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Articles 91 - 120 of 258

Full-Text Articles in Epidemiology

Aberrant Azin2 And Polyamine Metabolism Precipitates Tau Neuropathology, Leslie A. Sandusky-Beltran, Andrii Kovalenko, Devon S. Placides, Kevin Ratnasamy, Chao Ma, Jerry B. Hunt, Huimin Liang, John Ivan T. Calahatian, Camilla Michalski, Margaret Fahnestock, Laura J. Blair, April L. Darling, Jeremy D. Baker, Sarah N. Fontaine, Chad A. Dickey, Joshua J. Gamsby, Kevin R. Nash, Erin L. Abner, Maj-Linda B. Selenica, Daniel C. Lee Feb 2021

Aberrant Azin2 And Polyamine Metabolism Precipitates Tau Neuropathology, Leslie A. Sandusky-Beltran, Andrii Kovalenko, Devon S. Placides, Kevin Ratnasamy, Chao Ma, Jerry B. Hunt, Huimin Liang, John Ivan T. Calahatian, Camilla Michalski, Margaret Fahnestock, Laura J. Blair, April L. Darling, Jeremy D. Baker, Sarah N. Fontaine, Chad A. Dickey, Joshua J. Gamsby, Kevin R. Nash, Erin L. Abner, Maj-Linda B. Selenica, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Tauopathies display a spectrum of phenotypes from cognitive to affective behavioral impairments; however, mechanisms promoting tau pathology and how tau elicits behavioral impairment remain unclear. We report a unique interaction between polyamine metabolism, behavioral impairment, and tau fate. Polyamines are ubiquitous aliphatic molecules that support neuronal function, axonal integrity, and cognitive processing. Transient increases in polyamine metabolism hallmark the cell’s response to various insults, known as the polyamine stress response (PSR). Dysregulation of gene transcripts associated with polyamine metabolism in Alzheimer’s disease (AD) brains were observed, and we found that ornithine decarboxylase antizyme inhibitor 2 (AZIN2) increased to …


Sex, Diabetes Status And Cognition: Findings From The Study Of Longevity In Diabetes, Chris Moran, Paola Gilsanz, Michal S. Beeri, Rachel A. Whitmer, Mary E. Lacy Jan 2021

Sex, Diabetes Status And Cognition: Findings From The Study Of Longevity In Diabetes, Chris Moran, Paola Gilsanz, Michal S. Beeri, Rachel A. Whitmer, Mary E. Lacy

Epidemiology and Environmental Health Faculty Publications

INTRODUCTION: Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk.

RESEARCH DESIGN AND METHODS: We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D …


The Association Of Circulating Amylin With Β-Amyloid In Familial Alzheimer's Disease, Han Gia Ly, Nirmal Verma, Savita Sharma, Deepak Kotiya, Sanda Despa, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Donna M. Wilcock, Larry B. Goldstein, Rita Guerreiro, José Brás, Angela J. Hanson, Suzanne Craft, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Alzheimer’S Disease Exome Sequencing Group, Florin Despa Jan 2021

The Association Of Circulating Amylin With Β-Amyloid In Familial Alzheimer's Disease, Han Gia Ly, Nirmal Verma, Savita Sharma, Deepak Kotiya, Sanda Despa, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Donna M. Wilcock, Larry B. Goldstein, Rita Guerreiro, José Brás, Angela J. Hanson, Suzanne Craft, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Alzheimer’S Disease Exome Sequencing Group, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Introduction

This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods

Evidence of amylin‐AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non‐APP/PS1 rats.

