Publications by authors named "Taruni S Santanam"

6 Publications

  • Page 1 of 1

The Dose-Response Relationship Between Physical Activity and Cardiometabolic Health in Adolescents.

Am J Prev Med 2021 01;60(1):95-103

Duke Clinical Research Institute, Durham, North Carolina; Duke Center for Childhood Obesity Research, Duke University School of Medicine, Durham, North Carolina; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina; Duke Children's Health and Discovery Initiative, Duke University School of Medicine, Durham, North Carolina.

Introduction: This study examines the dose-response relationship between moderate-to-vigorous physical activity and cardiometabolic measures in adolescents.

Methods: Cross-sectional spline analyses were performed using 2003-2016 National Health and Nutrition Examination Survey data among adolescents (aged 12-19 years, N=9,195) on objectively measured (2003-2006) and self-reported (2007-2016) weekly mean minutes of moderate-to-vigorous physical activity and cardiometabolic measures (systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein, BMI, and cardiorespiratory fitness). Inflection points were determined for nonlinear relationships.

Results: For objective moderate-to-vigorous physical activity, female adolescents had significant nonlinear associations with inflection points at 90 minutes/week for BMI percentile and systolic blood pressure. Male adolescents had inflection points at 150 weekly minutes of objective activity for BMI percentile and cardiorespiratory fitness. BMI percentile was about 7% lower for female and male adolescents at 150 weekly minutes of objectively measured moderate-to-vigorous physical activity than at 0 minutes. For self-reported moderate-to-vigorous physical activity, inflection points were at 375 minutes/week (diastolic blood pressure for female adolescents) and 500 minutes/week (systolic blood pressure for male adolescents).

Conclusions: Among several significant dose-response relationships between physical activity and cardiometabolic health in adolescents, consistent and often nonlinear relationships were identified for BMI, with inflection points at 90-150 minutes of objective moderate-to-vigorous physical activity. Notable differences in associations and linearity were identified by sex and physical activity measure (objective or self-reported). These results support calls for any increase in physical activity among adolescents and suggest that recommendations closer to the adult guidelines of 150 weekly minutes of physical activity may be health promoting and more attainable for youth than the current recommendation of 420 weekly minutes.
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http://dx.doi.org/10.1016/j.amepre.2020.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769140PMC
January 2021

Applying Behavioral Economics to Improve Adolescent and Young Adult Health: A Developmentally-Sensitive Approach.

J Adolesc Health 2021 Jul 4;69(1):17-25. Epub 2020 Dec 4.

Duke Sanford School of Public Policy, Durham, North Carolina; Fuqua School of Business, Durham North Carolina.

Each day, adolescents and young adults (AYAs) choose to engage in behaviors that impact their current and future health. Behavioral economics represents an innovative lens through which to explore decision-making among AYAs. Behavioral economics outlines a diverse set of phenomena that influence decision-making and can be leveraged to develop interventions that may support behavior change. Up to this point, behavioral economic interventions have predominantly been studied in adults. This article provides an integrative review of how behavioral economic phenomena can be leveraged to motivate health-related behavior change among AYAs. We contextualize these phenomena in the physical and social environments unique to AYAs and the neurodevelopmental changes they undergo, highlighting opportunities to intervene in AYA-specific contexts. Our review of the literature suggests behavioral economic phenomena leveraging social choice are particularly promising for AYA health. Behavioral economic interventions that take advantage of AYA learning and development have the potential to positively impact youth health and well-being over the lifespan.
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http://dx.doi.org/10.1016/j.jadohealth.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175460PMC
July 2021

Pediatric accountable health communities: Insights on needed capabilities and potential solutions.

Healthc (Amst) 2020 Dec 7;8(4):100481. Epub 2020 Oct 7.

Duke-Margolis Center for Health Policy, Duke University, Durham, NC, USA; Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA; Duke Clinical Research Institute, Durham, NC, USA.

Background: Pediatric accountable health communities (AHCs) are emerging collaborative models that integrate care across health and social service sectors. We aimed to identify needed capabilities and potential solutions for implementing pediatric AHCs.

Methods: We conducted a directed content analysis of responses to a Request for Information (RFI) from the Center for Medicare & Medicaid Innovation on the Integrated Care for Kids Model (n = 1550 pages from 202 respondents). We then interviewed pediatric health policy stakeholders (n = 18) to further investigate responses from the RFI. All responses were coded using a consensual qualitative research approach in 2019.

