Research Update

April 2018

Understanding the Connection between Obstructive Sleep Apnea and Cardiovascular Disease and Diabetes

Dr. Elisabet Børsheim is contributing her expertise in stable isotope tracer analysis to a study of a link between obstructive sleep apnea and cardiovascular disease.

Obstructive sleep apnea (OSA) is a common breathing disorder affecting 30% of adults and over 50% of obese persons. OSA occurs during sleep due to the reclined position and decreased airway muscle tone. To open the obstructed airway for improved breathing, the sympathetic nervous system, the body’s fight-or-flight response, activates causing the diaphragm and chest muscles work harder, and breathing starts again with a gasp, snort, or body jerk. Though OSA may result in a bad night’s sleep, it can reduce oxygen to vital organs and cause an irregular heart rhythm. It is a known risk factor for diabetes and cardiovascular disease and is implicated in other conditions such as hypertension and inflammation.

The prevailing theory about the link between OSA and cardiovascular disease is recurrent episodes of hypoxia and oxidative stress. However, an alternative theory is that the mechanism works through the sympathetic nervous system (SNS). As OSA stimulates this system, it also stimulates the breakdown of fats to release free fatty acids (lipolysis). The increase in the release of free fatty acids normally provides fuel for the body. However, in a resting state such as sleep, unabsorbed free fatty acids continue to circulate with fewer being used by the tissues for energy. This chronic increase in free fatty acids may be toxic to the circulatory system leading to vascular endothelial dysfunction and cardiovascular disease. Free fatty acids are also a known link between obesity, insulin resistance, and type 2 diabetes as they can inhibit insulin-stimulated glucose uptake by muscle. Thus, a robust SNS response to OSA may induce a mismatch between release of fatty acids to the circulation and their usage for energy, leading to lipotoxicity.

The mechanistic links between OSA and cardiometabolic concerns are undefined. Identifying these links are crucial to developing clinical trials to better protect the health of OSA patients. If the driving force is the SNS, interventions to block its actions may prove beneficial in protection of development of cardiovascular disease. 

Dr. Jonathan Jun of Johns Hopkins has been leading studies to better understand metabolism of OSA patients. His work has included the study of blood samples taken during uninterrupted sleep by OSA patients both using and not using continuous positive airway pressure (CPAP). As Principal Investigator for a subsequent study recently funded by NIH, Dr. Jun will be studying blood, urine, and breath samples from OSA patients to identify risks for cardiometabolic dysfunction. Dr. Jun will also pilot a study investigating propranolol, which has been shown to make OSA-induced lipolysis less severe in an animal model, analyzing samples from patients taking either propranolol or a placebo. ACNC and ACRI Investigator Dr. Elisabet Børsheim is a Co-Investigator on the study, providing expertise in analyzing stable isotope tracers in plasma.

Dr. Børsheim’s laboratory is known for its work investigating physical activity, energetics, and metabolism. Her team uses stable isotope (non-radioactive) methodology to study energy and substrate metabolism. For this study, Dr. Børsheim will analyze the blood samples in her laboratory to determine the amount of tracers present. The data from Dr. Børsheim‘s laboratory will provide the study team with a precise description of the rate of fatty acid released and the rate of fatty acids used for energy.

“Though the study is in adults, not children,” noted Dr. Børsheim, “this study will provide valuable information that is relevant to children. Up to 10% of children may have OSA, and also in this group there is a link with obesity. This study will provide important knowledge about underlying mechanisms.”

In addition to this NIH-funded project, Dr. Børsheim’s research and laboratory receives additional NIH support through an R01 project for which she is a Co-Principal Investigator with ACNC Investigator Dr. Aline Andres (R01DK107516) and as Metabolism Core Director for the Center for Childhood Obesity Prevention (P20GM109096). As an investigator at the ACNC, Dr. Børsheim receives USDA-ARS funding for her research as well as for the Physical Activity Core. Dr. Robert Wolfe of the Department of Geriatrics and the Director of the Center for Translation Research in Aging and Longevity at UAMS, is an internationally recognized leader in stable isotope technology in nutritional and metabolic research and also a Co-Investigator on the project..

