED©, 5.80
(SD=5.31) vs. 5.43 (SD=3.55), t(26) = -0.19, p = .85; IES-6, 13.70 (SD=8.25) vs. 14.37 (SD=6.86), t(65) = .28, p =
.78.
Conclusions: Screening identified families who were more distressed, but those who ultimately received enhanced
care were not significantly more anxious or distressed than those who did not receive it. In our experience, coordinated,
free care was not consistently utilized by families who needed it most.
34
Prenatal Exposure to a Mixture of Metals and Associations with
Executive Function and Cognitive Development
Author Name(s): Megan K. Horton, Anny L. Bonilla, Katherine Svensson, Chris Gennings,
Deborah A. Cory-Slechta, Robert Wright
Department: Preventive Medicine
Institutional Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Prenatal and early childhood exposure to lead is associated with adverse neurodevelopmental
outcomes. Growing evidence suggests the presence of other metals may exacerbate the impact of lead. Evaluating the
health effects of individual metals may underestimate the health effects of exposure to mixtures of metals. Weighted
quantile sum (WQS) regression is a statistical approach recently proposed to examine mixture effects in epidemiologic
studies. This method can be used to estimate the total exposure burden due to a mixture of correlated contaminants and
identify influential compounds in the mixture.
Hypothesis: We hypothesized that higher prenatal exposure to a mixture of metals is associated with adverse
neurodevelopmental outcomes at 24 months of age.
Methods: Subjects were part of an ongoing longitudinal birth cohort of urban residents of Mexico City. Using WQS
regression, we examined associations between prenatal metal concentrations measured in cord blood and performance
on two standardized neurodevelopmental assessments administered to children at 24 months of age; Bayley Scales of
Infant Development-III (a standard test of cognitive, language and motor development) and the Delayed Spatial
Assessment Task (a measure of executive function) adjusting for sex, gestational age and socioeconomic status.
Results: The WQS index for metal exposure was negatively associated with cognitive development (p = 0.048) and
language development (p = 0.034) on the BSID-III and with overall performance on the DSAT (p < 0.05).
Conclusion: Higher metal exposure appears to be negatively associated with measures of executive function, cognitive
development and language development.
35
Gold-Standard Autism Assessment in an Ethnically and Racially Diverse Population
Author Name(s): J. M. Jamison, E. S. Fourie, M. Oliphant, P. M. Weinger, J. Krata, E. Holl, J. Shaoul, B. Hernandez,
J.D. Buxbaum, A. Kolevzon
Department: Psychiatry
Division: Child and Adolescent Psychiatry
Institute Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: This study seeks to establish autism spectrum disorder (ASD) the diagnosis using gold-standard
practices in an ethnically and racially diverse sample and to determine whether specific risk factors predict ASD
diagnosis in this population.
Hypothesis: We hypothesize that a proportion of children carrying diagnoses of ASD will not meet criteria using goldstandard assessments, despite the presence of risk factors.
Methods: Sixty children between the ages of 5 and 12 presented to the Seaver Autism Center for diagnostic
evaluations as part of ongoing studies examining evidence-based practices to improve the health and well-being of
Black and Hispanic children with ASD. Sixty percent of the sample presented with a previous diagnosis of ASD.
Results: Twenty-eight percent of the sample identified their child as Black, 47% as Hispanic, and 25% as both Black
and Hispanic. Of the 36 children presenting with a past diagnosis of ASD, approximately 70% of diagnoses were
confirmed and 30% did not meet criteria for an ASD diagnosis. Both groups endorsed multiple risk factors with no
significant differences in the number or type of risk factors reported between groups.
Conclusions: Our results suggest that there is a proportion of Black and Hispanic children who carry a diagnosis or
classification of ASD whose symptoms may be better explained by other diagnoses. Future studies must explore ways
to enhance diagnostic practices in community-based and educational settings to improve accuracy of diagnoses and to
ensure optimal treatment.
36
Expression Profiles of Genes that Regulates the Cellular Respiration Are
Associated with Intrauterine Growth Restriction
Author Name(s): Richard Jones, Elana Mystal, Juan Peña, Luca Lambertini
Department: Preventive Medicine
Division: Environmental Health
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Intrauterine growth restriction (IUGR) is characterized by suboptimal fetoplacental growth and
vascularization and increased infant risk for metabolic and neurodevelopmental syndromes. Suboptimal vascularization
leads to reduced supply of nutrients which may impair the metabolite flux through the tricarboxylic acid (TCA) cycle
of mitochondrial cellular respiration.
Hypothesis: The expression profiles of key genes regulating the metabolite flux through the TCA cycle are associated
with IUGR.
Methods: We monitored the expression of 7 key genes (PDK1, PDK2, PDK3, PDK4, PKLR, PKM, OGT) that regulate
the metabolite flux through the TCA cycle in 136 placentas (92 controls and 44 IUGRs) by real-time PCR. We
modeled the association between gene expression and IUGR by multinomial logistic regression, controlling for
maternal age, ethnicity and weight.
Results: Weak non-parametric bivariate correlations were determined between the IUGR diagnosis and the expression
of, respectively, PDK1 (rho = -0.224; p = 0.012) and PDK3
(rho = -0.275; p = 0.002). Multinomial regression analysis returned a significant model
(p = 0.011) with a strong pseudo r-squared = 0.366 driven by the expression of PDK1
(pseudo-Beta = -0.166; p = 0.007), PDK2 (pseudo-Beta = 0.236; p = 0.003) and PDK3 (pseudo-Beta = -0.317; p = 0.002).
The expression of PKM returned a borderline association (pseudo-Beta = -0.111; p = 0.059). None of the confounders
were significantly associated with the outcome.
Conclusions: These data support the association between alterations of the expression of genes that regulate the
metabolite flux through the TCA cycle and IUGR suggesting an impairment of the mitochondrial functioning rates.
37
Disruption in Placental Expression of Imprinted Genes is Associated with Birth Weight
Author Name(s): Maya Kappil1, Luca Lambertini1, Dylan Guerin2, Benjamin Green2, Carmen Marsit2, Jia Chen1
Department(s): 1Preventive Medicine, 2Pharmacology & Toxicology
Division: 1Environmental Health
Institution Affiliation(s): 1Icahn School of Medicine at Mount Sinai; 2Geisel School of Medicine at
Dartmouth College
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: The necessity of the timely expression of imprinted genes for embryonic and placental development has
been long established. Yet, a comprehensive assessment of the role of imprinted gene expression on gestational quality
as indicated by birth weight has yet to be conducted. In this study, we profiled imprinted genes in the placenta and
investigated their associations with birth weight.
Hypothesis: Infants with abnormal fetal development have dysregulated expression of imprinted genes.
Methods: Placental samples (n=693) were obtained from newborn infants enrolled in the Rhode Island Child Health
Study where small for gestational age (SGA) and large for gestational age (LGA) infants were matched to appropriate
for gestational age (AGA) infants. The expression profile was generated using a custom-designed code-set of 150
known and putative imprinted genes (Nanostring technologies, Seattle, WA).
Results: The expression level of nine imprinted genes were observed to be positively associated with LGA status: for
every one-fold increase in expression, the odds ratios (OR) for LGA are: BLCAP (OR=3.78, [1.83,7.82]), DLK1
(OR=1.63, [1.27,2.09]), H19 (OR=2.79, [1.77,4.42]), IGF2 (OR=1.43, [1.31,2.40]), MEG3 (OR=1.42, [1.19,1.71]),
MEST (OR=4.78, [2.64,8.65]), NNAT (OR=1.40, [1.05,1.86]), NDN (OR=2.52, [1.72,3.68], and PLAGL1 (OR=1.85,
[1.40,2.44]).
Conclusion: Our results support the pivotal role of the expression of imprinted genes in fetal growth and development.
The expression of this subset of monoallelically expressed genes may be developed into a unique biomarker indicative
of the in utero environment.
38
Soy Reactivity May be Better Identified by Component Testing
with Gly m 8 than Traditional Testing Methods
Author Names: Jacob D. Kattan, Hugh A. Sampson
Department: Pediatrics
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Skin prick testing and serum food-specific IgE (sIgE) levels are sensitive tests for identifying soy
allergy, but positive results are common even when soy is tolerated. We sought to perform soy component testing on
patients undergoing an oral food challenge (OFC) to soy to determine if this modality would improve predictability.
Hypothesis: We hypothesized that component testing would be more accurate than current testing for diagnosing soy
allergy.
Methods: We recruited children referred for OFC to soy. Challenge outcomes were compared with soy sIgE levels
and the sIgE levels to the soy components Gly m 4, 5, 6, and 8, measured by ImmunoCAP.
Results: We performed component testing on 41 patients, ages 1 to 19 years, who underwent an OFC to soy. 23
patients passed the OFC (56%), while 18 failed (44%). The median soy-sIgE in the patients who passed OFC (7.78
kUA/L) was lower, but not significantly different from those who failed (16.40 kUA/L). The median Gly m 4, 5, and 6
levels were not significantly different between those with a negative OFC (0.62, 5.39, and 7.73 kUA/L respectively)
and the soy reactive patients (0.50, 13.85, and 17.15 kUA/L respectively). There were significant differences in the
median Gly m 8 levels between patients who passed their soy OFC (1.43 kUA/L) and the soy reactive patients (5.03
kUA/L; P<0.001).
Conclusion: Soy component testing using the component Gly m 8 gives a better indication of patients who are
clinically reactive to soy. Additional studies with larger cohorts will be needed to establish specific diagnostic
protocols.
39
Parental Survey Study: Opinions of Informed Consent in Newborn Screening
and Dried Blood Spot Retention
Author Name(s): Nicole R. Kelly, Dalia Chehayeb Makarem, Melissa P. Wasserstein
Department: Genetics and Genomic Sciences
Division: Medical Genetics
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Every year over 4 million babies in the United States are screened at birth for conditions that can cause
long-term disability or death if left undetected. Technological advances have led to a remarkable expansion of newborn
screening (NBS) panels, which now include disorders that do not meet traditional criteria for inclusion. In addition, the
long-standing practice of saving residual dried blood spot (DBS) for quality assurance and public health research has
been recently challenged.
Hypothesis: This exploratory study assessed parental opinions of informed consent for NBS and DBS practices using
an anonymous survey.
Methods: English-speaking parents were recruited from the maternity ward at Mount Sinai Hospital to participate in
this survey between April and June 2014. They were asked to complete a brief questionnaire to assess their opinions
about requiring parental consent for types of diseases on the NBS panel and the storage and use of the DBS.
Results: 576 completed surveys were received from a relatively diverse population. Overall, 73% of parents support
requiring parental informed consent for NBS and for storing or using their child’s DBS. Further analyses revealed that
race/ethnicity, age, and education level significantly affected parents’ opinions.
Conclusion: When given the choice, most parents support requiring informed consent for NBS and DBS practices.
Parental demographic variables play a major role in the differing opinions. These findings suggest that improved
education, including targeted campaigns for people with lower levels of education, is necessary to encourage
knowledge, transparency and trust in NBS and DBS practices.
40
Changing Trends in Indications for Fetal Echocardiography: Impact on Referral Volume
and Prenatal Detection Rates of Congenital Heart Disease
Author Name(s): Jonathan Komisar1, Miwa Geiger, 2 Shubhika Srivastava,3 John Doucette,4 H. Helen Ko,2
Jay Shenoy3, Rajesh Shenoy2
Department: 2Pediatrics
Institution Affiliation(s): 1Icahn School of Medicine at Mount Sinai; 3Mount Sinai Medical Center, New York, NY;
4
Mount Sinai Hospital, New York, NY
Purpose: Obstetric screening guidelines and the indications for fetal echocardiography (FE) have evolved in an
attempt to improve the early prenatal detection of congenital heart disease (CHD). We sought to evaluate whether
these changes in referral patterns for FE over the past decade led to an increased utilization of FE and/or increased fetal
diagnosis rate of CHD at a single tertiary care center in New York City.
