Digital Commons Network^™

Differential Effects Of An Ed-To-Home Care Transitions Intervention In An Older Adult Population: A Latent Class Analysis, Rebecca K Green, Kenneth J Nieser, Gwen C Jacobsohn, Amy L Cochran, Thomas V Caprio, Jeremy T Cushman, Amy J H Kind, Michael Lohmeier, Manish N Shah

Faculty, Staff and Student Publications

BACKGROUND: Older adults frequently return to the emergency department (ED) within 30 days of a visit. High-risk patients can differentially benefit from transitional care interventions. Latent class analysis (LCA) is a model-based method used to segment the population and test intervention effects by subgroup.

OBJECTIVES: We aimed to identify latent classes within an older adult population from a randomized controlled trial evaluating the effectiveness of an ED-to-home transitional care program and test whether class membership modified the intervention effect.

RESEARCH DESIGN: Participants were randomized to receive the Care Transitions Intervention or usual care. Study staff collected outcomes data through medical …

Association Of Type 2 Diabetes Subgroups With Cognitive Status Without Modification From Lifestyle Intervention, Michael P Bancks, James Lovato, Ashok Balasubramanyam, Mace Coday, Karen C Johnson, Medha Munshi, Candida Rebello, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown.

OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD.

METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with …

Association Of Mitochondrial Dna Copy Number With Brain Mri Markers And Cognitive Function: A Meta-Analysis Of Community-Based Cohorts, Yuankai Zhang, Xue Liu, Kerri L Wiggins, Nuzulul Kurniansyah, Xiuqing Guo, Amanda L Rodrigue, Wei Zhao, Lisa R Yanek, Scott M Ratliff, Achilleas Pitsillides, Juan Sebastian Aguirre Patiño, Tamar Sofer, Dan E Arking, Thomas R Austin, Alexa S Beiser, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Lifang Hou, Timothy M Hughes, Sharon L R Kardia, Lenore J Launer, Daniel Levy, Thomas H Mosley, Ilya M Nasrallah, Stephen S Rich, Jerome I Rotter, Sudha Seshadri, Wassim Tarraf, Kevin A González, Vasan Ramachandran, Kristine Yaffe, Paul A Nyquist, Bruce M Psaty, Charles S Decarli, Jennifer A Smith, David C Glahn, Hector M González, Joshua C Bis, Myriam Fornage, Susan R Heckbert, Annette L Fitzpatrick, Chunyu Liu, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.

METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear …

Genome-Wide Analysis Of Structural Variants In Parkinson Disease, Kimberley J Billingsley, Jinhui Ding, Pilar Alvarez Jerez, Anastasia Illarionova, Kristin Levine, Francis P Grenn, Mary B Makarious, Anni Moore, Daniel Vitale, Xylena Reed, Dena Hernandez, Ali Torkamani, Mina Ryten, John Hardy, Uk Brain Expression Consortium (Ukbec), Ruth Chia, Sonja W Scholz, Bryan J Traynor, Clifton L Dalgard, Debra J Ehrlich, Toshiko Tanaka, Luigi Ferrucci, Thomas G Beach, Geidy E Serrano, John P Quinn, Vivien J Bubb, Ryan L Collins, Xuefang Zhao, Mark Walker, Emma Pierce-Hoffman, Harrison Brand, Michael E Talkowski, Bradford Casey, Mark R Cookson, Androo Markham, Mike A Nalls, Medhat Mahmoud, Fritz J Sedlazeck, Cornelis Blauwendraat, J Raphael Gibbs, Andrew B Singleton

Faculty, Staff and Students Publications

OBJECTIVE: Identification of genetic risk factors for Parkinson disease (PD) has to date been primarily limited to the study of single nucleotide variants, which only represent a small fraction of the genetic variation in the human genome. Consequently, causal variants for most PD risk are not known. Here we focused on structural variants (SVs), which represent a major source of genetic variation in the human genome. We aimed to discover SVs associated with PD risk by performing the first large-scale characterization of SVs in PD.

