Medical Specialties Commons^™

Trends In Cigarette Smoking Among United States Adolescents, Maria C Mejia, Adedamola Adele, Robert S Levine, Charles H Hennekens, Panagiota Kitsantas

Faculty, Staff and Students Publications

Background: Cigarette smoking remains the leading avoidable cause of premature death in the United States, accounting for approximately 500,000, or 1 in 5, deaths annually. We explored trends in cigarette smoking among US adolescents.

Methods: We used data for adolescents in grades 9 through 12 from 1991 to 2021 from the Youth Risk Behavior Survey provided by the US Centers for Disease Control and Prevention. We explored trends overall as well as by sex, race/ethnicity, and school grade.

Results: All cigarette use—assessed as ever, occasional, frequent, or daily—among adolescents declined markedly from 1991 to 2021. Specifically, ever use significantly decreased …

Acute Liver Failure And Unique Challenges Of Pediatric Liver Transplantation Amidst A Worldwide Cluster Of Adenovirus-Associated Hepatitis, Anna M Banc-Husu, Elizabeth A Moulton, Henry Shiau, Luz Helena Gutierrez Sanchez, Moreshwar S Desai, Dana Cerminara, Flor M Munoz, Leanne M Buffaloe, Kristen G Valencia-Deray, N Thao N Galvan, Julu Bhatnagar, Lindsey Estetter, Negar Rassaei, Sarah Reagan-Steiner, Jason Wicker, James J Dunn, Carl E Allen, Kalyani R Patel, Sanjiv Harpavat, John A Goss, Daniel H Leung

Faculty, Staff and Students Publications

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue …

Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lise E Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E Schunk, Michael J Stoner, Arleta Rewers, Julie K Mcmanemy, Kimberly S Quayle, Jennifer L Trainor, Leah Tzimenatos, Jonathan E Bennett, Maria Y Kwok, Sage R Myers, Kathleen M Brown, T Charles Casper, Cody S Olsen, Nicole S Glaser

Faculty, Staff and Students Publications

Background: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of childhood diabetes. However, the influence of demographic factors on presentation are not well-defined.

Methods: We included children from 12 centers who were < 18 years with DKA (glucose > 300 mg/dL, serum pH < 7.25, or serum bicarbonate < 15 mEq/L) enrolled in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Trial. Data were also collected for children who presented to the centers during the enrollment period but were not enrolled due to disease or treatment-related reasons. We compared demographic, clinical, and biochemical findings among children with newly and previously diagnosed diabetes and children in different age groups.

Results: Of the 1,679 DKA episodes in 1,553 children, 799 (47.5%) episodes occurred in children with newly diagnosed diabetes and 396 (23.6%) were severe (pH < 7.1). Newly diagnosed children < 6 years of age were not more likely to have severe DKA in terms of pH, but had more severe hypocarbia and higher blood urea nitrogen levels, factors previously associated with the risk of cerebral injury. Lower socioeconomic status (SES) (based on family income and maternal education level) were associated with more severe DKA in new onset children, and recurrent DKA in the previously diagnosed children.

Conclusions: Greater efforts are needed to identify the children with diabetes early and to prevent recurrent DKA, particularly among children in low-SES groups. Young children with DKA may need more intensive monitoring due to higher risk of cerebral injury.

Editorial: Biological Drivers Of Vector-Pathogen Interactions – Vol Ii, Ryan O M Rego, Job E Lopez, Alejandro Cabesas-Cruz

Faculty, Staff and Students Publications

No abstract provided.

Specialized Intensive Inpatient Rehabilitation Is Crucial And Time-Sensitive For Functional Recovery From Disorders Of Consciousness, Bei Zhang, Katherine O'Brien, Jean Woo, Bradley Chi, Colton Reeh, Sheng Li, Sunil Kothari

Faculty, Staff and Students Publications

Background: Disorders of consciousness (DoCs) after severe brain injury are considered to be conditions with dire prognosis. Despite the accumulating evidence, inpatient rehabilitation is often denied by payers referring to the Medicare/Medicaid criteria, under the assumption that such patients will not "actively" participate in therapy or make "measurable improvements."

