Pediatrics Commons^™

Using Mobile Technology For Family-Based Prevention In Families With Low Incomes: Lessons From A Randomized Controlled Trial Of A Childhood Obesity Prevention Program, Thomas G Power, Susan S Baker, Karen V Barale, M Catalina Aragón, Jane D Lanigan, Louise Parker, Karina Silva Garcia, Garry Auld, Nilda Micheli, Sheryl O Hughes

Faculty, Staff and Students Publications

Researchers are increasingly using web-based technologies to deliver family-based, prevention programming. Few studies have examined the success of such approaches for families with low incomes. The purpose of this study was to describe the level of in-class and online engagement in a childhood obesity prevention program for parents with low incomes, to examine the demographic correlates of parent engagement, and to examine dosage effects on parental feeding outcomes as a function of online exposure. All participants attended in-class nutrition education classes (Eating Smart · Being Active) as part of the Expanded Food and Nutrition Education Program (EFNEP) in Colorado and …

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

Single-Cell Multiomics Decodes Regulatory Programs For Mouse Secondary Palate Development, Fangfang Yan, Akiko Suzuki, Chihiro Iwaya, Guangsheng Pei, Xian Chen, Hiroki Yoshioka, Meifang Yu, Lukas M Simon, Junichi Iwata, Zhongming Zhao

Faculty, Staff and Student Publications

Perturbations in gene regulation during palatogenesis can lead to cleft palate, which is among the most common congenital birth defects. Here, we perform single-cell multiome sequencing and profile chromatin accessibility and gene expression simultaneously within the same cells (n = 36,154) isolated from mouse secondary palate across embryonic days (E) 12.5, E13.5, E14.0, and E14.5. We construct five trajectories representing continuous differentiation of cranial neural crest-derived multipotent cells into distinct lineages. By linking open chromatin signals to gene expression changes, we characterize the underlying lineage-determining transcription factors. In silico perturbation analysis identifies transcription factors SHOX2 and MEOX2 as important regulators …

Human Milk Polyunsaturated Fatty Acids Are Related To Neurodevelopmental, Anthropometric, And Allergic Outcomes In Early Life: A Systematic Review, Saori Mitguard, Olivia Doucette, John Miklavcic

Food Science Faculty Articles and Research

Polyunsaturated fatty acids are critically important for newborn nutrition and in the trajectory of growth and developmental processes throughout early life. This systematic review (PROSPERO ID: CRD42023400059) critically analyzes literature pertaining to how omega-3 and omega-6 fatty acids in human milk are related to health outcomes in early life. Literature selected for the review were published between 2005 and 2020 and included assessments in healthy term children between 0 and 5 years of age. The studies reported the relation between human milk fatty acids docosahexaenoic acid (C22:6n-3, DHA), eicosapentaenoic acid (C20:5n-3, EPA), alpha-linolenic acid (C18:3n-3, ALA), arachidonic acid (C20:4n-6, AA), …

Disruption Of The Arabidopsis Acyl-Activating Enzyme 3 Impairs Seed Coat Mucilage Accumulation And Seed Germination, Ninghui Cheng, Paul A Nakata

Faculty, Staff and Students Publications

The Acyl-activating enzyme (AAE) 3 gene encodes an oxalyl-CoA synthetase that catalyzes the conversion of oxalate to oxalyl-CoA as the first step in the CoA-dependent pathway of oxalate catabolism. Although the role of this enzyme in oxalate catabolism has been established, its biological roles in plant growth and development are less understood. As a step toward gaining a better understanding of these biological roles, we report here a characterization of the Arabidopsis thaliana aae3 (Ataae3) seed mucilage phenotype. Ruthidium red (RR) staining of Ataae3 and wild type (WT) seeds suggested that the observed reduction in Ataae3 …

Modeling The Health Impact And Cost-Effectiveness Of A Combined Schoolgirl Hpv Vaccination And Cervical Cancer Screening Program In Guangdong Province, China, Yating Huang, Dantao Zhang, Lihua Yin, Jianguo Zhao, Zhifeng Li, Jing Lu, Xiaoming Zhang, Chenggang Wu, Wei Wu