Results: To facilitate service integration, respondents emphasized the need for cross-sector organizational alignment and data sharing. Recommended solutions included designating "Bridge Organizations" to operationalize service integration across sectors and developing integrated data sharing systems. Respondents called for improved validation and collection methods for data relating to school performance, social drivers of health, family well-being, and patient experience. Recommended solutions included aligning health and education data privacy regulations and utilizing metrics with cross-sector relevance. Respondents identified that mechanisms are needed to blend health and social service funding in alternative payment models (APMs). Recommended solutions included guidance on cross-sector care coordination payments, shared savings arrangements, and capitation to maximize spending flexibility.

Conclusions: Pediatric AHCs could provide more integrated, high-value care for children. Respondents highlighted the need for shared infrastructure and cross-sector alignment of measures and financing.

Implications: Insights and solutions from this study can inform policymakers planning or implementing innovative, child-centered AHC models.

Level Of Evidence: Level V.
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http://dx.doi.org/10.1016/j.hjdsi.2020.100481DOI Listing
December 2020

The Dose-Response Relationship Between Physical Activity and Cardiometabolic Health in Young Adults.

J Adolesc Health 2020 08 19;67(2):201-208. Epub 2020 Jun 19.

Duke Clinical Research Institute, Durham, North Carolina; Duke Center for Childhood Obesity Research, Duke University School of Medicine, Durham, North Carolina; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina; Children's Health and Discovery Institute, Duke University School of Medicine, Durham, North Carolina. Electronic address:

Purpose: Guidelines recommend 150 minutes of weekly moderate-to-vigorous physical activity (MVPA) for all adults, although physical activity level correlation with cardiometabolic health is not well characterized for young adults. We determined the dose-response relationship of MVPA on measures of cardiometabolic health in young adults.

Methods: We examined young adults (aged 20-29 years; N = 5,395, 47.9% female) in the 2003-2016 National Health and Nutrition Examination Survey. Exposures were objective (accelerometer based) and self-reported weekly mean minutes of MVPA. Cardiometabolic outcome measures were body mass index (BMI), high-density lipoprotein (HDL), total cholesterol, systolic blood pressure, and diastolic blood pressure. The dose-response relationships were assessed with unadjusted spline analyses. Sex-stratified outcomes were modeled using multivariable linear regression with mean estimated change presented for 150-minute dose increases of MVPA.

Results: Among females, associations between objective activity and cardiometabolic measures were all linear. Compared with no activity, 150 minutes of objective activity was associated with a lower BMI (-1.37 kg/m) and total cholesterol (-4.89 mg/dL), whereas 150 minutes of self-reported activity was associated with a higher HDL (1 mg/dL) and lower diastolic blood pressure (-.42 mm Hg). Among males, an inflection point was identified in the dose-response curves for objective activity with BMI around 100 minutes. Compared with no activity, 150 self-reported minutes was associated with lower BMI (-.26 kg/m), higher HDL (.52 mg/dL), and lower total cholesterol (-1.35 mg/dL).

Conclusions: The dose-response relationships between physical activity and cardiometabolic markers in young adults were predominantly linear, supporting public health calls for any increase in physical activity in this population.
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http://dx.doi.org/10.1016/j.jadohealth.2020.04.021DOI Listing
August 2020

Pharmacological inhibition of glycogen synthase kinase 3 increases operant alcohol self-administration in a manner associated with altered pGSK-3β, protein interacting with C kinase and GluA2 protein expression in the reward pathway of male C57BL/6J mice.

Behav Pharmacol 2020 02;31(1):15-26

Bowles Center for Alcohol Studies.

