Pediatrics Commons^™

Using A Collaborative Learning Health System Approach To Improve Disease Activity Outcomes In Children With Juvenile Idiopathic Arthritis In The Pediatric Rheumatology Care And Outcomes Improvement Network, Julia G Harris, Catherine A Bingham, Sheetal S Vora, Cagri Yildirim-Toruner, Michelle Batthish, Danielle R Bullock, Jon M Burnham, Danielle C Fair, Kerry Ferraro, Suhas Ganguli, Mileka Gilbert, Beth S Gottlieb, Olha Halyabar, Melissa M Hazen, Ronald M Laxer, Tzielan C Lee, Alice Liu, Daniel J Lovell, Melissa L Mannion, Edward J Oberle, Nancy Pan, Michael Shishov, Jennifer E Weiss, Esi M Morgan

Faculty, Staff and Students Publications

INTRODUCTION: The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to …

Etiology Of Hospital Mortality In Children Living In Low- And Middle-Income Countries: A Systematic Review And Meta-Analysis, Teresa B Kortz, Rishi P Mediratta, Audrey M Smith, Katie R Nielsen, Asya Agulnik, Stephanie Gordon Rivera, Hailey Reeves, Nicole F O'Brien, Jan Hau Lee, Qalab Abbas, Jonah E Attebery, Tigist Bacha, Emaan G Bhutta, Carter J Biewen, Jhon Camacho-Cruz, Alvaro Coronado Muñoz, Mary L Dealmeida, Larko Domeryo Owusu, Yudy Fonseca, Shubhada Hooli, Hunter Wynkoop, Mara Leimanis-Laurens, Deogratius Nicholaus Mally, Amanda M Mccarthy, Andrew Mutekanga, Carol Pineda, Kenneth E Remy, Sara C Sanders, Erica Tabor, Adriana Teixeira Rodrigues, Justin Qi Yuee Wang, Niranjan Kissoon, Yemisi Takwoingi, Matthew O Wiens, Adnan Bhutta

Faculty, Staff and Students Publications

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, …

Colonic Malakoplakia In A Pediatric Renal Transplant Recipient Case Report, Kristen G Valencia Deray, Richard Kellermayer, Alexis C Gomez, Kalyani R Patel, Peace Imani, Seiji Kitagawa, Claire E Bocchini, Alvaro Orjuela

Faculty, Staff and Students Publications

Malakoplakia is a rare, chronic granulomatous disease that mainly affects the genitourinary system of immunocompromised adults. It is caused by a bactericidal deficit in macrophages and, therefore, the treatment includes antimicrobials that reach high concentrations in macrophages. To our knowledge, we present the first case of malakoplakia in a pediatric solid organ transplant recipient. Our patient is a 15-year-old male renal transplant recipient who presented with recurrent diarrhea. Blood, urine, and gastrointestinal pathogen panel testing were positive for enteroaggregative Escherichia coli. A colonoscopy revealed diffuse malakoplakia. He had a complete resolution of symptoms with trimethoprim-sulfamethoxazole therapy. Unfortunately, his malakoplakia recurred …

Recent Trends In The Incidence Of Gastric Cancer In The United States, Kyle S Liu, Syed Ahsan Raza, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Gastric cancer (GC) incidence rates overall in the United States have declined over recent decades and are predicted to continue declining. However, there have been mixed recent findings regarding the potential stabilization of rates and potential divergent trends by age group. We used the most recent cancer data for the United States and examined trends in GC between 1992 and 2019, overall and in important subgroups of the population.

METHODS: Age-adjusted GC incidence rates and trends in adults 20 years or older were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 12 program. Secular trends were …

Gene Content, Phage Cycle Regulation Model And Prophage Inactivation Disclosed By Prophage Genomics In The Helicobacter Pylori Genome Project, Filipa F Vale, Richard J Roberts, Ichizo Kobayashi, M Constanza Camargo, Charles S Rabkin, Hpgp Research Network

Faculty, Staff and Students Publications

Prophages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified …

Pseudoviruses, A Safer Toolbox For Vaccine Development Against Enveloped Viruses, Syamala R Thimmiraju, Jason T Kimata, Jeroen Pollet

Faculty, Staff and Students Publications

Introduction: Pseudoviruses are recombinant, replication-incompetent, viral particles designed to mimic the surface characteristics of native enveloped viruses. They are a safer, and cost-effective research alternative to live viruses. With the potential emergence of the next major infectious disease, more vaccine scientists must become familiar with the pseudovirus platform as a vaccine development tool to mitigate future outbreaks.

