Medical Sciences Commons^™

Maternal And Fetal Bile Acid Homeostasis Regulated By Sulfated Progesterone Metabolites Through Fxr Signaling Pathway In A Pregnant Sow Model, Peng Wang, Peiqiang Yuan, Sen Lin, Heju Zhong, Xiaoling Zhang, Yong Zhuo, Jian Li, Lianqiang Che, Bin Feng, Yan Lin, Shengyu Xu, De Wu, Douglas G Burrin, Zhengfeng Fang

Faculty, Staff and Students Publications

Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and the farrowing day (L0), to investigate the intercorrelation of reproductive hormone, including estradiol, progesterone and sulfated progesterone metabolites (PMSs), and BA in the peripheral blood of mother and fetuses during pregnancy. All data were analyzed by Student’s t-test or one-way ANOVA of GraphPad Prism and further compared by using the Student–Newman–Keuls test. Correlation analysis was …

Context Matters: Preliminary Evidence That The Association Between Positive Affect And Adiposity In Infancy Varies In Social Vs Non-Social Situations, Alexis C Wood, Shabnam R Momin, Mackenzie K Senn, David J Bridgett

Children’s Nutrition Research Center Staff Publications

Previous studies have suggested that infants high in negative affect have higher levels of adiposity, arising in part via changes in nutrition (e.g., “feeding to soothe”). Few studies have examined whether positive affect shows similar or inverse associations with adiposity. The current study examined cross-sectional and longitudinal relationships between adiposity and observations of positive affect in both a social and a non-social context, using data from infants at four (n = 125) and 12 (n = 80) months of age. Our analyses did not find any cross-sectional associations between positive affect and adiposity (all p > 0.05). However, in the longitudinal …

Challenges Created By The Covid-19 Pandemic: Pediatric Emergency Medicine And Disaster Management Perspectives, Thomas E Tanner, Nichole R Davis, Brent D Kaziny, Erin E Endom, Esther M Sampayo

Faculty, Staff and Students Publications

OBJECTIVE: The coronavirus disease (COVID-19) pandemic has presented unique challenges to pediatric emergency medicine (PEM) departments. The purpose of this study was to identify these challenges and ascertain how centers overcame barriers in creating solutions to continue to provide high-quality care and keep their workforce safe during the early pandemic.

METHODS: This is a qualitative study based on semi-structured interviews with physicians in leadership positions who have disaster or emergency management experience. Participants were identified through purposive sampling. Interviews were recorded and transcribed electronically. Themes and codes were extracted from the transcripts by 2 independent coders. Constant comparison analysis was …

Genomic Answers For Children: Dynamic Analyses Of >1000 Pediatric Rare Disease Genomes., Ana S A Cohen, Emily G. Farrow, Ahmed Abdelmoity, Joseph Alaimo, Shivarajan Manickavasagam Amudhavalli, John Anderson, Lalit R. Bansal, Lauren E. Bartik, Primo Baybayan, Bradley Belden, Courtney D. Berrios, Rebecca L. Biswell, Pawel Buczkowicz, Orion Buske, Shreyasee Chakraborty, Warren A. Cheung, Keith A. Coffman, Ashley M. Cooper, Laura A. Cross, Tom Curran, Thuy Tien T. Dang, Mary M. Elfrink, Kendra Engleman, Erin Day Fecske, Cynthia Fieser, Keely M. Fitzgerald, Emily Fleming, Randi N. Gadea, Jennifer L. Gannon, Rose N. Gelineau-Morel, Margaret Gibson, Jeffrey Goldstein, Elin Grundberg, Kelsee Halpin, Brian S. Harvey, Bryce Heese, Wendy Hein, Suzanne M. Herd, Susan Starling Hughes, Mohammed Ilyas, Jill Jacobson, Janda L. Jenkins, Shao Jiang, Jeffrey J. Johnston, Kathryn Keeler, Jonas Korlach, Jennifer Kussman, Christine Lambert, Caitlin E. Lawson, Jean-Baptist Lepichon, J Steven Leeder, Vicki C. Little, Daniel A. Louiselle, Michael Lypka, Brittany D. Mcdonald, Neil Miller, Ann Modrcin, Annapoorna Nair, Shelby H. Neal, Christopher M. Oermann, Donna M. Pacicca, Kailash Pawar, Nyshele L. Posey, Nigel Price, Laura M B Puckett, Julio Quezada, Nikita Raje, William J. Rowell, Eric T. Rush, Venkatesh Sampath, Carol J. Saunders, Caitlin Schwager, Richard M. Schwend, Elizabeth Shaffer, Craig Smail, Sarah E. Soden, Meghan Strenk, Bonnie Sullivan, Brooke Sweeney, Jade B. Tam-Williams, Adam Walter, Holly Welsh, Aaron M. Wenger, Laurel K. Willig, Yun Yan, Scott T. Younger, Dihong Zhou, Tricia N. Zion, Isabelle Thiffault, Tomi Pastinen