Results

Amylin‐Aβ cross‐seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected …


Memory-Related Frontal Brainwaves Predict Transition To Mild Cognitive Impairment In Healthy Older Individuals Five Years Before Diagnosis, Yang Jiang, Juan Li, Frederick A. Schmitt, Gregory A. Jicha, Nancy B. Munro, Xiaopeng Zhao, Charles D. Smith, Richard J. Kryscio, Erin L. Abner Jan 2021

Memory-Related Frontal Brainwaves Predict Transition To Mild Cognitive Impairment In Healthy Older Individuals Five Years Before Diagnosis, Yang Jiang, Juan Li, Frederick A. Schmitt, Gregory A. Jicha, Nancy B. Munro, Xiaopeng Zhao, Charles D. Smith, Richard J. Kryscio, Erin L. Abner

Behavioral Science Faculty Publications

BACKGROUND: Early prognosis of high-risk older adults for amnestic mild cognitive impairment (aMCI), using noninvasive and sensitive neuromarkers, is key for early prevention of Alzheimer's disease. We have developed individualized measures in electrophysiological brain signals during working memory that distinguish patients with aMCI from age-matched cognitively intact older individuals.

OBJECTIVE: Here we test longitudinally the prognosis of the baseline neuromarkers for aMCI risk. We hypothesized that the older individuals diagnosed with incident aMCI already have aMCI-like brain signatures years before diagnosis.

METHODS: Electroencephalogram (EEG) and memory performance were recorded during a working memory task at baseline. The individualized baseline neuromarkers, …


Estimating The Population Attributable Fraction Of Asthma Due To Electronic Cigarette Use And Other Risk Factors Using Kentucky Behavioral Risk Factor Survey Data, 2016-2017, W. Jay Christian, Courtney J. Walker Jan 2021

Estimating The Population Attributable Fraction Of Asthma Due To Electronic Cigarette Use And Other Risk Factors Using Kentucky Behavioral Risk Factor Survey Data, 2016-2017, W. Jay Christian, Courtney J. Walker

Epidemiology and Environmental Health Faculty Publications

Introduction: Electronic nicotine delivery systems ENDS have become popular in the United States among both new users of nicotine and those seeking less harmful alternatives to traditional cigarettes. Users often perceive ENDS as being less harmful than traditional cigarettes. This study investigated the relationship between use of ENDS and asthma in a representative sample of adults. Methods: For this cross-sectional study, we used data from the Kentucky Behavioral Risk Factor Surveillance System telephone survey data from 2016-2017. Using a weighted multivariable logistic regression analysis, we identified important covariates to adjust for to calculate the population attributable fraction (PAF) of asthma …


Maternal Proximity To Mountaintop Removal Mining And Birth Defects In Appalachian Kentucky, 1997-2003, Daniel B. Cooper Jan 2021

Maternal Proximity To Mountaintop Removal Mining And Birth Defects In Appalachian Kentucky, 1997-2003, Daniel B. Cooper

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: Extraction of coal through mountaintop removal mining (MTR) alters many dimensions of the landscape, and explosive blasts, exposed rock, and coal washing have the potential to pollute air and water with substances known to increase risk of developmental and birth anomalies. Previous research suggests that infants born to mothers living in MTR coal mining counties have higher prevalence of most types of birth defects.

Objectives: This study seeks to examine further the relationship between MTR activity and birth defects by employing individual level exposure estimation through precise satellite data of MTR activity in the Appalachian region and maternal residence …


Investigations Into The Genetics Of Mixed Pathologies In Dementia, Adam Dugan Jan 2021

Investigations Into The Genetics Of Mixed Pathologies In Dementia, Adam Dugan

Theses and Dissertations--Epidemiology and Biostatistics

Alzheimer’s disease (AD) is an irreversible, progressive brain disorder that leads to a loss of memory and thinking skills. While tremendous progress has been made in our understanding of the genetics underlying AD, currently known genetic variants explain only approximately 30% of the heritable risk of developing AD. One hurdle to AD research is that it can only be definitively diagnosed at autopsy, making cruder, clinic-based diagnoses more common. In recent years, several brain pathologies that mimic AD’s clinical presentation have been identified including brain arteriolosclerosis, hippocampal sclerosis (HS), and, most recently, limbic-predominant age-related TDP-43 encephalopathy (LATE). It has become …


An Assessment Of Kentucky Birth Records, Focusing On Early-Onset Hypertensive Disorders Of Pregnancy, Environmental Metal Exposures, And Geocoding Precision, 2008-2017, Courtney J. Walker Jan 2021