Objective: This study aimed to report on the effectiveness and efficiency of a specialized inpatient DoC rehabilitation program based on measurable clinical parameters.

Methods: A retrospective cohort study was conducted. The cohort comprised 137 patients with DoC admitted to a specialized acute inpatient rehabilitation program between January …

Religion, Spirituality, And Coping During The Pandemic: Perspectives Of Dementia Caregivers, Katherine Carroll Britt, Kathy C Richards, Kavita Radhakrishnan, Andrea Vanags-Louredo, Eunice Park, Nalaka S Gooneratne, Liam Fry

Faculty, Staff and Students Publications

Religious and spiritual (R/S) practices support individuals during difficult situations. The COVID-19 social distancing restrictions may have limited access to R/S practices for older adults with Alzheimer’s disease related dementia (ADRD) and their caregivers, affecting coping and well-being. This qualitative study explored the impact of social distancing on R/S practices and coping in ADRD-caregiver dyads from the perspective of caregivers. Interviews were conducted with 11 family caregivers of older adults with ADRD residing in nursing homes (n = 4) or private homes (n = 7). Caregivers continued individual and started virtual R/S practices which improved their ability to …

Can Mild Traumatic Brain Injury Alter Cognition Chronically? A Limbic-Cenc Multicenter Study, William C Walker, Maya E O'Neil, Zhining Ou, Terri K Pogoda, Heather G Belanger, Randall S Scheibel, Angela P Presson, Shannon R Miles, Elisabeth A Wilde, David F Tate, Maya Troyanskaya, Mary Jo Pugh, Amy Jak, David X Cifu

Faculty, Staff and Students Publications

Objective: While outcome from mild traumatic brain injury (mTBI) is generally favorable, concern remains over potential negative long-term effects, including impaired cognition. This study examined the link between cognitive performance and remote mTBIs within the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) multicenter, observational study of Veterans and service members (SMs) with combat exposure.

Method: Baseline data of the participants passing all cognitive performance validity tests (n = 1,310) were used to conduct a cross-sectional analysis. Using multivariable regression models that adjusted for covariates, including age and estimated preexposure intellectual function, positive mTBI history …

Behavioral Improvements Following Lesion Resection For Pediatric Epilepsy: Pediatric Psychosurgery?, Huy Dang, Abdul Basit Khan, Nisha Gadgil, Himanshu Sharma, Cristina Trandafir, Fatema Malbari, Howard L Weiner

Faculty, Staff and Students Publications

Introduction: Resection of brain lesions associated with refractory epilepsy to achieve seizure control is well accepted. However, concurrent behavioral effects of these lesions such as changes in mood, personality, and cognition and the effects of surgery on behavior have not been well characterized. We describe 5 such children with epileptogenic lesions and significant behavioral abnormalities which improved after surgery.

Case descriptions: Five children (ages 3-14 years) with major behavioral abnormalities and lesional epilepsy were identified and treated at our center. Behavioral problems included academic impairment, impulsivity, self-injurious behavior, and decreased social interaction with diagnoses of ADHD, oppositional defiant disorder, and …

Atrial Standstill In The Pediatric Population: A Multi-Institution Collaboration, Taylor S Howard, David Y Chiang, Scott R Ceresnak, Virginie Beausejour Ladouceur, Robert D Whitehill, Richard J Czosek, Timothy K Knilans, Agnethe M Ahnfeldt, Malene Lando Borresen, Edgar Jaeggi, Sharmila Udupa, Robert Gow, Jeremy P Moore, Roberto G Galloti, Doug Y Mah, Jeffrey J Kim, Santiago O Valdes, Dianna M Milewicz, Christina Y Miyake

Faculty, Staff and Students Publications

Background: Atrial standstill (AS) is a rare condition characterized by absence of electrical activity within the atria. Studies to date have been limited.