Faculty, Staff and Student Publications

Low human papillomavirus (HPV) vaccine uptake is a key barrier to cervical cancer elimination. We aimed to evaluate the health impact and cost-effectiveness of introducing different HPV vaccines into immunization programs and scaling up the screening program in Guangdong. We used a dynamic compartmental model to estimate the impact of intervention strategies during 2023-2100. We implemented the incremental cost-effectiveness ratio (ICER) in costs per averted disability-adjusted life year (DALY) as an indicator to assess the effectiveness of the intervention. We used an age-standardized incidence of 4 cases per 100,000 women as the threshold for the elimination of cervical cancer. Compared …

Armc5 Controls The Degradation Of Most Pol Ii Subunits, And Armc5 Mutation Increases Neural Tube Defect Risks In Mice And Humans, Hongyu Luo, Linjiang Lao, Kit Sing Au, Hope Northrup, Xiao He, Diane Forget, Marie-Soleil Gauthier, Benoit Coulombe, Isabelle Bourdeau, Wei Shi, Lucia Gagliardi, Maria Candida Barisson Villares Fragoso, Junzheng Peng, Jiangping Wu

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II).

RESULTS: We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised. The enlarged Pol II pool does not lead to generalized Pol II stalling or a generalized …

Factors Associated With Blood Mercury Concentrations And Their Interactions With Three Glutathione S-Transferase Genes (Gstt1, Gstm1, And Gstp1): An Exposure Assessment Study Of Typically Developing Jamaican Children, Sheikh Farzana Zaman, Maureen Samms-Vaughan, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare Pellington, Katherine A Loveland, Mohammad H Rahbar

Faculty, Staff and Student Publications

BACKGROUND: Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms.

METHODS: In this exposure assessment study we used data from 375 typically developing (TD) 2-8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general …

Too Hot To Thrive: A Qualitative Inquiry Of Community Perspectives On The Effect Of High Ambient Temperature On Postpartum Women And Neonates In Kilifi, Kenya., Adelaide Lusambili, Sari Kovats, Britt Nakstad, Veronique Filippi, Peter Khaemba, Nathalie Roos, Cherie Part, Stanley Luchters, Matthew Chersich, Jeremy Hess

Institute for Human Development, East Africa

Objectives; To understand community perspectives on the effects of high ambient temperature on the health and wellbeing of neonates, and impacts on post-partum women and infant care in Kilifi.

Design; Qualitative study using key informant interviews, in-depth interviews and focus group discussions with pregnant and postpartum women (n = 22), mothers-in-law (n = 19), male spouses (n = 20), community health volunteers (CHVs) (n = 22) and stakeholders from health and government ministries (n = 16).

Settings; We conducted our research in Kilifi County in Kenya’s Coast Province. The area is largely rural and during …

Advancing School Nursing Practice: A Novel Approach To Screening For Gastrointestinal Disorders In Children, Ashley Bunting, Isabella Cavlan

Nursing | Senior Theses

Background: Currently, mandated health screenings in California schools are limited to vision, hearing, and scoliosis; this leaves several other body systems unmonitored during the crucial years of childhood development. One such system is the gastrointestinal (GI) system, which plays a vital role in the normal growth, nutrition status, development, and overall health of children. Objective: By developing and implementing a GI-specific screening tool in the outpatient school setting, this research aims to increase the detection of GI disorders in children. Not only that, but school nurses can use this novel screening tool to promote early diagnosis, intervention, and …

Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn

Faculty, Staff and Students Publications

Introduction

Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40^phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells.

Case presentation

We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE …

Autophagy Determines Distinct Cell Fates In Human Amnion And Chorion Cells, Mary Elise L Severino, Lauren Richardson, Ananth Kumar Kammala, Enkhtuya Radnaa, Kamil Khanipov, Leslie Michelle M Dalmacio, Indira U Mysorekar, Marian Kacerovsky, Ramkumar Menon