Areas covered: This review aims at vaccine developers to provide a basic understanding of pseudoviruses, list their production methods, and discuss their utility to assess vaccine efficacy against enveloped viral pathogens. We further illustrate their usefulness as wet-lab simulators for emerging mutant variants, …

Functional Genomics And Small Molecules In Mitochondrial Neurodevelopmental Disorders, Daniel G Calame, Lisa T Emrick

Faculty, Staff and Students Publications

Mitochondria are critical for brain development and homeostasis. Therefore, pathogenic variation in the mitochondrial or nuclear genome which disrupts mitochondrial function frequently results in developmental disorders and neurodegeneration at the organismal level. Large-scale application of genome-wide technologies to individuals with mitochondrial diseases has dramatically accelerated identification of mitochondrial disease-gene associations in humans. Multi-omic and high-throughput studies involving transcriptomics, proteomics, metabolomics, and saturation genome editing are providing deeper insights into the functional consequence of mitochondrial genomic variation. Integration of deep phenotypic and genomic data through allelic series continues to uncover novel mitochondrial functions and permit mitochondrial gene function dissection on an …

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 …

The Zebrafish As A Potential Model For Vaccine And Adjuvant Development, Peter J Hotez, Maria Elena Bottazzi, Nelufa Yesmin Islam, Jungsoon Lee, Jeroen Pollet, Cristina Poveda, Ulrich Strych, Syamala Rani Thimmiraju, Nestor L Uzcategui, Leroy Versteeg, Daniel Gorelick

Faculty, Staff and Students Publications

Introduction: Zebrafishes represent a proven model for human diseases and systems biology, exhibiting physiological and genetic similarities and having innate and adaptive immune systems. However, they are underexplored for human vaccinology, vaccine development, and testing. Here we summarize gaps and challenges.

Areas covered: Zebrafish models have four potential applications: 1) Vaccine safety: The past successes in using zebrafishes to test xenobiotics could extend to vaccine and adjuvant formulations for general safety or target organs due to the zebrafish embryos' optical transparency. 2) Innate immunity: The zebrafish offers refined ways to examine vaccine effects through signaling via Toll-like or NOD-like receptors …

Efficacy And Safety Of Lumasiran For Infants And Young Children With Primary Hyperoxaluria Type 1: 30-Month Analysis Of The Phase 3 Illuminate-B Trial, Yaacov Frishberg, Wesley Hayes, Hadas Shasha-Lavsky, David J Sas, Mini Michael, Anne-Laure Sellier-Leclerc, Julien Hogan, Richard Willey, John M Gansner, Daniella Magen

Faculty, Staff and Students Publications

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a genetic disorder resulting in overproduction of hepatic oxalate, potentially leading to recurrent kidney stones, nephrocalcinosis, chronic kidney disease, and kidney failure. Lumasiran, the first RNA interference therapeutic approved for infants and young children, is a liver-directed treatment that reduces hepatic oxalate production. Lumasiran demonstrated sustained efficacy with an acceptable safety profile over 12 months in infants and young children (age <6 >years) with PH1 in ILLUMINATE-B (clinicaltrials.gov: NCT03905694), an ongoing, Phase 3, multinational, open-label, single-arm study.

