Medicine and Health Sciences Commons^™

Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu

Biostatistics Faculty Publications

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults > 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. …

Can Capture Be Used To Identify Undiagnosed Patients With Mild-To-Moderate Copd Likely To Benefit From Treatment?, Nancy K. Leidy, Fernando J. Martinez, Karen G. Malley, David M. Mannino, Meilan K. Han, Elizabeth D. Bacci, Randall W. Brown, Julia F. Houfek, Wassim W. Labaki, Barry J. Make, Catherine A. Meldrum, Wilson Quezada, Stephen Rennard, Byron Thomashow, Barbara P. Yawn

Preventive Medicine and Environmental Health Faculty Publications

Background: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC)11 60%–80% predicted) who may also benefit from diagnosis and treatment.

Methods: Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all COPD cases (mild to severe; n=259) from those without COPD (n=87) were …

Exacerbation Recovery Patterns In Newly Diagnosed Or Maintenance Treatment-Naïve Patients With Copd: Secondary Analyses Of Ticari 1 Trial Data, David M. Mannino, Emmanuelle M. Clerisme-Beaty, Joanne Franceschina, Naitee Ting, Nancy K. Leidy

Preventive Medicine and Environmental Health Faculty Publications

Background: Little is known about the recovery patterns from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in newly diagnosed or maintenance treatment-naïve patients with COPD. This study describes the course of AECOPD in these patients at the time of treatment for the symptoms of acute respiratory tract infection (RTI).

Methods: This study was a secondary analysis of data from a 12-week, randomized clinical trial (TICARI 1) testing the efficacy and safety of once-daily tiotropium 18 µg maintenance therapy versus placebo in newly diagnosed or maintenance treatment-naïve COPD patients with acute RTI symptoms for ≤7 days. Patients received standard care …

Treated Hypothyroidism Is Associated With Cerebrovascular Disease But Not Alzheimer's Disease Pathology In Older Adults, Willa D. Brenowitz, Fang Han, Walter A. Kukull, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Thyroid hormone (TH) disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common form of TH disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer’s Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2,146 with no known thyroid disease; hypothyroidism was associated with severe atherosclerosis (OR=1.35 95% CI: 1.02, 1.79) but not Alzheimer’s disease (AD) pathologies (amyloid plaques or neurofibrillary tangles). …

Influence Of Dietary Salt Knowledge, Perceptions, And Beliefs On Consumption Choices After Stroke In Uganda, Martin N. Kaddumukasa, Elly Katabira, Martha Sajatovic, Svetlana Pundik, Mark Kaddumukasa, Larry B. Goldstein

Neurology Faculty Publications

Background

Previous research on Uganda's poststroke population revealed that their level of dietary salt knowledge did not lead to healthier consumption choices.

Purpose

Identify barriers and motivators for healthy dietary behaviors and evaluate the understanding of widely accepted salt regulation mechanisms among poststroke patients in Uganda.

Methods

Convergent parallel mixed methods triangulation design comprised a cross-sectional survey (n = 81) and 8 focus group discussions with 7-10 poststroke participants in each group. We assessed participant characteristics and obtained insights into their salt consumption attitudes, perceptions, and knowledge. Qualitative responses were analyzed using an inductive approach with thematic analytic procedures. Relationships …

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing In Persons With Mild Cognitive Impairment, Lucas S. Broster, Shonna L. Jenkins, Sarah D. Holmes, Gregory A. Jicha, Yang Jiang

Behavioral Science Faculty Publications

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD …

Cerebral Amyloid Angiopathy In Down Syndrome And Sporadic And Autosomal-Dominant Alzheimer's Disease, María Carmona-Iragui, Mircea Balasa, Bessy Benejam, Daniel Alcolea, Susana Fernández, Laura Videla, Isabel Sala, María Belén Sánchez-Saudinós, Estrella Morenas-Rodriguez, Roser Ribosa-Nogué, Ignacio Illán-Gala, Sofía Gonzalez-Ortiz, Jordi Clarimón, Frederick A. Schmitt, David K. Powell, Beatriz Bosch, Albert Lladó, Michael S. Rafii, Elizabeth Head, José Luis Molinuevo, Rafael Blesa, Sebastián Videla, Alberto Lleó, Raquel Sánchez-Valle, Juan Fortea

Sanders-Brown Center on Aging Faculty Publications

Introduction—We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]).

Methods—Neuroimaging features of CAA, APOE, and cerebrospinal fluid-Aβ40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68).