Methods: Indications for all FE performed between 2000 and 2010 were categorized and those diagnosed with CHD
were identified. In cases referred for multiple indications, the primary indication obtained from the referring physician
was used. In multiple gestations (MG), all fetuses scanned were included in the analysis. No fetus was counted more
than once. A Mantel-Haenszel test was used to analyze the trends in proportions.
Results: The total number of patients referred for FE increased over ten years. The higher proportion of increase was
in those referred for, suspected CHD, increased nuchal translucency (NT), MG, and suboptimal imaging. The
indication of “suboptimal imaging” had the highest impact on the increase in FE utilization but also also had the lowest
yield for diagnoses of CHD. Suspected CHD remained the indication with the highest yield.
Conclusions: Over the last decade, there has been an increase in utilization of FE with a proportional increase in
prenatally diagnosed CHD. For suspected CHD, NT and MG, increases in referrals have led to a proportionate
increase in fetal diagnosis of CHD. Referral for suboptimal imaging has contributed the most to utilization of FE
resources, but has the lowest yield of fetal diagnosis of CHD. Strategies that balance obstetrical imaging modalities in
this patient population, coupled with increased utilization of FE for indications with a high yield, should continue to
improve the antenatal detection of CHD.
41
Preseason Pediatrics: A Preclinical Hands-on Experience for Medical Students
Author Name(s): Benjamin M. Laitman, Scott Moerdler, Suzanne Friedman, Blair Hammond,
Alefiyah Malbari, Kathleen Gibbs
Department: Pediatrics
Division: General Pediatrics
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Medical students have limited preclinical exposure to pediatrics. In a needs assessment of graduating
medical students at our institution, students reported decreased knowledge, interest and preparedness for the clerkship
when starting their clinical years compared to other fields of medicine. In order to increase preclinical opportunities,
we created an optional experience, “Preseason Pediatrics” (PSP), focusing on pediatric-specific knowledge and clinical
skills.
Hypothesis: PSP would significantly increase students’ pediatrics knowledge, skills, and comfort level.
Methods: Curriculum consisted of monthly didactic sessions, followed by resident mentored hands-on clinical
experiences directly related to the topic of the month. Topics corresponded with courses taught in the medical school at
that time including newborn physical exam, developmental milestones, cardiac exam, and infectious diseases. Students
completed a questionnaire to assess clinical knowledge and attitudes and perceptions towards pediatrics before and
after the program.
Results: 60 students participated in the pilot program. Percent correct scores on a pediatric knowledge assessment
increased from 37% to 63% (p<0.05) and 83% reported feeling more prepared for their pediatric clerkship. Overall,
95% of students would recommend the PSP experience to other students.
Conclusions: PSP is a novel preclinical program introducing medical students to pediatrics. The combination of
didactics paired with clinical experiences improved knowledge of pediatrics and perception of preparedness for their
clerkship. Based on feedback we restructured the sessions for next year to incorporate additional topics including
pediatric rashes and nutrition. We are also expanding the curriculum to include a subsequent year, focused on skills
utilized in the pediatric clerkship and beyond.
42
Uncovering the Genetic Architecture of Congenital Heart Disease:
Ebstein’s Anomaly
Author Name(s): Kathryn B. Landy and Bruce D. Gelb
Department: Pediatrics
Institute Affiliation: The Mindich Child Health and Development Institute
Institution Affiliation(s): Icahn School of Medicine at Mount Sinai; The Graduate School of Biomedical Sciences
Introduction: Congenital heart disease (CHD) is a collection of different phenotypes, affecting 2-3% of neonates.
Ebstein’s anomaly (EA) constitutes ~1% of CHD and is characterized by a malformation of the tricuspid valve, leading
to atrialization of the right ventricle. Mutations in the gene MYH7 have been associated with a small percentage of EA,
but further research into EA genetics is needed.
Hypothesis: De novo mutations cause EA.
Methods: Whole exome sequencing (WES) was performed for affected probands and their unaffected parents. Variant
calling was performed using Mount Sinai’s WES pipeline. Variant classification programs including, plinkseq, gemini
and XHMM were used to detect different types of mutations. Metrics such as CADD and heart expression levels were
used to assess variant pathogenicity, and the literature was used to determine relevance to EA.
Results: WES for 32 trios detected 1.25 de novo mutations/trio. A GUCY1A3 missense mutation predicted to be
pathologic was observed and confirmed with Sanger sequencing. This gene has an established role in heart valve
development. Other de novo missense mutations found in genes with relevance to heart development included
IQGAP1 and ZNF418. No evidence for causal copy number variants or inherited variants was found, nor was a de novo
MYH7 mutation observed.
Conclusions: Analysis of WES data did not reveal de novo or other variants that are likely to be causal for EA, except
for a missense mutation in GUCY1A3. The lack of variants suggests pathogenic variants leading to EA may be in noncoding regions of the genome. This could warrant whole-genome sequencing studies.
43
Relationship Between Living Situation and Substance Use
in an Urban Adolescent Population
Author Name(s): Janet Lee, Angela Diaz, Christopher Ochner
Department: Pediatrics
Division: Adolescent Medicine
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Family structure has been shown to be related to substance abuse. However, little data exists about how
living arrangement may be related to substance use. This study sought to test this potential relationship in an urban
adolescent population.
Hypothesis: We hypothesized that living situation would be related to substance use such that, irrespective of age,
individuals living at home would be more likely to have abused prescription medications than individuals living
alone or with others.
Methods: Data was obtained from a self-reported survey study of the Adolescent Health Center at Mount Sinai
conducted by an independent agency (ICF International). We performed a cross-sectional analysis of baseline data.
Multinomial logistic regressions were performed, controlling for adult status, healthy center vs. community recruitment
group, gender, and zip code.
Results: Results indicated that adolescents who have their own place vs. living with their parents were significantly
more likely to have (ever) abused prescription drugs Exp(B) = 2.12, p = 0.019. However, living in their own place or in
another person’s home relative to with parents was not associated with increased odds of smoking cigarettes, excessive
alcohol use, or marijuana use (all p’s > 0.13).
Conclusions: It is known that most prescription drugs of abuse are obtained from a friend or family member. We
expected living with family/other would lead to a higher likelihood of abusing prescription drugs, as opposed to living
alone. Special consideration should be taken when counseling patients specifically about prescription drug abuse as
part of the “HEADDSS” assessment.
44
Variability of Repeat Egg sIgE Levels
Author Name(s): Tricia D. Lee, Manish Ramesh, Jacob Kattan, Julie Wang
Department: Pediatrics
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Food specific IgE (sIgE) levels correlate with oral food challenge outcomes, however no guidelines
exist regarding the interval to repeat testing. We examined the change for egg sIgE levels over time.
Hypothesis: We hypothesized that extremely high egg sIgE levels are unlikely to change quickly, while low sIgE
levels are likely to vary greatly from year to year.
Methods: This retrospective chart review included all patients at our teaching institution who had egg sIgE drawn on 2
or more occasions and had a diagnosis code of food allergy (693.1), personal history of allergy to egg (V15.03), or
anaphylaxis (995), between January 1, 2003, and November 1, 2012.
Results: 1077 patients had 2 or more egg sIgE levels performed. 206 (19.1%) patients , <2 years old (median age 1.26
years) had an initial sIgE ≥2 kUA/L (95% predictive of clinical reactivity, median sIgE 15.10 kUA/L), and 40 (19.4%)
of these patients (median initial sIgE 4.23 kUA/L) had any subsequent sIgE <2 kUA/L, which all achieved by 5.54 years
old. 394 (36.6%) patients , ≥2 years old (median age 4.87 years ) had an initial sIgE ≥7 kUA/L (median initial sIgE 21.7
kUA/L). Of these patients, 97 (24.6%) patients had any subsequent sIgE <5 kUA/L, and 13 (3.3%) patients (median
initial age 4.57 years, median initial sIgE 11.1kUA/L) had any subsequent sIgE level <2 kUA/L, which all achieved by
10.56 years old.
Conclusions: Patients who have lower initial values and are younger are more likely to have a subsequent sIgE level
<2 kUA/L. Patients should have yearly egg sIgE levels until 11 years of age.
45
Discovering Thyroid Stimulating Hormone Receptor (TSHR)
T-cell Epitopes in Autoimmune Thyroiditis
Author Name(s): Cheuk Wun Li, Francesca Menconi, Roman Osman, Chella David, Erlinda Concepcion,
Yaron Tomer
Department: Medicine
Division: Endocrinology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Graves’ disease (GD) is characterized by hyperthyroidism, production of thyroid stimulating hormone
receptor (TSHR)-stimulating antibodies (TRAb), as well as infiltration of thyroid by T and B cells reactive to thyroid
antigens. The extracellular domain (ECD) of the human TSHR is the crucial antigen in GD. Our lab previously showed
that an HLA-DR variant that contains arginine at position 74 of the DRβ1 chain (DRb1-Arg74) is the specific MHC
variant conferring risk for GD while glutamine is protective. The major TSHR peptide triggering GD remains to be
determined.
Hypothesis: We hypothesized that the key T-cell epitope in GD will bind specifically to the HLA-DRb1-Arg74
pocket.
Methods: We screened 38 TSHR peptides spanning the ECD using a novel in vitro binding assay. After identifying
the best binders to DRb1-Arg74, we tested these peptides using “humanized” NOD-DR3 mice that are null for murine
MHC class II and expressing human HLA-DR3 (DRb1-Arg74 positive). We immunized them with TSHR132 and
TSHR197 and assessed T-cell responses to the peptides using CFSE test of proliferation and evaluating their cytokine
responses.
Results: We identified TSHR132 and TSHR197 as the best binders to DRb1-Arg74, with TSHR132 binding with
higher affinity. NOD-DR3 mice injected with TSHR132 showed T-cell proliferation, accompanied by strong cytokine
responses, but mice injected with TSHR197 did not show T-cell responses.
Conclusions: Our data suggest that TSHR132 is a major TSHR T-cell epitope. Our findings set the stage of designing
inhibitors of binding of TSHR epitopes to HLA-DRb1-Arg74 as a potential novel therapeutic modality in AITD.
46
Exploring the Associations Between microRNA Expression Profiles and Environmental
Pollutants in Human Placenta from the National Children’s Study (NCS)
Author Name(s): Qian Li1*, Maya Kappil1*, An Li2, PS Dassanyake2, Tom Darrah3, Alan E. Friedman4,
Michelle R. Friedman4, Luca Lambertini1, Philip Landrigan1, Chris J. Stodgell4,
Kjersti M. Aagaard5, Eric Schadt6, Jeffrey Murray7, Edward B. Clark8, Nancy Dole9,
Jennifer Culhane10, James Swanson11, Michael Varner8, Jack Moye12, Carol Kasten13,
Richard K. Miller4, Jia Chen1, National Children’s Study Consortium12.
