Pediatrics Commons^™

Decreased Fxr Agonism In The Bile Acid Pool Is Associated With Impaired Fxr Signaling In A Pig Model Of Pediatric Nafld, Magdalena A Maj, Douglas G Burrin, Rodrigo Manjarín

Faculty, Staff and Students Publications

The objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with …

Apixaban For Prevention Of Thromboembolism In Pediatric Heart Disease, R Mark Payne, Kristin M Burns, Andrew C Glatz, Christoph Male, Andrea Donti, Leonardo R Brandão, Gunter Balling, Christina J Vanderpluym, Frances Bu'lock, Lazaros K Kochilas, Brigitte Stiller, James F Cnota, Otto Rahkonen, Asra Khan, Rachele Adorisio, Serban Stoica, Lindsay May, Jane C Burns, Jose Francisco K Saraiva, Kimberly E Mchugh, John S Kim, Agustin Rubio, Nadia G Chía-Vazquez, Marcie R Meador, Joshua L Dyme, Alison M Reedy, Toni Ajavon-Hartmann, Praneeth Jarugula, Lauren E Carlson-Taneja, Donna Mills, Olivia Wheaton, Paul Monagle

Faculty, Staff and Students Publications

Background: Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages.

Objectives: The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease.

Methods: Phase 2, open-label trial in children (ages, 28 days to < 18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis.

Primary endpoint: a composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy.

Results: From 2017 to 2021, 192 participants were randomized, 129 …

Development And Validation Of A Multiplex Real-Time Pcr Assay For Detection And Quantification Of Streptococcus Pneumoniae In Pediatric Respiratory Samples, Molly Butler, Garrett Breazeale, Eric Mwangi, Elaine Dowell, Samuel R Dominguez, Linda Lamberth, Kristina G Hultén, Sarah A Jung

Faculty, Staff and Students Publications

Streptococcus pneumoniae (Spn) is a bacterial pathogen that causes a range of disease manifestations in children, from acute otitis media to pneumonia, septicemia, and meningitis. Primary Spn laboratory diagnostic identification methods include culture, antigen testing, single-plex real-time PCR, and syndromic PCR panels. However, each method lacks sensitivity, specificity, and/or cost efficiency. We developed and validated a quantitative, multiplex PCR assay using three Spn genomic targets (lytA, piaB, and SP2020) for improved sensitivity and specificity to detect Spn in pleural fluid (PF), bronchoalveolar lavage (BAL), tracheal aspirate (TA), and upper respiratory (UR, research only) samples. Validation testing …

Therapeutic Effect Of Echinococcus Granulosus Cyst Fluid On Bacterial Sepsis In Mice, Shuying Wang, Donghui Jiang, Feifei Huang, Yayun Qian, Meitao Qi, Huihui Li, Xiaoli Wang, Zhi Wang, Kaigui Wang, Yin Wang, Pengfei Du, Bin Zhan, Rui Zhou, Liang Chu, Xiaodi Yang

Faculty, Staff and Students Publications

BACKGROUND: The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model.

METHODS: The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by …

Trajectories Of Egfr And Risk Of Albuminuria In Youth With Type 2 Diabetes: Results From The Today Cohort Study, Laure El Ghormli, Hui Wen, Diane Uschner, Morey W Haymond, Kara S Hughan, Katherine Kutney, Lori Laffel, Sherida E Tollefsen, Elia N Escaname, Jane Lynch, Petter Bjornstad, Today Study Group

Faculty, Staff and Students Publications

BACKGROUND: We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories.

RESULTS: At baseline, participants' mean age …

Nonsense Variant Prdm16-Q187x Causes Impaired Myocardial Development And Tgf-Β Signaling Resulting In Noncompaction Cardiomyopathy In Humans And Mice, Bo Sun, Omid M T Rouzbehani, Ryan J Kramer, Rajeshwary Ghosh, Robin M Perelli, Sage Atkins, Amir Nima Fatahian, Kathryn Davis, Marta W Szulik, Michael A Goodman, Marissa A Hathaway, Ellenor Chi, Tarah A Word, Hari Tunuguntla, Susan W Denfield, Xander H T Wehrens, Kevin J Whitehead, Hala Y Abdelnasser, Junco S Warren, Mingfu Wu, Sarah Franklin, Sihem Boudina, Andrew P Landstrom

Faculty, Staff and Students Publications

BACKGROUND: PRDM16 plays a role in myocardial development through TGF-β (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans.