Glycogen synthase kinase 3 (GSK-3) is a constitutively active serine-threonine kinase that regulates numerous signaling pathways and has been implicated in neurodegenerative and neuropsychiatric diseases. Alcohol exposure increases GSK-3β (ser9) phosphorylation (pGSK-3β); however, few studies have investigated whether GSK-3 regulates the positive reinforcing effects of alcohol, which drive repetitive drug use. To address this goal, male C57BL/6J mice were trained to lever press on a fixed-ratio 4 schedule of sweetened alcohol or sucrose-only reinforcement in operant conditioning chambers. The GSK-3 inhibitor CHIR 99021 (0-10 mg/kg, i.p.) was injected 45 minutes prior to self-administration sessions. After completion of the self-administration dose-effect curve, potential locomotor effects of the GSK-3 inhibitor were assessed. To determine molecular efficacy, CHIR 99021 (10 mg/kg, i.p.) was evaluated on pGSK-3β, GSK-3β, protein interacting with C kinase (PICK1), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA2 subunit protein expression in amygdala, nucleus accumbens (NAcb), and frontal cortex. Results showed that CHIR 99021 (10 mg/kg) dose-dependently increased alcohol reinforced responding with no effect on sucrose self-administration or locomotor activity. CHIR 99021 (10 mg/kg) significantly decreased pGSK-3β expression in all brain regions tested, reduced PICK1 and increased GluA2 total expression only in the NAcb. We conclude that GSK-3 inhibition increased the reinforcing effects of alcohol in mice. This was associated with reduced pGSK-3β and PICK1, and increased GluA2 expression. Given prior results showing that AMPA receptor activity regulates alcohol self-administration, we propose that signaling through the GSK-3/PICK1/GluA2 molecular pathway drives the positive reinforcing effects of the drug, which are required for abuse liability.
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http://dx.doi.org/10.1097/FBP.0000000000000501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954298PMC
February 2020

Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice.

Psychopharmacology (Berl) 2018 06 3;235(6):1681-1696. Epub 2018 Mar 3.

Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB #7178, Thurston Bowles Building, Chapel Hill, NC, 27599, USA.

Rationale: There is a clear need for discovery of effective medications to treat behavioral pathologies associated with alcohol addiction, such as chronic drinking.

Objective: The goal of this preclinical study was to assess effects of chronic alcohol drinking on the nucleus accumbens (NAcb) proteome to identify and validate novel targets for medications development.

Materials And Methods: Two-dimensional difference in-gel electrophoresis (2D-DIGE) with matrix-assisted laser desorption ionization tandem time-of-flight (MALDI-TOF/TOF) was used to assess effects of chronic voluntary home-cage (24-h access) alcohol drinking on the NAcb proteome of C57BL/6J mice. To extend these findings to a model of alcohol self-administration and reinforcement, we investigated potential regulation of the positive reinforcing effects of alcohol by the target protein glutathione S-transferase Pi 1 (GSTP1) using a pharmacological inhibition strategy in mice trained to self-administer alcohol or sucrose.

Results: Expression of 52 unique proteins in the NAcb was changed by chronic alcohol drinking relative to water control (23 upregulated, 29 downregulated). Ingenuity Pathway Analysis showed that alcohol drinking altered an array of protein networks associated with neurological and psychological disorders, molecular and cellular functions, and physiological systems and development. DAVID functional annotation analysis identified 9 proteins (SNCA, GSTP1, PRDX3, PPP3R1, EIF5A, PHB, PEBP1/RKIP, GAPDH, AND SOD1) that were significantly overrepresented in a functional cluster that included the Gene Ontology categories "response to alcohol" and "aging." Immunoblots confirmed changes in Pebp1 (RKIP) and GSTP1 in NAcb with no change in amygdala or frontal cortex, suggesting anatomical specificity. Systemic inhibition of GSTP1 with Ezatiostat (0-30 mg/kg, i.p.) dose-dependently reduced the reinforcing effects of alcohol as measured by operant self-administration, in the absence of motor effects. Sucrose self-administration was also reduced but in a manner associated with nonspecific motor inhibition.

Conclusions: Protein expression profiling identified an array of proteins and networks in the NAcb, including GSTP1, that are novel molecular targets of chronic alcohol drinking. Pharmacological inhibition of GSTP1 significantly reduced the positive reinforcing effects of alcohol, which regulate repetitive use and abuse liability. The observation that this protein was both upregulated after chronic drinking and that its inhibition could modulate the reinforcing properties of alcohol suggests that it is a key target for alcohol-related pathologies. Proteomic strategies combined with specific preclinical models has potential to identify and validate novel targets of alcohol that may be useful in the medical management of alcohol addiction.
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http://dx.doi.org/10.1007/s00213-018-4870-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949261PMC
June 2018