Department(s): Preventive Medicine, Pediatrics, Oncological Science,
Institute Affiliation(s): Icahn School of Medicine at Mount Sinai; 1 School of Public Health, University of Illinois at
Chicago, IL;2 Department of Environmental Sciences, Ohio State University, Columbus OH;3
Departments of Obs/Gyn, of Environmental Medicine, University of Rochester School of
Medicine and Dentistry, Rochester, NY; 4 Department of Obs/Gyn, Baylor School of
Medicine, Houston, TX; 5 Department of Genomics and Multiscale Biology, Ichan School of
Medicine at Mt. Sinai, New York City, NY; 6 Department of Genetics, University of Iowa,
Iowa City, IA; 7 Department of Pediatrics and Obs/Gyn, University of Utah, Salt Lake City,
UT; 8 Department of Pediatrics, University of North Carolina, Chapel Hill, NC;9 The
Children’s Hospital of Philadelphia, Philadelphia, PA;10 Department of Pediatrics, University
of California at Irvine, CA; 11 The National Children’s Study, National Institutes of Health,
Bethesda, MD; 12 Division of Pediatric and Maternal Health, US Food and Drug
Administration, Silver Spring, MD; 13
* These authors contributed equally to this work.
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: The in utero environment plays a critical role on health outcomes of the offspring later in life; of which,
the placenta is a principal component in this environment.
Hypothesis: We hypothesized there are alterations in miRNA expression by known environmental toxicants.
Method: This study analyzed villous samples from 110 placentas collected within 6 hours of delivery from singleton
vaginal deliveries. MicroRNA expression profiling was conducted using the nCounter Analysis System by NanoString
Technologies. The organic pollutants DDE, BPA, PBDEs, PCBs, Hg and lead Pb were measured in these placentas.
Results: Placental miRNA expression levels were highly variable, with 112 miRNAs consistently expressed in >30%
of the samples. Out of the top ten most abundant miRNAs, four miRNAs (mir-517a, mir-517c, mir-522, mir-23a) are
located within the imprinted placenta-specific C19MC cluster. A positive association between congener PBDE209 and
miR-188-5p and an inverse association between PBDE99 and let-7c were observed. Positive associations were also
observed between miR-1537 expression and total PCBs as well as specific congeners 52, and 101. High levels of Hg
and Pb were associated with significant changes in multiple miRNAs, many of them belonging to the let-7. We did not
observe any associations between expression of miRNA and placental DDE or BPA levels.
Conclusion: This is the first study linking exposure to environmental toxicants and microRNA expression in placentas
with normal deliveries. Our results suggest that placental miRNA profiles may function as sensors for in utero
exposures to toxic environmental chemicals. (Supported in part by NIH – LOI-2- BIO-18)
47
The Flavonoid 7, 4'- Dihydroxyflavone Inhibits MUC5AC Gene Expression, Production,
and Secretion Via Regulation of NF-κB, STAT6 and HDAC2
Author Name(s): Changda Liu, 1*David Weir, 2*Paula Busse, 2 Nan Yang,1 Zhenwen Zhou, 1,3 Charles Emala,4
Xiu-Min Li1
* These authors contributed equally to this study
1
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
3
Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, P.R.C
4
Department of Anesthesiology, Columbia University, New York, NY, USA
Department: Pediatrics
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Mucus overproduction is a significant component of the pathophysiology of obstructive lung diseases
with only a few medications available. Previous studies showed that glycyrrhizin, a triterpenoid in Glycyrrhiza
uralensis (G. uralensis) inhibits mucin 5AC (MUC5AC) mRNA and protein expression.
Hypothesis: The aim of the present study was to determine if the G. uralensis flavonoid 7,4'-dihydroxyflavone (7,4'DHF), inhibits MUC5AC gene expression, mucus production and secretion and if so, to elucidate the mechanism of
this inhibition.
Methods: Human airway epithelial cells NCI-H292 were pretreated with 7,4'-DHF for 30 minutes prior to phorbol 12myristate 13-acetate (PMA) exposure. Supernatants and cells were collected 24 hours later and MUC5AC protein
levels and gene expression were measured using ELISA and RT-qPCR, respectably. Phosphorylated-(p-)IκBα, pSTAT6, and HDAC2 expression changes by 7,4'-DHF treatment were measured by Western blot assay. 7,4'-DHF
inhibitory effect on MUC5AC secretion in the bronchoalveolar lavage (BAL) fluid was investigated on established
OVA sensitized and challenged murine asthma model.
Results:7,4'-DHF decreased PMA stimulated NCI-H292 MUC5AC gene expression and mucus production, also
inhibited MUC5AC mucus secretion at a 28 fold lower concentration than glycyrrhizin, associated with the
suppression of NF-κB, STAT6 activation and enhanced HDAC2 expression. In a murine model of asthma, 7,4'-DHF
treated mice exhibited a marked reduction in MUC5AC secretion in the BAL fluid compared with control mice.
Conclusions: These findings demonstrate that 7,4'-DHF is a newly identified component of G. uralensis that regulates
MUC5AC expression and secretion via regulation of NF-κB, STAT6 and HDAC2. 7,4'-DHF may have a potential for
relieving symptoms in mucus hypersecretion related obstructive lung diseases.
48
Visual Evoked Potentials in Autism Spectrum Disorder
Author Names: Stacey Lurie, Paige M. Siper, Vance Zemon, James Gordon, Joseph D. Buxbaum,
Alexander Kolevzon
Department(s): Pediatrics, Psychiatry
Division(s): Child and Adolescent Psychiatry
Institute Affiliation(s): Icahn School of Medicine at Mount Sinai
Introduction: There is a critical need to identify objective measures that quantify neural functioning in children with
autism spectrum disorder (ASD), particularly those who are severely affected. Visual evoked potentials (VEPs) offer a
noninvasive technique to probe disease pathophysiology and may be used as an electrophysiological biomarker that
reflects specific neural mechanisms in the brain, including the balance between glutamatergic and GABAergic activity.
Hypothesis: We expect children with idiopathic and monogenic forms of ASD to display selective abnormalities in
early-stage visual processing that are distinct from typically developing (TD) controls.
Methods: VEPs were extracted from ongoing electroencephalography (EEG) using a single recording channel. A
contrast-reversing checkerboard stimulus was used to elicit a transient VEP, which produces a characteristic waveform
and enables the examination of multiple frequency mechanisms. VEPs were obtained from children with idiopathic
ASD, Phelan-McDermid syndrome (PMS), and TD controls between the ages of 2-12.
Results: Results indicate that both the ASD and control groups demonstrate the characteristic waveform with no
significant differences in response latencies. Amplitudes were significantly smaller in the ASD group. Results from a
frequency domain analysis indicate that the ASD group shows significantly weaker activity in several frequency bands.
Children with PMS display distinct transient VEP responses relative to both the idiopathic ASD and TD groups.
Conclusions: These results support findings from animal models which indicated glutamatergic dysregulation
in PMS (Yang et al. 2012, Bozdagi et al. 2013). In addition, VEPs may have the capacity to yield objective, rapid,
and reliable biomarkers of idiopathic ASD.
49
Surgical Treatment of Pediatric Craniofacial Fractures: A National Perspective
Author Name(s): Benjamin B. Massenburg, Paymon Sanati-Mehrizy, Peter J. Taub
Department: Surgery
Division: Plastic and Reconstructive Surgery
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: This study aimed to characterize the cost, demographics, and short-term complications associated with
the surgical and non-surgical repair of craniofacial fractures in the pediatric inpatient population in the United States.
Methods: A retrospective cohort study was performed using the 2012 Kids’ Inpatient Database which identified
20,070 patients who had a skull or facial fracture, of whom 5,324 (26.5%) were treated surgically. Epidemiologic
patient and hospital data were analyzed and analyzed as potential determinants of surgical treatment, prolonged
hospitalizations, and higher charges.
Results: Pediatric craniofacial fractures are estimated to represent $1.2 billion of national healthcare expenditures
annually. The average hospital charge for surgical treatment of a craniofacial fracture in the pediatric population is
$80,896 compared to $56,278 for non-surgical management (p=0.000). The average length of stay was not
significantly different for surgical treatment compared to non-surgical management for craniofacial fractures (5.0 days
vs. 4.8 days, p=0.102). Demographics showed that 70.6% of all pediatric craniofacial fractures were male and that the
incidence of craniofacial fractures increased with age. The incidence of surgical repair of craniofacial fractures also
increased with age. The most common causes of craniofacial fractures were motor vehicle traffic (27.0%), fall (21.9%),
accidental/intentional strike by object/person (18.6%), and bicycle accidents (3.2%).
Significantly longer hospitalizations occurred in older patients, females, motor vehicle accidents and in hospitals in the
South geographic region, in rural areas, teaching hospitals, and government-owned hospitals. Significantly higher
charges were associated with older patients, motor vehicle accidents and with hospitals in the West geographic region,
in rural areas, large hospitals, and private for-profit hospitals.
Conclusions: Though the incidence of craniofacial fractures in the pediatric population is low, it still represents a large
economic burden on the patient, family and healthcare system. The identified demographics that are associated with
both prolonged hospitals stays and higher charges may represent potential barriers to care, and additional research to
elucidate these factors is warranted.
50
Learning by Educating: Mastering Pediatric Core Competencies Through
Simulation Case Development and Implementation
Author Name(s): Sheera Minkowitz, Keila Veiga, Sheemon Zackai M
Department: Pediatrics
Division: Pediatric Intensive Care
Institute Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Traditional pediatric simulation curriculums have generally focused on “mock codes” that are heavily
weighted toward emergent situations. A simulation curriculum should however encompass the varied general pediatric
topics as listed in the pediatric core competencies. In traditional simulation exercises the resident typically participates
as an active learner. Asking the resident to take part in the scenario and curriculum development might significantly
enhance the learning experience. Participation in case development encourages the resident to think about topics on
multiple levels including communication, medical knowledge and skills. After review of the literature we created a
novel template and tool for residents to design their own simulation scenario and debrief for compilation into a
curriculum.
Summary: As part of the pediatric acute care rotation residents have been asked, with faculty guidance, to take the
role of educator and facilitator by creating a simulation scenario and debrief. These cases are reviewed with a plan to
compile and publish them at the end of each academic year.
Discussion: Broadening simulation scenarios to include topics as listed in the ACGME pediatric core competencies
will improve resident comfort with both general and emergent pediatric situations. We hypothesize that by preparing
cases, residents will learn new skills and have the ability to identify common themes in medical scenarios which will
further enhance the resident experience.
51
Remission Induction in Mixed Lineage T/Myeloid Leukemia with Clofarabine in Patients
who Fail ALL-type Therapy Followed by Hematopoietic Stem Cell Transplantation
Author Name(s): Sheera Minkowitz*, Jaclyn Davis*, Bruce Petersen, Birte Wistinghausen MD*
Department(s): *Pediatrics, Pathology
Division: Hematology/ Oncology
Institution Affiliation: Kravis Children’s Hospital, Icahn School of Medicine at Mount Sinai
Introduction: Mixed phenotype leukemias, a rare subset of leukemia with poor prognosis compared to ALL or AML,
require aggressive treatment without any known standard of care. Treatment includes chemotherapy with AML or
ALL type regimen to achieve complete remission (CR) followed by hematopoietic stem cell transplantation (HSCT).
The Mount Sinai pediatric experience with acute T-Myeloid leukemia (AT-ML) was reviewed.
Cases: A 15 year old female, a 5 year old male and a 18 year old male were diagnosed with AT-ML between 2009
and 2014 by immunophenotyping of bone marrow aspirates using flow cytometry: Patient 1: CD3+, MPO partial+,
CD34 partial+, CD117+, Tdt dim+. Patient 2: CD3+ and CD14+, CD64+, CD34 partial+. Patient 3: CD3+ and
MPO+, CD4 partial dim+, CD117 partial dim+. Patients received ALL-type induction chemotherapy. Only patient 1
achieved CR. Patient 2 and 3 required retrieval therapy but only achieved remission with negative MRD after addition
of clofarabine. All three underwent HSCT without relapse. The third patient died 190 days after HSCT due to
transplant related complications.
Discussion: We report three cases of AT-ML that achieved MRD negativity prior to HSCT which has been associated
with improved prognosis in ALL. Based on our and others experience ALL type induction regimen are reasonable.