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study aimed to provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids program.

METHODS: Extensive analyses of 960 families with suspected genetic disorders included short-read exome sequencing and short-read genome sequencing (srGS); PacBio HiFi long-read genome sequencing (HiFi-GS); variant calling for single nucleotide variants (SNV), structural variant (SV), and repeat variants; and machine-learning variant prioritization. Structured phenotypes, prioritized variants, and pedigrees were stored in PhenoTips database, with data sharing through controlled access the database of Genotypes and Phenotypes.

RESULTS: Diagnostic rates ranged from 11% in patients with prior negative …

Using Artificial Neural Networks To Predict Intra-Abdominal Abscess Risk Post-Appendectomy, Morouge M Alramadhan, Hassan S Al Khatib, James R Murphy, Kuojen Tsao, Michael L Chang

Faculty, Staff and Student Publications

OBJECTIVE: To determine if artificial neural networks (ANN) could predict the risk of intra-abdominal abscess (IAA) development post-appendectomy.

BACKGROUND: IAA formation occurs in 13.6% to 14.6% of appendicitis cases with "complicated" appendicitis as the most common cause of IAA. There remains inconsistency in describing the severity of appendicitis with variation in treatment with respect to perforated appendicitis.

METHODS: Two "reproducible" ANN with different architectures were developed on demographic, clinical, and surgical information from a retrospective surgical dataset of 1574 patients less than 19 years old classified as either negative (n = 1,328) or positive (n = 246) for IAA post-appendectomy …

Lmod2-Related Dilated Cardiomyopathy Presenting In Late Infancy, Erica Lay, Mahshid S Azamian, Susan W Denfield, William Dreyer, Joseph A Spinner, Debra Kearney, Lilei Zhang, Kim C Worley, Weimin Bi, Seema R Lalani

Faculty, Staff and Students Publications

Leiomodin-2 (LMOD2) is an important regulator of the thin filament length, known to promote elongation of actin through polymerization at pointed ends. Mice with Lmod2 deficiency die around 3 weeks of age due to severe dilated cardiomyopathy (DCM), resulting from decreased heart contractility due to shorter thin filaments. To date, there have been three infants from two families reported with biallelic variants in LMOD2, presenting with perinatal onset DCM. Here, we describe a third family with a child harboring a previously described homozygous frameshift variant, c.1243_1244delCT (p.L415Vfs*108) with DCM, presenting later in infancy at 9 months of age. Family history …

A Novel Automated Junctional Ectopic Tachycardia Detection Tool For Children With Congenital Heart Disease, Jamie L S Waugh, Raajen Patel, Yilong Ju, Ankit B Patel, Craig G Rusin, Parag N Jain

Faculty, Staff and Students Publications

BACKGROUND: Junctional ectopic tachycardia (JET) is a prevalent life-threatening arrhythmia in children with congenital heart disease (CHD), with marked resemblance to normal sinus rhythm (NSR) often leading to delay in diagnosis.

OBJECTIVE: To develop a novel automated arrhythmia detection tool to identify JET.