An Assessment Of Kentucky Birth Records, Focusing On Early-Onset Hypertensive Disorders Of Pregnancy, Environmental Metal Exposures, And Geocoding Precision, 2008-2017, Courtney J. Walker

Theses and Dissertations--Epidemiology and Biostatistics

Using live and stillbirth records from Kentucky (2008-2017), this dissertation assessed the county-level prevalence and geospatial patterns of early-onset hypertensive disorders of pregnancy (eHDP); examined the geocoding precision of addresses recorded on birth records, and evaluated the association between individual risk factors and environmental metal exposures on eHDP prevalence. After adjusting for maternal demographic factors and pre-existing health conditions, we observed that eHDP prevalence was 38% higher (aPR=1.38, 95%CI:1.16, 1.64) in counties with the highest prevalence of married women (> 53.8%) compared to lower prevalence areas (31.6%) had a 20% higher prevalence of eHDP(aPR=1.20, 95%CI:1.00, 1.44) compared to counties with …


Evaluating The Incidence Of Melanoma And Lung Cancer Of Current And Former Active-Duty U.S. Military Who Were Deployed In Support Of Operation Enduring Freedom And Operation Iraqi Freedom, Brian Kovacic Jan 2021

Evaluating The Incidence Of Melanoma And Lung Cancer Of Current And Former Active-Duty U.S. Military Who Were Deployed In Support Of Operation Enduring Freedom And Operation Iraqi Freedom, Brian Kovacic

Theses and Dissertations--Epidemiology and Biostatistics

The incidence of melanoma and lung cancer has been gradually increasing in the United States over the past three decades with the reputed causes due to etiological and environmental exposures, and tobacco usage. There has been concern that melanoma and lung cancer incidence among military personnel may be associated with deployment to environments with intense sun exposure and increased smoking rates due to post-traumatic stress disorder. The aim of this study was to examine associations between deployment in support of Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF), from 2001 through 2015, with subsequent melanoma and lung cancer incidence. …


Sexual Behaviors Associated With Online Partner-Seeking Among Men Who Have Sex With Men From Small/Midsized Towns Or Rural Areas In Kentucky, Vira Pravosud Jan 2021

Sexual Behaviors Associated With Online Partner-Seeking Among Men Who Have Sex With Men From Small/Midsized Towns Or Rural Areas In Kentucky, Vira Pravosud

Theses and Dissertations--Epidemiology and Biostatistics

The HIV epidemic remains one of the most significant public health issues in the United States, particularly among men who have sex with men (MSM). New avenues for partner-seeking have emerged over the past three decades, including through the Internet, social media, and geosocial networking applications. Consisting of three cross-sectional studies, this dissertation research aimed to determine associations between the use of various online tools for partner-seeking (hereafter collectively referred to as “apps”) and HIV-related sexual behaviors among 252 young adult MSM residing in small/midsized towns or rural areas in Central Kentucky, a group that has been under-represented in the …


Introduction To Special Issue Of Plant Virus Emergence, Michael M. Goodin, Jeanmarie Verchot Jan 2021

Introduction To Special Issue Of Plant Virus Emergence, Michael M. Goodin, Jeanmarie Verchot

Plant Pathology Faculty Publications

No abstract provided.


Prevalence And Correlates Of Secondary Syringe Exchange (Sse) Among People Who Inject Drugs (Pwid) In Rural Kentucky, Jordan R. Wilson Jan 2021

Prevalence And Correlates Of Secondary Syringe Exchange (Sse) Among People Who Inject Drugs (Pwid) In Rural Kentucky, Jordan R. Wilson

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Aim: To describe the prevalence of secondary syringe exchange (SSE) in a sample of syringe service program (SSP) clients in rural Appalachian Kentucky and to identify the correlates of SSE.

Methods: Participants (n=338) completed interviewer-administered questionnaires. Only those who reported having ever exchanged syringes at a SSP (n=140) were included in analysis. SSE was measured through self-report of obtaining syringes for someone else at a SSP in the past 6 months. Prevalence and correlates of SSE were examined using bivariate analysis and multiple logistic regression.