Results—CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. …

Randomized Phase Ii Study Comparing Prophylactic Cranial Irradiation Alone To Prophylactic Cranial Irradiation And Consolidative Extracranial Irradiation For Extensive-Disease Small Cell Lung Cancer (Ed Sclc): Nrg Oncology Rtog 0937, Elizabeth M. Gore, Chen Hu, Alexander Y. Sun, Daniel F. Grimm, Suresh S. Ramalingam, Neal E. Dunlap, Kristin A. Higgins, Maria Werner-Wasik, Aaron M. Allen, Puneeth Iyengar, Gregory M. M. Videtic, Russell K. Hales, Ronald C. Mcgarry, James J. Urbanic, Anthony T. Pu, Candice A. Johnstone, Volker W. Stieber, Rebecca Paulus, Jeffrey D. Bradley

Radiation Medicine Faculty Publications

Introduction—RTOG-0937 is a randomized phase-II trial evaluating 1-year OS with PCI or PCI plus consolidative radiation therapy (cRT) to intra-thoracic disease and extracranial metastases for ED-SCLC.

Methods—Patients with 1–4 extracranial metastases were eligible after CR or PR to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included PR vs CR after chemotherapy and 1 vs 2–4 metastases; age < 65 vs ≥ 65 was added after an observed imbalance. PCI was 25GY/10 fractions. cRT was 45GY/15 fractions. To detect an OS improvement from 30% to 45% with a 34% hazard reduction (HR=0·66) under a 0.1 type-1 error (1-sided) and 80% power, 154 patients were required.

Results—Ninety-seven patients were randomized between March, 2010 and February, 2015. Eleven patients were ineligible (nine PCI, two PCI+cRT), leaving 42 randomized to PCI and 44 to PCI+cRT. At planned interim analysis the study …

Increasing Use Of Allogeneic Hematopoietic Cell Transplantation In Patients Aged 70 Years And Older In The United States, Lori Muffly, Marcelo C. Pasquini, Michael Martens, Ruta Brazauskas, Xiaochun Zhu, Kehinde Adekola, Mahmoud Aljurf, Karen K. Ballen, Ashish Bajel, Frederic Baron, Minoo Battiwalla, Amer Beitinjaneh, Jean-Yves Cahn, Mathew Carabasi, Yi-Bin Chen, Saurabh Chhabra, Stefan Ciurea, Edward Copelan, Anita D'Souza, John Edwards, James Foran, Cesar O. Freytes, Henry C. Fung, Robert Peter Gale, Sergio Giralt, Shahrukh K. Hashmi, Gerhard C. Hildebrandt, Vincent Ho, Ann Jakubowski, Hillard Lazarus

Internal Medicine Faculty Publications

In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥ 70 years with hematologic malignancies across the United States. Adults ≥ 70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥ 70 years underwent HCT across 103 transplant centers. The number and proportion of allografts …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Higher Mineralized Bone Volume Is Associated With A Lower Plain X-Ray Vascular Calcification Score In Hemodialysis Patients, Teresa Adragao, Anibal Ferreira, Joao M. Frazao, Ana Luisa Papoila, Iola Pinto, Marie-Claude Monier-Faugere, Hartmut H. Malluche

Internal Medicine Faculty Publications

Background and objectives

In dialysis patients, there is an increasing evidence that altered bone metabolism is associated with cardiovascular calcifications. The main objective of this study was to analyse, in hemodialysis patients, the relationships between bone turnover, mineralization and volume, evaluated in bone biopsies, with a plain X-ray vascular calcification score.

Design, setting, participants and measurements

In a cross-sectional study, bone biopsies and evaluation of vascular calcifications were performed in fifty hemodialysis patients. Cancellous bone volume, mineralized bone volume, osteoid volume, activation frequency, bone formation rate/bone surface, osteoid thickness and mineralization lag time were determined by histomorphometry. Vascular calcifications were …

White Matter Hyperintensity Associations With Cerebral Blood Flow In Elderly Subjects Stratified By Cerebrovascular Risk, Ahmed A. Bahrani, David K. Powell, Guoqiang Yu, Eleanor S. Johnson, Gregory A. Jicha, Charles D. Smith

Biomedical Engineering Faculty Publications

Objective: This study aims to add clarity to the relationship between deep and periventricular brain white matter hyperintensities (WMHs), cerebral blood flow (CBF), and cerebrovascular risk in older persons. Methods: Deep white matter hyperintensity (dWMH) and periventricular white matter hyperintensity (pWMH) and regional gray matter (GM) and white matter (WM) blood flow from arterial spin labeling were quantified from magnetic resonance imaging scans of 26 cognitively normal elderly subjects stratified by cerebrovascular disease (CVD) risk. Fluidattenuated inversion recovery images were acquired using a high-resolution 3-dimensional (3-D) sequence that reduced partial volume effects seen with slicebased techniques. Results: dWMHs but not …

A Cognitive Electrophysiological Signature Differentiates Amnestic Mild Cognitive Impairment From Normal Aging, Juan Li, Lucas S. Broster, Gregory A. Jicha, Nancy B. Munro, Frederick A. Schmitt, Erin L. Abner, Richard J. Kryscio, Charles D. Smith, Yang Jiang

Behavioral Science Faculty Publications

Background: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education.