METHODS: A single-center retrospective cohort study of children with CHD was performed. Electrocardiographic (ECG) data produced by bedside monitors is captured automatically by the Sickbay platform. Based on the detection of R and P wave peaks, 2 interpretable ECG features are calculated: P prominence median and PR interval interquartile range (IQR). These features are used as input …

Relationship Between Arterial Stiffness And Subsequent Cardiac Structure And Function In Young Adults With Youth-Onset Type 2 Diabetes: Results From The Today Study, Amy S Shah, Samuel S Gidding, Laure El Ghormli, Jeanie B Tryggestad, Kristen J Nadeau, Fida Bacha, Lorraine E Levitt Katz, Steven M Willi, Joao Lima, Elaine M Urbina

Faculty, Staff and Students Publications

BACKGROUND: Higher arterial stiffness may contribute to future alterations in left ventricular systolic and diastolic function. We tested this hypothesis in individuals with youth-onset type 2 diabetes from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Arterial stiffness (pulse wave velocity [carotid-femoral, femoral-foot, and carotid-radial], augmentation index, brachial distensibility) was measured in 388 participants with type 2 diabetes (mean age, 21 years; diabetes duration, 7.7 ± 1.5 years). To reflect overall (composite) vascular stiffness, the five arterial stiffness measures were aggregated. An echocardiogram was performed in the same cohort 2 years later. Linear regression …

Evolution Of International Pediatric Endoscopic Practice Changes During The Coronavirus Disease 2019 Pandemic, Wenly Ruan, Douglas S Fishman, Diana G Lerner, Raoul I Furlano, Mike Thomson, Catharine M Walsh

Faculty, Staff and Students Publications

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has drastically altered endoscopic practices. We initially reported the international impact of COVID-19 on pediatric endoscopic practice. This follow-up study aimed to assess changes 7 months following the initial survey to delineate practice change patterns as the pandemic evolved.

METHODS: Pediatric gastroenterologists who responded to the initial survey were re-surveyed seven months later using Research Electronic Data Capture (REDCap). The survey recorded information on changes in pediatric endoscopic practice patterns, including COVID-19 screening and testing processes and personal protective equipment (PPE) utilization. Additionally, endoscopists' risk tolerance of COVID-19 transmission was evaluated.

RESULTS: Seventy-five …

Risk For Post-Colonoscopy Irritable Bowel Syndrome In Patients With And Without Antibiotic Exposure: A Retrospective Cohort Study, Ravy K Vajravelu, Jordan M Shapiro, Josephine Ni, Shivani U Thanawala, James D Lewis, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Laboratory studies have demonstrated that antibiotic use in conjunction with bowel purgatives causes alterations to the gut microbiota. Because gut microbiota changes may be a trigger for the development of irritable bowel syndrome (IBS), we sought to assess whether individuals who undergo bowel cleansing for colonoscopy and have concurrent antibiotic exposure develop IBS at higher rates than individuals who undergo colonoscopy without antibiotic exposure.

METHODS: We used data from Optum's de-identified Clinformatics Data Mart Database in the United States to study a cohort of 50- to 55-year-olds who underwent screening colonoscopy. Individuals exposed to antibiotics within 14 …

Social And Demographic Disparities In The Severity Of Multisystem Inflammatory Syndrome In Children, Fabio Savorgnan, Sebastian Acosta, Alexander Alali, Axel Moreira, Ananth Annapragada, Craig G Rusin, Saul Flores, Rohit S Loomba, Alvaro Moreira

Faculty, Staff and Students Publications

Social constructs are known risk factors for multisystem inflammatory syndrome in children. A review of 206 patients demonstrated that children who were non-Hispanic Black, over the age of 12 years or living in a disadvantaged neighborhood associated with severe multisystem inflammatory syndrome in children (intensive care unit admission, intubation and/or vasopressor use).

Neurovascular Abnormalities In Retinopathy Of Prematurity And Emerging Therapies, Chang Dai, Jun Xiao, Chenguang Wang, Wei Li, Guanfang Su

Faculty, Staff and Students Publications

Blood vessels in the developing retina are formed in concert with neural growth, resulting in functional neurovascular network. Disruption of the neurovascular coordination contributes to the pathogenesis of retinopathy of prematurity (ROP), a potentially blinding retinal neovascular disease in preterm infants that currently lacks an approved drug therapy in the USA. Despite vasculopathy as predominant clinical manifestations, an increasing number of studies revealed complex neurovascular interplays among neurons, glial cells and blood vessels during ROP. Coordinated expression of glia-derived vascular endothelial growth factor (VEGF) in spatio-temporal gradients is pivotal to the formation of well-organized vascular plexuses in the healthy retina, …