Objectives: The authors sought to describe the clinical characteristics, genetics, and outcomes of patients with AS.

Methods: This was a retrospective multicenter study of patients < 18 years at AS diagnosis, defined as absence of atrial activity documented during an electrophysiology study, device placement, or noninvasive rhythm tracings and confirmed by echocardiogram. Patients with acquired disorders were excluded. Clinical details and genetic variants were recorded and analyzed.

Results: Twenty patients were diagnosed at a median age of 6.6 years (IQR: 2.9-10.8 years). Arrhythmias included 16 (80%) with atrial/supraventricular arrhythmias and 8 (40%) with ventricular tachycardia, including 4 with cardiac arrests. A type 1 Brugada pattern was documented in 4. Pacemakers were implanted in 18 (90%). Although atrial leads were …

Clinical Hypoxemia Score For Outpatient Child Pneumonia Care Lacking Pulse Oximetry In Africa And South Asia, Holly B Schuh, Shubhada Hooli, Salahuddin Ahmed, Carina King, Arunangshu D Roy, Norman Lufesi, Asmd Ashraful Islam, Tisungane Mvalo, Nabidul H Chowdhury, Amy Sarah Ginsburg, Tim Colbourn, William Checkley, Abdullah H Baqui, Eric D Mccollum

Faculty, Staff and Students Publications

BACKGROUND: Pulse oximeters are not routinely available in outpatient clinics in low- and middle-income countries. We derived clinical scores to identify hypoxemic child pneumonia.

METHODS: This was a retrospective pooled analysis of two outpatient datasets of 3-35 month olds with World Health Organization (WHO)-defined pneumonia in Bangladesh and Malawi. We constructed, internally validated, and compared fit & discrimination of four models predicting SpO

RESULTS: 12,712 observations were included. The independent and composite LASSO models discriminated moderately (both C-statistic 0.77) between children with a SpO

CONCLUSIONS: In the absence of pulse oximeters, both LASSO models better identified outpatient hypoxemic pneumonia cases …

Clostridioides Difficile Infection In Hospitalized Pediatric Patients: Comparisons Of Epidemiology, Testing, And Treatment From 2013 To 2019, Price T Edwards, Cary W Thurm, Matthew Hall, Jordan D Busing, Stacy A Kahn, Richard Kellermayer, Larry K Kociolek, Maria M Oliva-Hemker, Julia S Sammons, Madison Weatherly, Kathryn M Edwards, Maribeth R Nicholson

Faculty, Staff and Students Publications

OBJECTIVES: To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to 2019.

STUDY DESIGN: The Pediatric Health Information System database was queried for patient admissions (age 0-17 years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment.

RESULTS: We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 …

A Systematic Review Of Associations Between Gut Microbiota Composition And Growth Failure In Preterm Neonates, Larissa L Neves, Amy B Hair, Geoffrey A Preidis

Faculty, Staff and Students Publications

Growth failure is among the most prevalent and devastating consequences of prematurity. Up to half of all extremely preterm neonates struggle to grow despite modern nutrition practices. Although elegant preclinical models suggest causal roles for the gut microbiome, these insights have not yet translated into biomarkers that identify at-risk neonates or therapies that prevent or treat growth failure. This systematic review aims to identify features of the neonatal gut microbiota that are positively or negatively associated with early postnatal growth. We identified 860 articles, of which 14 were eligible for inclusion. No two studies used the same definitions of growth, …

Emerging Issues In Probiotic Safety: 2023 Perspectives, Daniel Merenstein, Bruno Pot, Gregory Leyer, Arthur C Ouwehand, Geoffrey A Preidis, Christopher A Elkins, Colin Hill, Zachery T Lewis, Andi L Shane, Niv Zmora, Mariya I Petrova, Maria Carmen Collado, Lorenzo Morelli, Gina A Montoya, Hania Szajewska, Daniel J Tancredi, Mary Ellen Sanders