Instead of switching to AML type therapy, early initiation of clofarabine may be indicated to improve prognosis of
HSCT if negative MRD is not achieved at the end of induction.
52
A Longitudinal Approach to Developing Educators in Medicine:
The Pediatric Resident Teaching Group
Author Name(s): Scott Moerdler, Suzanne Friedman, Benjamin Laitman, Alefiyah Malbari,
Kathleen Gibbs, Blair Hammond
Department: Pediatrics
Division: Pediatric Medical Education
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Background: The approach to developing residents as teachers is variable, often consisting of workshops or rotations.
We created a pediatric resident teaching group (PRTG) open to residents in any year of training to provide a
longitudinal approach to developing and utilizing teaching skills and career development as medical educators.
Methods: A longitudinal pilot curriculum of learning theory and technique was taught by senior pediatric faculty in
monthly sessions. Topics included Teaching Skills, Setting Goals, Creating a Learning Climate, Questioning as a Tool,
Bedside Teaching and Giving Effective Feedback. This enhanced the existing resident as teacher (RAT) curriculum as
it spans the entire 3 years of residency, is open to residents in all years of training, provides extensive monthly formal
lectures on teaching methods and uniquely allows residents to apply these skills by acting as resident mentors for
preclinical medical students. PRTG members developed and taught a series of didactics to medical students and
received direct feedback from faculty on content and presentation skills. Subsequently, members supervised medical
students in interactive patient experiences. Residents completed a survey measuring their comfort level teaching and a
self-assessment of their skills prior to participating in the program and at completion of the first year.
Results: In this pilot year, 16 pediatric residents (26% of residency program) participated, all of whom completed the
pre-survey; 13 completed the post-survey. Chi square tests were used for analysis of the data. Residents’ confidence in
their ability to effectively teach doubled at the end of the program. Their comfort in developing interactive lessons
increased three-fold (p-value <0.05). There was an increase in residents’ comfort teaching and perception of teaching
skills, with 84% and 92% respectively strongly agreeing or agreeing, based on a 5 point Likert scale. 100% of nongraduating residents who completed the post-survey intend to continue participation in the PRTG.
Conclusion: The PRTG is a novel program to enhance teaching skills as early as intern year and support residents’
development into medical educators. This novel yearlong approach and departure from the traditional RAT curriculum
increased resident reported use of teaching skills and comfort teaching. Based on pilot year data, this academic year
the PRTG has expanded to include 23 residents with implementation of a more in depth curriculum. Future plans
include teaching residents to develop curriculums and educator’s portfolios and objective assessment of resident
teaching skills before and after the program.
53
Mutants and Morphants: Can’t We All Just Get Along?
Author Name(s): Shikha Nayar, Nataly Shtraizent, Jaime Chu
Department: Pediatrics
Division: Gastroenterology & Hepatology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Morpholino oligonucleotides (MO) have been widely used in zebrafish to drive gene discovery and
study disease phenotypes. However, one recent study by Kok et al., Dev Cell 2015 has shed controversial criticism on
the ability of MO to recapitulate mutants of the same gene. We previously published the use of MO to knockdown
mannose-6-phosphate isomerase (Mpi) to study a congenital disorder of glycosylation (MPI-CDG). Here, we show the
various tools that can be used to validate morpholino specificity.
Hypothesis: MO-mediated Mpi knockdown in zebrafish is specific and reveals a new role of p53 in mannose
metabolism.
Methods: mpi MO is injected into zebrafish embryos via microinjection. Mpi enzymatic measurements are done using
fluorometric assays. MO-injected embryos can be treated with mannose, injected into p53-/- MT lines, or co-injected
with mpi mRNA. Cleaved caspase 3 staining is used as a marker for apoptosis. Fertilized eggs are injected with
transcription activator–like effector nuclease (TALEN) mRNAs targeting mpi.
Results: Mpi-deficient zebrafish display morphological defects with correlated decreases in Mpi enzyme activity in the
range reported for MPI-CDG patients. We observed significant rescue of the morphant phenotype with 1.) mpi mRNA,
2.) exogenous mannose supplementation, and 3.) concurrent p53 knockdown (similar to our findings in tissue culture).
Zebrafish heterozygous for the mpi TALEN mutation have been identified in the F1 generation.
Conclusions: Here, we validate our established mpi MO phenotype using a number of different methods, and conclude
that morpholinos can still be valuable to uncover developmental processes with thorough control experiments.
54
Impact of Pasteurization on the Oligosaccharide Concentration of Human Breast Milk
Author Name(s): Sarah A. Nitka, Aimee R. Herdt, Javier Pacheco-Quinto, Caryn Peters, Nancy Mejias-Cepeda,
Annemarie Stroustrup, Robert D. Voyksner, Denise C. Hassinger
Department: Pediatrics
Division: Newborn Medicine
Institution Affiliation: Icahn School of Medicine at Mount Sinai & Morristown Medical Center
Background: Despite decades of improvements to preterm formulas, human milk remains the best and safest enteral
nutrition for preterm infants. Human milk feeding is associated with a decreased incidence of sepsis and necrotizing
enterocolitis (NEC) among preterm infants. Specific human milk oligosaccharides are thought to play a preventative
role against NEC. Therefore, if a mother’s breast milk is inadequate or unavailable, administration of pasteurized
donor breast milk to preterm infants is recommended. Holder pasteurization is a widely used method of processing
breast milk by donor banks and the impact of pasteurization on the concentration of oligosaccharides remains unclear.
Objective: To evaluate the impact of pasteurization on the concentration of diasialyllacto-N-tetraose (DSLNT) which
has been shown to reduce NEC in neonatal rats.
Methods: Pasteurized and unpasteurized breast milk was evaluated. Milk was thawed, pooled (n=3), treated, and
analyzed by LC/MS (ESI-Q-TOF). Milk was heated to 62.5 ᴼC for 30 minutes (Holder) or 72 ᴼC for 15 seconds
(flash). Samples were filtered, purified and concentrated prior to MS analysis.
Results: Holder pasteurization decreased the concentration of DSLNT in breast milk samples (68.1% ± 5%), while FP
had no effect on the concentration in the same samples.
Table 1. ESI-Q-TOF Analysis of
DSLNT
Results*
Treatment
Peak Area
DSLNT Conc. (µM)
% Loss of DSLNT
w/pasteurization
Unpasteurized
4.09 x 106
177.5 ± 24
----------
Holder
1.63 x 106
57.0 ± 10**
68.1 ± 5
Flash
4.52 x 106
201.5 ± 43
----------
* Data presented as the mean of
two sample batches ± SE
**p < 0.05, Unpaired students t-test
Conclusions: Flash pasteurization was superior to Holder pasteurization in preserving the DSLNT concentration in
breast milk. Confirmation of this result in a larger number of samples and evaluation of the impact of other donor bank
methods is ongoing.
55
Bacterial Culture Result in Pediatrics at Elmhurst Hospital Center in 2014
Author Name(s): Chikara Ogimi, Shanna Kowalsky, David Rhee
Department: Pediatrics
Institution Affiliation: Elmhurst Hospital Center
Introduction: Bacterial cultures are very important when evaluating patients with suspected bacterial infection. While
definitive antibiotic therapy is based on culture results, the initial selection of empiric antibiotic therapy should be
guided by the susceptibility from the antibiogram of a specific community. However, ordering cultures without
thoughtful and rational consideration are not productive or cost-effective. In addition, contamination with
inappropriately-sterilized technique can potentially lead to unnecessary hospital stays and medical costs.
Hypothesis: We hypothesized that there may be a non-negligible number of contaminants and unnecessary cultures.
We also hypothesized that our usual practice of selecting empiric antibiotics may not be based on the evidence of
susceptibility in our community.
Methods:We prospectively gathered the results of all bacterial cultures in the Department of Pediatrics at Elmhurst
Hospital Center from May 12, 2014 to Dec 31, 2014.
Results: We found a significant number of throat cultures with a low positive rate (6.4%, 151/2,354). The positive rate
of real bacteremia was only 0.7% (9/1,271). Although the contamination rate of blood cultures was not high (0.6%),
that of CSF cultures was high (3%, 3/90). Our own antibiogram was made based on our patient population.
Conclusions: When ordering bacterial cultures, strong consideration should be given to the appropriate indications for
these tests. Additionally, careful aseptic technique is desired for sample collection. By using this antibiogram, we hope
that clinicians will be able to select more reasonable empiric antibiotic therapy for patients with suspected bacterial
infections.
56
Genetic and Allele-Specific Expression Analysis of Congenital Heart Disease
Author Name(s): Neil Patel, Andrew J. Sharp, Bruce D. Gelb
Department: Pediatrics
Institution Affiliation: Icahn School of Medicine at Mount Sinai, New York, NY 10029
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Congenital heart disease (CHD) is the most common birth defect with an estimated prevalence of 0.8%
in live births. Changes in the expression pattern of key developmental genes contribute to CHD and allele-specific
expression (ASE), the preferential expression of one of two alleles in a diploid genome, has been hypothesized as
possible mechanism.
Hypothesis: The goal of this project was to identify novel CHD genes by creating a pipeline to determine if ASE
contributes to CHD pathogenesis.
Methods: Whole exome sequencing and RNA-seq data were obtained from 140 individuals in the Congenital Heart
Disease Genetic Network Study of the NHLBI-funded Pediatric Cardiac Genomics Consortium. Genomic alignments
and allelic counts were generated and several customized filters were implemented to determine genomic sites prone to
mapping errors leading to erroneous allelic counts.
Results: SNPs (n=523) demonstrated evidence of ASE across 378 unique genes with an average of 4.15 ASE sites per
individual. Thirty-one of these sites occurred in known imprinted regions. Three SNPs demonstrated evidence of
nonsense-mediated decay. Of SNPs demonstrating ASE, 22 occurred in genes implicated in CHD, including PLAG1,
CRELD1, and MYH6; seven of these were rare missense changes.
Conclusions: Systematic biases associated with mapping RNA-Seq data makes detecting ASE challenging, although
some evidence for ASE in CHD-related genes can be detected. Future work will include validation of candidate ASE
sites and functional analysis of the true positives.
57
Dilated Intercellular Spaces and Increased Esophageal Permeability
in Eosinophilic Esophagitis
Author Name(s): Mary Ellen Riffle1, Ronald E. Gordon2, Mirna Chehade1
Department(s): 1Pediatrics, ²Pathology
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Eosinophilic esophagitis (EoE) is an esophageal inflammatory disease triggered by food/environmental
allergens. Dilated intercellular spaces (IS) are seen in the EoE esophagus. We aimed to assess for disruption of major
regulators of the esophageal epithelial barrier in EoE and to study the extent of IS dilation throughout the esophageal
epithelium.
Hypothesis: Patients with EoE have a disrupted esophageal epithelial barrier.
Methods: Real time PCR was performed on esophageal biopsies (8 EoE/7 controls) for regulators of tight junctions
(CLDN-1,3,4), adherens junction (CDH1), and desmosomes (DSG-1,2,3). Using images captured via electron
microscopy (EM) (5 EoE/4 controls), IS were measured in the various layers of the esophageal epithelium.
Results: Esophageal CLDN-1, DSG-1, and DSG-3 mRNA expression was significantly down-regulated in EoE
compared to controls (CLDN-1: 0.98 vs 5.96, p=0.03; DSG-1: 0.11 vs 14.48, p=0.0003; DSG-3: 22.63 vs 304.10,
p=0.001). CLDN-4 mRNA expression was up-regulated in EoE compared to controls (92.87 vs 39.58, p=0.02). CDH1,
DSG-2, and CLDN-3 mRNA levels were comparable or undetectable. On EM, an increase in IS in the stratum
spinosum and germinativum was seen in EoE patients compared to controls.