METHODS: Here, we report interim efficacy and safety findings from ILLUMINATE-B following 30 months of lumasiran treatment. …

Improving Lupus Care Index Documentation In Patients With Childhood-Onset Systemic Lupus Erythematosus, Fatima A Barbar-Smiley, Cagri Yildirim-Toruner, Shoghik Akoghlanian, Ohoud Alahmed, Stacy P Ardoin, Ashlee Leone, Edward Oberle, Vidya Sivaraman

Faculty, Staff and Students Publications

INTRODUCTION: Childhood-onset systemic lupus erythematosus (c-SLE) presents unique challenges due to increased risk for severe morbidity and mortality compared to adult-onset SLE. Effective disease management relies on accurate disease assessment and documentation. Our project aimed to improve the documentation of the Lupus Care Index (LCI), a disease assessment bundle, by implementing a quality improvement (QI) initiative.

METHODS: A QI project was conducted at Nationwide Children's Hospital (NCH), targeting patients with c-SLE. The LCI, comprising the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2k) Physician Global Assessment (PGA) and patient-reported pain score, was introduced to capture comprehensive disease assessment. Interventions included provider …

Anomalous Aortic Origin Of A Coronary Artery In Pediatric Patients, Tam T Doan, Charles Puelz, Craig Rusin, Silvana Molossi

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: We present a contemporary approach to risk assessment and management of patients with anomalous aortic origin of a coronary artery (AAOCA).

RECENT FINDINGS: Anomalous left coronary artery from the right aortic sinus (L-AAOCA) with interarterial course carries a high risk of sudden cardiac death (SCD); therefore, current guidelines recommend exercise restriction and surgical intervention. Recent data in intraseptal and juxtacommissural L-AAOCA showed inducible perfusion abnormalities, leading to consideration of surgical intervention. Anomalous right coronary artery from the left aortic sinus (R-AAOCA) carries a much lower risk and stress perfusion imaging is helpful in identifying patients with inducible …

Rapid Gene Fusion Testing Using The Nanostring Ncounter Platform To Improve Pediatric Leukemia Diagnoses In Sub-Saharan Africa, Julie M Gastier-Foster, Fredrick Lutwama, Olive Mbabazi, Steven Mlenga, Kennedy Ulaya, Ruth Namazzi, E Faith Hollingsworth, Dolores Lopez-Terrada, Kevin E Fisher, Angshumoy Roy, Carl E Allen, David G Poplack, Rizine Mzikamanda, Nmazuo Ozuah, Peter Wasswa

Faculty, Staff and Students Publications

Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries. In contrast, precise diagnosis in low-resource settings is hindered by insufficient pathology infrastructure. The Global HOPE program aims to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA) by building local clinical care and diagnostic capacity. This study aimed to assess the feasibility of implementing molecular assays to improve leukemia diagnoses in SSA. Custom NanoString nCounter gene fusion assays, previously validated in the US, were used to test samples from suspected leukemia patients. The NanoString platform was chosen due to relatively low …

Systemic Complications Of Aicardi Goutières Syndrome Using Real-World Data, Isabella Peixoto De Barcelos, Amanda K Jan, Nicholson Modesti, Sarah Woidill, Francesco Gavazzi, David Isaacs, Russell D'Aiello, Anjana Sevagamoorthy, Lauren Charlton, Amy Pizzino, Johanna Schmidt, Keith Van Haren, Stephanie Keller, Florian Eichler, Lisa T Emrick, Jamie L Fraser, Justine Shults, Adeline Vanderver, Laura A Adang

Faculty, Staff and Students Publications

Objective: Aicardi Goutières Syndrome (AGS) is a rare genetic interferonopathy associated with diverse multisystemic complications. A critical gap exists in our understanding of its longitudinal, systemic disease burden, complicated by delayed diagnosis. To address this need, real-world data extracted from existing medical records were used to characterize the longitudinal disease burden.