Faculty, Staff and Students Publications

Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related …

Cholestasis Impairs Gut Microbiota Development And Bile Salt Hydrolase Activity In Preterm Neonates, Lauren E Lynch, Amy B Hair, Krishnakant G Soni, Heeju Yang, Laura A Gollins, Monica Narvaez-Rivas, Kenneth D R Setchell, Geoffrey A Preidis

Faculty, Staff and Students Publications

Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops …

Insulin-Like Growth Factor 1 Supplementation Supports Motor Coordination And Affects Myelination In Preterm Pigs, Line I Christiansen, Gemma C Ventura, Bo Holmqvist, Karoline Aasmul-Olsen, Sandy E H Lindholm, Matthew D Lycas, Yuki Mori, Jan Bojsen-Møller Secher, Douglas G Burrin, Thomas Thymann, Per T Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

INTRODUCTION: Preterm infants have increased risk of impaired neurodevelopment to which reduced systemic levels of insulin-like growth factor 1 (IGF-1) in the weeks after birth may play a role. Hence, we hypothesized that postnatal IGF-1 supplementation would improve brain development in preterm pigs, used as a model for preterm infants.

METHODS: Preterm pigs delivered by cesarean section received recombinant human IGF-1/IGF binding protein-3 complex (rhIGF-1/rhIGFBP-3, 2.25 mg/kg/day) or vehicle from birth to postnatal day 19. Motor function and cognition were assessed by monitoring of in-cage and open field activities, balance beam test, gait parameters, novel object recognition and operant conditioning …

Determinants Of Retention In Care Of Newborns Diagnosed With Sickle Cell Disease In Liberia: Results From A Mixed-Methods Study Of Caregivers, Kanagasabai Udhayashankar, Patience D Franklin, Cecelia J Nuta, Adolphus K Cherue, Heather Haq, Debbe Thompson, Venée N Tubman

Faculty, Staff and Students Publications

High-income nations have established that early diagnosis and preventive treatment reduces early deaths in sickle cell disease (SCD). However, in low-/middle-income countries where SCD is common, attrition from clinical care is common. Reasons for poor retention in care are multi-factorial and poorly understood. The objective of this study was to identify factors that influence caregiver decision-making around chronic health care needs of a child with SCD. We conducted an exploratory sequential mixed methods study of caregivers of children diagnosed with SCD during a newborn screening program in Liberia. Caregivers completed questionnaires and semi-structured interviews designed to identify drivers of health …

Impact Of The Covid Pandemic On Mental Health And Training Opportunities Of Public Health Residents From 4 European Countries: A Cross-Sectional Study, Giovanna Failla, Marta Caminiti, José Chen-Xu, Giuseppina Lo Moro, Nausicaa Berselli, Madalena Cabral Ferreira, Filipa Malcata, David Peyre-Costa, Roberto Croci, Giorgia Soldà, Angelo Capodici, Caterina Morcavallo, Francesco Traglia, Fabrizio Cedrone, Ilaria Storti, Alfonso Alonso Jaquete, Martina Antinozzi, Anca Vasiliu

Faculty, Staff and Students Publications

OBJECTIVES: There is little evidence on the impact of the COVID-19 pandemic on Public Health Residents' (PHR) mental health (MH). This study aims at assessing prevalence and risk factors for depression, anxiety and stress in European PHR during the COVID-19 pandemic.

METHODS: Between March and April 2021, an online survey was administered to PHR from France, Italy, Portugal and Spain. The survey assessed COVID-19 related changes in working conditions, training opportunities and evaluated MH outcomes using the Depression Anxiety Stress Scales-21. Multivariable logistic regressions were applied to identify risk factors.