METHODS: We leveraged a recently developed computational pipeline to detect and genotype SVs from 7,772 …

Genetic Associations Between Modifiable Risk Factors And Alzheimer Disease, Jiao Luo, Jesper Qvist Thomassen, Céline Bellenguez, Benjamin Grenier-Boley, Itziar De Rojas, Atahualpa Castillo, Kayenat Parveen, Fahri Küçükali, Aude Nicolas, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Deckert Jürgen, Steffi Riedel-Heller, Lucrezia Hausner, Laura Molina Porcel, Emrah Düzel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Jordi Clarimon, Fermin Moreno, Jordi Pérez-Tur, María J Bullido, Pau Pastor, Raquel Sánchez-Valle, Victoria Álvarez, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M Real, Gerard Piñol-Ripoll, Jose María García-Alberca, Jose Luís Royo, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Teemu Kuulasmaa, Alexandre De Mendonça, Shima Mehrabian, Jakub Hort, Martin Vyhnalek, Sven Van Der Lee, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Delphine Bacq-Daian, Jean-François Deleuze, Gael Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Luisa Benussi, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Sandro Sorbi, Paolo Caffarra, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Carlo Masullo, Gianfranco Spalletta, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick Kehoe, Magda Tsolaki, Giacomina Rossi, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Ole A Andreassen, Mikko Hiltunen, Cornelia Van Duijn, Rebecca Sims, Wiesje Van Der Flier, Agustín Ruiz, Alfredo Ramirez, Jean-Charles Lambert, Ruth Frikke-Schmidt

Faculty, Staff and Students Publications

IMPORTANCE: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.

OBJECTIVE: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for …

Genetic Loci Of Beta-Aminoisobutyric Acid Are Associated With Aging-Related Mild Cognitive Impairment, Einat Granot-Hershkovitz, Brian Spitzer, Yunju Yang, Wassim Tarraf, Bing Yu, Eric Boerwinkle, Myriam Fornage, Thomas H Mosley, Charles Decarli, Bruce S Kristal, Hector M González, Tamar Sofer

Faculty, Staff and Student Publications

We studied the genetic associations of a previously developed Metabolomic Risk Score (MRS) for Mild Cognitive Impairment (MCI) and beta-aminoisobutyric acid metabolite (BAIBA)-the metabolite highlighted by results from a genome-wide association study (GWAS) of the MCI-MRS, and assessed their association with MCI in datasets of diverse race/ethnicities. We first performed a GWAS for the MCI-MRS and BAIBA, in Hispanic/Latino adults (n = 3890) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We identified ten independent genome-wide significant (p value <5 × 10-8) variants associated with MCI-MRS or BAIBA. Variants associated with the MCI-MRS are located in the Alanine-Glyoxylate Aminotransferase 2 (AGXT2 gene), which is known to be associated with BAIBA metabolism. Variants associated with BAIBA are located in the AGXT2 gene and in the SLC6A13 gene. Next, we tested the variants' association with MCI in independent datasets of n = 3178 HCHS/SOL older individuals, n = 3775 European Americans, and n = 1032 African Americans from the Atherosclerosis Risk In Communities (ARIC) study. Variants were considered associated with MCI if their p value <0.05 in the meta-analysis of the three datasets and their direction of association was consistent with expectation. Rs16899972 and rs37369 from the AGXT2 region were associated with MCI. Mediation analysis supported the mediation effect of BAIBA between the two genetic variants and MCI (p value = 0.004 for causal mediated effect). In summary, genetic variants in the AGXT2 region are associated with MCI in Hispanic/Latino, African, and European American populations in the USA, and their effect is likely mediated by changes in BAIBA levels.

Plasma Metabolites Associated With Cognitive Function Across Race/Ethnicities Affirming The Importance Of Healthy Nutrition, Einat Granot-Hershkovitz, Shan He, Jan Bressler, Bing Yu, Wassim Tarraf, Casey M Rebholz, Jianwen Cai, Queenie Chan, Tanya P Garcia, Thomas Mosley, Bruce S Kristal, Charles Decarli, Myriam Fornage, Guo-Chong Chen, Qibin Qi, Robert Kaplan, Hector M González, Tamar Sofer

Faculty, Staff and Student Publications

INTRODUCTION: We studied the replication and generalization of previously identified metabolites potentially associated with global cognitive function in multiple race/ethnicities and assessed the contribution of diet to these associations.

