Medicine and Health Sciences Commons^™

Hyperhomocysteinemia-Induced Gene Expression Changes In The Cell Types Of The Brain, Erica M. Weekman, Abigail E. Woolums, Tiffany L. Sudduth, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk factor for vascular cognitive impairment and dementia, which is the second leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages and cognitive decline in mice, the specific effect of hyperhomocysteinemia on each cell type remains unknown. We took separate cultures of astrocytes, microglia, endothelial cells, and neuronal cells and treated each with moderate levels of homocysteine for 24, 48, 72, and 96 hr. We then determined the gene expression changes for cell-specific markers and neuroinflammatory markers including the matrix metalloproteinase 9 system. Astrocytes had decreased levels of several astrocytic end feet …

Negative Outcomes Of Teen Sexual Activity: Is There A Regional Effect?, Hannah Latta, Said Shahtahmasebi, Hatim A. Omar

Pediatrics Faculty Publications

A recent victory with respect to teen sexual behavior is the reduction of the national teen birth rate. In 1991, there were 61.8 births per 1000 females aged 15-19. By 2014, this rate plummeted to 24.2 births per 1000 adolescent females. Averages, however, do not reflect state-level variation. For example, in 2014, Kentucky reported 35.3 births per 1000 adolescent females, while New York reported a teen birth rates of 16.1 births per 1000 adolescent females. This report asks: are these discrepancies due to regional factors, and are these differences statistically significant? To examine rural and urban differences in outcomes of …

Cerebrovascular Pathology In Down Syndrome And Alzheimer Disease, Elizabeth Head, Michael J. Phelan, Eric Doran, Ronald C. Kim, Wayne W. Poon, Frederick A. Schmitt, Ira T. Lott

Sanders-Brown Center on Aging Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, …

Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in …

Pathway Of Protection: Ethnic Identity, Self-Esteem, And Substance Use Among Multiracial Youth, Sycarah Fisher, Tamika C. B. Zapolski, Chelsea Sheehan, Jessica Barnes-Najor

Educational, School, and Counseling Psychology Faculty Publications

Fifty percent of adolescents have tried an illicit drug and 70% have tried alcohol by the end of high school, with even higher rates among multiracial youth. Ethnic identity is a protective factor against substance use for minority groups. However, little is known about the mechanisms that facilitate its protective effects, and even less is known about this relationship for multiracial youth. The purpose of the present study was to examine the protective effect of ethnic identity on substance use and to determine whether this relationship operated indirectly through self-esteem, a strong predictor of substance use for among adolescent populations. …

A New Opportunity For Memri, Ryan Cloyd, Moriel H. Vandsburger, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

Availability Of Healthcare Resources And Epithelial Ovarian Cancer Stage Of Diagnosis And Mortality Among Blacks And Whites, Swati Sakhuja, Huifeng Yun, Maria Pisu, Tomi Akinyemiju

Epidemiology and Environmental Health Faculty Publications

Background: The purpose of this study is to examine whether racial disparities in epithelial ovarian cancer stage at diagnosis and survival may be explained by geographic availability of healthcare resources among Blacks and Whites.

Methods: Data from the Surveillance, Epidemiology and End Results (SEER) database was used to identify White and Black women ages 40 years and above diagnosed with epithelial ovarian cancer between 2000 and 2010. Data on county-level availability of healthcare resources was obtained from the Area Resource File. Multi-level regression models, overall and stratified by race and age, were used to examine the associations of health care …

Pro-Angiogenesis Therapy And Aging: A Mini-Review, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from major illnesses and chronic afflictions, the elderly experience lesser ailments, such as muscle weakness, cold intolerance, and transient memory lapses. Physical signs in the aged include wrinkled skin and the slow healing of skin abrasions. These ailments and signs are grouped together because they may be due in part to an age-linked, waning microcirculation. A reduced capillary density (CD) throughout the body of aged people and animals has been reported in over 40 papers. The reduced CD is due in turn to declining levels of angiogenic growth factors (AGFs) throughout the body during old age, as documented in …

Examining The Protective Effect Of Ethnic Identity On Drug Attitudes And Use Among A Diverse Youth Population, Tamika C. B. Zapolski, Sycarah Fisher, Devin E. Banks, Devon J. Hensel, Jessica Barnes-Najor

Educational, School, and Counseling Psychology Faculty Publications

Ethnic identity is an important buffer against drug use among minority youth. However, limited work has examined pathways through which ethnic identity mitigates risk. School-aged youth (N = 34,708; 52 % female) of diverse backgrounds (i.e., African American (n = 5333), Asian (n = 392), Hispanic (n = 662), Multiracial (n = 2129), Native American (n = 474), and White (n = 25718) in grades 4–12 provided data on ethnic identity, drug attitudes, and drug use. After controlling for gender and grade, higher ethnic identity was associated with lower past month drug use …