RESULTS: Among the 443 respondents, many showed symptoms of depression …

Combined Immunodeficiency Caused By Pathogenic Variants In The Zap70 C-Terminal Sh2 Domain, Cédric Mongellaz, Rita Vicente, Lenora M Noroski, Nelly Noraz, Valérie Courgnaud, Javier Chinen, Emilia Faria, Valérie S Zimmermann, Naomi Taylor

Faculty, Staff and Students Publications

INTRODUCTION: ZAP-70, a protein tyrosine kinase recruited to the T cell receptor (TCR), initiates a TCR signaling cascade upon antigen stimulation. Mutations in the ZAP70 gene cause a combined immunodeficiency characterized by low or absent CD8+ T cells and nonfunctional CD4+ T cells. Most deleterious missense ZAP70 mutations in patients are located in the kinase domain but the impact of mutations in the SH2 domains, regulating ZAP-70 recruitment to the TCR, are not well understood.

METHODS:Genetic analyses were performed on four patients with CD8 lymphopenia and a high resolution melting screening for ZAP70 mutations was developed. The impact of SH2 …

The Epidemiology Of Cephalosporin Allergy Labels In Pediatric Primary Care, Torsten Joerger, Margaret G Taylor, Debra L Palazzi, Jeffrey S Gerber

Faculty, Staff and Students Publications

BACKGROUND: Recent studies have sought to understand the epidemiology and impact of beta-lactam allergy labels on children; however, most of these studies have focused on penicillin allergy labels. Fewer studies assess cephalosporin antibiotic allergy labels in children. The objective of this study was to determine the prevalence, factors associated with, and impact of cephalosporin allergy labels in children cared for in the primary care setting.

METHODS: Cephalosporin allergy labels were reviewed among children in a dual center, retrospective, birth cohort who were born between 2010 and 2020 and followed in 90 pediatric primary care practices. Antibiotic prescriptions for acute otitis …

Review Of Acute Kidney Injury And Progression To Chronic Kidney Disease In Pediatric Patients Undergoing Hematopoietic Cell Transplant, Kim T Vuong, Catherine Joseph, Joseph R Angelo

Faculty, Staff and Students Publications

While acute kidney injury (AKI) after hematopoietic cell transplant (HCT) has been well-described in pediatric patients, literature regarding the long term renal consequences of HCT-related AKI, the development of chronic kidney disease (CKD), and CKD care in pediatric patients post-HCT is limited. CKD affects almost 50% of patients after HCT with multifactorial etiology including infection, nephrotoxic medications, transplant-associated thrombotic microangiopathy, graft-versus-host disease, and sinusoidal obstruction syndrome. As renal function declines in CKD, eventually progressing to end stage kidney disease (ESKD), mortality increases and is more than 80% among patients requiring dialysis. Using society guidelines and current literature, this review summarizes …

Cefepime Dosing In A Critically Ill Neonate Receiving Continuous Renal Replacement Therapy With The Cardio-Renal Pediatric Dialysis Emergency Machine (Carpediem), Cynthia Toy, Grant Stimes, Megan Moore, Poyyapakkam Srivaths, Ayse Akcan Arikan

Faculty, Staff and Students Publications

We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age while receiving cefepime treatment for an Enterobacter cloacae bacteremia and persistent peritonitis secondary to an infected peritoneal dialysis catheter. Using therapeutic drug monitoring while assessing the clearance of cefepime on continuous renal replacement therapy (CRRT), we were able to successfully treat this patient's infection while also minimizing the risk of side effects from this medication. Current literature supports dosing in adult patients on all modalities of CRRT with effluent flow rates of 20 to 25 …

Clinical Correlates Of Cholestasis In Preterm Infants With Surgical Necrotizing Enterocolitis, Parvesh Mohan Garg, Isabella Pittman, Joe Yi, Victoria G Weis, Ricardo Jorge Rodriguez, Mitchell R Ladd, Jessica L Rauh, Anna Greene Mcdonald, Cherrie Welch, Muralidhar Hebbur Premkumar, Padma P Garg, Akhil Maheshwari

Faculty, Staff and Students Publications

BACKGROUND: We sought to investigate the clinical determinants and outcomes of cholestasis in preterm infants with surgical necrotizing enterocolitis (sNEC).