Results: Overall, 30% of participants reported SSE. Participants in the second [aOR= 3.83; 95% CI: …


Injuries Among Distillery Workers: Workers' Compensation First Reports Of Injury, 2010-2019, Mira Hali Mirzaian Jan 2021

Injuries Among Distillery Workers: Workers' Compensation First Reports Of Injury, 2010-2019, Mira Hali Mirzaian

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

AIMS: To identify the most frequent type, nature, and cause of work-related injury amongst distillery workers as well as contributing factors to the injurious event in an effort to inform potential intervention.

METHODS: Workers’ Compensation First Reports of Injury (FROI) from the years 2010-2019 (N=974) were obtained. Variables were created for ‘occupational category’ and ‘accident description’ to assist in the elucidation of the injurious event. The Ratchet Circular Scan Test was used to assess seasonal variation in injury. Kernal Density Analysis was conducted to assess rates of injury by calendar year.

RESULTS: Amongst injured distillery workers, 908 of the injuries …


Multiple Proteinopathies And Their Role In Cognitive Impairment And Neurodegenerative Diseases, Shama D. Karanth Jan 2021

Multiple Proteinopathies And Their Role In Cognitive Impairment And Neurodegenerative Diseases, Shama D. Karanth

Theses and Dissertations--Epidemiology and Biostatistics

Most age-related neurodegenerative disorders are associated with the aggregation of misfolded and aberrant proteins. Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders and is highly prevalent in older adults. Neuropathologically, AD is characterized by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Other misfolded proteins, including α-synuclein and transactive response DNA-binding protein 43 (TDP-43), are also commonly observed in aged brains. Aberrant α-synuclein has been associated with Parkinson's disease, Dementia with Lewy bodies, and multiple system atrophy, whereas TDP-43 has been associated with multiple neurological diseases, the most common of which was designated as limbic-predominant, …


Enhancing Drug Overdose Mortality Surveillance Through Natural Language Processing And Machine Learning, Patrick J. Ward Jan 2021

Enhancing Drug Overdose Mortality Surveillance Through Natural Language Processing And Machine Learning, Patrick J. Ward

Theses and Dissertations--Epidemiology and Biostatistics

Epidemiological surveillance is key to monitoring and assessing the health of populations. Drug overdose surveillance has become an increasingly important part of public health practice as overdose morbidity and mortality has increased due in large part to the opioid crisis. Monitoring drug overdose mortality relies on death certificate data, which has several limitations including timeliness and the coding structure used to identify specific substances that caused death. These limitations stem from the need to analyze the free-text cause-of-death sections of the death certificate that are completed by the medical certifier during death investigation. Other fields, including clinical sciences, have utilized …


Environmental Respiratory Exposures And Pulmonary Function Among Residents Of Rural Appalachia, Kentucky, John C. Flunker Jan 2021

Environmental Respiratory Exposures And Pulmonary Function Among Residents Of Rural Appalachia, Kentucky, John C. Flunker

Theses and Dissertations--Epidemiology and Biostatistics

Introduction

Resource extraction exposures are hypothesized to promote adverse respiratory health outcomes among residents of rural Appalachia, yet no studies to date have simultaneously quantified small-scale geographic variation in residential exposure, individual level health factors, and respiratory health outcomes.

Methods

The Mountain Air Project (MAP) is a community engaged cross-sectional study based in Harlan and Letcher counties of Southeastern Kentucky. MAP utilized a novel small-scale method to define residential exposure boundaries: hydrologic unit code (HUC), which represents distinct drainages (AKA “hollows”) where residents cluster. We assigned the HUC level density of active and abandoned surface and underground mining, oil/gas wells, …


Loss-Of-Function Genomic Variants Highlight Potential Therapeutic Targets For Cardiovascular Disease, Jonas B. Nielsen, Oren Rom, Ida Surakka, Sarah E. Graham, Wei Zhou, Tanmoy Roychowdhury, Lars G. Fritsche, Sarah A. Gagliano Taliun, Carlo Sidore, Yuhao Liu, Maiken E. Gabrielsen, Anne Heidi Skogholt, Brooke Wolford, William Overton, Ying Zhao, Jin Chen, He Zhang, Whitney E. Hornsby, Akua Acheampong, Austen Grooms, Amanda Schaefer, Gregory J. M. Zajac, Luis Villacorta, Jifeng Zhang, Ben Brumpton, Mari Løset, Vivek Rai, Pia R. Lundegaard, Morten S. Olesen, Kent D. Taylor, Donna K. Arnett Dec 2020