Taking the Field for Clinical Research

On Opening Night 2018, ACRI's Kimberly Voight (left) and Brandi Poe (right) shared information about participating in clinical research at Arkansas Childrens's. 

High-quality clinical research at ACRI increases our knowledge to improve the diagnosis, treatment, and prevention of pediatric diseases and disorders. Our pediatric clinical researchers conduct studies to answer specific questions about new biomedical and behavioral interventions, such as drugs, treatments, and devices, or new ways to use known interventions. Often known as clinical trials, these studies help researchers better understand these interventions to improve health care. An essential element of these studies is the participation of consenting patients and their families.

Many families already support clinical trials at ACRI, and to express the need for continued participation in this important work, ACRI has teamed up with the Arkansas Travelers for the seventh consecutive season. This year, Brandi Poe, Clinical Research Recruiting Coordinator, has scheduled 12 Travelers home games as promotional nights to encourage clinical trial participation. During those games along the concourse of Dickey-Stephens Park, Brandi and ACRI staff raise awareness of pediatric clinical research at Arkansas Children’s. They help interested families register for the clinical trials database and subscribe to ACRI’s text service. The families are eligible for ACRI promotional items and a gift card drawing.

This year’s efforts started on Opening Night 2018. In addition to the promotional booth, information on participating in clinical research at ACRI is in rotation on the LED screens on the outfield scoreboard and in the concourse concession stands. An advertisement for ACRI is also included in the “Discover Your Travs” bulletin given to all in attendance at games. Some of the promotional nights also coincide with heavily attended Travelers home games with promotional highlights such as kids running the bases, TV remote dig, and Independence Day fireworks.

Dr. Tamara Perry to Serve on NIH Study Section

Congratulations to Dr. Tamara Perry, Associate Professor, Allergy and Immunology, on accepting an invitation to join the Behavioral Medicine, Interventions and Outcomes Study Section, National Institutes of Health (NIH) Center for Scientific Review. Study section members are selected on the basis of their demonstrated competence and achievement in their scientific discipline as evidenced by the quality of research accomplishments, publications in scientific journals, and other significant scientific activities, achievements and honors.

Dr. Perry’s research focuses on developing and implementing innovative programs to reduce asthma burden particularly among high risk and vulnerable populations. She is the principal investigator on an ACRI-funded project that delivers follow-up asthma care via telemedicine to children living in rural Arkansas communities. The study will compare health outcomes, clinic utilization rates, and patient satisfaction between patients receiving asthma care via telemedicine to those receiving in person visits. The project will inform future efforts to provide remote pediatric specialist-driven care for chronic health conditions.

Dr. Perry also is a co-investigator on a NIH-funded project (PI: Dr. Jill Halterman, University of Rochester; R01HL091835) that examines the impact of telemedicine follow up visits for inner-city children with asthma who are enrolled in a school-based asthma intervention. Participants in the study receive directly observed therapy at school plus telemedicine follow-up visits to help guide asthma medication management while allowing students to remain at school. Participants in the intervention arm will be compared to participants who receive traditional in person care from their regular provider.

Dr. Perry has recently published findings from her NIH-funded study (R01HL102388) that examined the impact of school-based asthma education via telemedicine. Although a difference in asthma symptoms between intervention and control subjects was not shown, participants who were in the intervention arm had evidence of improved medication adherence and reported that they took their medications as prescribed by their provider at a higher rate than those in the control group. Intervention participants also self-monitored their asthma symptoms at home more frequently than control participants. In addition, participants were very satisfied with the program and the majority of children completed all telemedicine visits as planned.

Dr. Perry has also published results of a clinical project examining the implementation of remote PFTs (pulmonary function tests) via telemedicine for pediatric asthma patients. She and her colleagues found that patients were able to successfully complete PFTs via remote access and telemedicine allowed patients to stay in their home communities and receive specialty asthma care. These findings suggest that telemedicine can significantly improve access to specialized pediatric care in rural communities which is particularly important in medically underserved regions.

Dr. Perry has served as an ad hoc reviewer for several study sections. The quality of her reviews were another factor in her invitation to serve as a permanent member of the Behavioral Medicine, Interventions and Outcomes Study Section. Dr. Perry’s four-year term to the study section will begin this summer.