Conclusions: We found significant down-regulation of desmosomes and of CLDN-1, a key regulator of the tight
junction barrier in EoE. Dilated IS were found in the deeper layers of the esophagus where DSG-1,3/CLDN-1 are
mostly expressed. Our findings are likely specific to EoE, since the opposite is seen in gastroesophageal reflux disease.
Reduction in DSG-1,3/CLDN-1 expression may potentially enhance food/environmental antigen penetration, enabling
greater allergen sensitization in EoE.
58
Esophageal Granular Cell Tumor and Eosinophilic Esophagitis:
More than a Coincidence?
Author Name(s): Mary Ellen Riffle1, Alexandros D. Polydorides², Jessica Niakan², Mirna Chehade1
Department(s): 1Pediatrics, ²Pathology
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Granular cell tumors (GCTs) are neuroectodermal tumors arising throughout the body at sites of
scarring/inflammation. Eosinophilic esophagitis (EoE) is characterized by esophageal symptoms and esophageal
eosinophilia (≥15 eosinophils/HPF) despite proton pump inhibitor (PPI) therapy. We sought to determine the
prevalence of esophageal eosinophilia, and EoE in particular, in patients with esophageal GCTs.
Hypothesis: Esophageal GCTs are linked to esophageal eosinophilia including EoE.
Methods: The Mount Sinai pathology database was searched for esophageal GCT specimens received 1995-2014.
Slides were reviewed and GCTs were scored for atypical cytological features and eosinophilic infiltration of the tumor.
Surrounding esophageal mucosa was evaluated for eosinophilia (≥15 eosinophils/HPF). Medical records were
reviewed.
Results: From a database of >30,000 esophageal cases (4.3% with EoE/esophageal eosinophilia), 25 esophageal
GCTs were identified, 18 of which (16 adult/2 pediatric) were available for review. Two GCTs displayed atypical
features. 4/16 adult cases had concurrent esophageal eosinophilia. Two of these were confirmed to have EoE, one had
PPI-responsive esophageal eosinophilia, and one had not received PPI. Both pediatric esophageal GCT cases had
confirmed EoE. 12/18 GCTs had eosinophils in the tumor, and all 6 cases with esophageal eosinophilia also had
eosinophils in the tumor.
Conclusion: Esophageal GCTs are rare in adults and children. Significant eosinophilia of surrounding esophageal
mucosa was present in 25% of adult and 100% of pediatric GCTs; the majority had confirmed EoE. Eosinophilic
infiltration of the tumor was seen in 67% of cases. Further research into an underlying immunologic/inflammatory link
between EoE and esophageal GCTs is needed.
59
Modeling Multifocal Atrial Tachycardia and Hypertrophic Cardiomyopathy in Costello
Syndrome Using Patient-Derived iPSCs
Author Name(s): Nelson A. Rodriguez, Rebecca Josowitz, Salomeh M. Salari, Bruce D. Gelb
Department: Pediatrics
Institution Affiliation: Graduate School of Biomedical Sciences at Mount Sinai
Institute Affiliation: Mindich Child Health and Development Institute
Introduction: RASopathies are inherited disorders of the RAS/MAPK pathway and clinically associated with aberrant
transformative effects in cellular signaling. Patients with Costello syndrome (CS) have gain-of-function mutations
exclusively in the HRAS gene. Fifty percent of CS patients develop multifocal atrial tachycardia (MAT), a difficult-totreat tachyarrhythmia, and/or hypertrophic cardiomyopathy (HCM), thickening of heart muscle, during infancy/early
childhood. The pathogenesis by which HRAS mutations result in MAT or HCM in CS patients remains unknown.
Hypothesis: We hypothesize that overactive HRAS activity contributes to abnormal calcium handling and triggers
arrhythmogenesis and cardiomyopathy in the developing heart of CS patients.
Methods: With CS patient-derived iPSCs, we are utilizing gene editing tools to generate isogenic lines to study the
absolute effects of HRAS gain-of-function mutations within iPSC-derived cardiomyocytes. To directly assess MAT,
we are employing an atrial gene-specific reporter to isolate atrial cardiomyocytes from culture.
Results: Irregular intracellular calcium handling is present in cardiomyocytes differentiated from CS patient derived
iPSCs, when compared to wild-type iPSCs derived cardiomyocytes. With a CRISPR gene editing efficiency of 0.1%,
we corrected the point mutation in the HRAS gene of a CS patient-derived iPSC line.
Conclusions: Overactive HRAS activity and MAPK dysregulation may influence atrial cardiomyocyte differentiation
and calcium handling, thus providing insight into the pathogenesis of HCM and MAT in CS.
60
Transition of IBD Care: Assessment of Transition Readiness Factors and Disease
Outcomes in a Young Adult Population
Author Names: Danya Rosen, Rachel Annunziato, Eyal Shemesh, Aaron Lipskar, Jean Fred Colombel,
Marla Dubinsky, Keith Benkov
Department: Pediatrics
Division: Gastroenterology and Hepatology
Institution: Icahn School of Medicine at Mount Sinai
Introduction: The incidence of Inflammatory Bowel Disease (IBD) in the pediatric age group is increasing, and
patients may become lost to follow up during transition to adult care.
Hypothesis: A subset of patients are at risk for worse outcomes during the transition period.
Methods: IBD patients ages 18-25 were surveyed at an outpatient visit with a pediatric or adult gastroenterologist.
Medical records were reviewed to assess compliance and ED visits/hospitalizations during a 6 month follow up period.
Results: 95 patients were surveyed. Average age was 23.5(±2.2) years in the adult setting (n=46) and 20.5(±1.6) years
in the pediatric setting (n=49). In the adult setting, 17 patients had never been followed by a pediatric
gastroenterologist. Of the remaining 29 patients, 34% reported their pediatric gastroenterologist had not mentioned
transition. 25% were not given the name of an adult GI to contact, and 42% reported records were not sent. In the
pediatric setting, 49% reported that transition had not been discussed. 55% of pediatric patients did not feel ready to
transition and of those, 15% missed appointments or infusions during a preliminary 4-month follow up period. Average
Transition Readiness Assessment Questionnaire (TRAQ) self-management score was significantly higher in the adult
setting (3.7±0.9 vs. 3±0.9, p<0.001).
Conclusions: Transition is not being universally discussed by pediatric gastroenterologists, and many young adults do
not identify themselves as being ready to transition. By assessing transition readiness and identifying early predictors
of transition success, we can work towards establishing a transition program that meets the needs of all IBD patients.
61
Prenatal Arsenic Exposure and Childhood Blood Pressure at 4-6 Years of Age
Author Name(s): Alison P. Sanders, Katherine Svensson, Chitra Amarasiriwardena, Priyanka Basnet,
Adriana Mercado-García, Lourdes Schnaas, Andrea A. Baccarelli, Martha M. Tellez-Rojo,
Chris Gennings, Lisa M. Satlin, Robert O. Wright
Department: Preventive Medicine
Division: Environmental Health
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Prenatal metal exposure occurs during a susceptible period of renal development and may program later
life cardiovascular and renal disease.
Hypothesis: We hypothesized that prenatal exposure to arsenic would alter childhood blood pressure measured at 4
years of age.
Methods: Systolic and diastolic blood pressure (SBP and DBP) was obtained using a Dinamap automated oscillometer
from 397 children between 4 and 6 years of age in the PROGRESS cohort located in Mexico City, Mexico. Maternal
blood arsenic levels collected in the second trimester were analyzed via inductively coupled plasma-mass
spectrometry. We performed linear regression to examine the associations between prenatal arsenic levels and
children’s SBP, DBP, and pulse pressure (μSBP-μDBP) adjusting for child’s age, sex, body mass index, as well as
maternal education and environmental tobacco smoke.
Results: Maternal arsenic levels ranged between 0.03 and 1.9 μg/dL. Maternal second trimester arsenic exposure was
significantly associated with decreased childhood SBP (p=0.05) and pulse pressure (p=0.002).
Conclusions: These findings suggest that prenatal arsenic exposure may contribute to subclinical changes in the
developing kidney or cardiovascular system. Future studies will assess the contributions of early life metal exposure to
blood pressure outcomes at 7 years of age.
62
Trends in Soy sIgE Levels in Food Allergic Patients
Author Name(s): Edith Schussler, Manish Ramesh, Jacob Kattan, Julie Wang
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Department: Pediatrics
Division: Allergy and Immunology
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Soy allergy is one of the most common food allergies affection 0.4% of children. We examined trends
in soy serum IgE levels over time.
Hypothesis: We hypothesized that at some levels soy sIgE levels may not change significantly in the course of 1 year
and yearly testing may not be indicated.
Methods: This was a retrospective chart review of all patients at our teaching institution who had soy sIgE drawn on 2
or more occasions and had a diagnosis code of 693.1 (food allergy) or 995 (anaphylaxis), between January 1, 2003 and
January 1, 2013.
Results: Those with starting values of >5 kUA/L showed greater variability in their levels on subsequent visits (median
change -1.04, mean -0.17, range -63.9 to 77.1), than those with starting values of <5 kUA/L, (median change 0, mean
0.85, range -28.4 to 32.84). When initial soy sIgE was determined before age 3 years (147 patients), levels tended to
rise over the course of 1 year (median sIgE change 0 kUA/L, mean change 4.5 kUA/L, median interval between visits 1
year), whereas levels determined after age 3 years (168 patients) tended to decrease (median sIgE change -0.25 , mean
change -1.51, median interval between visits 1.2 years).
Conclusions: Patients with initial soy sIgE >5kUA/L show greater variability in levels on subsequent visits than those
with levels <5 kUA/L. When initial soy sIgE was performed under age 3, subsequent levels tended to increase. When
levels were performed above age 3, levels trended down on subsequent visits.
63
Follow-Up After a Mental Health Hospital Discharge
Author Name(s): Sandeep Sharma1, Barbara Rabin Fastman1, Eyal Shemesh2, Amy Balbierz1,
Lawrence C. Kleinman1,2
Department(s): 1Population Health Science and Policy, 2Pediatrics
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Objective: To identify constructs in optimal follow-up care
Study Design: 2-stage systematic-scoping literature review. Stage 1 was an ad hoc review by a clinical expert,
included 29 articles producing a conceptual model. Stage 2, searches were conducted on MEDLINE, EMBASE,
Cochrane Library and PsycINFO. The work was part of a national measure development project.
Results: We found 8835 articles using identified search terms which reduced to 653 on the basis of reviewing titles,
abstracts, and articles. We identified major categories as: 1) coordination and continuity 2) privacy and
confidentiality 3) medication management 4) health information technology 5) reminders.
Coordination and continuity are distinct constructs within the broad topic of coordination of care for patients receiving
mental health care. Follow-up care coordinators improved coordination and continuity. Reminder interventions were
mixed in effectiveness to promote follow up. Texting and postcards were not effective compared to a human
interaction phone call reminder. Advancement of health information technology in follow-up care resulting in better
clinical outcomes is uncertain.
Confidentiality and privacy in practice may hinder coordination by delaying or preventing sharing of patient
information between providers. Encrypted e-mails facilitated communication between providers for multidisciplinary
care. However, while convenient for the patient, unsecured e-mail use between patient and provider precipitated
concerns of privacy, confidentiality, and potential misuse of personal health information.
Conclusions: Follow-up care requires coordination and continuity across mental health and primary care health
systems. Confidentiality and privacy rules hinder the sharing of patient information and greater patient engagement.
Phone call appointment reminders were more effective than other methods.