Loss-Of-Function Genomic Variants Highlight Potential Therapeutic Targets For Cardiovascular Disease, Jonas B. Nielsen, Oren Rom, Ida Surakka, Sarah E. Graham, Wei Zhou, Tanmoy Roychowdhury, Lars G. Fritsche, Sarah A. Gagliano Taliun, Carlo Sidore, Yuhao Liu, Maiken E. Gabrielsen, Anne Heidi Skogholt, Brooke Wolford, William Overton, Ying Zhao, Jin Chen, He Zhang, Whitney E. Hornsby, Akua Acheampong, Austen Grooms, Amanda Schaefer, Gregory J. M. Zajac, Luis Villacorta, Jifeng Zhang, Ben Brumpton, Mari Løset, Vivek Rai, Pia R. Lundegaard, Morten S. Olesen, Kent D. Taylor, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of …


Cellphone Laws And Teens' Calling While Driving: Analysis Of Repeated Cross-Sectional Surveys In 2013, 2015, 2017, And 2019, Li Li, Caitlin N. Pope, Rebecca R. Andridge, Julie K. Bower, Guoqing Hu, Motao Zhu Dec 2020

Cellphone Laws And Teens' Calling While Driving: Analysis Of Repeated Cross-Sectional Surveys In 2013, 2015, 2017, And 2019, Li Li, Caitlin N. Pope, Rebecca R. Andridge, Julie K. Bower, Guoqing Hu, Motao Zhu

Graduate Center for Gerontology Faculty Publications

BACKGROUND: Distracted driving among teens is a public health and safety concern. Most states in the U.S. have sought to restrict cellphone use while driving by enacting laws. This study examines the difference in prevalence of self-reported calling while driving (CWD) between states with different cellphone bans.

METHODS: Demographics and CWD data were extracted from state Youth Risk Behavior Surveys (YRBS) from 14 states in 2013, 2015, 2017, and 2019. The state YRBS is conducted every 2 years with a representative sample of 9th through 12th grade students attending public school. States were grouped by type of cellphone law(s): no …


Evidence Of Nickel And Other Trace Elements And Their Relationship To Clinical Findings In Acute Mesoamerican Nephropathy: A Case-Control Analysis, Rebecca S. B. Fischer, Jason M. Unrine, Chandan Vangala, Wayne T. Sanderson, Sreedhar Mandayam, Kristy O. Murray Nov 2020

Evidence Of Nickel And Other Trace Elements And Their Relationship To Clinical Findings In Acute Mesoamerican Nephropathy: A Case-Control Analysis, Rebecca S. B. Fischer, Jason M. Unrine, Chandan Vangala, Wayne T. Sanderson, Sreedhar Mandayam, Kristy O. Murray

Plant and Soil Sciences Faculty Publications

BACKGROUND: Although there are several hypothesized etiologies of Mesoamerican Nephropathy (MeN), evidence has not yet pointed to the underlying cause. Exposure to various trace elements can cause the clinical features observed in MeN.

METHODS AND FINDINGS: We measured 15 trace elements, including heavy metals, in renal case-patients (n = 18) and healthy controls (n = 36) in a MeN high-risk region of Nicaragua. Toenails clippings from study participants were analyzed using inductively coupled plasma mass spectrometry. A case-control analysis was performed, and concentrations were also analyzed over participant characteristics and clinical parameters. Nickel (Ni) concentrations were significantly higher in toenails …


Distinct Clinicopathologic Clusters Of Persons With Tdp-43 Proteinopathy, Yuriko Katsumata, Erin L. Abner, Shama Karanth, Merilee A. Teylan, Charles N. Mock, Matthew D. Cykowski, Edward B. Lee, Kevin L. Boehme, Shubhabrata Mukherjee, John S. K. Kauwe, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Peter T. Nelson Nov 2020