Prune1 C933g>A Synonymous Variant Induces Exon 7 Skipping, Disrupts The Dhha2 Domain, And Leads To An Atypical Nmihba Syndrome Presentation: Case Report And Review Of The Literature, Christina L Magyar, David R Murdock, Lindsay C Burrage, Hongzheng Dai, Seema R Lalani, Richard A Lewis, Yuezhen Lin, Marcela F Astudillo, Jill A Rosenfeld, Alyssa A Tran, James B Gibson, Undiagnosed Diseases Network, Carlos A Bacino, Brendan H Lee, Hsiao-Tuan Chao

Faculty, Staff and Students Publications

Prune exopolyphosphatase-1 (PRUNE1) encodes a member of the aspartic acid-histidine-histidine (DHH) phosphodiesterase superfamily that regulates cell migration and proliferation during brain development. In 2015, biallelic PRUNE1 loss-of-function variants were identified to cause the neurodevelopmental disorder with microcephaly, hypotonia, and variable brain abnormalities (NMIHBA, OMIM#617481). NMIHBA is characterized by the namesake features and structural brain anomalies including thinning of the corpus callosum, cerebral and cerebellar atrophy, and delayed myelination. To date, 47 individuals have been reported in the literature, but the phenotypic spectrum of PRUNE1-related disorders and their causative variants remains to be characterized fully. Here, we report a novel homozygous …

Electrographic Seizures In Neonates With A High Risk Of Encephalopathy, Wan-Hsuan Chen, Oi-Wa Chan, Jainn-Jim Lin, Ming-Chou Chiang, Shao-Hsuan Hsia, Huei-Shyong Wang, En-Pei Lee, Yi-Shan Wang, Cheng-Yen Kuo, Kuang-Lin Lin, On The Behalf Of The Icns Group

Faculty, Staff and Student Publications

Background: Neonatal encephalopathy is caused by a wide variety of acute brain insults in newborns and presents with a spectrum of neurologic dysfunction, such as consciousness disturbance, seizures, and coma. The increased excitability in the neonatal brain appears to be highly susceptible to seizures after a variety of insults, and seizures may be the first clinical sign of a serious neurologic disorder. Subtle seizures are common in the neonatal period, and abnormal clinical paroxysmal events may raise the suspicion of neonatal seizures. Continuous video electroencephalographic (EEG) monitoring is the gold standard for the diagnosis of neonatal seizures. The aim of …

Berenice Final Analysis: Cardiac Safety Study Of Neoadjuvant Pertuzumab, Trastuzumab, And Chemotherapy Followed By Adjuvant Pertuzumab And Trastuzumab In Her2-Positive Early Breast Cancer, Chau Dang, Michael S Ewer, Suzette Delaloge, Jean-Marc Ferrero, Ramon Colomer, Luis De La Cruz-Merino, Theresa L Werner, Katherine Dadswell, Mark Verrill, Daniel Eiger, Sriparna Sarkar, Sanne Lysbet De Haas, Eleonora Restuccia, Sandra M Swain

Duncan NRI Faculty and Staff Publications

Simple Summary

A combination of pertuzumab, trastuzumab, and chemotherapy is a standard treatment for patients with a type of breast cancer called HER2-positive. Before the BERENICE study, little was known about the safety and effectiveness of pertuzumab with trastuzumab after surgery. Cardiac safety was a particular concern, especially when the chemotherapy given before surgery included drugs called anthracyclines. BERENICE was designed to assess the cardiac safety of pertuzumab with trastuzumab before surgery in combination with two different types of anthracycline-based chemotherapies. This paper describes additional safety and effectiveness data from BERENICE after patients had undergone surgery and when they had …

Rapid Molecular Diagnostics Of Tuberculosis Resistance By Targeted Stool Sequencing, Doctor B Sibandze, Alexander Kay, Viola Dreyer, Welile Sikhondze, Qiniso Dlamini, Andrew Dinardo, Godwin Mtetwa, Bhekumusa Lukhele, Debrah Vambe, Christoph Lange, Muyalo Glenn Dlamini, Tara Ness, Rojelio Mejia, Barbara Kalsdorf, Jan Heyckendorf, Martin Kuhns, Florian P Maurer, Sindisiwe Dlamini, Gugu Maphalala, Stefan Niemann, Anna Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: Stool is an important diagnostic specimen for tuberculosis in populations who struggle to provide sputum, such as children or people living with HIV. However, the culture of Mycobacterium tuberculosis (M. tuberculosis) complex strains from stool perform poorly. This limits the opportunity for phenotypic drug resistance testing with this specimen. Therefore, reliable molecular methods are urgently needed for comprehensive drug resistance testing on stool specimens.