METHODS: We tested metabolite-cognitive function associations in U.S.A. Hispanic/Latino adults (n = 2222) from the Community Health Study/ Study of Latinos (HCHS/SOL) and in European (n = 1365) and African (n = 478) Americans from the Atherosclerosis Risk In Communities (ARIC) Study. We applied Mendelian Randomization (MR) analyses to assess causal associations between the metabolites and cognitive function and between Mediterranean diet and cognitive function.

RESULTS: Six metabolites were consistently associated …

Emotional, Behavioral, And Physical Health Consequences Of Loneliness In Young Adult Survivors Of Childhood Cancer: Results From The Childhood Cancer Survivor Study, Chiara Papini, Ameera A Fayad, Mingjuan Wang, Fiona S M Schulte, I-Chan Huang, Yu-Ping Chang, Rebecca M Howell, Deokumar Srivastava, Wendy M Leisenring, Gregory T Armstrong, Todd M Gibson, Leslie L Robison, Kevin C Oeffinger, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

Background: Young adults in the general population are at risk of experiencing loneliness, which has been associated with physical and mental health morbidities. The prevalence and consequences of loneliness in young adult survivors of childhood cancer remain unknown.

Methods: A total of 9664 young adult survivors of childhood cancer (median age at diagnosis 10.5 years [interquartile range (IQR), 5-15], 27.1 years at baseline [IQR, 23-32]) and 2221 siblings enrolled in the Childhood Cancer Survivor Study completed a self-reported survey question assessing loneliness on the Brief Symptom Inventory-18 at baseline and follow-up (median follow-up, 6.6 years). Multivariable models evaluated the prevalence …

Pilot Clinical Trial Of Macimorelin To Assess Safety And Efficacy In Patients With Cancer Cachexia, Megan Herodes, Lindsey J Anderson, Samuel Shober, Ellen A Schur, Solomon A Graf, Nicola Ammer, Ramiro Salas, Marco Marcelli, Jose M Garcia

Faculty, Staff and Students Publications

BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects.

METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined a priori as 1-week change in body weight (≥0.8 kg), plasma insulin-like growth factor (IGF)-1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non-parametrically.

RESULTS: …

Altered Lateralization Of The Cingulum In Deployment-Related Traumatic Brain Injury: An Enigma Military-Relevant Brain Injury Study, Emily L Dennis, Mary R Newsome, Hannah M Lindsey, Maheen Adamson, Tara A Austin, Seth G Disner, Blessen C Eapen, Carrie Esopenko, Carol E Franz, Elbert Geuze, Courtney Haswell, Sidney R Hinds, Cooper B Hodges, Andrei Irimia, Kimbra Kenney, Inga K Koerte, William S Kremen, Harvey S Levin, Rajendra A Morey, John Ollinger, Jared A Rowland, Randall S Scheibel, Martha E Shenton, Danielle R Sullivan, Leah D Talbert, Sophia I Thomopoulos, Maya Troyanskaya, William C Walker, Xin Wang, Ashley L Ware, John Kent Werner, Wright Williams, Paul M Thompson, David F Tate, Elisabeth A Wilde

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with …

Baseline Characteristics Of The North American Prodromal Synucleinopathy Cohort, Jonathan E Elliott, Jennifer Mcleland, Susan R Criswell, Yo-El S Ju, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment.

