Medicine and Health Sciences Commons^™

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

Analysis Of Rna Expression Of Normal And Cancer Tissues Reveals High Correlation Of Cop9 Gene Expression With Respiratory Chain Complex Components, Christina A. Wicker, Tadahide Izumi

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The COP9 signalosome, composed of eight subunits, is implicated in cancer genetics with its deneddylase activity to modulate cellular concentration of oncogenic proteins such as IkB and TGFβ. However, its function in the normal cell physiology remains elusive. Primarily focusing on gene expression data of the normal tissues of the head and neck, the cancer genome atlas (TCGA) database was used to identify groups of genes that were expressed synergistically with the COP9 genes, particularly with the COPS5 (CSN5), which possesses the catalytic activity of COP9.

RESULTS: Expressions of seven of the COP9 genes (COPS2, COPS3, COPS4, COPS5, COPS6, …

Subjective Report Of Side Effects Of Prescribed And Nonprescribed Psychostimulant Use In Young Adults, Tess E. Smith, Michelle M. Martel, Alan D. Desantis

Psychology Faculty Publications

Background: Side effects of prescribed and nonprescribed psychostimulant use are understudied. Objectives: The study examined side effects of prescribed and nonprescribed psychostimulant use in a college sample with attention to possible gender differences. Methods: 2716 undergraduates (1448 male) between the ages of 17 and 57 years (M = 19.43 years, SD = 1.7 years) completed an online survey that included questions about the subjective side effects of prescribed and nonprescribed psychostimulant use. Results: Results suggested that prescribed users more frequently reported side effects, compared to nonprescribed users. For prescribed users, females more frequently reported appetite, somatic, and anxiety-related side …

Administration Of Electroconvulsive Therapy For Depression Associated With Deep Brain Stimulation In A Patient With Post-Traumatic Parkinson's Disease: A Case Study, Miles G. Cunningham, Golnaz Yadollahikhales, Gordana Vitaliano, Craig Van Horne

Neurosurgery Faculty Publications

Background: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression.

Case Presentation: The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. …

Accuracy Of Name And Age Data Provided About Network Members In A Social Network Study Of People Who Use Drugs: Implications For Constructing Sociometric Networks, April M. Young, Abby E. Rudolph, Amanda E. Su, Lee King, Susan Jent, Jennifer R. Havens

Epidemiology and Environmental Health Faculty Publications

Purpose—Network analysis has become increasingly popular in epidemiologic research, but the accuracy of data key to constructing risk networks is largely unknown. Using network data from people who use drugs (PWUD), the study examined how accurately PWUD reported their network members’ (i.e., alters’) names and ages.

Methods—Data were collected from 2008 to 2010 from 503 PWUD residing in rural Appalachia. Network ties (n=897) involved recent (past 6 months) sex, drug co-usage, and/or social support. Participants provided alters’ names, ages, and relationship-level characteristics; these data were cross-referenced to that of other participants to identify participant-participant relationships and to determine …

Living With Traumatic Brain Injury In A Rural Setting: Supports And Barriers Across The Continuum Of Care, Anne L. Harrison, Elizabeth G. Hunter, Heather Thomas, Paige Bordy, Erin Stokes, Patrick H. Kitzman

Physical Therapy Faculty Publications

Purpose: Traumatic brain injury (TBI) is prevalent in Kentucky and comes with a high cost in care and quality of life for individuals and caregivers affected. Many people living with the condition of TBI have unmet needs. Research among people living with TBI in rural areas is limited. The purposes of this study were to (1) increase understanding of the lived experience of people with TBI and caregivers in rural regions of Kentucky across the continuum of their care and (2) provide their perspectives on barriers and facilitators of optimal function and well-being.

Methods: A qualitative descriptive interview study was …

Integrated Molecular Pathway Analysis Informs A Synergistic Combination Therapy Targeting Pten/Pi3k And Egfr Pathways For Basal-Like Breast Cancer, Qing-Bai She, Sofia K. Gruvberger-Saal, Matthew Maurer, Yilun Chen, Mervi Jumppanen, Tao Su, Meaghan Dendy, Ying-Ka Ingar Lau, Lorenzo Memeo, Hugo M. Horlings, Marc J. Van De Vijver, Jorma Isola, Hanina Hibshoosh, Neal Rosen, Ramon Parsons, Lao H. Saal

Markey Cancer Center Faculty Publications

Background: The basal-like breast cancer (BLBC) subtype is characterized by positive staining for basal mammary epithelial cytokeratin markers, lack of hormone receptor and HER2 expression, and poor prognosis with currently no approved molecularly-targeted therapies. The oncogenic signaling pathways driving basal-like tumorigenesis are not fully elucidated.