METHODS: We evaluated the performance of targeted next-generation sequencing (tNGS, Deeplex® Myc-TB) for the detection of mutations associated with M. tuberculosis complex drug resistance on DNA isolated from stool specimens provided by participants from a …

Cathelicidin Anti-Microbial Peptide (Camp) Is Toxic During Neonatal Influenza Virus Infection, Nneka Ugwu

St. Chris Research Day

No abstract provided.

Evaluation Of A Circadian Rhythm And Sleep-Focused Mobile Health Intervention For The Prevention Of Accelerated Summer Weight Gain Among Elementary School-Age Children: Protocol For A Randomized Controlled Feasibility Study, Jennette P Moreno, Hafza Dadabhoy, Salma Musaad, Tom Baranowski, Debbe Thompson, Candice A Alfano, Stephanie J Crowley

Children’s Nutrition Research Center Staff Publications

Background: The i♥rhythm project is a mobile health adaptation of interpersonal and social rhythm therapy designed to promote healthy sleep and behavioral rhythms among 5-8-year olds during summer for the prevention of accelerated summer weight gain.

Objective: This pilot study will examine the feasibility, acceptability, and preliminary efficacy of the i♥rhythm intervention. This will ensure that the research protocol and procedures work as desired and are acceptable to families in preparation for the fully powered randomized controlled trial. The proposed study will examine the willingness of participants to participate in the intervention and determine whether modifications to the intervention, procedures, …

Novel Fold Of Rotavirus Glycan-Binding Domain Predicted By Alphafold2 And Determined By X-Ray Crystallography, Liya Hu, Wilhelm Salmen, Banumathi Sankaran, Yi Lasanajak, David F Smith, Sue E Crawford, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

The VP8* domain of spike protein VP4 in group A and C rotaviruses, which cause epidemic gastroenteritis in children, exhibits a conserved galectin-like fold for recognizing glycans during cell entry. In group B rotavirus, which causes significant diarrheal outbreaks in adults, the VP8* domain (VP8*B) surprisingly lacks sequence similarity with VP8* of group A or group C rotavirus. Here, by using the recently developed AlphaFold2 for ab initio structure prediction and validating the predicted model by determining a 1.3-Å crystal structure, we show that VP8*B exhibits a novel fold distinct from the galectin fold. This fold with a β-sheet clasping …

Elucidating Human Milk Oligosaccharide Biosynthetic Genes Through Network-Based Multi-Omics Integration, Benjamin P Kellman, Anne Richelle, Jeong-Yeh Yang, Digantkumar Chapla, Austin W T Chiang, Julia A Najera, Chenguang Liang, Annalee Fürst, Bokan Bao, Natalia Koga, Mahmoud A Mohammad, Anders Bech Bruntse, Morey W Haymond, Kelley W Moremen, Lars Bode, Nathan E Lewis

Children’s Nutrition Research Center Staff Publications

Human Milk Oligosaccharides (HMOs) are abundant carbohydrates fundamental to infant health and development. Although these oligosaccharides were discovered more than half a century ago, their biosynthesis in the mammary gland remains largely uncharacterized. Here, we use a systems biology framework that integrates glycan and RNA expression data to construct an HMO biosynthetic network and predict glycosyltransferases involved. To accomplish this, we construct models describing the most likely pathways for the synthesis of the oligosaccharides accounting for >95% of the HMO content in human milk. Through our models, we propose candidate genes for elongation, branching, fucosylation, and sialylation of HMOs. Our …

Admission Pao2 And Mortality Among Pediatric Icu Patients And Critically Ill Subgroups, Cara Holton

Research Days

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Background and Objectives: Studies analyzing the association between hyperoxia and mortality in critically ill pediatric patients and those admitted after cardiac arrest are conflicting and limited by small sample sizes. The aim of this study is to evaluate the association between PaO2 on admission to the pediatric ICU and mortality in a heterogeneous, multicenter cohort and among subgroups of critically ill patients.