METHODS: Individuals with PRDM16 variants were identified and consented. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from a proband hosting a Q187X nonsense variant as an in vitro model and underwent proliferative and transcriptional analyses. CRISPR-mediated knock-in mouse model hosting the Prdm16Q187X allele was generated …

Body Surface Area Compared To Body Weight Dosing Of Valganciclovir Is Associated With Increased Toxicity In Pediatric Solid Organ Transplantation Recipients, Salih Demirhan, Flor M Munoz, Kristen G Valencia Deray, Claire E Bocchini, Lara Danziger-Isakov, Samantha Blum, Tanvi S Sharma, Gilad Sherman, Juri Boguniewicz, Samantha Bacon, Monica I Ardura, Gabriela M Maron, Jose Ferrolino, Marc Foca, Betsy C Herold

Faculty, Staff and Students Publications

Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (P = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (P = …

Temporary Ventricular Assist Device Support With A Catheter-Based Axial Pump: Changing The Paradigm At A Pediatric Heart Center, Sebastian C Tume, Andres A Fuentes-Baldemar, Marc Anders, Joseph A Spinner, Hari Tunuguntla, Michiaki Imamura, Asma Razavi, Edward Hickey, Gary Stapleton, Athar M Qureshi, Iki Adachi

Faculty, Staff and Students Publications

Objective: We report the largest pediatric single-center experience with an Impella (Abiomed Inc) catheter-based axial pump support.

Methods: We conducted a retrospective cohort study of all patients with acute decompensated heart failure or cardiogenic shock requiring catheter-based axial pump support between October 2014 and February 2022. The primary outcome per individual encounter (hospital admission) was defined as bridge-to-recovery, bridge-to-durable ventricular assist device support, bridge-to-cardiac transplantation, or death at 6 months after catheter-based axial pump explantation. Adverse events were defined according to the Pediatric Interagency Registry for Mechanical Circulatory Support criteria.

Results: Our final study cohort included 37 encounters with 43 …

Understanding Burnout In Pediatric Residency Through The Lens Of The ‘Areas Of Worklife’, Linessa M Zuniga, Julieana Nichols, Teri Turner, Carla Falco

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: Burnout is a widespread problem in medicine, especially among trainees. Despite this, data on effective interventions are limited. An organizational context for burnout entitled Areas of Worklife identified six areas of the work environment that can affect burnout through mismatches between individuals expectations of that area and the reality of the work environment. This study aimed to gain a deeper understanding of pediatric residents’ perspectives of the Areas of Worklife to allow programs to utilize this framework in the development of future interventions.

METHODS: Using qualitative methodology founded in grounded theory, we employed an iterative data collection …

Recommendations To Improve Quality Of Probiotic Systematic Reviews With Meta-Analyses, Lynne V Mcfarland, Gail Hecht, Mary E Sanders, Debra A Goff, Ellie J C Goldstein, Colin Hill, Stuart Johnson, Maryam R Kashi, Ravina Kullar, Maria L Marco, Daniel J Merenstein, Mathieu Millette, Geoffrey A Preidis, Eamonn M M Quigley, Gregor Reid, Seppo Salminen, Jason C Sniffen, Harry Sokol, Hania Szajewska, Daniel J Tancredi, Kristin Woolard

Faculty, Staff and Students Publications

Importance: Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing.

Objective: To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity.

Evidence review: For this consensus statement, an updated literature review was conducted (January 1, 2020, to June 30, 2022) to supplement a previously published 2018 literature search to identify areas where …

Associations Between Avocado Intake And Measures Of Glucose And Insulin Homeostasis In Hispanic Individuals With And Without Type 2 Diabetes: Results From The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Mackenzie K Senn, Mark O Goodarzi, Gautam Ramesh, Matthew A Allison, Mariaelisa Graff, Kristin L Young, Gregory A Talavera, Amanda C Mcclain, Tanya P Garcia, Jerome I Rotter, Alexis C Wood

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry.