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 …

Using Neonatal Skin To Study The Developmental Programming Of Aging, Leryn J. Reynolds, Brett J. Dickens, Benjamin B. Green, Carmen J. Marsit, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Numerous studies have examined how both negative and positive maternal exposures (environmental contaminants, nutrition, exercise, etc.) impact offspring risk for age-associated diseases such as obesity, type 2 diabetes, hypertension, and others. The purpose of this study was to introduce the foreskin as a novel model to examine developmental programming in human neonates, particularly in regard to adipogenesis and insulin receptor signaling, major contributors to age-associated diseases such as obesity and diabetes. Neonatal foreskin was collected following circumcision and primary dermal fibroblasts were isolated to perform adipocyte differentiation and insulin stimulation experiments. Human neonatal foreskin primary fibroblasts take up lipid when …

Functional Limitation And Depressive Symptomatology: Considering Perceived Stigma And Discrimination Within A Stress And Coping Framework, Robyn Lewis Brown

Sociology Faculty Publications

This study examines whether perceived stigma and discrimination moderate the associations between functional limitation, psychosocial coping resources, and depressive symptoms among people with physical disabilities. Using two waves of data from a large community study including a representative sample of persons with physical disabilities (N = 417), an SEM-based moderated mediation analysis was performed. Mediation tests demonstrate that mastery significantly mediates the association between functional limitation and depressive symptoms over the study period. Moderated mediation tests reveal that the linkage between functional limitation and mastery varies as a function of perceived stigma and experiences of major discrimination and day-to-day discrimination, …

Rct Testing Bystander Effectiveness To Reduce Violence, Ann L. Coker, Heather M. Bush, Patricia G. Cook-Craig, Sarah A. Degue, Emily R. Clear, Candace J. Brancato, Bonnie S. Fisher, Eileen A. Recktenwald

Obstetrics and Gynecology Faculty Publications

Introduction: Bystander-based programs have shown promise to reduce interpersonal violence at colleges, yet limited rigorous evaluations have addressed bystander intervention effectiveness in high schools. This study evaluated the Green Dot bystander intervention to reduce sexual violence and related forms of interpersonal violence in 26 high schools over 5 years.

Design: A cluster RCT was conducted.

Setting/participants: Kentucky high schools were randomized to intervention or control (wait list) conditions.

Intervention: Green Dot−trained educators conducted schoolwide presentations and recruited student popular opinion leaders to receive bystander training in intervention schools beginning in Year 1.

Main outcome measures: The primary outcome was sexual …

Retention Of Normal Glia Function By An Isoform-Selective Protein Kinase Inhibitor Drug Candidate That Modulates Cytokine Production And Cognitive Outcomes, Zhengqiu Zhou, Adam D. Bachstetter, Claudia B. Späni, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Background: Brain p38α mitogen-activated protein kinase (MAPK), a potential therapeutic target for cognitive dysfunction based on the neuroinflammation-synaptic dysfunction cycle of pathophysiology progression, offers an innovative pharmacological strategy via inhibiting the same activated target in both glia and neurons, thereby enhancing the possibility for efficacy. The highly selective, brain-penetrant p38αMAPK inhibitor MW150 attenuates cognitive dysfunction in two distinct Alzheimer's disease (AD)-relevant models and avoids the problems encountered with previous mixed-kinase inhibitor drug candidates. Therefore, it is essential that the glial effects of this CNS-active kinase inhibitor be addressed in order to anticipate future use in clinical investigations.

Methods: …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

Tuning Up The Old Brain With New Tricks: Attention Training Via Neurofeedback, Yang Jiang, Reza Abiri, Xiaopeng Zhao

Sanders-Brown Center on Aging Faculty Publications

Neurofeedback (NF) is a form of biofeedback that uses real-time (RT) modulation of brain activity to enhance brain function and behavioral performance. Recent advances in Brain-Computer Interfaces (BCI) and cognitive training (CT) have provided new tools and evidence that NF improves cognitive functions, such as attention and working memory (WM), beyond what is provided by traditional CT. More published studies have demonstrated the efficacy of NF, particularly for treating attention deficit hyperactivity disorder (ADHD) in children. In contrast, there have been fewer studies done in older adults with or without cognitive impairment, with some notable exceptions. The focus of this …

The Juvenile Justice Behavioral Health Services Cascade: A New Framework For Measuring Unmet Substance Use Treatment Services Needs Among Adolescent Offenders, Steven Belenko, Danica Knight, Gail A. Wasserman, Michael L. Dennis, Tisha Wiley, Faye S. Taxman, Carrie B. Oser, Richard Dembo, Angela A. Robertson, Jessica Sales

Sociology Faculty Publications

Overview—Substance use and substance use disorders are highly prevalent among youth under juvenile justice (JJ) supervision, and related to delinquency, psychopathology, social problems, risky sex and sexually transmitted infections, and health problems. However, numerous gaps exist in the identification of behavioral health (BH) problems and in the subsequent referral, initiation and retention in treatment for youth in community justice settings. This reflects both organizational and systems factors, including coordination between justice and BH agencies.