METHODS: Retrospective comparison of clinical information in preterm infants who developed cholestasis vs those who did not.

RESULTS: Sixty-two (62/91, 68.1%) infants with NEC developed cholestasis at any time following the onset of illness. Cholestasis was seen more frequently in those who had received ionotropic support at 24 hours following sNEC diagnosis (87.1% vs 58.6%;

CONCLUSION: Cholestasis was seen in 68% of infants following surgical NEC. The most likely contributive factors are intestinal failure and subsequent PN dependence for longer …

Multiomics, Artificial Intelligence, And Precision Medicine In Perinatology, Mohan Pammi, Nima Aghaeepour, Josef Neu

Faculty, Staff and Students Publications

Technological advances in omics evaluation, bioinformatics, and artificial intelligence have made us rethink ways to improve patient outcomes. Collective quantification and characterization of biological data including genomics, epigenomics, metabolomics, and proteomics is now feasible at low cost with rapid turnover. Significant advances in the integration methods of these multiomics data sets by machine learning promise us a holistic view of disease pathogenesis and yield biomarkers for disease diagnosis and prognosis. Using machine learning tools and algorithms, it is possible to integrate multiomics data with clinical information to develop predictive models that identify risk before the condition is clinically apparent, thus …

A Rapid, Low-Cost, And Highly Sensitive Sars-Cov-2 Diagnostic Based On Whole-Genome Sequencing, Per A Adastra, Neva C Durand, Namita Mitra, Saul Godinez Pulido, Ragini Mahajan, Alyssa Blackburn, Zane L Colaric, Joshua W M Theisen, David Weisz, Olga Dudchenko, Andreas Gnirke, Suhas S P Rao, Parwinder Kaur, Erez Lieberman Aiden, Aviva Presser Aiden

Faculty, Staff and Students Publications

Early detection of SARS-CoV-2 infection is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosing and studying SARS-CoV-2 infection. Dubbed Pathogen-Oriented Low-Cost Assembly & Re-Sequencing (POLAR), this method amplifies the entirety of the SARS-CoV-2 genome. This contrasts with typical RT-PCR-based diagnostic tests, which amplify only a few loci. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. Using this method, we can reliably ( …

Mass Spectrometry Imaging As An Emerging Tool For Studying Metabolism In Human Brain Organoids, Gerarda Cappuccio, Saleh M Khalil, Sivan Osenberg, Feng Li, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an in vitro system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain …

Initial Insights Into The Genetic Variation Associated With Metformin Treatment Failure In Youth With Type 2 Diabetes, Shylaja Srinivasan, Ling Chen, Miriam Udler, Jennifer Todd, Megan M Kelsey, Morey W Haymond, Silva Arslanian, Philip Zeitler, Rose Gubitosi-Klug, Kristen J Nadeau, Katherine Kutney, Neil H White, Josephine H Li, James A Perry, Varinderpal Kaur, Laura Brenner, Josep M Mercader, Adem Dawed, Ewan R Pearson, Sook-Wah Yee, Kathleen M Giacomini, Toni Pollin, Jose C Florez

Faculty, Staff and Students Publications

Metformin is the first-line treatment for type 2 diabetes (T2D) in youth but with limited sustained glycemic response. To identify common variants associated with metformin response, we used a genome-wide approach in 506 youth from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study and examined the relationship between T2D partitioned polygenic scores (pPS), glycemic traits, and metformin response in these youth. Several variants met a suggestive threshold (P < 1 × 10−6), though none including published adult variants reached genome-wide significance. We pursued replication of top nine variants in three cohorts, and rs76195229 in ATRNL1 was associated with worse metformin response in the Metformin Genetics Consortium (n = 7,812), though statistically not being significant after Bonferroni correction (P …