METHODS AND RESULTS: The associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%β), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Jeffrey V Lazarus, Vlad Ratziu, Sven M Francque, Arun J Sanyal, Fasiha Kanwal, Diana Romero, Manal F Abdelmalek, Quentin M Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D Byrne, Graciela E Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D Guy, Stephen A Harrison, Seung Up Kim, Bart G Koot, Marko Korenjak, Kris V Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R Morgan, Elisabeth E Powell, Michael Roden, Manuel Romero-Gómez, Marcelo Silva, Shivaram Prasad Singh, Silvia C Sookoian, C Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, Philip N Newsome, Nafld Nomenclature Consensus Group

Faculty, Staff and Students Publications

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 …

Job Characteristics That Enrich Clinician-Educators’ Career: A Theory-Informed Exploratory Survey, M Hossein Tcharmtchi, Shelley Kumar, Jennifer Rama, Brian Rissmiller, Danny Castro, Satid Thammasitboon

Faculty, Staff and Students Publications

Clinician educators (CEs) play a vital role in helping academic institutions achieve the missions of patient care, education and research. The driving forces that motivate pediatric CEs in professional growth and personal satisfaction remain unexplored. An exploratory survey research to investigate the job characteristics and factors that motivate CEs to pursue professional growth with personal satisfaction. Using the Job Characteristics Model (JCM) as a framework, we developed a 22-item survey comprised of the JCM derived Job Diagnostic Survey, Global Job Satisfaction scales and demographics. We collected data from January 2020 to March 2020 from self-identified pediatric CEs (with and without …

Rehydration Rates And Outcomes In Overweight Children With Diabetic Ketoacidosis, Kathleen M Brown, Nicole S Glaser, Julie K Mcmanemy, Andrew Depiero, Lise E Nigrovic, Kimberly S Quayle, Michael J Stoner, Jeff E Schunk, Jennifer L Trainor, Leah Tzimenatos, Arleta Rewers, Sage R Myers, Maria Y Kwok, Simona Ghetti, T Charles Casper, Cody S Olsen, Nathan Kuppermann, Pediatric Emergency Care Applied Research Network Diabetic Ketoacidosis Fluid Study Group

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: The Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis (DKA) (FLUID) Trial found that rapid fluid infusion does not increase the risk of cerebral injury. Concern persists, however, whether fluid rates should be adjusted for overweight or obese patients. We used the FLUID Trial database to evaluate associations between fluid infusion rate and outcomes in these patients.

METHODS: We compared children and youth who were overweight, obese, or normal weight, in regard to protocol adherence, mental status changes, time to DKA resolution, and electrolyte abnormalities. We investigated associations between outcomes and the …

Nutrition Assessment And Mash Severity In Children Using The Healthy Eating Index, Ajay Kumar Jain, Paula Buchannan, Katherine P Yates, Patricia Belt, Jeffrey B Schwimmer, Philip Rosenthal, Karen F Murray, Jean P Molleston, Ann Scheimann, Stavra A Xanthakos, Cynthia A Behling, Paula Hertel, Jamie Nilson, Brent A Neuschwander-Tetri, James Tonascia, Miriam B Vos, Nonalcoholic Steatohepatitis Clinical Research Network (Nash Crn)

Faculty, Staff and Students Publications

BACKGROUND: Pediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized an objectively measured healthier diet would positively modulate MAFLD.

METHODS: Diet was assessed using the Nutrition Data System for Research in children enrolled from 10 tertiary clinical centers to determine the Healthy Eating Index (HEI, 0-100) and individual food components.

RESULTS: In all, 119 children were included (13.3 ± 2.7 y), 80 (67%) male, 67 (18%) White, and 90 (76%) Hispanic, with an average body mass index …

Emerging Bedaquiline-Resistant Tuberculosis, Christoph Lange, Anca Vasiliu, Anna M Mandalakas

Faculty, Staff and Students Publications

No abstract provided.