Methods: One hundred sixteen unselected breast tumors were subjected to integrated analysis of phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations by immunohistochemistry, mutation analysis, and gene expression profiling. Incidence and relationships between molecular biomarkers were characterized. Findings for select biomarkers were validated in an independent series. Synergistic cell killing in vitro and in vivo tumor …

Elevated Integrin Α6Β4 Expression Is Associated With Venous Invasion And Decreased Overall Survival In Non-Small Cell Lung Cancer, Rachel L. Stewart, Dava West, Chi Wang, Heidi L. Weiss, Tamas S. Gal, Eric B. Durbin, William O'Connor, Min Chen, Kathleen L. O'Connor

Pathology and Laboratory Medicine Faculty Publications

Lung cancer carries a poor prognosis and is the most common cause of cancer-related death worldwide. The integrin α6β4, a laminin receptor, promotes carcinoma progression in part by cooperating with various growth factor receptors to facilitate invasion and metastasis. In carcinoma cells with mutant TP53, the integrin α6β4 promotes cell survival. TP53 mutations and integrin α6β4 overexpression co-occur in many aggressive malignancies. Because of the high frequency of TP53 mutations in lung squamous cell carcinoma (SCC), we sought to investigate the association of integrin β4 expression with clinicopathologic features and survival in non–small cell lung cancer (NSCLC). We constructed …

Development Of The Chronic Obstructive Pulmonary Disease Morning Symptom Diary (Copd-Msd), Gary Globe, Brooke Currie, Nancy Kline Leidy, Paul Jones, David M. Mannino, Fernando Martinez, Paul Klekotka, Sean O'Quinn, Niklas Karlsson, Ingela Wiklund

Preventive Medicine and Environmental Health Faculty Publications

Background: The morning tends to be the most difficult time of day for many patients with chronic obstructive pulmonary disease (COPD) when symptoms can limit one’s ability to perform even simple activities. Morning symptoms have been linked to higher levels of work absenteeism, thereby increasing the already substantial economic burden associated with COPD. A validated patient-reported outcome (PRO) instrument designed to capture morning symptoms will allow for a more comprehensive approach to the evaluation of treatment benefit in COPD clinical trials.

Methods: A qualitative interview study was conducted among a sample of symptomatic adults with COPD. Concept elicitation interviews ( …

Adverse Childhood Experiences, Support, And The Perception Of Ability To Work In Adults With Disability, Sophia Miryam Schüssler-Fiorenza Rose, Jessica G. Eslinger, Lindsey Zimmerman, Jamie Scaccia, Betty S. Lai, Catrin Lewis, Eva Alisic

Psychiatry Faculty Publications

Objective To examine the impact of adverse childhood experiences (ACEs) and support on self-reported work inability of adults reporting disability.

Participants Adults (ages 18-64) who participated in the Behavioral Risk Factor Surveillance System in 2009 or 2010 and who reported having a disability (n = 13,009).

Design and Main Outcome Measures The study used a retrospective cohort design with work inability as the main outcome. ACE categories included abuse (sexual, physical, emotional) and family dysfunction (domestic violence, incarceration, mental illness, substance abuse, divorce). Support included functional (perceived emotional/social support) and structural (living with another adult) support. Logistic regression was …

A Randomized, Double-Blind, Placebo-Controlled Phase Ii Trial Investigating The Safety And Immunogenicity Of Modified Vaccinia Ankara Smallpox Vaccine (Mva-Bn®) In 56-80-Year-Old Subjects, Richard N. Greenberg, Christine M. Hay, Jack T. Stapleton, Thomas C. Marbury, Eva Wagner, Eva Kreitmeir, Siegfried Röesch, Alfred Von Krempelhuber, Philip Young, Richard Nichols, Thomas P. Meyer, Darja Schmidt, Josef Weigl, Garth Virgin, Nathaly Arndtz-Wiedemann, Paul Chaplin

Internal Medicine Faculty Publications

Background Modified Vaccinia Ankara MVA-BN^® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN^® (MVA) was assessed in a 56–80 years old population.