Methods/Design: A retrospective cohort study was conducted using data from Virtual Pediatric Systems (VPS) database. VPS is a clinical pediatric critical care database with over 135 participating hospitals in North America. All VPS …

Maternal Antepartum Administration Of Lactoferrin Ameliorates Neonatal Infection By Bacteremia-Producing Escherichia Coli In Mice, Charity Dunlop

Research Days

Background: E. coli is a major cause of neonatal sepsis. Vaginal pathogenic E. coli strains ascend into the pregnant uterus infecting the offspring of colonized mothers. Lactoferrin (LF) is an antibacterial and immunomodulatory glycoprotein that has been given to preterm newborns to prevent lateonset sepsis. However, the effects of maternal LF administration to prevent neonatal E. coli invasive infection have not been studied.

Objectives/Goal: Our goal was to test the hypothesis that LF pre-treatment of pregnant mice administered prenatally will significantly reduce the bacterial load in their embryos following infection with E. coli.

Methods/Design: Human LF 100 mcg/mL or placebo …

Whole Exome Sequencing Identifies Potential Candidate Genes For Spina Bifida Derived From Mouse Models, Chunyan Wang, Steve Seltzsam, Bixia Zheng, Chen-Han Wilfred Wu, Camille Nicolas-Frank, Kirollos Yousef, Kit Sing Au, Nina Mann, Dalia Pantel, Sophia Schneider, Luca Schierbaum, Thomas M Kitzler, Dervla M Connaughton, Youying Mao, Rufeng Dai, Makiko Nakayama, Jameela A Kari, Sherif El Desoky, Mohammed Shalaby, Loai A Eid, Hazem S Awad, Velibor Tasic, Shrikant M Mane, Richard P Lifton, Michelle A Baum, Shirlee Shril, Carlos R Estrada, Friedhelm Hildebrandt

Faculty, Staff and Student Publications

Spina bifida (SB) is the second most common nonlethal congenital malformation. The existence of monogenic SB mouse models and human monogenic syndromes with SB features indicate that human SB may be caused by monogenic genes. We hypothesized that whole exome sequencing (WES) allows identification of potential candidate genes by (i) generating a list of 136 candidate genes for SB, and (ii) by unbiased exome-wide analysis. We generated a list of 136 potential candidate genes from three categories and evaluated WES data of 50 unrelated SB cases for likely deleterious variants in 136 potential candidate genes, and for potential SB candidate …

A D2 To D1 Shift In Dopaminergic Inputs To Midbrain 5-Ht Neurons Causes Anorexia In Mice, Xing Cai, Hailan Liu, Bing Feng, Meng Yu, Yang He, Hesong Liu, Chen Liang, Yongjie Yang, Longlong Tu, Nan Zhang, Lina Wang, Na Yin, Junying Han, Zili Yan, Chunmei Wang, Pingwen Xu, Qi Wu, Qingchun Tong, Yanlin He, Yong Xu

Faculty, Staff and Students Publications

Midbrain dopamine (DA) and serotonin (5-HT) neurons regulate motivated behaviors, including feeding, but less is known about how these circuits may interact. In this study, we found that DA neurons in the mouse ventral tegmental area bidirectionally regulate the activity of 5-HT neurons in the dorsal raphe nucleus (DRN), with weaker stimulation causing DRD2-dependent inhibition and overeating, while stronger stimulation causing DRD1-dependent activation and anorexia. Furthermore, in the activity-based anorexia (ABA) paradigm, which is a mouse model mimicking some clinical features of human anorexia nervosa (AN), we observed a DRD2 to DRD1 shift of DA neurotransmission on 5-HT

Association Of Physical Activity, Sports, And Screen Time With Adolescent Behaviors In Youth Who Visit The Pediatric Emergency Department, Rohit P Shenoi, James G Linakis, Julie R Bromberg, T Charles Casper, Rachel Richards, Thomas H Chun, Victor M Gonzalez, Michael J Mello, Anthony Spirito