Management Of Adults With Anomalous Aortic Origin Of The Coronary Arteries: State-Of-The-Art Review, Mario Gaudino, Antonino Di Franco, Eloisa Arbustini, Emile Bacha, Eric R Bates, Duke E Cameron, Davide Cao, Tirone E David, Ruggero De Paulis, Ismail El-Hamamsy, Kanwal M Farooqi, Leonard N Girardi, Christoph Gräni, Jonathan D Kochav, Silvana Molossi, John D Puskas, Sunil V Rao, Sigrid Sandner, James Tatoulis, Quynh A Truong, Jonathan W Weinsaft, Daniel Zimpfer, Carlos M Mery

Faculty, Staff and Students Publications

As a result of increasing adoption of imaging screening, the number of adult patients with a diagnosis of anomalous aortic origin of the coronary arteries (AAOCA) has grown in recent years. Existing guidelines provide a framework for management and treatment, but patients with AAOCA present with a wide range of anomalies and symptoms that make general recommendations of limited applicability. In particular, a large spectrum of interventions can be used for treatment, and there is no consensus on the optimal approach to be used. In this paper, a multidisciplinary group of clinical and interventional cardiologists and cardiac surgeons performed a …

Neonatal Cholestasis In Children With Alpha-1-At Deficiency Is A Risk For Earlier Severe Liver Disease With Male Predominance, Jeffrey Teckman, Philip Rosenthal, Rosalinda V Ignacio, Cathie Spino, Lee M Bass, Simon Horslen, Kasper Wang, John C Magee, Saul Karpen, Akihiro Asai, Jean P Molleston, Robert H Squires, Binita M Kamath, Stephen L Guthery, Kathleen M Loomes, Benjamin L Shneider, Ronald J Sokol, Children (Childhood Liver Disease Research Network)

Faculty, Staff and Students Publications

BACKGROUND: Our objective was to better understand the natural history and disease modifiers of Alpha-1-antitrypsin deficiency (AATD), a common genetic liver disease causing hepatitis and cirrhosis in adults and children. The clinical course is highly variable. Some infants present with neonatal cholestasis, which can resolve spontaneously or progress to cirrhosis; others are well in infancy, only to develop portal hypertension later in childhood.

METHODS: The Childhood Liver Disease Research Network has been enrolling AATD participants into longitudinal, observational studies at North American tertiary centers since 2004. We examined the clinical courses of 2 subgroups of participants from the several hundred …

The Perfect Storm: A Case Of Rapid-Onset Obesity With Hypoventilation, Hypothalamic, Autonomic Dysregulation, Neuroendocrine Tumor (Rohhadnet) With Heart Failure, Narcolepsy, And A Rare Location Of A Pelvic Neuroendocrine Tumor, Paul Roby, Gretta Smith Beltran, Casey Finch, Sonal Malhotra, Krista Reiling, Ehab Dayyat, Krista Birkemeier, Muppala Raju, Colleen Macmurdo, Edwin Hernandez, Malvika Sagar

Faculty, Staff and Students Publications

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disease of concurrent respiratory dysfunction and autonomic dysregulation with endocrine abnormalities. ROHHADNET includes ROHHAD plus coexisting neuroendocrine tumors (NETs). We describe an eight-year-old boy, who originally presented at four years of age with rapid weight gain and hyperhidrosis and who developed mild obstructive sleep apnea (OSA). His clinical course was eventually complicated by hypoxic respiratory failure requiring admission to the pediatric intensive care unit (PICU). Echocardiogram at that time demonstrated dilated cardiomyopathy left ventricular ejection fraction (LVEF) of 28% at time of admission. His respiratory failure …

Effectiveness Of A Community-Based Approach For The Investigation And Management Of Children With Household Tuberculosis Contact In Cameroon And Uganda: A Cluster-Randomised Trial, Maryline Bonnet, Anca Vasiliu, Boris K Tchounga, Benjamin Cuer, Katherine Fielding, Bob Ssekyanzi, Boris Tchakounte Youngui, Jennifer Cohn, Peter J Dodd, Georges Tiendrebeogo, Patrice Tchendjou, Leonie Simo, Richard F Okello, Albert Kuate Kuate, Stavia Turyahabwe, Daniel Atwine, Stephen M Graham, Martina Casenghi, Contact Study Group