METHODS: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD without Parkinson's disease, dementia, multiple system atrophy, or narcolepsy were …

Epigenome-Wide Association Study Reveals Cpg Sites Associated With Thyroid Function And Regulatory Effects On Klf9, Antoine Weihs, Layal Chaker, Tiphaine C Martin, Kim V E Braun, Purdey J Campbell, Simon R Cox, Myriam Fornage, Christian Gieger, Hans J Grabe, Harald Grallert, Sarah E Harris, Brigitte Kühnel, Riccardo E Marioni, Nicholas G Martin, Daniel L Mccartney, Allan F Mcrae, Christa Meisinger, Joyce B J Van Meurs, Jana Nano, Matthias Nauck, Annette Peters, Holger Prokisch, Michael Roden, Elizabeth Selvin, Marian Beekman, Diana Van Heemst, Eline P Slagboom, Brenton R Swenson, Adrienne Tin, Pei-Chien Tsai, Andre Uitterlinden, W Edward Visser, Henry Völzke, Melanie Waldenberger, John P Walsh, Anna Köttgen, Scott G Wilson, Robin P Peeters, Jordana T Bell, Marco Medici, Alexander Teumer

Faculty, Staff and Student Publications

Background:

Thyroid hormones play a key role in differentiation and metabolism and are known regulators of gene expression through both genomic and epigenetic processes including DNA methylation. The aim of this study was to examine associations between thyroid hormones and DNA methylation.

Methods:

We carried out a fixed-effect meta-analysis of epigenome-wide association study (EWAS) of blood DNA methylation sites from 8 cohorts from the ThyroidOmics Consortium, incorporating up to 7073 participants of both European and African ancestry, implementing a discovery and replication stage. Statistical analyses were conducted using normalized beta CpG values as dependent and log-transformed thyrotropin (TSH), free thyroxine, …

Developing A Parsimonious Frailty Index For Older, Multimorbid Adults With Heart Failure Using Machine Learning, Javad Razjouyan, Molly J Horstman, Ariela R Orkaby, Salim S Virani, Orna Intrator, Parag Goyal, Christopher I Amos, Aanand D Naik

Faculty, Staff and Student Publications

Frailty is associated with adverse outcomes in heart failure (HF). A parsimonious frailty index (FI) that predicts outcomes of older, multimorbid patients with HF could be a useful resource for clinicians. A retrospective study of veterans hospitalized from October 2015 to October 2018 with HF, aged ≥50 years, and discharged home developed a 10-item parsimonious FI using machine learning from diagnostic codes, laboratory results, vital signs, and ejection fraction (EF) from outpatient encounters. An unsupervised clustering technique identified 5 FI strata: severely frail, moderately frail, mildly frail, prefrail, and robust. We report hazard ratios (HRs) of mortality, adjusting for age, …

Dissociating Statistically Determined Normal Cognitive Abilities And Mild Cognitive Impairment Subtypes With Dctclock., Emily F. Matusz, Catherine C. Price, Melissa Lamar, Rod Swenson, Rhoda Au, Sheina Emrani, Victor Wasserman, David J Libon, Louisa I. Thompson

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.

METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.

RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total …

Biomarkers For Dementia In Latin American Countries: Gaps And Opportunities, Mario A Parra, Paulina Orellana, Tomas Leon, Cabello G Victoria, Fernando Henriquez, Rodrigo Gomez, Constanza Avalos, Andres Damian, Andrea Slachevsky, Agustin Ibañez, Henrik Zetterberg, Betty M Tijms, Jennifer S Yokoyama, Stefanie D Piña-Escudero, J Nicholas Cochran, Diana L Matallana, Daisy Acosta, Ricardo Allegri, Bianca P Arias-Suárez, Bernardo Barra, Maria Isabel Behrens, Sonia M D Brucki, Geraldo Busatto, Paulo Caramelli, Sheila Castro-Suarez, Valeria Contreras, Nilton Custodio, Sergio Dansilio, Myriam De La Cruz-Puebla, Leonardo Cruz De Souza, Monica M Diaz, Lissette Duque, Gonzalo A Farías, Sergio T Ferreira, Nahuel Magrath Guimet, Ana Kmaid, David Lira, Francisco Lopera, Beatriz Mar Meza, Eliane C Miotto, Ricardo Nitrini, Alberto Nuñez, Santiago O'Neill, John Ochoa, Maritza Pintado-Caipa, Elisa De Paula França Resende, Shannon Risacher, Luz Angela Rojas, Valentina Sabaj, Lucas Schilling, Allis F Sellek, Ana Sosa, Leonel T Takada, Antonio L Teixeira, Martha Unaucho-Pilalumbo, Claudia Duran-Aniotz

Faculty, Staff and Student Publications

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a …

Acculturation, Dietary Behaviors, And Macronutrient Intake Among Mexican Americans With Prediabetes: The Starr County Diabetes Prevention Initiative, Sharon A Brown, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, Mary A Winter, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis

Faculty, Staff and Student Publications

PURPOSE: The purpose of the study was to examine the influences of sex and acculturation on dietary behaviors, macronutrient intake, and dietary quality in participants enrolled in a diabetes prevention initiative in Starr County, Texas.