Faculty, Staff and Students Publications

Moderate to vigorous physical activity (MVPA), sports, and reduced screen time are associated with favorable youth risk profiles. We evaluated the association of MVPA, sports, and screen time with adolescent behaviors among pediatric emergency department youth. Adolescents were assessed for alcohol/drug use, risky behavior, conduct disorder, and depressive mood. MVPA was activity for ≥5 days/week and ≥60 minutes/day. Increased screen time was ≥3 hours/day computer/TV use for non-schoolwork. Multivariable regression studied association between MVPA, sports, and increased screen time and outcomes adjusting for demographics and academic achievement. Older age and lower academic achievement were significantly associated with risky behaviors, conduct …

Sirolimus (Rapamycin) Induced Mucosal Healing In Anti-Tumor Necrosis Factor Refractory Pediatric Ulcerative Colitis, Richard Kellermayer, Andrew Chang, Kalyani Patel

Faculty, Staff and Students Publications

Sirolimus (rapamycin) has been sparsely reported in the treatment of pediatric ulcerative colitis (PUC). Mucosal healing has not been examined in responders to the drug. We describe a case of infliximab refractory PUC where rapamycin induced sustained clinical remission along with mucosal healing. We conclude that rapamycin should be positioned into the expanding treatment repertoire of PUC.

Prevalence And Clinical Correlates Of Antinuclear Antibody In Patients With Gastroparesis, Henry P Parkman, Mark L Van Natta, Ashima Makol, Madhusudan Grover, Richard W Mccallum, Zubair Malik, Kenneth L Koch, Irene Sarosiek, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Laura Miriel, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Thomas L Abell, Niddk Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

BACKGROUND: Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders.

AIMS: 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA.

METHODS: Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP).

RESULTS: Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), …

Evaluating Eosinophilic Colitis As A Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study, Tetsuo Shoda, Margaret H Collins, Mark Rochman, Ting Wen, Julie M Caldwell, Lydia E Mack, Garrett A Osswald, John A Besse, Yael Haberman, Seema S Aceves, Nicoleta C Arva, Kelley E Capocelli, Mirna Chehade, Carla M Davis, Evan S Dellon, Gary W Falk, Nirmala Gonsalves, Sandeep K Gupta, Ikuo Hirano, Paneez Khoury, Amy Klion, Calies Menard-Katcher, John Leung, Vincent A Mukkada, Philip E Putnam, Jonathan M Spergel, Joshua B Wechsler, Guang-Yu Yang, Glenn T Furuta, Lee A Denson, Marc E Rothenberg, Consortium Of Eosinophilic Gastrointestinal Diseases Researchers (Cegir)

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.

METHODS: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations …

Health-Related Quality Of Life In Pediatric Acute Recurrent Or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors, See Wan Tham, Fuchenchu Wang, Cheryl E Gariepy, Gretchen A Cress, Maisam A Abu-El-Haija, Melena D Bellin, Kate M Ellery, Douglas S Fishman, Tanja Gonska, Melvin B Heyman, Tom K Lin, Asim Maqbool, Brian A Mcferron, Veronique D Morinville, Jaimie D Nathan, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Uzma Shah, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Tonya M Palermo, International Study Group Of Pediatric Pancreatitis: In Search For A Cure (Insppire) And Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

OBJECTIVES: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL.

METHODS: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment.

RESULTS: The sample included …

Signal-To-Noise Analysis Can Inform The Likelihood That Incidentally Identified Variants In Sarcomeric Genes Are Associated With Pediatric Cardiomyopathy, Leonie M Kurzlechner, Edward G Jones, Amy M Berkman, Hanna J Tadros, Jill A Rosenfeld, Yaping Yang, Hari Tunuguntla, Hugh D Allen, Jeffrey J Kim, Andrew P Landstrom

Faculty, Staff and Students Publications

Background: Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and can predispose individuals to sudden death. Most pediatric HCM patients host a known pathogenic variant in a sarcomeric gene. With the increase in exome sequencing (ES) in clinical settings, incidental variants in HCM-associated genes are being identified more frequently. Diagnostic interpretation of incidental variants is crucial to enhance clinical patient management. We sought to use amino acid-level signal-to-noise (S:N) analysis to establish pathogenic hotspots in sarcomeric HCM-associated genes as well as to refine the 2015 American College of Medical Genetics (ACMG) criteria to predict incidental variant pathogenicity.

Methods and …