Methods: All subjects (n = 167) with genetically confirmed AGS enrolled in the Myelin Disorders Biorepository Project (MDBP) were included. As available in medical records, information was collected on subject demographics, age of onset, and disease complications. Information from published cases of AGS (2007-2022; n = 129) with individual-level …

Mecp2-Related Disorders While Gene-Based Therapies Are On The Horizon, Katherine Allison, Mirjana Maletic-Savatic, Davut Pehlivan

Faculty, Staff and Students Publications

The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities. This creates exciting opportunities for research and treatment development, and a few genetic disorders (e.g., spinal muscular atrophy) have recently been treated with gene-based therapies. MECP2 is found on the X chromosome and regulates the transcription of thousands of genes. Loss of MECP2 gene product leads to Rett Syndrome, a disease found primarily in females, and is characterized by developmental regression, motor dysfunction, midline hand stereotypies, autonomic nervous system dysfunction, epilepsy, scoliosis, and autistic-like behavior. Duplication of MECP2 causes …

Associations Of Chronic Pain With Psychosocial Outcomes After Traumatic Brain Injury: A Nidilrr And Va Tbi Model Systems Collaborative Project, Robin Hanks, Jessica M Ketchum, Mackenzie Peckham, Mitch Sevigny, Angelle M Sander, Aaron M Martin, Stephanie Agtarap, Cynthia L Beaulieu, Librada Callender, Flora M Hammond, Jean Lengenfelder, Amanda R Rabinowitz, William C Walker, Jeanne M Hoffman, Cynthia Harrison-Felix, Risa Nakase-Richardson

Faculty, Staff and Students Publications

OBJECTIVE: To examine the differences in participation, life satisfaction, and psychosocial outcomes among individuals with traumatic brain injury (TBI) endorsing current, past, or no chronic pain.

SETTING: Community.

PARTICIPANTS: Three thousand eight hundred four TBI Model Systems participants 1 to 30 years of age postinjury classified into 1 of 3 groups based on their pain experience: current pain, past pain, no pain completed a Pain Survey at their usual follow-up appointment which on average was approximately 8 years postinjury.

DESIGN: Multisite, cross-sectional observational cohort study.

MAIN OUTCOME MEASURES: Sociodemographic and injury characteristics and psychosocial outcomes (ie, satisfaction with life, depression, …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Tanayott Thaweethai, Erika B Rosenzweig, James Chan, Lori B Chibnik, Mine S Cicek, Amy J Elliott, Valerie J Flaherman, Andrea S Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L Jernigan, Elizabeth W Karlson, Stuart D Katz, Patricia A Kinser, Lawrence C Kleinman, Michelle F Lamendola-Essel, Joshua D Milner, Sindhu Mohandas, Praveen C Mudumbi, Jane W Newburger, Kyung E Rhee, Amy L Salisbury, Jessica N Snowden, Cheryl R Stein, Melissa S Stockwell, Kelan G Tantisira, Moriah E Thomason, Dongngan T Truong, David Warburton, John C Wood, Shifa Ahmed, Almary Akerlundh, Akram N Alshawabkeh, Brett R Anderson, Judy L Aschner, Andrew M Atz, Robin L Aupperle, Fiona C Baker, Venkataraman Balaraman, Dithi Banerjee, Deanna M Barch, Arielle Baskin-Sommers, Sultana Bhuiyan, Marie-Abele C Bind, Amanda L Bogie, Tamara Bradford, Natalie C Buchbinder, Elliott Bueler, Hülya Bükülmez, B J Casey, Linda Chang, Maryanne Chrisant, Duncan B Clark, Rebecca G Clifton, Katharine N Clouser, Lesley Cottrell, Kelly Cowan, Viren D'Sa, Mirella Dapretto, Soham Dasgupta, Walter Dehority, Audrey Dionne, Kirsten B Dummer, Matthew D Elias, Shari Esquenazi-Karonika, Danielle N Evans, E Vincent S Faustino, Alexander G Fiks, Daniel Forsha, John J Foxe, Naomi P Friedman, Greta Fry, Sunanda Gaur, Dylan G Gee, Kevin M Gray, Stephanie Handler, Ashraf S Harahsheh, Keren Hasbani, Andrew C Heath, Camden Hebson, Mary M Heitzeg, Christina M Hester, Sophia Hill, Laura Hobart-Porter, Travis K F Hong, Carol R Horowitz, Daniel S Hsia, Matthew Huentelman, Kathy D Hummel, Katherine Irby, Joanna Jacobus, Vanessa L Jacoby, Pei-Ni Jone, David C Kaelber, Tyler J Kasmarcak, Matthew J Kluko, Jessica S Kosut, Angela R Laird, Jeremy Landeo-Gutierrez, Sean M Lang, Christine L Larson, Peter Paul C Lim, Krista M Lisdahl, Brian W Mccrindle, Russell J Mcculloh, Kimberly Mchugh, Alan L Mendelsohn, Torri D Metz, Julie Miller, Elizabeth C Mitchell, Lerraughn M Morgan, Eva M Müller-Oehring, Erica R Nahin, Michael C Neale, Manette Ness-Cochinwala, Sheila M Nolan, Carlos R Oliveira, Onyekachukwu Osakwe, Matthew E Oster, R Mark Payne, Michael A Portman, Hengameh Raissy, Isabelle G Randall, Suchitra Rao, Harrison T Reeder, Johana M Rosas, Mark W Russell, Arash A Sabati, Yamuna Sanil, Alice I Sato, Michael S Schechter, Rangaraj Selvarangan, S Kristen Sexson Tejtel, Divya Shakti, Kavita Sharma, Lindsay M Squeglia, Shubika Srivastava, Michelle D Stevenson, Jacqueline Szmuszkovicz, Maria M Talavera-Barber, Ronald J Teufel, Deepika Thacker, Felicia Trachtenberg, Mmekom M Udosen, Megan R Warner, Sara E Watson, Alan Werzberger, Jordan C Weyer, Marion J Wood, H Shonna Yin, William T Zempsky, Emily Zimmerman, Benard P Dreyer, Recover-Pediatric Consortium