Long-Term Neuropsychological Outcomes In Children With Febrile Infection-Related Epilepsy Syndrome (Fires) Treated With Anakinra, Anima Shrestha, E Lynne Wood, Gretchen Berrios-Siervo, Coral M Stredny, Katrina Boyer, Clemente Vega, Srishti Nangia, Eyal Muscal, Krista Eschbach

Faculty, Staff and Students Publications

BACKGROUND: Febrile-infection related epilepsy syndrome (FIRES) is a rare epilepsy syndrome in which a previously healthy individual develops refractory status epilepticus in the setting of a preceding febrile illness. There are limited data regarding detailed long-term outcomes. This study aims to describe the long-term neuropsychological outcomes in a series of pediatric patients with FIRES.

METHODS: This is a retrospective multi-center case series of pediatric patients with a diagnosis of FIRES treated acutely with anakinra who had neuropsychological testing at least 12 months after status epilepticus onset. Each patient underwent comprehensive neuropsychological evaluation as part of routine clinical care. Additional data …

The Role Of Supervised School Therapy In Poorly Controlled Asthma In Children, Muppala Raju, Malvika Sagar, Andrew Bush, Eugene Quaye, Shekhar Ghamande, Sonal Malhotra, Mercedes E Arroliga

Faculty, Staff and Students Publications

BACKGROUND: In children, nonadherence to inhaled corticosteroid (ICS) therapy leads to poor asthma control and complications.

METHODS: We evaluated the benefit from initiation of ICS administration once daily at school. We retrospectively chose patients from our pediatric pulmonary clinic who had poorly controlled asthma and prescribed ICS daily. For the study period, we examined the number of corticosteroid courses, emergency room visits, hospital admissions, symptom history, and pulmonary function tests.

RESULTS: Thirty-four patients who satisfied the inclusion criteria began the intervention. Preintervention, there were a mean number of 2.6 oral corticosteroid courses compared to 2 courses in the year following …

Heterologous Mrna-Protein Vaccination With Tc24 Induces A Robust Cellular Immune Response Against Trypanosoma Cruzi, Characterized By An Increased Level Of Polyfunctional Cd8+ T-Cells, Cristina Poveda, Ana Carolina Leão, Chiara Mancino, Francesca Taraballi, Yi-Lin Chen, Rakesh Adhikari, Maria Jose Villar, Rakhi Kundu, Duc M Nguyen, Leroy Versteeg, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Jeroen Pollet, Kathryn M Jones

Faculty, Staff and Students Publications

Tc24 is a Trypanosoma cruzi-derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against T. cruzi. This work evaluates the immunogenicity of a heterologous prime/boost vaccination regimen using protein and mRNA-based Tc24 vaccines. Mice (C57BL/6) were vaccinated twice subcutaneously, three weeks apart, with …

Immunomodulatory Proteins From Hookworms Reduce Cardiac Inflammation And Modulate Regulatory Responses In A Mouse Model Of Chronic Trypanosoma Cruzi Infection, Kathryn M Jones, Bin Zhan, Keenan J Ernste, Maria Jose Villar, Nalini Bisht, Duc Nguyen, Li-Yen Chang, Cristina Poveda, Gonteria J Robinson, Akshar J Trivedi, Colby J Hofferek, William K Decker, Vanaja Konduri

Faculty, Staff and Students Publications

Introduction

Hookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4+Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite Trypanosoma cruzi, the causative agent of Chagas disease, leads to chronic inflammation in tissues. Persistence of the parasites in tissues drives chronic low-grade inflammation, with increased infiltration of inflammatory cells into the heart, accompanied by increased …