Distinct Clinicopathologic Clusters Of Persons With Tdp-43 Proteinopathy, Yuriko Katsumata, Erin L. Abner, Shama Karanth, Merilee A. Teylan, Charles N. Mock, Matthew D. Cykowski, Edward B. Lee, Kevin L. Boehme, Shubhabrata Mukherjee, John S. K. Kauwe, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Peter T. Nelson

Biostatistics Faculty Publications

To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer’s Coordinating Center (NACC) data set. All subjects (n = 495) had autopsy-proven TDP-43 proteinopathy as an inclusion criterion. Subjects underwent comprehensive longitudinal clinical evaluations yearly for 6.9 years before death on average. We tested whether an unsupervised clustering algorithm could detect coherent groups of TDP-43 immunopositive cases based on age at death and extensive neuropathologic data. Although many of the brains had mixed pathologies, four discernible clusters were identified. Key differentiating features were age at …


Multi-Ancestry Genome-Wide Association Study Accounting For Gene-Psychosocial Factor Interactions Identifies Novel Loci For Blood Pressure Traits, Daokun Sun, Melissa A. Richard, Soloman K. Musani, Yun Ju Sung, Thomas W. Winkler, Karen Schwander, Jin Fang Chai, Xiuqing Guo, Tuomas O. Kilpeläinen, Dina Vojinovic, Hugues Aschard, Traci M. Bartz, Lawrence F. Bielak, Michael R. Brown, Kumaraswamy Chitrala, Fernando P. Hartwig, Andrea R. V. R. Horimoto, Yongmei Liu, Alisa K. Manning, Raymond Noordam, Donna K. Arnett Oct 2020

Multi-Ancestry Genome-Wide Association Study Accounting For Gene-Psychosocial Factor Interactions Identifies Novel Loci For Blood Pressure Traits, Daokun Sun, Melissa A. Richard, Soloman K. Musani, Yun Ju Sung, Thomas W. Winkler, Karen Schwander, Jin Fang Chai, Xiuqing Guo, Tuomas O. Kilpeläinen, Dina Vojinovic, Hugues Aschard, Traci M. Bartz, Lawrence F. Bielak, Michael R. Brown, Kumaraswamy Chitrala, Fernando P. Hartwig, Andrea R. V. R. Horimoto, Yongmei Liu, Alisa K. Manning, Raymond Noordam, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A …


Genetic-Based Hypertension Subtype Identification Using Informative Snps, Yuanjing Ma, Hongmei Jiang, Sanjiv J. Shah, Donna K. Arnett, Marguerite R. Irvin, Yuan Luo Oct 2020

Genetic-Based Hypertension Subtype Identification Using Informative Snps, Yuanjing Ma, Hongmei Jiang, Sanjiv J. Shah, Donna K. Arnett, Marguerite R. Irvin, Yuan Luo

Epidemiology and Environmental Health Faculty Publications

In this work, we proposed a process to select informative genetic variants for identifying clinically meaningful subtypes of hypertensive patients. We studied 575 African American (AA) and 612 Caucasian hypertensive participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) study and analyzed each race-based group separately. All study participants underwent GWAS (Genome-Wide Association Studies) and echocardiography. We applied a variety of statistical methods and filtering criteria, including generalized linear models, F statistics, burden tests, deleterious variant filtering, and others to select the most informative hypertension-related genetic variants. We performed an unsupervised learning algorithm non-negative matrix factorization (NMF) to identify hypertension …


Genome-Wide Association Study Of Smoking Trajectory And Meta-Analysis Of Smoking Status In 842,000 Individuals, Ke Xu, Boyang Li, Kathleen A. Mcginnis, Rachel Vickers-Smith, Cecilia Dao, Ning Sun, Rachel L. Kember, Hang Zhou, William C. Becker, Joel Gelernter, Henry R. Kranzler, Hongyu Zhao, Amy C. Justice, Va Million Veteran Program Oct 2020