Methods and Results—This paper presents a new framework, the Juvenile Justice Behavioral Health Services Cascade (“Cascade”), for measuring unmet substance use treatment needs to …

Adverse Events And Treatment Discontinuations Of Antimuscarinics For The Treatment Of Overactive Bladder In Older Adults: A Systematic Review And Meta-Analysis, Scott Martin Vouri, Clark D. Kebodeaux, Paul M. Stranges, Besu F. Teshome

Pharmacy Practice and Science Faculty Publications

Introduction

Antimuscarinics should be used with caution in older adults with overactive bladder (OAB) due to anticholinergic adverse events (AEs). Systematic reviews and meta-analyses (SRMAs) have analyzed safety-related outcomes but have not specified risk in the elderly, the population at highest risk for AEs. The aim of this review is to explore and evaluate AEs and treatment discontinuations in adults 65 or older taking antimuscarinics for OAB.

Methods

Keywords were searched in MEDLINE, EMBASE, SCOPUS, and Cochrane Central Register for Controlled Trials. Randomized controlled trials (RCTs) along with sub-analyses and pooled analyses that compared antimuscarinics to placebo or another antimuscarinic …

Understanding The Influence Of Stigma And Discrimination For The Functional Limitation Severity - Psychological Distress Relationship: A Stress And Coping Perspective, Robyn Lewis Brown

Sociology Faculty Publications

No abstract provided.

Evaluation Of A Community-Based Positive Youth Development Program For Adolescents With Greater Psychosocial Needs: Views Of The Program Participants, Daniel T. L. Shek, Cecilia M. S. Ma, Moon Y. M. Law, Zoe Zhao

Pediatrics Faculty Publications

The present study attempted to investigate the perceptions of Chinese secondary school students with greater psychosocial needs of the Tier 2 Program in the community-based phase of P.A.T.H.S. Project in Hong Kong (n=4245). Using a subjective outcome evaluation tool (Form C), the results revealed that a great majority of the students held positive attitudes toward the program, implementers and the effectiveness of the program. Also, the three domains of the program (“program quality”, “implementer quality” and “program effectiveness”) were significantly associated with each other. In line with previous findings, both program content and program implementer quality were significant predictors of …

Mental Health Treatment Seeking Patterns And Preferences Of Appalachian Women With Depression, Claire Snell-Rood, Emily Hauenstein, Carl G. Leukefeld, Frances Feltner, Amber Marcum, Nancy E. Schoenberg

Behavioral Science Faculty Publications

This qualitative study explored social-cultural factors that shape treatment seeking behaviors among depressed rural, low-income women in Appalachia—a region with high rates of depression and a shortage of mental health services. Recent research shows that increasingly rural women are receiving some form of treatment and identifying their symptoms as depression. Using purposive sampling, investigators recruited 28 depressed low-income women living in Appalachian Kentucky and conducted semistructured interviews on participants’ perceptions of depression and treatment seeking. Even in this sample of women with diverse treatment behaviors (half reported current treatment), participants expressed ambivalence about treatment and its potential to promote recovery. …

A Systems Approach To The Problem Of Falls In Old Age, Patrick A. Dillon

Theses and Dissertations--Gerontology

The problem of falls in old age is enormously costly and disruptive for the older individual, others, and society, and its severity is likely to intensify as our population ages. This dissertation takes a systems-oriented approach toward the falls problem and is presented in two parts. The first part critically develops a new approach to the problem of falls. The second part describes an empirical study that applies this new approach in a pragmatic manner.

Conventional fall prevention strategies employ a reductionist approach to the problem of falls. This approach is questioned because it corresponds poorly to the holistic nature …

A Theory Of Veteran Identity, Travis L. Martin

Theses and Dissertations--English

More than 2.6 million troops have deployed in support of the wars in Iraq and Afghanistan. Still, surveys reveal that more than half feel “disconnected” from their civilian counterparts, and this feeling persists despite ongoing efforts, in the academy and elsewhere, to help returning veterans overcome physical and mental wounds, seek an education, and find meaningful ways to contribute to society after taking off the uniform. This dissertation argues that Iraq and Afghanistan War veterans struggle with reassimilation because they lack healthy, complete models of veteran identity to draw upon in their postwar lives, a problem they’re working through collectively …

Intimate Partner Violence And Women's Cancer Quality Of Life, Ann L. Coker, Diane R. Follingstad, Lisandra S. Garcia, Heather M. Bush

CRVAW Faculty Journal Articles

Purpose

Because intimate partner violence (IPV) may disproportionately impact women’s quality of life (QOL) when undergoing cancer treatment, women experiencing IPV were hypothesized to have (a) more symptoms of depression or stress and (b) lower QOL as measured with the Functional Assessment of Cancer Therapy (FACT-B) and Functional Assessment of Chronic Illness Therapy—Spiritual Well-being (FACIT-SP) Scales relative to those never experiencing IPV.

Methods

Women, aged 18–79, who were included in one of two state cancer registries from 2009 to 2015 with a recent incident, primary, invasive biopsy-confirmed cancer diagnosis were recruited and asked to complete a phone interview, within 12 …