64
The Relationship between Anxiety and Tic Severity Revisited: Beyond DSM Classification
Author Name(s): Zoey A. Shaw, Julia A. C. Case, Laura Ibanez Gomez, Amira Hanna, Barbara J. Coffey,
Vilma Gabbay
Department: Psychiatry
Division: Division of Tics, OCD, and Related Disorders
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: The relationship between anxiety and tic severity in Tourette’s Disorder (TD) has long been
documented. TD youth have high rates of anxiety disorders; findings have been limited to categorically-defined DSM
anxiety disorders, thus excluding dimensional analyses of anxiety severity. We sought to examine the distribution of
anxiety severity in youth with TD, and the relationship between anxiety—evaluated quantitatively and categorically—
and tic severity.
Hypotheses: 1) Anxiety severity among TD youth would be higher than in healthy controls (HC); 2) findings would
remain significant when subjects with anxiety disorders were excluded; and 3) anxiety severity would be associated
with tic severity both dimensionally and categorically.
Methods: Sample was 72 youth with TD, referred for tics and not anxiety, and 37 HC. Analysis of covariance was
used to compare HC and TD groups on measures of anxiety severity. To examine relationships between anxiety and tic
severity, Spearman correlations were applied.
Results: TD subjects had significantly higher anxiety severity compared to HC. Findings remained significant when
subjects with DSM-IV anxiety disorders were excluded. Anxiety scores were significantly positively correlated with
total tic, tic-related impairment, and global severity scores. Two categorically distinct high and low anxiety TD
subgroups were created; findings revealed the high-anxiety TD subjects had significantly greater total tic scores than
low anxiety TD subjects.
Conclusions: These findings support our hypotheses regarding the relationship between anxiety and tic severity, and
the importance of using of a dimensional approach to account for anxiety variability in TD patients.
65
Ambient Ozone Exposure and Children’s Acute Asthma in
New York City: A Case-Crossover Analysis
Author Name(s): Perry E. Sheffield1, Jiang Zhou2, Jessie Loving-Carr Shmool2,
Jane E. Clougherty2
Department: Preventive Medicine
Division: Environmental Health
Institution Affiliation(s): 1Icahn School of Medicine at Mount Sinai; 2University of Pittsburgh Graduate
School of Public Health, Department of Environmental and Occupational Health,
Pittsburgh, PA
Introduction: Childhood asthma morbidity has been associated with ambient ozone. Varying effects of ozone by
child age and sex, however, have been less explored.
Hypothesis: We hypothesized that subcategories of child age and sex would show different associations between
short-term ozone concentrations and asthma events.
Methods: This study evaluates associations between ozone exposure and asthma emergency department visits and
hospitalizations among boys and girls aged 5-17 years in New York City for the 2005-2011 warm season. Timestratified case-crossover analysis was conducted controlling for same-day and delayed effects of temperature and
relative humidity.
Results: For an increase of interquartile range (0.013 ppm) in ozone, there was a 2.9-8.4% increased risk for boys
and 5.4-6.5% for girls in asthma emergency department visits; and 8.2% increased risk for girls in hospitalizations.
Among girls, we observed stronger associations among older children (10-13 and 14-17 year age groups). We did
not observe significant modification by age for boys. Boys exhibited a more prompt response (lag day 1) to ozone
than did girls (lag day 3), but significant associations for girls were retained longer, through lag day 6.
Conclusions: Our study found variation in associations between short-term ozone concentrations and asthma events
by child sex and age. These differences for boys and girls, before and after puberty, may point towards both social
(gendered) and biological (sex-linked) sources of effect modification.
66
Parent / Child Perceptions of Children’s Readiness to Self-Inject Epinephrine
Author Name(s): Caitlin Shneider, Evan Wiley, Brianna Lewis, Melissa Rubes, Eyal Shemesh, Rachel A. Annunziato,
Scott H. Sicherer
Department: Pediatrics
Division(s): Allergy and Immunology; Behavioral and Developmental Health
Institution Affiliation: Icahn School of Medicine at Mount Sinai; Department of Psychology at Fordham University
Institute Affiliation: The Mindich Child Health and Development Institute; Jaffe Food Allergy Institute
Introduction: To decide upon a food-allergic child’s autonomy, the parent and child must be comfortable with the
child self-injecting epinephrine; however, little is known about the consistency of parent-child assessment of this
responsibility.
Hypothesis: We hypothesized that there will be substantial agreement (Kappa > 0.7) between parent and child reports,
but less agreement with adolescents.
Methods: Children with food allergies ages 8-18 years and their parents attending a food allergy clinic independently
completed surveys containing the query: “Can you (your child) use an epinephrine auto-injector on your (his/her) own
if needed” (“Never”, “Sometimes”, “Most of the time,” “Always” or “Don’t know”). We predefined a child (ages 8-11
years) and an “adolescent” (ages 12-18 years) age group.
Results: There were 413 parent-child pairs (273 children, 140 adolescents). Overall, 38% of parents and 22% of
children reported “don’t know”; those responses were excluded from the correlational analyses. In the child age group,
parents and children’s perception about the child’s ability to self-inject aligned well with each other (Kappa=.79), but
there was substantial disagreement between adolescents and parents (Kappa = .48). Even in instances in which an
auto-injector was previously used (34.9% of the sample), many parents reported that they "don't know" if their child
(33.7%) or adolescent (32.8%) can self-inject, and agreement between parents and adolescents remained low
(Kappa=.44).
Conclusions: Parents and adolescents disagree about whether the adolescent can self-inject epinephrine. This lack of
agreement may lead to confusion in decisions related to granting autonomy to the food-allergic adolescent.
67
A Novel Negative Feedback Loop of p53 and Mannose Phosphoisomerase (Mpi)
is Essential in Development and Cancer
Author Name(s): Nataly Shtraizent, Shikha Nayar, Jaime Chu
Department: Pediatrics
Division: Pediatric Gastroenterology and Hepatology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: p53 is instrumental in defining cell fate, both in development and in cancer. High expression of p53
correlates with increased proliferation and glycolytic energy production. Mannose phosphoisomerase (Mpi) functions
to regulate the levels of metabolic intermediates and is an essential embryonic survival factor. Both p53 and Mpi have
been shown to independently regulate glycolysis, although our data point to a novel co-regulation essential for
development.
Hypothesis: Mpi is both a negative regulator of p53 and a p53-responsive gene and this feedback loop is essential for
cell survival.
Methods: We measured Mpi activity and expression following UV irradiation in a wild type or p53-null background,
as well as p53 expression and transcriptional activity following mpi shRNA knockdown or mpi mRNA injection in
both zebrafish embryos and primary and cancer cell lines. In addition, UV-induced cell damage is assessed by acridine
orange staining.
Results: UV-induced increase in p53 led to dose-dependent decreases in Mpi activity. In parallel, morpholinomediated Mpi knockdown resulted in increased p53 and its transcriptional targets. Apoptotic phenotype resulting from
UV treatment was rescued by mpi overexpression in zebrafish embryos. This co-regulation was recapitulated in
primary tissue culture cells. However, in cancer cells, this reciprocal relationship was lost .
Conclusions: Mpi down-regulates p53 and upon stress up-regulation of p53 leads to down-regulation of Mpi. This
negative feedback loop could be a key in regulation of cell proliferation and survival in both emrbyogenesis and in
cancer.
68
Sophora Flavescens Alkaloid-Rich Fraction Induction of IL-10 Production and Prevention
of Dexamethasone Suppression of Asthma Patient PBMC IL-10 Production Is Associated
with Altered DNA Methylation at foxp3 Gene Promoter
Author Name(s): Ying Song1, Dr. Li Xin Wang1, 2, Changda Liu1, Lauren Lisann1, David Weir3,
Ching-feng Huang1, 4, Paula J Busse3, Xiu-Min Li1
Department(s): 1Pediatrics, 3Medicine
Institution Affiliation: 1Icahn School of Medicine at Mount Sinai; 2 Shanghai Municipal Hospital of Traditional
Chinese Medicine affiliated with Shanghai TCM University, China; 4Department of Pediatrics,
Tri-Service General Hospital, National Defense Medical Center, Taiwan
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Allergic asthma is associated with increased Th2 and impaired Th1/Treg responses. Corticosteroids
suppress inflammation, but also cause unwanted generalized immunosuppression. ASHMITM, a 3-herb formula, had a
beneficial immunomodulatory effect in asthma patients.
Hypothesis: This study focused on IL-5 and IL-10 as signature Th2 and Treg cytokines to characterize ASHMITM
immunodulatory components.
Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from physician diagnosed asthma patients
(n=21). The effect of ASHMITM and individual herb constituents on anti-CD3/28 Dynabeads-stimulated production of
IL-5 and IL-10 by PBMCs was determined. Sophora flavescens (SF), an herbal constituent with significant
immunomodulatory effects, was fractionated to 4 fractions (F) and their effects on PBMC IL-10 and IL-5 production in
the presence or absence of dexamethasone were determined. Pyrosequencing was employed to determine DNA
methylation levels at the foxp3 gene promoter.
Results: ASHMITM dose dependently reduced IL-5 and increased IL-10 secretion (p<0.05-0.001). SF-F2 (contained
alkaloid compounds) was most effective in increasing IL-10 but had no effect on IL-5, whereas SF-F4 (contained
flavonoid compounds) was most effective in suppressing IL-5 but did not affect IL-10 production. Dexamethasonetreated PBMCs produced significantly less IL-5 as well as IL-10 (p<0.05). Co-culture with dexamethasone and SF-F2
significantly prevented dexamethasone suppression of IL-10, but not IL-5 production. Furthermore co-culture with SFF2 and dexamethasone significantly reduced DNA methylation levels at the foxp3 gene promoter.
Conclusions: The SF alkaloid-rich fraction was responsible for ASHMITM induction of IL-10 production by PBMCs,
and also prevented dexamethasone suppression of IL-10 production in association with acquired epigenetic
modification of the foxp3 gene promoter.
69
ASHMI, But Not Corticosteroid Treatment Restores Maternal Allergen Long-term Tolerance
and Prevents Offspring Asthma Risk via Epigenetic Modulation
Author Name(s): Kamal D. Srivastava, Ying Song, Jia Chen and Xiu-Min Li
Department(s): Pediatrics, Preventive Medicine
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: DNA methylation silences, whereas demethylation activates, cytokine gene expression. ASHMI, in
contrast to dexamethasone (Dex), produces persistent post-therapy protection against allergic airway response in an
asthma model that protects otherwise high-risk offspring from developing asthma.
Hypothesis: We hypothesize that epigenetic mechanisms contribute to preconception ASHMI modulation of T
helper cytokine profiles
Methods: Ovalbumin (OVA) allergic-asthmatic female BALB/c mice were treated with ASHMI, Dex, or water
(sham) for 7 weeks (n=5-9 per group). Genomic DNA isolated from lung tissues, collected immediately and 8
weeks post-therapy, was bisulfite converted, and PCR was performed to amplify IFN- and IL4 promoters
containing CpG methylation sites. Pyrosequencing was used to determine methylation profiles at IFN- and IL4
promoters.
Results: Immediately post-therapy, methylation at the IFN- promoter was significantly decreased in ASHMI group
as compared to Sham(P<0.05) at CpG-53, -45, -34 sites, and to Dex group lung tissues at CpG-53 sites (p<0.05),
whereas methylation of CpG-314 in the IL-4 promoter was significantly increased when compared to Dex
treatment (P<0.01). Significant decreases in methylation at the IFN- promoter at CpG-53, -45 sites in ASHMI
group lung tissues persisted for at least 8weeks post-therapy(P<0.01 vs. Sham; P<0.001 vs. Dex). Methylation of
CpG -408 at the IL-4 promoter in the ASHMI group was significantly higher than in Dex treated group lung tissues
(P<0.01).