Genome-Wide Association Study Of Smoking Trajectory And Meta-Analysis Of Smoking Status In 842,000 Individuals, Ke Xu, Boyang Li, Kathleen A. Mcginnis, Rachel Vickers-Smith, Cecilia Dao, Ning Sun, Rachel L. Kember, Hang Zhou, William C. Becker, Joel Gelernter, Henry R. Kranzler, Hongyu Zhao, Amy C. Justice, Va Million Veteran Program

Epidemiology and Environmental Health Faculty Publications

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP …


Limbic-Predominant Age-Related Tdp-43 Encephalopathy Differs From Frontotemporal Lobar Degeneration, John L. Robinson, Sílvia Porta, Filip G. Garrett, Panpan Zhang, Sharon X. Xie, Eunran Suh, Vivianna M. Van Deerlin, Erin L. Abner, Gregory A. Jicha, Justin M. Barber, Virginia M-Y Lee, Edward B. Lee, John Q. Trojanowski, Peter T. Nelson Aug 2020

Limbic-Predominant Age-Related Tdp-43 Encephalopathy Differs From Frontotemporal Lobar Degeneration, John L. Robinson, Sílvia Porta, Filip G. Garrett, Panpan Zhang, Sharon X. Xie, Eunran Suh, Vivianna M. Van Deerlin, Erin L. Abner, Gregory A. Jicha, Justin M. Barber, Virginia M-Y Lee, Edward B. Lee, John Q. Trojanowski, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

TAR-DNA binding protein-43 (TDP-43) proteinopathy is seen in multiple brain diseases. A standardized terminology was recommended recently for common age-related TDP-43 proteinopathy: limbic-predominant, age-related TDP-43 encephalopathy (LATE) and the underlying neuropathological changes, LATE-NC. LATE-NC may be co-morbid with Alzheimer’s disease neuropathological changes (ADNC). However, there currently are ill-defined diagnostic classification issues among LATE-NC, ADNC, and frontotemporal lobar degeneration with TDP-43 (FTLD-TDP). A practical challenge is that different autopsy cohorts are composed of disparate groups of research volunteers: hospital- and clinic-based cohorts are enriched for FTLD-TDP cases, whereas community-based cohorts have more LATE-NC cases. Neuropathological methods also differ across laboratories. Here, …


Egfr Testing And Erlotinib Use In Non-Small Cell Lung Cancer Patients In Kentucky, Kara L. Larson, Bin Huang, Quan Chen, Thomas C. Tucker, Marissa Schuh, Susanne M. Arnold, Jill M. Kolesar Aug 2020

Egfr Testing And Erlotinib Use In Non-Small Cell Lung Cancer Patients In Kentucky, Kara L. Larson, Bin Huang, Quan Chen, Thomas C. Tucker, Marissa Schuh, Susanne M. Arnold, Jill M. Kolesar

Markey Cancer Center Faculty Publications

This study determined the frequency and factors associated with EGFR testing rates and erlotinib treatment as well as associated survival outcomes in patients with non small cell lung cancer in Kentucky. Data from the Kentucky Cancer Registry (KCR) linked with health claims from Medicaid, Medicare and private insurance groups were evaluated. EGFR testing and erlotinib prescribing were identified using ICD-9 procedure codes and national drug codes in claims, respectively. Logistic regression analysis was performed to determine factors associated with EGFR testing and erlotinib prescribing. Cox-regression analysis was performed to determine factors associated with survival. EGFR mutation testing rates rose from …


Insufficient Sun Exposure Has Become A Real Public Health Problem, Lars Alfredsson, Bruce K Armstrong, D. Allan Butterfield, Rajiv Chowdhury, Frank R. De Gruijl, Martin Feelisch, Cedric F. Garland, Prue H. Hart, David G. Hoel, Ramune Jacobsen, Pelle G. Lindqvist, David J. Llewellyn, Henning Tiemeier, Richard B. Weller, Antony R. Young Jul 2020