METHODS: Baseline data from the Starr County diabetes prevention study (N = 300) were analyzed-acculturation (country of origin, years in Starr County, language and food preferences), depressive symptoms (Patient Health Questionnaire-9), healthy eating self-efficacy (Weight Efficacy Lifestyle Questionnaire-Short Form), diet quality (USDA Healthy Eating Index), fat avoidance (Fat Avoidance Scale, Spanish version), and macronutrients. Descriptive statistics and univariate analysis of covariance were used to examine …

Effect Of Hiv And Antiretroviral Therapy Use On Body Weight Changes In A Cohort Of Us Veterans Living With And Without Hiv, Jose M Garcia, Yongquan Dong, Peter Richardson, Jennifer R Kramer, Christine M Hartman, Kathryn Royse, Donna L White, Elizabeth Y Chiao

Center for Medical Ethics and Health Policy Staff Publications

Objective: People living with HIV have high rates of obesity and obesity-related comorbidities. Our study sought to evaluate weight trajectory in a retrospective cohort of people living with HIV and matched HIV-negative veterans (controls) and to evaluate risk factors for weight gain.

Methods: This was a retrospective database analysis of data extracted from the VA Corporate Data Warehouse that included people living with HIV (n = 22 421) and age-matched HIV-negative controls (n = 63 072). The main outcomes were baseline body weight and weight change from baseline at 1, 2, and 5 years after diagnosis (baseline visit for controls). …

Does The Osteopathic Pedal Pump Reduce Lower Limb Volume In Healthy Subjects?, Jill S. Adams, Sahil H. Parikh, Brandon J. Goodwin, Donald R. Noll

Rowan-Virtua School of Osteopathic Medicine Departmental Research

CONTEXT: Lymphatic treatments are gentle and passive techniques believed to enhance movement of lymph back into the central circulatory system. Animal studies provide supportive evidence, yet there are few studies in humans.

OBJECTIVES: The aim of this study is to investigate whether the osteopathic pedal pump protocol reduces volume in the lower limbs of healthy subjects.

METHODS: A total of 30 first- and second-year medical students were recruited. Subjects were excluded from participating if they had acute asthma, chronic obstructive pulmonary disease (COPD), congestive heart failure, active infections, fractures of the lower extremities, or metastatic cancer. A within-subjects study design …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were …

Prospective Association Of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis, Amanda E Paluch, Shivangi Bajpai, Marcel Ballin, David R Bassett, Thomas W Buford, Mercedes R Carnethon, Ariel Chernofsky, Erin E Dooley, Ulf Ekelund, Kelly R Evenson, Deborah A Galuska, Barbara J Jefferis, Lingsong Kong, William E Kraus, Martin G Larson, I-Min Lee, Charles E Matthews, Robert L Newton, Anna Nordström, Peter Nordström, Priya Palta, Alpa V Patel, Kelley Pettee Gabriel, Carl F Pieper, Lisa Pompeii, Erika Rees-Punia, Nicole L Spartano, Ramachandran S Vasan, Peter H Whincup, Shengping Yang, Janet E Fulton, Steps For Health Collaborative

Faculty, Staff and Students Publications

Background: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines.

Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional …

Short-Term Removal Of Exercise Impairs Glycemic Control In Older Adults: A Randomized Trial, Leryn J. Reynolds, Troy M. Williams, Joel E. Harden, Hannah M. Twiddy, Monica L. Kearney

Human Movement Studies & Special Education Faculty Publications

Postprandial glycemia (PPG) predicts cardiovascular disease, and short-term physical inactivity increases PPG in young, active adults. Whether this occurs in older, active adults who may be more prone to bouts of inactivity is unknown. This study determined if postprandial interstitial glucose (PPIG) was impaired in active older adults following the removal of exercise for 3 days (NOEX) compared to active young adults. In this randomized, crossover study, 11 older (69.1 ± 1.9 years) and 9 young (32.8 ± 1.8 years) habitually active (≥90 min/week of exercise) adults completed 3-days of NOEX and 3-days of normal habitual exercise (EX), separated by …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Studies & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

Brain-Derived Neurotrophic Factor In Fibromyalgia: A Systematic Review And Meta-Analysis Of Its Role As A Potential Biomarker, Amir Hossein Behnoush, Amirmohammad Khalaji, Shaghayegh Khanmohammadi, Parsa Alehossein, Behrad Saeedian, Parnian Shobeiri, Antonio L Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

BACKGROUND: Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM.

METHODS: A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant …

A Global Perspective Of Advanced Practice Nursing Research: A Review Of Systematic Reviews Protocol, Kelley Kilpatrick, Isabelle Savard, Li-Anne Audet, Abby Kra-Friedman, Reneé Atallah, Mira Jabbour, Wentao Zhou, Kathy Wheeler, Elissa Ladd, Deborah C. Gray, Colette Henderson, Lori A. Spies, Heather Mcgrath, Melanie Rogers

Ellmer School of Nursing Faculty Publications

Introduction

In 2020, the World Health Organization called for the expansion and greater recognition of all nursing roles, including advanced practice nurses (APNs), to better meet patient care needs. As defined by the International Council of Nurses (ICN), the two most common APN roles include nurse practitioners (NPs) and clinical nurse specialists (CNSs). They help ensure care to communities as well as patients and families with acute, chronic or complex conditions. Moreover, APNs support providers to deliver high quality care and improve access to services. Currently, there is much variability in the use of advanced practice nursing roles globally. A …

Multimethod Process Evaluation Of A Community Paramedic Delivered Care Transitions Intervention For Older Emergency Department Patients, Gwen Costa Jacobsohn, Apoorva P Maru, Rebecca K Green, Angela N Gifford, Matthew D Lukasik, Tikiri Bandara, Thomas V Caprio, Amy L Cochran, Jeremy T Cushman, Courtney M C Jones, Amy J H Kind, Michael Lohmeier, Manish N Shah

Faculty, Staff and Student Publications

OBJECTIVE: We assessed fidelity of delivery and participant engagement in the implementation of a community paramedic coach-led Care Transitions Intervention (CTI) program adapted for use following emergency department (ED) visits.

METHODS: The adapted CTI for ED-to-home transitions was implemented at three university-affiliated hospitals in two cities from 2016 to 2019. Participants were aged ≥60 years old and discharged from the ED within 24 hours of arrival. In the current analysis, participants had to have received the CTI. Community paramedic coaches collected data on program delivery and participant characteristics at each transition contact via inventories and assessments. Participants provided commentary on …

Predicting Incident Cardiovascular Disease Among African-American Adults: A Deep Learning Approach To Evaluate Social Determinants Of Health In The Jackson Heart Study, Matthew C. Morris, Hamidreza Moradi, Maryam Aslani, Mario Sims, David Schlundt, Chrystyna D. Kouros, Burel Goodin, Crystal Lim, Kerry Kinney

2020-Current year OA Pubs

The present study sought to leverage machine learning approaches to determine whether social determinants of health improve prediction of incident cardiovascular disease (CVD). Participants in the Jackson Heart study with no history of CVD at baseline were followed over a 10-year period to determine first CVD events (i.e., coronary heart disease, stroke, heart failure). Three modeling algorithms (i.e., Deep Neural Network, Random Survival Forest, Penalized Cox Proportional Hazards) were used to evaluate three feature sets (i.e., demographics and standard/biobehavioral CVD risk factors [FS1], FS1 combined with psychosocial and socioeconomic CVD risk factors [FS2], and FS2 combined with environmental features [FS3]) …