Faculty, Staff and Students Publications

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Electronic Vapor Products: Alarming Trends In United States Adolescents, Charles H Hennekens, Adedamola Adele, Maria C Mejia, Robert S Levine, Panagiota Kitsantas

Faculty, Staff and Students Publications

Background: The use of electronic vapor products (EVPs) increases the risks of nicotine addiction, drug-seeking behavior, mood disorders, and avoidable premature morbidities and mortality. We explored temporal trends in EVP use among US adolescents.

Methods: We used data from the Youth Risk Behavior Survey for school grades 9 through 12 from 2015 (earliest available data) to 2021 (the most recently available data) from the US Centers for Disease Control and Prevention (n=57,006).

Results: Daily use of EVPs increased from 2.0% in 2015 to 7.2% in 2019, a greater than 3.5-fold increase. Although the percentage decreased to 5.0% in 2021, it …

Hepatic Failure And Hyperbilirubinemia Secondary To Hemolytic Disease Of The Newborn, Matthew Reinhardt, Marya L Strand, Dajana Sabic

Faculty, Staff and Students Publications

Anti-D antibody is the most common cause of hemolytic disease of the newborn (HDN). Other antigens have emerged, causing significant damage to the newborn. We report a case of a 31-week dichorionic diamniotic twin born emergently to a mother with anti-C and anti-D antibodies who required multiple percutaneous umbilical cord blood sampling (PUBS) and transfusions. Extensive resuscitation at birth was required due to severe anemia, hypovolemia, and prematurity. Ensuing liver damage occurred with subsequent profound coagulopathy, transaminitis, and direct hyperbilirubinemia that required significant support. This patient developed several unique findings including the inability to monitor oxygen saturations due to dermal …

Population-Based Screening Strategies For Biliary Atresia In The Newborn: A Systematic Review And Meta-Analysis, Srirupa Hari Gopal, Rema Zebda, Arvind Mohan, Kristin Borovsky, Yemisi Takwoingi, Katie Scandrett, Mohan Pammi

Faculty, Staff and Students Publications

BACKGROUND: Newborn screening for biliary atresia (BA) may facilitate earlier diagnosis and intervention for improved clinical outcomes.

METHODS: We systematically reviewed the accuracy of population-based screening strategies for BA in the newborn using PRISMA-DTA guidelines. We included cohort or cross-sectional studies. The screening (index) tests included stool color card (SCC) and direct/conjugated bilirubin (DB/CB) and the reference standard was intraoperative cholangiogram. Meta-analysis was performed using random-effects logistic regression models.