Insufficient Sun Exposure Has Become A Real Public Health Problem, Lars Alfredsson, Bruce K Armstrong, D. Allan Butterfield, Rajiv Chowdhury, Frank R. De Gruijl, Martin Feelisch, Cedric F. Garland, Prue H. Hart, David G. Hoel, Ramune Jacobsen, Pelle G. Lindqvist, David J. Llewellyn, Henning Tiemeier, Richard B. Weller, Antony R. Young

Chemistry Faculty Publications

This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer's disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. …


Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen May 2020

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …


Skin Cancer And Uv Exposure-Related Behaviors Among Appalachian And Non-Appalachian Adults, Minal Patel, Katrina Serrano, Elise Rice, Chan Thai, Kelly Blake, Robin C. Vanderpool Apr 2020

Skin Cancer And Uv Exposure-Related Behaviors Among Appalachian And Non-Appalachian Adults, Minal Patel, Katrina Serrano, Elise Rice, Chan Thai, Kelly Blake, Robin C. Vanderpool

Journal of Appalachian Health

Introduction: Appalachian communities experience elevated rates of cancer incidence and mortality relative to other regions in the U.S. Specifically, melanoma mortality rates are higher in Appalachia compared to the national average, despite comparable incidence rates.

Purpose: To examine differences in self-reported history of skin cancer and prevalence of two UV exposure behaviors between Appalachian and non-Appalachian adults in a nationally representative sample.

Methods: Data are from four cross-sectional cycles of the Health Information National Trends Survey (2011–2014) (N=14,451). We examined sunscreen use and tanning bed use, and self-reported history of melanoma and non-melanoma skin cancer. Descriptive and weighted …


Impact Of The Affordable Care Act On Referral To Care For People Living With Hiv In Appalachia, Cameron A. Wade, Timothy N. Crawford, Nicole Leedy, Alice C. Thornton Apr 2020

Impact Of The Affordable Care Act On Referral To Care For People Living With Hiv In Appalachia, Cameron A. Wade, Timothy N. Crawford, Nicole Leedy, Alice C. Thornton

Journal of Appalachian Health

Introduction: The Affordable Care Act (ACA) enacted on March 23, 2010 significantly impacted access to healthcare for people living with HIV (PLWH). Expansion of care was accomplished in three areas: eliminating exclusions for pre-existing conditions, elimination of lifetime caps on healthcare expenditures, and expansion of Medicaid eligibility.

Purpose: This study evaluated the impact of state implementation of the ACA Medicaid expansion on referral to HIV care at a Ryan White federally funded clinic in Kentucky (University of Kentucky Bluegrass Care Clinic [UK BCC]).

Methods: Retrospective chart review of all newly enrolled patients at the UK BCC between March 2010 and …


Cardiac Biomarkers And Subsequent Risk Of Hospitalization With Bleeding In The Community: Atherosclerosis Risk In Communities Study, Lena Mathews, Junichi Ishigami, Ning Ding, Ron C. Hoogeveen, Anna Kucharska-Newton, Christie M. Ballantyne, Rebecca Gottesman, Elizabeth Selvin, Kunihiro Matsushita Mar 2020

Cardiac Biomarkers And Subsequent Risk Of Hospitalization With Bleeding In The Community: Atherosclerosis Risk In Communities Study, Lena Mathews, Junichi Ishigami, Ning Ding, Ron C. Hoogeveen, Anna Kucharska-Newton, Christie M. Ballantyne, Rebecca Gottesman, Elizabeth Selvin, Kunihiro Matsushita

Epidemiology and Environmental Health Faculty Publications

Background

hs-cTnT (high-sensitivity cardiac troponin T), but not NT-proBNP (N-terminal pro-B natriuretic peptide), has been shown to predict bleeding in patients with atrial fibrillation. Whether these biomarkers are independently associated with bleeding in the general population is unknown.

Methods and Results

We used Cox proportional hazards models to examine the association of hs‐cTnT and NT‐proBNP with incident bleeding (defined by International Classification of Diseases, Ninth Revision [ICD‐9] codes) among 9550 middle‐aged men and women without a history of cardiovascular disease or bleeding. There were 847 hospitalizations with bleeding (92% from gastrointestinal bleeding) during a median follow‐up of …