Methods MVA with a virus titer of 1 x 10⁸ TCID₅₀/dose was administered via subcutaneous injection to 56–80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated …

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 …

Continuing To Confront Copd International Patient Survey: Economic Impact Of Copd In 12 Countries, Jason Foo, Sarah H. Landis, Joe Maskell, Yeon-Mok Oh, Thys Van Der Molen, Meilan K. Han, David M. Mannino, Masakazu Ichinose, Yogesh Punekar

Preventive Medicine and Environmental Health Faculty Publications

Background The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries. Using data from this survey we evaluated the economic impact of COPD.

Methods This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications. Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale. Combined direct …

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 …

Colorectal Cancer Prevention: Perspectives Of Key Players From Social Networks In A Low-Income Rural Us Region, Nancy E. Schoenberg, Kathryn Eddens, Adam Jonas, Claire Snell-Rood, Christina R. Studts, Benjamin Broder-Oldach, Mira L. Katz

Behavioral Science Faculty Publications

Social networks influence health behavior and health status. Within social networks, “key players” often influence those around them, particularly in traditionally underserved areas like the Appalachian region in the USA. From a total sample of 787 Appalachian residents, we identified and interviewed 10 key players in complex networks, asking them what comprises a key player, their role in their network and community, and ideas to overcome and increase colorectal cancer (CRC) screening. Key players emphasized their communication skills, resourcefulness, and special occupational and educational status in the community. Barriers to CRC screening included negative perceptions of the colonoscopy screening procedure, …

Project Achieve – Using Implementation Research To Guide The Evaluation Of Transitional Care Effectiveness, Jing Li, Jane Brock, Brian Jack, Brian Mittman, Mary Naylor, Joann Sorra, Glen P. Mays, Mark V. Williams, Arnold J. Stromberg, Heather M. Bush, Allison Scott, Robert Duff, Emily R. Clear, Hannah Keeler, Project Achieve

Internal Medicine Faculty Publications

Background: Poorly managed hospital discharges and care transitions between health care facilities can cause poor outcomes for both patients and their caregivers. Unfortunately, the usual approach to health care delivery does not support continuity and coordination across the settings of hospital, doctors’ offices, home or nursing homes. Though complex efforts with multiple components can improve patient outcomes and reduce 30-day readmissions, research has not identified which components are necessary. Also we do not know how delivery of core components may need to be adjusted based on patient, caregiver, setting or characteristics of the community, or how system redesign can be …

Elevated Transpulmonary Gradient And Cardiac Magnetic Resonance-Derived Right Ventricular Remodeling Predict Poor Outcomes In Sickle Cell Disease, Kim-Lien Nguyen, Xin Tian, Shoaib Alam, Alem Mehari, Steve W. Leung, Catherine Seamon, Darlene Allen, Caterina P. Minniti, Vandana Sachdev, Andrew E. Arai, Gregory J. Kato

Saha Cardiovascular Research Center Faculty Publications

No abstract provided.

Differences And Similarities In The Clinicopathological Features Of Pancreatic Neuroendocrine Tumors In China And The United States: A Multicenter Study, Li-Ming Zhu, Laura Tang, Xin-Wei Qiao, Edward M. Wolin, Nicholas N. Nissen, Deepti Dhall, Jie Chen, Lin Shen, Yihebali Chi, Yao-Zong Yuan, Qi-Wen Ben, Bin Lv, Ya-Ru Zhou, Chun-Mei Bai, Jie Chen, Yu-Li Song, Tian-Tian Song, Chong-Mei Lu, Run Yu, Yuan-Jia Chen

Markey Cancer Center Faculty Publications

The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria.

This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based …

Association Of Dna Methylation At Cpt1a Locus With Metabolic Syndrome In The Genetics Of Lipid Lowering Drugs And Diet Network (Goldn) Study, Mithun Das, Jin Sha, Bertha Hidalgo, Stella Aslibekyan, Anh N. Do, Degui Zhi, Dianjianyi Sun, Tao Zhang, Shengxu Li, Wei Chen, Sathanur R. Srinivasan, Hemant K. Tiwari, Devin Absher, Jose M. Ordovas, Gerald S. Berenson, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10⁻⁷ was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = …

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. …