Faculty, Staff and Students Publications

Human fetal membranes (amniochorion) that line the intrauterine cavity consist of two distinct cell layers; single-layer amnion epithelial cells (AEC) and multilayer chorion trophoblast cells (CTC). These layers are connected through a collagen-rich extracellular matrix. Cellular remodeling helps support membrane growth and integrity during gestation and helps to maintain pregnancy. Preterm prelabor rupture of the human amniochorionic (fetal) membrane (pPROM) is antecedent to 40% of all spontaneous preterm birth. Oxidative stress (OS) induced activation of the p38 MAPK due to various maternal risk exposures and the amniochorion cells' senescence are reported pathological features of pPROM. Our transcriptomics analysis implicated dysregulated …

Childhood And Adolescent Relapsed/Refractory Aggressive B-Cell Lymphomas With T(8;14) And Bcl2 Expression, Burkitt Lymphoma Versus Diffuse Large B-Cell Lymphoma: A Diagnostic Challenge, Fouad El Dana, Sofia Alexandra Garces Narvaez, Nader K El-Mallawany, Jennifer E Agrusa, Zoann E Dreyer, Andrea N Marcogliese, Mohamed Tarek Elghetany, Jyotinder N Punia, Chi Young Ok, Keyur P Patel, Dolores H Lopez-Terrada, Kevin E Fisher, Choladda V Curry

Faculty, Staff and Students Publications

We present 2 diagnostically challenging cases of pediatric/adolescent relapsed/refractory aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) within the spectrum of Burkitt lymphoma and diffuse large B-cell lymphoma and illustrate the different therapeutic regimens that are employed for pediatric and adult cancer centers. Both cases displayed varying-sized lymphoma cells with occasional single prominent nucleoli and heterogeneous BCL2 expression. Cytogenetics revealed complex karyotypes with t(8:14)(q24.2;q32) and IGH::MYC rearrangement by FISH. Next generation sequencing revealed deleterious TP53 and MYC mutations. We concluded that both could be diagnosed as “DLBCL-NOS with MYC rearrangement” using the current pathologic classifications, 2022 International Consensus Classification (ICC) and World …

Nutritional Importance Of Animal-Sourced Foods In A Healthy Diet, Sydney Sheffield, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Animal-sourced foods, such as meats, poultry, eggs, milk, and fish are nutrient-dense foods that are rich sources of protein, essential amino acids, and micronutrients that can be challenging to obtain solely through plant-based foods. Animal-sourced protein foods provide crucial nutrients that support the growth and development in children, maintenance of muscle mass and function in adults, gain in muscle mass and strength in exercising individuals, and mitigation of sarcopenia in the elderly. The 2020–2025 Dietary Guidelines for Americans have identified the important role of animal-sourced foods in the diet at every stage of life. Animal-sourced foods are consumed worldwide and …

Critical Dialogue And Capacity-Building Projects Reduced Alcohol And Substance Use In A Randomized Clinical Trial Among Formerly Incarcerated Men, Liliane Cambraia Windsor, Ellen Benoit, Carol Lee, Alexis Jemal, Kari Kugler, Douglas C Smith, Rogério M Pinto, Salma Musaad

Faculty, Staff and Students Publications

Background:

Rates of alcohol and/or substance use (ASU) among residents of predominantly Black and marginalized communities are similar to ASU rates in White communities. Yet ASU has worse consequences in predominantly Black and marginalized communities (e.g., higher incarceration).

Objective:

We randomized participants to one of 16 intervention conditions using a 2⁴ full factorial design to optimize a multilevel intervention reducing ASU among 602 formerly incarcerated men with substance-use-disorders (SUD). Candidate intervention components included (1) critical dialogue (CD; six weekly 2-hour-long group sessions vs. no CD sessions), (2) Quality of Life Wheel (QLW; six weekly 1-hour-long group sessions vs. no …

Citrulline And Adi-Peg20 Reduce Inflammation In A Juvenile Porcine Model Of Acute Endotoxemia, Caitlin Vonderohe, Barbara Stoll, Inka Didelija, Trung Nguyen, Mahmoud Mohammad, Yava Jones-Hall, Miguel A Cruz, Juan Marini, Douglas Burrin

Faculty, Staff and Students Publications

BACKGROUND: Arginine is a conditionally essential amino acid that is depleted in critically ill or surgical patients. In pediatric and adult patients, sepsis results in an arginine-deficient state, and the depletion of plasma arginine is associated with greater mortality. However, direct supplementation of arginine can result in the excessive production of nitric oxide (NO), which can contribute to the hypotension and macrovascular hypo-reactivity observed in septic shock. Pegylated arginine deiminase (ADI-PEG20, pegargiminase) reduces plasma arginine and generates citrulline that can be transported intracellularly to generate local arginine and NO, without resulting in hypotension, while maintaining microvascular patency. The objective of …

Branched-Chain Amino Acid Accumulation Fuels The Senescence-Associated Secretory Phenotype, Yaosi Liang, Christopher Pan, Tao Yin, Lu Wang, Xia Gao, Ergang Wang, Holly Quang, De Huang, Lianmei Tan, Kun Xiang, Yu Wang, Peter B Alexander, Qi-Jing Li, Tso-Pang Yao, Zhao Zhang, Xiao-Fan Wang

Faculty, Staff and Students Publications

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence-associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation-related diseases. Altered BCAA metabolism driving the SASP is mediated by robust activation of the BCAA transporters Solute Carrier Family 6 Members 14 and 15 as well as downregulation …

Polygenic Scores And Mendelian Randomization Identify Plasma Proteins Causally Implicated In Alzheimer’S Disease, Davis B Cammann, Yimei Lu, Jerome I Rotter, Alexis C Wood, Jingchun Chen

Faculty, Staff and Students Publications

BACKGROUND: An increasing body of evidence suggests that neuroinflammation is one of the key drivers of late-onset Alzheimer's disease (LOAD) pathology. Due to the increased permeability of the blood-brain barrier (BBB) in older adults, peripheral plasma proteins can infiltrate the central nervous system (CNS) and drive neuroinflammation through interactions with neurons and glial cells. Because these inflammatory factors are heritable, a greater understanding of their genetic relationship with LOAD could identify new biomarkers that contribute to LOAD pathology or offer protection against it.

METHODS: We used a genome-wide association study (GWAS) of 90 different plasma proteins (

RESULTS: We identified …

Genetic And Epigenetic Features Of Bilateral Wilms Tumor Predisposition In Patients From The Children’S Oncology Group Aren18b5-Q, Andrew J Murphy, Changde Cheng, Justin Williams, Timothy I Shaw, Emilia M Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay A Renfro, Brett Tornwall, Vicki Huff, Andrew L Hong, Elizabeth A Mullen, Brian Crompton, Jeffrey S Dome, Conrad V Fernandez, James I Geller, Peter F Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M Jablonowski, Andrew M Fleming, Prahalathan Pichavaram, Christopher L Morton, John Easton, Kim E Nichols, Michael R Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P Zambetti, Zhaoming Wang, Andrew M Davidoff, Xiang Chen

Faculty, Staff and Student Publications

Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of …

Effects Of Antiresorptive Medications On Tooth Root Formation And Tooth Eruption In Paediatric Patients, Yuki Arai, Jeryl D English, Noriaki Ono, Wanida Ono

Faculty, Staff and Student Publications

Tooth eruption is a pivotal milestone for children's growth and development. This process involves with the formation of the tooth root, the periodontal ligament (PDL) and the alveolar bone, as the tooth crown penetrates the bone and gingiva to enter the oral cavity. This review aims to outline current knowledge of the adverse dental effects of antiresorptive medications. Recently, paediatric indications for antiresorptive medications, such as bisphosphonates (BPs), have emerged, and these agents are increasingly used in children and adolescents to cure pathological bone resorption associated with bone diseases and cancers. Since tooth eruption is accompanied by osteoclastic bone resorption, …

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 …

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 …

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 …

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 …

Early Skeletal Muscle Loss In Adolescent And Young Adult Cancer Patients Treated With Anthracycline Chemotherapy, Savannah V Wooten, Fei Wang, Michael E Roth, Guanshu Liu, J Andrew Livingston, Behrang Amini, Susan C Gilchrist, Michelle Hildebrandt, Eugenie S Kleinerman

Faculty, Staff and Student Publications

BACKGROUND: Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline-induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status.