Faculty, Staff and Students Publications

Background: Globally, the uptake of tuberculosis-preventive treatment (TPT) among children with household tuberculosis contact remains low, partly due to the necessity of bringing children to health facilities for investigations. This study aimed to evaluate the effect on TPT initiation and completion of community-based approaches to tuberculosis contact investigations in Cameroon and Uganda.

Methods: We did a parallel, cluster-randomised, controlled trial across 20 clusters (consisting of 25 district hospitals and primary health centres) in Cameroon and Uganda, which were randomised (1:1) to receive a community-based approach (intervention group) or standard-of-care facility-based approach to contact screening and management (control group). The community-based …

Autogenous Reproduction By Ornithodoros Turicata (Ixodida: Argasidae) Females And Vertical Transmission Of The Tick-Borne Pathogen Borrelia Turicatae (Spirochaetales: Borreliaceae), Serhii Filatov, Aparna Krishnavajhala, Job E Lopez

Faculty, Staff and Students Publications

Ornithodoros turicata is a vector of relapsing fever spirochetes in North America and transmits Borrelia turicatae to a variety of vertebrate hosts. The remarkably long lifespan of O. turicata and its ability to maintain spirochetes horizontally (between life stages) and vertically (to progeny) promote the perpetuation of B. turicatae in nature. Nevertheless, the reproductive biology of O. turicata is poorly understood. In this report, we collected ticks from a park within a neighborhood of Austin, TX. They were reared to adulthood, and male ticks were individually housed with females. We observed autogenous reproduction, which is the ability to produce eggs …

Quality Of Life Is Lower In Food Allergic Adolescents Compared To Young Children At A Community Educational Symposium, Diem-Tran I Nguyen, Kathleen Pitts, Kristen A Staggers, Carla M Davis

Faculty, Staff and Students Publications

INTRODUCTION: Food allergies (FA) can detrimentally impact physical, emotional, and psychological quality of life (QoL) among pediatric patients. Given the changes from childhood into adolescence, the impact of FA on QoL likely evolves with age. The purpose of this study was to determine whether QoL differed between adolescents and children with FA who participated in a Food Allergy Symposium (FAS).

METHODS: Patients with confirmed FA were recruited at an educational community symposium in September 2018 and September 2019. Patients and/or their parents were invited to complete the Food Allergy Quality of Life Questionnaires (FAQLQ). The Food Allergy Independent Measure (FAIM) …

Hyperleptinemia Contributes To Antipsychotic Drug-Associated Obesity And Metabolic Disorders, Shangang Zhao, Qian Lin, Wei Xiong, Li Li, Leon Straub, Dinghong Zhang, Rizaldy Zapata, Qingzhang Zhu, Xue-Nan Sun, Zhuzhen Zhang, Jan-Bernd Funcke, Chao Li, Shiuhwei Chen, Yi Zhu, Nisi Jiang, Guannan Li, Ziying Xu, Steven C Wyler, May-Yun Wang, Juli Bai, Xianlin Han, Christine M Kusminski, Ningyan Zhang, Zhiqiang An, Joel K Elmquist, Olivia Osborn, Chen Liu, Philipp E Scherer

Faculty, Staff and Students Publications

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly …

Stratification Of Risk For Emergent Intracranial Abnormalities In Children With Headaches: A Pediatric Emergency Care Applied Research Network (Pecarn) Study Protocol, Daniel S Tsze, Nathan Kuppermann, T Charles Casper, Bradley J Barney, Lawrence P Richer, Danica B Liberman, Pamela J Okada, Claudia R Morris, Sage R Myers, Jane K Soung, Rakesh D Mistry, Lynn Babcock, Sandra P Spencer, Michael D Johnson, Eileen J Klein, Kimberly S Quayle, Dale W Steele, Andrea T Cruz, Alexander J Rogers, Danny G Thomas, Jacqueline M Grupp-Phelan, Tiffani J Johnson, Peter S Dayan, Pediatric Emergency Care Applied Research Network (Pecarn)