RESULTS: We included 15 studies (1,816,722 participants) that assessed 5 different population-based screening strategies. QUADAS-2 assessment revealed high risk of bias for patient selection in one study and uncertain risks for …

Understanding The Role Of Ampa Receptors In Autism: Insights From Circuit And Synapse Dysfunction, Andres Jimenez-Gomez, Megan X Nguyen, Jason S Gill

Faculty, Staff and Students Publications

Autism spectrum disorders represent a diverse etiological spectrum that converge on a syndrome characterized by discrepant deficits in developmental domains often highlighted by concerns in socialization, sensory integration, and autonomic functioning. Importantly, the incidence and prevalence of autism spectrum disorders have seen sharp increases since the syndrome was first described in the 1940s. The wide etiological spectrum and rising number of individuals being diagnosed with the condition lend urgency to capturing a more nuanced understanding of the pathogenic mechanisms underlying the autism spectrum disorders. The current review seeks to understand how the disruption of AMPA receptor (AMPAr)-mediated neurotransmission in the …

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 …

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 …

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 …

Stepped-Care Cognitive Behavioral Therapy In Children On The Autism Spectrum With Co-Occurring Anxiety, Eric A Storch, Sophie C Schneider, Sean M Olsen, Ana C Ramirez, Leandra N Berry, Robin P Goin-Kochel, Morgan Mcneel, Abigail E Candelari, Andrew G Guzick, Sandra L Cepeda, Saira Weinzimmer, Robert G Voigt, Troy Quast, Wayne K Goodman, Alison Salloum

Faculty, Staff and Students Publications

This trial examined stepped-care cognitive-behavioral treatment (CBT) among 96 autistic youth with co-occurring anxiety. Step 1 included an open trial of parent-led, therapist-guided bibliotherapy. Step 2 was family-based CBT for those who did not respond to Step 1 or maintenance for those who did. Eighteen participants (28%) who completed Step 1 responded. Responders reported significantly lower pre-treatment anxiety, internalizing symptoms, and functional impairment than non-responders. After Steps 1 and 2, 80% of completers (55% intent-to-treat) were responders. Anxiety, impairment, and ASD-related impairments significantly improved. Youth in maintenance experienced faster improvement through post-treatment, though there were no group differences at 3-month-follow-up. …

Predictors Of Making A Referral To Child Protective Services Prior To Expert Consultation, Danielle Zamalin, Irene Hamlin, Justine Shults, M Katherine Henry, Kristine A Campbell, James D Anderst, Angela N Bachim, Rachel P Berger, Lori D Frasier, Nancy S Harper, Megan M Letson, John D Melville, Daniel M Lindberg, Joanne N Wood

Faculty, Staff and Students Publications

OBJECTIVE: Suspicion for child abuse is influenced by implicit biases. Evaluation by a Child Abuse Pediatrician (CAP) may reduce avoidable child protective services (CPS) referrals. Our objective was to investigate the association of patient demographic, social and clinical characteristics with CPS referral before consultation by a CAP (preconsultation referral).

METHODS: Children <5 years-old undergoing in-person CAP consultation for suspected physical abuse from February 2021 through April 2022 were identified in CAPNET, a multicenter child abuse research network. Marginal standardization implemented with logistic regression analysis examined hospital-level variation and identified demographic, social, and clinical factors associated with pre-consultation referral adjusting for CAP’s final assessment of abuse likelihood.

RESULTS: Among the 61% (1005/1657) of cases with preconsultation referral, the CAP consultant had low concern for abuse in 38% (384/1005). Preconsultation referrals ranged from 25% to 78% of cases across 10 hospitals (P < .001). In multivariable analyses, preconsultation referral was associated with public insurance, caregiver history of CPS involvement, history of intimate partner violence, higher CAP level of concern for abuse, hospital transfer, and near-fatality (all P < .05). The difference in preconsultation referral prevalence for children with public versus private insurance was significant for children with low CAP concern for abuse (52% vs 38%) but not those with higher concern for abuse (73% vs 73%), (P = .023 for interaction of insurance and abuse likelihood category). There were no differences in preconsultation referral based on race or ethnicity.