Conclusions: ASHMI resets epigenetic modulation of IFN- and IL-4 expression which is favorable for long-term
tolerance induction.
70
Use of Pediatric Fundamental Critical Care Support (PFCCS) to
Improve Pediatric Resident Confidence in Acute Care
Author Name(s): Sheemon Zackai and Cecilia Thompson
Department: Pediatrics
Division: Critical Care Medicine
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Pediatric residents are trained to assess and manage critically ill children. In programs where
Intensivists are not in-house 24/7, such as ours, pediatric residents are expected to perform initial assessment,
resuscitation, and management without direct supervision. The Pediatric Fundamental Critical Care Support (PFCCS)
course, established by the Society of Critical Care Medicine, teaches non-critical care providers how to assess and
stabilize critically ill pediatric patients in the absence of an Intensivist. We wanted to determine whether the addition of
PFCCS to the pediatric residency curriculum would improve resident self-efficacy in acute care.
Hypothesis: Residents will report more confidence in acute care scenarios after completing PFCCS.
Methods: Thirty pediatric residents were randomly divided into two groups, matched for level of training. The
treatment group (n=15) completed the two day PFCCS course. After course completion, both groups completed a
confidential survey assessing self-efficacy in various acute care scenarios.
Results: Residents in the treatment group reported an overall 20% higher self-efficacy in acute care. Specifically, in
the following scenarios compared with the control: ability to admit a critically ill child to the PICU when the Attending
is not in-house, ability to manage a pediatric code on the general floor, taking call in the PICU, and taking call as the
Senior Resident with double coverage responsibilities on the general floors.
Conclusions: Residents have higher reported self-efficacy after completing PFCCS. Results after the inaugural
offering of PFCCS for this purpose are promising, and suggest it is a valuable addition to our standard curriculum.
71
Epicutaneous but not Oral Immunotherapy Induces Antigen-Specific Gastrointestinal Tregs
and Protects against Food-Induced Anaphylaxis
Author Name(s): Leticia Tordesillas1, Lucie Mondoulet2, Pierre-Henri Benhamou2,
Hugh Sampson1, Cecilia Berin1
Department: Pediatrics1
Division: Allergy and Immunology1
Institution Affiliation(s): Icahn School of Medicine at Mount Sinai1, DBV Technologies, Bagneux, France2
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: Epicutaneous (EPIT) and oral (OIT) immunotherapy were investigated for the prevention of foodinduced anaphylaxis in mice.
Hypothesis: We hypothesized that efficacy of immunotherapy by the skin or oral routes would relate to differential
capacity to generate gastrointestinal Tregs.
Methods: C3H/HeJ mice were sensitized to ovalbumin (OVA) and treated with EPIT using OVA- Viaskin® patches or
OIT with oral OVA. After treatment, mice were orally challenged with OVA to induce anaphylaxis, measured by drop
in body temperature. Antigen-specific Treg induction
was assessed by flow cytometry using a transgenic T cell transfer model.
Results: EPIT induced the appearance of antigen-specific LAP+Foxp3- Tregs in the mesenteric lymph nodes and
small intestine that were absent in OIT-treated mice. LAP+ cells primed in the skin-draining lymph nodes expressed
high levels of the gut-homing markers CCR9 and CCR6, in addition to the skin-homing marker CCR4. The induction
of antigen-specific Tregs in the gut by EPIT was associated with sustained protection from food-induced anaphylaxis.
100% of EPIT and OIT-treated mice were protected from anaphylaxis immediately after treatment, whereas only
EPIT-treated mice retained protection 4 weeks after stopping therapy. Administration of anti-neutralizing
antibodies abolished EPIT-induced protection, and adoptive transfer of Tregs directly suppressed mast cell activation
in passively sensitized mice, showing that Tregs can directly suppress hypersensitivity reactions.
Conclusions: Epicutaneous immunotherapy is a treatment that induces sustained protection against food-induced
anaphylaxis through a novel mechanism of direct mast cell suppression by gastrointestinal-homing Tregs. Optimization
of this treatment may lead to an effective generation of sustained tolerance response in patients with food allergy.
72
Early Liquid Protein Supplementation of Human Milk in Very Low Birth Weight Infants
Author Name(s): Megan Tracy, Robert Green, Ian Holzman, Andrea Weintraub
Department: Pediatrics
Division: Newborn Medicine
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Although survival of very low birth weight (VLBW) infants has improved significantly, these infants
remain at high risk for extrauterine growth restriction and neurodevelopmental disability. Human milk (HM) has
benefits for intestinal development and immune system support that premature infant formulas cannot provide.
However, without supplementation, HM does not contain adequate protein and calories to meet the nutritional needs of
a growing VLBW infant (HM: 1 -1.5 g protein/100 mL; preterm formula: 2.5 - 3 g protein/100 mL). Fortified HM,
although providing adequate total calories, still provides less than the recommended 4 g/kg/day of protein.
Hypothesis: We hypothesized that early increases in enteral protein intake in VLBW infants would mitigate
extrauterine growth restriction.
Design/Methods: Infants born between 26 and 32 weeks gestation were randomized to a standard of care nutrition
protocol (control group) or an early enteral protein supplementation protocol (intervention group).
Results: Gestational ages of infants were similar in the control and intervention groups (29.2 weeks vs. 28.5 weeks,
respectively). There was a significant association between weight gain in the first 28 days of life and average daily
enteral protein intake (R2=0.232; p=0.02) as well as average daily enteral volume (R2 = 0.18, p=0.043). There was no
significant association between weight gain in the first 28 days of life and average daily total fluid volume total daily
calorie or average total daily protein intake.
Conclusions: Interim analysis of the first 23 study infants suggests that enteral protein intake is more closely
associated with weight gain than total fluid volume, enteral volume, total caloric intake, or total protein intake.
73
Comparison of Baseline Characteristics between Adolescents Recruited in Community
Versus Clinical Sites in a Pilot Diabetes Prevention Study
Author Name(s): Nita Vangeepuram, Kenya Townsend, LaTanya Phelps-Waldropt, Guedy Arniella,
Carol R. Horowitz
Department: Pediatrics, Population Health Science and Policy
Division: General Pediatrics
Institution Affiliation: Icahn School of Medicine at Mount Sinai
INTRODUCTION: We used a community-based participatory research approach to develop TEEN HEED (Help
Educate to Eliminate Diabetes), a peer-led diabetes prevention program for pre-diabetic ethnic minority adolescents
from a low income urban community.
METHODS: We screened 56 overweight/obese adolescents for pre-diabetes using oral glucose tolerance testing, and
administered adiposity and blood pressure measurements and a health and lifestyle survey. We analyzed survey data
for 55 adolescents (excluding one girl diagnosed with diabetes) using descriptive statistics and bivariate analyses (chisquare and t-tests) to compare baseline attitudes and behaviors among adolescents recruited in community versus
clinical sites.
RESULTS: Previously undiagnosed pre-diabetes was found in 9/34 (27%) adolescents from community sites and
10/21 (48%) adolescents from clinical sites, p=0.1. Demographic characteristics (gender, race/ethnicity, age, and level
of parent education) and BMI did not vary across groups. Adolescents from community sites reported eating smaller
portions of cereal (p=0.01) and fast food (p=0.05), greater weekly hours of vigorous physical activity (p=0.03), and
fewer hours playing video games (p=0.04). Adolescents from community sites also had higher physical activity selfefficacy (p=0.05), higher self-esteem (p=0.08), greater body satisfaction (p=0.08), less media internalization of body
image (p=0.007), and higher levels of friend support (p=0.006). Adolescents from clinical sites were more likely to eat
meals with their family >4 times per week (p=0.06) and reported higher levels of family support for healthy behaviors
(p=0.05).
CONCLUSION: Adolescents recruited in community sites had lower prevalence of previously un-diagnosed prediabetes, and overall healthier self-reported behaviors and attitudes than those recruited in clinical sites.
74
Quality Assurance: Streamlining Chemotherapy Admissions from Clinic
Author Name(s): Keila Veiga, Victoria Shakhin, Rose Morales, Christine Angrisani, Jaclyn Davis,
Birte Wistinghausen
Department: Pediatrics
Division: Pediatric Hematology/Oncology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Pediatric oncology patients are frequently admitted from clinic for chemotherapy. Prior to switching to
electronic medical records (EMR), handwritten orders were sent to the chemotherapy pharmacy from clinic once a
patient was cleared for admission and chemotherapy. Chemotherapy was prepared and ready for administration when
patients arrived on the floor. Within the EMR, orders are routed to the pharmacist after release by nurses and can only
be released in the encounter in which they are to be administered. Due to lack of bed availability, patients do not arrive
on the inpatient floor until the late afternoon. Because pharmacy is not aware of chemotherapy orders until orders are
released in the inpatient encounter, significant delays in preparation and administration of chemotherapy were
identified.
Methods: A Cross Encounter Medication Administration EMR logic (CEMA) was developed that allows release of
chemotherapy orders in the clinic encounter with transfer of orders to the inpatient encounter.
Hypothesis: Release of chemotherapy orders when the patient is cleared for admission instead of after arrival to the
inpatient floor will lead to earlier infusion start times and to shorter hospital stays.
Results: Prior to CEMA (n=15), the average time between arrival to clinic and floor admission was 4.5 hours. The
average time from floor arrival to chemotherapy start time was 5 hours 6 minutes. In a limited sample (n=3) after
CEMA, average time from floor arrival time to administration of chemotherapy was 3 hours. Further data analysis on a
larger patient sample is ongoing.
Conclusion: After CEMA, chemotherapy start time is expedited.
75
Recipe for a Healthy Lifestyle: An Obesity Prevention Program
for Hispanic Families in East Harlem
Author Name(s): Lindsey Waldman,1, Marilyn Figuero,2 Heather Mitchell,2, Robert Fallar3, Leora Mogilner4
Department(s): 1Pediatrics, 3Medical Education, 4Pediatrics
Division(s): 1Pediatric Endocrinology and Diabetes
Institution Affiliation(s): 1Icahn School of Medicine at Mount Sinai, 2Little sisters of the Assumption,
Icahn School of Medicine at Mount Sinai,4 Icahn School of Medicine at
Mount Sinai
Introduction: More than 1 in 4 children in Headstart and elementary school in East Harlem are obese. Little exists in
the literature about obesity prevention in this very young age group.
Hypothesis: To assess the impact of an obesity prevention program on knowledge, attitudes and behaviors in mothers
of children ages 0-5 years
Methods: With a grant from the AAP, we developed an obesity prevention curriculum for parents of children 0-5 years
old designed to provide them with skills they need to promote healthy living. A pilot program was held from May-July
2014 and after analyzing initial data, the curriculum was revised and run again from October-December 2014.
Pre/post surveys were obtained. We analyzed textural responses using qualitative methods and continually compared
and contrasted responses to identify themes. Chi square and t-tests were used to analyze data.
Results: 13 mother-child dyads enrolled and 7 completed the course. At the end of the course, 86% of families ate
together 5+ times/week, up from 38% pre-course, trending towards significance (p=0.055). Similarly, at the end of the
course, 43% of families had TV the bedroom, down from 85% pre-course, trending towards significance (p=0.05). At
the end of the 10 weeks, all parents reported that they would recommend this class and 100% felt well prepared to feed
their child at home compared to before the classes.
Conclusions: After completion of the program, all participants felt well prepared to feed their children and there was a
trend towards more family meals and fewer TVs in the bedroom among participants.