Faculty, Staff and Students Publications

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA …

Coregnet: Unraveling Gene Co-Regulation Networks From Public Rna-Seq Repositories Using A Beta-Binomial Statistical Model, Jiasheng Wang, Ying-Wooi Wan, Rami Al-Ouran, Meichen Huang, Zhandong Liu

Faculty, Staff and Students Publications

Millions of RNA sequencing samples have been deposited into public databases, providing a rich resource for biological research. These datasets encompass tens of thousands of experiments and offer comprehensive insights into human cellular regulation. However, a major challenge is how to integrate these experiments that acquired at different conditions. We propose a new statistical tool based on beta-binomial distributions that can construct robust gene co-regulation network (CoRegNet) across tens of thousands of experiments. Our analysis of over 12 000 experiments involving human tissues and cells shows that CoRegNet significantly outperforms existing gene co-expression-based methods. Although the majority of the genes …

Qa-Snare Syntaxin 18 Mediates Lipid Droplet Fusion With Snap23 And Sec22b, Yuhui Fu, Binbin Ding, Xiaoxia Liu, Shangang Zhao, Fang Chen, Linsen Li, Yi Zhu, Jingxuan Zhao, Zhen Yuan, Yafeng Shen, Chaofeng Yang, Mengle Shao, She Chen, Perry E Bickel, Qing Zhong

Faculty, Staff and Students Publications

Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)-SNAP23-SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18-SNAP23-SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, …

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

Retrieval Of Large Balloon Fragments During Transcatheter Pulmonary Valve Implantation Using A Novel Retrieval System, Anne C Taylor, Mohamed Ali H Ghandour, Asra Khan, Srinath T Gowda, Flora Nunez-Gallegos, Lynn F Peng, Jamil A Aboulhosn, Daniel S Levi, Doff B Mcelhinney, Athar M Qureshi

Faculty, Staff and Students Publications

The removal of balloon fragments from the pulmonary artery without damaging the pulmonary and tricuspid valves can be difficult. Four cases during transcatheter pulmonary valve replacement are described in which a novel retrieval system was used to facilitate safe removal. (Level of Difficulty: Advanced.)

See Me, Hear Me, Know Me: Perspectives On Diet And Physical Activity Influences Among Teens Living In Rural Texas Communities, Debbe Thompson, Julie Miranda, Chishinga Callender, Jayna M Dave, Godlove Appiah, Salma M A Musaad

Faculty, Staff and Students Publications

Teens in rural communities are at greater risk of obesity than teens in urban areas. Diet and physical activity influence obesity risk. Understanding their perspectives is an important step in intervention design. This qualitative investigation explored teen perspectives on how living in a rural community influenced their diet and physical activity choices. Forty parent-teen pairs were recruited. Data collection included surveys and telephone interviews. This paper reports teen perspectives identified in the first interview. Thematic analysis was used to code and analyze the data. Findings revealed that the primary factor driving teens' diet and physical activity behaviors was the teens …

Late-Gadolinium Enhancement Is Common In Older Pediatric Heart Transplant Recipients And Is Associated With Lower Ejection Fraction, Andrew A Lawson, Kae Watanabe, Lindsay Griffin, Christina Laternser, Michael Markl, Cynthia K Rigsby, Melanie Sojka, Joshua D Robinson, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Chronic graft failure and cumulative rejection history in pediatric heart transplant recipients (PHTR) are associated with myocardial fibrosis on endomyocardial biopsy (EMB). Cardiovascular magnetic resonance imaging (CMR) is a validated, non-invasive method to detect myocardial fibrosis via the presence of late gadolinium enhancement (LGE). In adult heart transplant recipients, LGE is associated with increased risk of future adverse clinical events including hospitalization and death. We describe the prevalence, pattern, and extent of LGE on CMR in a cohort of PHTR and its associations with recipient and graft characteristics.

METHODS: This was a retrospective study of consecutive PHTR who underwent …