CONCLUSIONS: Biases based on socioeconomic status and social factors may impact decisions to refer to …

5-Htp Inhibits Eosinophilia Via Intracellular Endothelial 5-Htrs; Snps In 5-Htrs Associate With Asthmatic Lung Function, Matthew T Walker, Jeffrey C Bloodworth, Timothy S Kountz, Samantha L Mccarty, Jeremy E Green, Ryan P Ferrie, Jackson A Campbell, Samantha H Averill, Kenneth B Beckman, Leslie C Grammer, Celeste Eng, Pedro C Avila, Harold J Farber, William Rodriguez-Cintron, Jose R Rodriguez-Santana, Denise Serebrisky, Shannon M Thyne, Max A Seibold, Esteban G Burchard, Rajesh Kumar, Joan M Cook-Mills

Faculty, Staff and Students Publications

BACKGROUND: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers.

OBJECTIVE: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans.

METHODS: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts.

RESULTS: Pharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil …

Optimizing Immunogenicity And Product Presentation Of A Sars-Cov-2 Subunit Vaccine Composition: Effects Of Delivery Route, Heterologous Regimens With Self-Amplifying Rna Vaccines, And Lyophilization, William R Lykins, Jeroen Pollet, Jessica A White, Brian Keegan, Leroy Versteeg, Ulrich Strych, Wen-Hsiang Chen, Raodoh Mohamath, Gabi Ramer-Denisoff, Sierra Reed, Christina Renshaw, Samuel Beaver, Alana Gerhardt, Emily A Voigt, Mark A Tomai, Robert Sitrin, Robert K M Choy, Frederick J Cassels, Peter J Hotez, Maria Elena Bottazzi, Christopher B Fox

Faculty, Staff and Students Publications

INTRODUCTION: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.) route has been shown to improve protective mucosal responses in comparison to intramuscular (i.m.) delivery. As we gain knowledge of the limitations of existing vaccines, it is of interest to understand if changes in product presentation or combinations of multiple vaccine modalities can further improve immunological outcomes.

METHODS: We investigated a commercial-stage SARS-CoV-2 receptor binding domain (RBD) antigen adjuvanted with a clinical-stage TLR-7/8 agonist …

Crystal Structure Of Trichinella Spiralis Calreticulin And The Structural Basis Of Its Complement Evasion Mechanism Involving C1q, Zhihui Jia, Wen Yu, Jingmo Li, Mingming Zhang, Bin Zhan, Liming Yan, Zhenhua Ming, Yuli Cheng, Xiaolin Tian, Shuai Shao, Jingjing Huang, Xinping Zhu

Faculty, Staff and Students Publications

Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth Trichinella spiralis produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway. Here, we used x-ray crystallography to resolve the structure of truncated TsCRT (TsCRTΔ), the first structure of helminth-derived CRT. TsCRTΔ was observed to share the same binding region on C1q with IgG based on the structure and molecular docking, which explains the inhibitory effect of TsCRT …

Increasing Social Determinants Of Health Screening Rates Among Six Endocrinology Centers Across The United States: Results From The T1d Exchange Quality Improvement Collaborative, Ori Odugbesan, Trevon Wright, Nana-Hawa Yayah Jones, Selorm Dei-Tutu, Mary Pat Gallagher, Emily Dewit, Roberto E Izquierdo, Marisa Desimone, Nicole Rioles, Osagie Ebekozien

Faculty, Staff and Students Publications

Social determinants of health (SDOH) are strongly associated with outcomes for people with type 1 diabetes. Six centers in the T1D Exchange Quality Improvement Collaborative applied quality improvement principles to design iterative Plan-Do-Study-Act cycles to develop and expand interventions to improve SDOH screening rates. The interventions tested include staff training, a social risk index, an electronic health record patient-facing portal, partnerships with community organizations, and referrals to community resources. All centers were successful in improving SDOH screening rates, with individual site improvements ranging from 41 to 70% and overall screening across the six centers increasing from a baseline of 1% …