76
Fetoplacental Environment and the Origin of the
Infant Gut Microbiome: A Twin Study
Author Name(s): Ryan W. Walker, Ruth J.F. Loos
Department: Pediatrics
Division: Preventive Medicine
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation(s): The Mindich Child Health and Development Institute; The Charles Bronfman Institute for
Personalized Medicine
Introduction: Offspring acquire maternal bacteria during birth, however detection of bacteria in meconium suggests
that the fetal gut may be colonized in utero, prior to delivery.
Twins develop in varied fetoplacental environments, determined by zygosity, chorionicity and amnionicity, and fetuses
may have their own placenta, chorion and amnion or share it with their co-twin. Thus, twins may experience different
intrauterine environments depending on the fetoplacental environment.
Bacteria residing in amniotic fluid and placenta could be a source of transmission. Therefore, twins provide a unique
opportunity to determine if fetoplacental environment impacts bacterial colonization of the gut.
Aims: To determine if the fetoplacental environment impacts the early gut microbiomes of newborn twins. We
hypothesize that gut microbiome similarity in twins increases as a function of shared intrauterine environment.
Methods: We propose to record fetoplacental environment, zygosity and collect meconium from newborn twins.
Meconium microbiome composition will be determined by 16s rRNA sequencing. We propose inter-pair correlation
analysis to characterize microbiome similarity between twins and across twin types. We propose structural equation
modeling to identify sources of variation that contribute to the fetoplacental environment.
Results: We expect the strength of intra-pair microbiome correlation to be dependent on degree of shared fetoplacental
environment. If genes impact the microbiome, then intra-pair correlation will be larger in mono- vs. dizygotic twins.
Conclusions: The degree of shared maternal environment in twins may contribute to similarity in gut microbiota.
These findings could provide further evidence of in utero colonization of the gut and inform potential mechanisms of
maternal transfer.
77
Feature Tracking-Derived Longitudinal and Circumferential Peak Systolic Strain vs. Late Gadolinium
Enhancement in Troponin-Positive Myocarditis: a Cardiac
Magnetic Resonance Case- Control Study
Author Name(s): Justin Weigand, James C. Nielsen, Partho P. Sengupta, Javier Sanz,
Shubhika Srivastava, Santosh Uppu
Department(s): Pediatrics, Internal Medicine
Division(s): Pediatric Cardiology, Cardiology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Introduction: Cardiac magnetic resonance imaging (CMR) is used to assess myocardial involvement in myocarditis
(MYO). Currently employed techniques are qualitative, subjective, and prone to interpretation error. Feature tracking
(FT) analyzes myocardial strain using cine CMR images. FT has not been fully examined in MYO.
Hypothesis: Regional left ventricular (LV) strain is abnormal in MYO. Regional strain by FT was compared to late
gadolinium enhancement (LGE) & troponin leak as a measure of myocardial involvement.
Methods: Single center, retrospective CMR study reviewed patients with MYO & structurally normal hearts.
Consecutive healthy young adults with normal cardiac anatomy, function & absent LGE served as controls. MYO
patients with documented troponin leak & normal global function were included in comparison. FT determined
regional myocardial peak systolic strain (pkS) obtained in standard CMR distributions. T-tests compared strain values
between cases & controls. Receiver operating characteristic curves determined pkS values with highest sensitivity &
specificity for concurrent troponin leak & LGE.
Results: FT was performed on 57 patients: 37 MYO and 20 controls. Twenty-eight cases with normal EF & 20 control
patients were included in final analysis. Nearly all cases with normal function demonstrated abnormal regional pkS
(27/28, 96%). Cases had significantly diminished pkS when compared to controls. FT intraobserver and interobserver
agreement was good for all regional pkS.
Conclusions: FT-derived longitudinal & circumferential pkS are sensitive & specific in identifying myocardial
involvement. FT may prove advantageous in MYO where LV function is normal and has the potential for detecting
myocarditis throughout its temporal course.
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Approach to Food Allergy by Non-Specialty Providers
Author Name(s): Kate Welch, Julie Wang
Department: Pediatrics
Division: Allergy and Immunology
Institution Affiliation: Icahn School of Medicine at Mount Sinai
Institute Affiliation(s): The Mindich Child Health and Development Institute; The Jaffe Food Allergy Institute
Introduction: Many children who present to an allergy clinic for the management and diagnosis of food allergy
have previously been evaluated by a physician and received management advice. However, the prior work-up as
well as the degree of education and instruction to family members varies widely.
Hypothesis: We hypothesized that advice to food allergy patients is not uniform and does not meet guideline
recommendations.
Methods: An anonymous survey was distributed to parents of children presenting to the pediatric allergy clinic for
their initial specialist evaluation of suspected food allergy. The data was analyzed for trends in avoidance advice,
epinephrine prescriptions, and allergy testing. Because the survey was anonymous without identifying information,
it was exempt from IRB approval.
Results: Of 114 completed surveys, 93% of patients were referred to the allergy clinic by pediatricians for concern
of food allergy. Self-injectable epinephrine was prescribed by the referring provider for 68% of patients. Of those
prescribed epinephrine, 94% filled the prescription, and 62% were trained in its use.
17% of all referred patients were provided with an emergency action plan, outlining steps for treatment in the case
of an allergic reaction. Approximately 40% of patients had already undergone some form of allergy testing, the
majority food-specific lgE levels, and all those referred with testing had prior positive results. Of patients who did
have testing by the referring provider, 72% were prescribed epinephrine.
Conclusions: The majority of referring physicians prescribed epinephrine for patients with suspected
food allergy, but only a minority was concurrently provided with an emergency action plan. The majority of
patients who had undergone prior testing had been prescribed epinephrine.
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Early Life Housing Stress and Urban Childhood Asthma
Author Name(s): Lauren Zajac1, Rosalind Wright1,2, Marina Jacobson Canner3, Harriet Fernandez3
Department(s): 1Preventive Medicine, 2Pediatrics
Division: Pediatric Environmental Health
Institution Affiliation(s): Icahn School of Medicine at Mount Sinai, 3Harvard Medical School
Institute Affiliation: The Mindich Child Health and Development Institute
Introduction: The role of early life stress in the pathogenesis of asthma is emerging, however, little is known about
the role of housing-related stress.
Hypothesis: High levels of early life housing stress will be associated with childhood asthma, and chronic housing
stress will have a greater impact.
Methods: This study utilizes data from an established urban pregnancy cohort. Early life housing stress was measured
using the Crisis in Family Systems (CRISYS) scale during pregnancy and when children were approximately 18
months old. The outcome was maternal-reported, physician-diagnosed asthma by age 6 years. Multivariable
regression models estimated the association between housing stress and asthma, adjusted for child sex, season of birth,
race, education, maternal atopy, and presence of environmental housing issues (cockroaches, moisture/mold).
Results: Analyses included 573 mother-child pairs with complete data on housing stress and asthma. About one third
(35%) of mothers reported high housing stress in both periods. Women with high housing stress in both periods were
more likely to be atopic, obese, report environmental housing problems, and have an asthmatic child compared to those
with low stress in both periods. Children of mothers with high stress in both periods were more likely to have asthma
(OR 2.1, 95%CI 1.1-4.0) in an adjusted logistic regression model.
Conclusions: Chronic housing stress in early life may influence asthma expression in urban children even when
adjusting for in-home physical environmental factors. These results may inform interventions to better address both
psychosocial and environmental housing issues.
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Food Allergies in a Pediatric Clinic – Interventions to Improve Management
Author Name(s): Ari Zelig, Ilana Harwayne-Gidansky, Allison Gault, Julie Wang
Department: Pediatrics
Division: Allergy and Immunology
Institution Affiliation(s): Icahn School of Medicine at Mount Sinai, New York-Presbyterian Hospital,
Weill Cornell Medical Center
Institute Affiliation(s): The Mindich Child Health and Development Institute; Jaffe Food Allergy Institute
Introduction: The growing prevalence of food allergies among children indicates a responsibility among general
pediatricians to ensure that their patients receive accurate diagnosis and management.
Hypothesis: Implementation of educational and electronic medical record interventions will improve physician
knowledge and management of food allergies.
Methods: Pre and post-test scores of pediatric residents and faculty were analyzed to assess effectiveness of an
educational session designed to improve knowledge of food allergy management. One year later, a best practice
advisory was implemented in the EMR alerting providers to consider allergy referral whenever a diagnosis code for
food allergy or epinephrine autoinjector prescription was entered. A review of charts 6 months prior to and 6 months
after each intervention was completed to determine the impact of both interventions. Outcome measurements included
referrals to allergy clinic, prescription of self-injectable epinephrine, and documentation that written emergency action
plans were provided.
Results: There was a significant increase in test scores immediately after the educational intervention (mean 56.2% vs.
84.3%, p <0.001). Post-test scores remained significantly higher than pre-intervention scores 6 months later (mean
score 68.0% vs 56.2%, p=0.006). Although knowledge improved, there was no significant difference in the percentage
of patients who were provided allergy referral, prescribed an epinephrine autoinjector, or given an emergency action
plan before and after both interventions.
Conclusion: Neither intervention resulted in improvements in the management of children with food allergies at our
general pediatrics clinic. Further studies are needed to identify effective strategies to improve management of food
allergies by general pediatricians.
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The Chinese Herbal Formula Seasonal Tea Alleviated Rhinitis and Conjunctivitis
Symptoms in a Murine Ragweed Allergy Model
Authors Name(s): Lianzhu Zhang1,2, Ying Song1, Banghao Liang1, and Xiu-Min Li1
Department: Pediatrics
Division: Allergy & Immunology
Institution Affiliation(s): 1 Pediatric Allergy & Immunology, Icahn School of Medicine at Mount Sinai,
New York, NY; 2 The Affiliated Hospital to Changchun University of Chinese
Medicine, Changchun, Jilin, P.R.C
Institute Affiliation(s): The Mindich Child Health and Development Institute;
Jaffe Food Allergy Institute; Center for Integrative Medicine for Allergies and
Wellness at Icahn School of Medicine at Mount Sinai
Introduction: Allergic rhinitis (AR) affects up to 30% of the population worldwide, and is increasing in prevalence.
The typical nasal symptoms of AR are itching, rhinorrhea, sneezing, and nasal obstruction. Up to 90% of the patients
with AR suffer from conjunctivitis, so the term allergic rhinoconjunctivitis (ARC) has been coined.
Hypothesis: Seasonal Tea might have good effects on a murine model by reducing the symptoms and inflammation of
ARC.
Methods: BALB/c mice were sensitized by 2 weekly intraperitoneal (i.p.) injections of 200 µg ragweed and 2mg of
alum followed by intranasal (i.n.) challenges with 500 µg ragweed and ocular challenges (o.c.) with 5 µg ragweed
weekly for 3 weeks. They then received four daily ragweed challenges to induce symptoms of allergic
rhinoconjunctivitis. After the first challenge, mice received intragastric Seasonal Tea (10.3 mg/mouse/day) or water
(sham) treatment twice daily for 3 weeks. Frequency of sneezing and numbers of eosinophils in nasal lavage fluids
(NLF) as well as eye puffiness were evaluated following the last challenge. Nasal airway mucosae sections were
stained with H&E and analyzed to evaluate nasal inflammation.
Results: Repeated antigen challenges induced sneezing, and infiltration of eosinophils into the nasal tissues. Seasonal
Tea treatment significantly reduced sneezing frequency (P<0.001) and number of eosinophils in the NLF (P < 0.001)
compared to samples from sham group. Histological analysis showed that it reduced the number of nasal mucosa
eosinophils. Seasonal Tea also reduced eye puffiness as compared the sham treated mice (P<0.05).
Conclusions: Seasonal Tea treatment had beneficial effects on ragweed-induced allergic rhinoconjunctivitis in murine
model, and may be valuable for treating these conditions.
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