METHODS: Computed tomography (CT) scans were used to investigate changes in skeletal muscle of 153 AYA sarcoma and Hodgkin lymphoma patients at thoracic vertebra 4 after anthracycline treatment. Images were examined at three time …

Effect Of The Covid-19 Pandemic On The Epidemiology Of Pediatric Traumatic Brain Injury In Brazil, Leopoldo Mandic Ferreira Furtado, José Aloysio Da Costa Val Filho, Victor Da Silva Pereira, Yasmin S Coimbra, Vitor Hugo R Caldas, Anne R Magalhães, Bruna Athayde S De Carvalho, Saulo G Moreira, Antônio L Teixeira, Aline Silva De Miranda

Faculty, Staff and Student Publications

Aim: In response to the coronavirus 2019 disease (COVID-19) pandemic, governments worldwide implemented measures to prevent infection, resulting in restricted school activities, restricted children’s freedom of movement, and increased risk of violence and injuries at home, including traumatic brain injury (TBI), among children. In Brazil, the consequences of the COVID-19 pandemic on the causes, severity, and mortality of pediatric TBI have not yet been investigated. Thus, our study aimed to determine whether the COVID-19 pandemic has affected the epidemiology of pediatric TBI among Brazilian children.

Materials and methods: We investigated the patients with TBI aged <18 years who visited a tertiary trauma center in Brazil in 2019 and 2020. TBI-related variables, such as classification, mechanism, clinical manifestations, need for intervention, morbidity, and mortality, were recorded. Furthermore, we used a nationwide databank to collect information on mortality from external causes of trauma and violence in the pediatric population in 2019 and 2020. The Mann-Whitney test was used to compare quantitative variables related to the mechanisms and severity of TBI in both periods in order to determine the impact of the COVID-19 pandemic.

Results: Of the patients with …

Once-Weekly Transcon Cnp (Navepegritide) In Children With Achondroplasia (Accomplish): A Phase 2, Multicentre, Randomised, Double-Blind, Placebo-Controlled, Dose-Escalation Trial, Ravi Savarirayan, Daniel G Hoernschemeyer, Merete Ljungberg, Yuri A Zarate, Carlos A Bacino, Michael B Bober, Janet M Legare, Wolfgang Högler, Teresa Quattrin, M Jennifer Abuzzahab, Paul L Hofman, Klane K White, Nina S Ma, Dirk Schnabel, Sérgio B Sousa, Meng Mao, Alden Smith, Mukta Chakraborty, Adebola Giwa, Bent Winding, Birgitte Volck, Aimee D Shu, Ciara Mcdonnell

Faculty, Staff and Students Publications

BACKGROUND: TransCon CNP (navepegritide) is an investigational prodrug of C-type natriuretic peptide (CNP) designed to allow for continuous CNP exposure with once-weekly dosing. This 52-week phase 2 (ACcomplisH) trial assessed the safety and efficacy of TransCon CNP in children with achondroplasia.

METHODS: ACcomplisH is a global, randomised, double-blind, placebo-controlled, dose-escalation trial. Study participants were recruited between June 10, 2020, and September 24, 2021. Eligible participants were prepubertal, aged 2-10 years, with genetically confirmed achondroplasia, and randomised 3:1 to once-weekly subcutaneous injections of TransCon CNP (6, 20, 50, or 100 μg CNP/kg/week) or placebo for 52 weeks. Primary objectives were safety …

Utilization And Predictors Of Adjuvant Metformin For Children And Adolescents On Mixed Receptor Antagonists (Second-Generation Antipsychotics), Hua Chen, Ning Lyu, Wenyaw Chan, Austin De La Cruz, Chadi Calarge

Faculty, Staff and Student Publications

OBJECTIVE: to examine utilization and predictors of adjuvant metformin among pediatric recipients of second-generation antipsychotics (SGAs) (mixed receptor antagonist).

METHOD: This study used 2016-2021 data of a national electronic medical record database. Eligible participants were children aged 6 to 17 with a new SGA prescription for at least 90 days. Predictors of prescribing adjuvant metformin in general and to nonobese pediatric SGA recipients in particular were assessed using conditional logistic regression and logistic regression analyses, respectively.

RESULTS: Of 30,009 pediatric SGA recipients identified, 2.3% (n = 785) received adjuvant metformin. Among 597 participants with a body mass index z score …