Researcher Spotlight: Marie Schluterman Burdine, PhD

Dr. Marie Schluterman Burdine is an Assistant Professor of Surgery in the Division of Surgical Research at UAMS

How did you become involved in pediatric research?

As a research technician at UT Southwestern in Dallas, I worked with an investigator who focused on the genetics behind the development of congenital heart disease in pediatric patients. This inspired me to continue to work on diseases in children which typically lacks research and funding.

What types of sponsors (industry, federal, foundations, etc.) support your studies?

I am funded as a Junior Investigator at the Center for Translational Pediatric Research (P20GM121293).

What is your area of study?

Novel therapy for transplant immunosuppression therapy.

How is your research program innovative?

Novel approach to therapy solutions.

How has your work led to (or will lead to) changes in pediatric care?

It will lead to simplified treatment for pediatric patients who have received organ transplants.

Who do you collaborate with and what are the benefits of these collaborations?

Dr. Sarah Blossom, analysis of T cell differentiation techniques.

President's Choice Publications

The following articles were selected as this month's feature publications.

  • Bolouri H, Farrar JE, Triche T Jr, Ries RE, Lim EL, Alonzo TA, Ma Y, Moore R, Mungall AJ, Marra MA, Zhang J, Ma X, Liu Y, Liu Y, Auvil JMG, Davidsen TM, Gesuwan P, Hermida LC, Salhia B, Capone S, Ramsingh G, Zwaan CM, Noort S, Piccolo SR, Kolb EA, Gamis AS, Smith MA, Gerhard DS, Meshinchi S.  The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions.  Nat Med. 2018 Jan;24(1):103-112. doi: 10.1038/nm.4439. Epub 2017 Dec 11.

  • Kennedy JL, Koziol-White CJ, Jeffus S, Rettiganti MR, Fisher P, Kurten M, Eze A, House S, Sikes JD, Askew E, Putt C, Panettieri RA, Jones SM, Kurten RC.  Effects of Rhinovirus (RV) 39 Infection on Airway Hyper-responsiveness (AHR) to Carbachol in Human Airways Precision Cut Lung Slices (PCLS). J Allergy Clin Immunol. 2018 Jan 6. pii: S0091-6749(18)30024-1. doi: 10.1016/j.jaci.2017.11.041. [Epub ahead of print]

Recent Grant Activity

Grant Proposal Submissions

PI Agency Project Title Project Period Total Funding
Dolapo Adejumobi NIH Modeling Barrier Dysfunction Relevant to Eosinophilic Esophagitis (EoE) in Human Esophageal Mucosal Explant Cultures 7/18-6/22 $160,123
Stepan Melnyk DOD/Phoenix Children's Hospital A safe and effective treatment for autism targeting core symptoms through normalizing metabolism 5/18-4/22 $100,324
Shannon Rose Binational Science Foundation/Tel Aviv University Transcriptomic blood biomarkers for diagnostics and precision medicine prognostics in autism spectrum disorder: effects of candidate therapeutics on gene expression profiles 10/18-9/21 $23,432
Judy Weber USDA Developing and Sustaining School Gardens to Impact Child Health 9/18-8/20 $100,000

Clinical Trial Activity

Principal Investigator


Project Description

Project Period

Total Cost

Michael Schmitz


Oral Morphine

3/18 -


Ariel Berlinski


Tezacaftor- CF

4/18 -


Jose Romero


Asymptomatic CMV

4/18 -


Kathleen Neville



4/18 -


It All Begins with a Child: ACRI’s 2017 Annual Report

CLICK HERE To Download ACRI's 2017 Annual Reprot

In its 2017 annual report, It All Begins with a Child, ACRI reviews the successes of its diverse research expertise, ranging from basic science to clinical and community-based research. As ACRI envisions a future in which all children grow up to be happy and healthy, the work of its cross-disciplinary teams of physicians, biomedical scientists, and health care practitioners will continue until this vision becomes a reality. The report highlights ACRI’s culture of curiosity that inspires researchers to question, seek, and discover new and better ways to treat children.

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