Methods: Eighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be …

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …

Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski

Sanders-Brown Center on Aging Faculty Publications

Background

Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies.

Methods

In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of …

Walking Performance Is Positively Correlated To Calf Muscle Fiber Size In Peripheral Artery Disease Subjects, But Fibers Show Aberrant Mitophagy: An Observational Study, Sarah H. White, Mary M. Mcdermott, Robert L. Sufit, Kate Kosmac, Alex W. Bugg, Marta Gonzalez-Freire, Luigi Ferrucci, Lu Tian, Lihui Zhao, Ying Gao, Melina R. Kibbe, Michael H. Criqui, Christiaan Leeuwenburgh, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background: Patients with lower extremity peripheral artery disease (PAD) have decreased mobility, which is not fully explained by impaired blood supply to the lower limb. Additionally, reports are conflicted regarding fiber type distribution patterns in PAD, but agree that skeletal muscle mitochondrial respiration is impaired.

Methods: To test the hypothesis that reduced muscle fiber oxidative activity and type I distribution are negatively associated with walking performance in PAD, calf muscle biopsies from non-PAD (n = 7) and PAD participants (n = 26) were analyzed immunohistochemically for fiber type and size, oxidative activity, markers of autophagy, and capillary density. Data were …

Health Behaviors And Their Correlates Among Participants In The Continuing To Confront Copd International Patient Survey, Hana Müllerová, Sarah H. Landis, Zaurbek Aisanov, Kourtney J. Davis, Masakazu Ichinose, David M. Mannino, Joe Maskell, Ana M. Menezes, Thys Van Der Molen, Yeon-Mok Oh, Maggie Tabberer, Meilan K. Han

Preventive Medicine and Environmental Health Faculty Publications

Background and aims: We used data from the Continuing to Confront COPD International Patient Survey to test the hypothesis that patients with COPD who report less engagement with their disease management are also more likely to report greater impact of the disease.

Methods: This was a population-based, cross-sectional survey of 4,343 subjects aged ≥ 40 years from 12 countries, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. The impact of COPD was measured with COPD Assessment Test, modified Medical Research Council Dyspnea Scale, and hospital admissions and emergency department visits for COPD in the prior …

Development Of A Spirometry T-Score In The General Population, Sei Won Lee, Hyun Kuk Kim, Seunghee Baek, Ji-Ye Jung, Young Sam Kim, Jae Seung Lee, Sang-Do Lee, David M. Mannino, Yeon-Mok Oh

Preventive Medicine and Environmental Health Faculty Publications

Background and objective: Spirometry values may be expressed as T-scores in standard deviation units relative to a reference in a young, normal population as an analogy to the T-score for bone mineral density. This study was performed to develop the spirometry T-score.

Methods: T-scores were calculated from lambda-mu-sigma-derived Z-scores using a young, normal age reference. Three outcomes of all-cause death, respiratory death, and COPD death were evaluated in 9,101 US subjects followed for 10 years; an outcome of COPD-related health care utilization (COPD utilization) was evaluated in 1,894 Korean subjects followed for 4 years.

Results: The …

Differences In Rhodococcus Equi Infections Based On Immune Status And Antibiotic Susceptibility Of Clinical Isolates In A Case Series Of 12 Patients And Cases In The Literature, Praveen Gundelly, Yasuhiro Suzuki, Julie A. Ribes, Alice C. Thornton

Internal Medicine Faculty Publications

Rhodococcus equi is an unusual zoonotic pathogen that can cause life-threatening diseases in susceptible hosts. Twelve patients with R. equi infection in Kentucky were compared to 137 cases reported in the literature. Although lungs were the primary sites of infection in immunocompromised patients, extrapulmonary involvement only was more common in immunocompetent patients (P > 0.0001). Mortality in R. equi-infected HIV patients was lower in the HAART era (8%) than in pre-HAART era (56%) (P > 0.0001), suggesting that HAART improves prognosis in these patients. Most (85–100%) of clinical isolates were susceptible to vancomycin, clarithromycin, rifampin, aminoglycosides, ciprofloxacin, and imipenem. …

New Oral Anticoagulants Are Not Superior To Warfarin In Secondary Prevention Of Stroke Or Transient Ischemic Attacks, But Lower The Risk Of Intracranial Bleeding: Insights From A Meta-Analysis And Indirect Treatment Comparisons, Partha Sardar, Saurav Chatterjee, Wen-Chih Wu, Edgar Lichstein, Joydeep Ghosh, Shamik Aikat, Debabrata Mukherjee

Internal Medicine Faculty Publications

PURPOSE: Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).

METHODS: Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan …