Social and Behavioral Sciences Commons^™

Microglial P38Α Mapk Is Critical For Lps-Induced Neuron Degeneration, Through A Mechanism Involving Tnfα, Bin Xing, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The p38α MAPK isoform is a well-established therapeutic target in peripheral inflammatory diseases, but the importance of this kinase in pathological microglial activation and detrimental inflammation in CNS disorders is less well understood. To test the role of the p38α MAPK isoform in microglia-dependent neuron damage, we used primary microglia from wild-type (WT) or p38α MAPK conditional knockout (KO) mice in co-culture with WT cortical neurons, and measured neuron damage after LPS insult.

RESULTS: We found that neurons in co-culture with p38α-deficient microglia were protected against LPS-induced synaptic loss, neurite degeneration, and neuronal death. The involvement of the proinflammatory …

Driving Qi With Research: Findings From Public Health Pbrns, Glen P. Mays

Health Management and Policy Presentations

Public health agencies are increasingly experimenting with quality improvement (QI) strategies designed to enhance the effectiveness and efficiency of their efforts. Does QI work in public health, and if so for whom and under what circumstances? What QI strategies work best for which types of public health process failures, and at what cost? Research underway through the Public Health Practice-Based Research Networks (PBRN) Program is examining these types of questions to build an evidence base for public health QI.

The Science Of Public Health Delivery: Evidence, Uncertainties & Research Needs, Glen P. Mays

Health Management and Policy Presentations

Policy initiatives to reform the nation's health system increasingly recognize the need to incorporate public health and prevention strategies. The nation's delivery system for public health, however, varies widely across states and communities in its structure, authority, and capabilities. This session examines research from the growing field of public health services and systems research to identify directions for improving public health delivery.

Estimating The Value Of Public Health Services & Systems: Evidence, Uncertainties, And Research Needs, Glen P. Mays

Health Management and Policy Presentations

The Affordable Care Act authorized the largest expansion in federal funding for public health services and delivery systems in decades. These provisions, designed to support programs and services that promote health and prevent disease and injury on a population-wide basis, remain controversial because of uncertainties regarding their effectiveness in improving health and constraining medical cost growth. This session examines a series of recent studies to shed light on the health and economic value of spending on public health.

The Consequences Of Early Onset Alcohol Experimentation: Adaptive Exploration On Downward Trajectory, Marjorie Grefer

Kaleidoscope

No abstract provided.

The Design Of A Psychiatric Residential Treatment Facility In Wheelwright, Kentucky Serving Adolescent Males, Jenna Clem

Kaleidoscope

During the spring semester of 2010, I have been working on the design of a psychiatric residential treatment facility in Wheelwright, Kentucky as part of the requirements for ID 659, Interior Design Graduate Studio. I am a senior, but was allowed permission to enroll in this class because of my interest in research-based design. The facility will offer therapy services in a home environment for seven adolescents between the ages of ten and seventeen. This paper describes the process that I followed throughout the design process and the specific issues that were addressed in the final solution. The design process …

Disparities Research In Public Health Pbrns, Glen P. Mays

Health Management and Policy Presentations

Public health agencies are well positioned within the health system to play key roles in addressing oral health issues on a population-wide basis, However, current evidence reveals wide geographic variation in the delivery of public health interventions for oral health promotion. This session explores the factors contributing to this variation, and it highlights studies underway through the Public Health Practice-Based Research Networks (PBRNs) to produce more and better evidence about public health delivery and impact.

Elevated Stearoyl-Coa Desaturase In Brains Of Patients With Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Vitaly Vasilevko, Nicholas V. Dipatrizio, Sarah K. Martin, David H. Cribbs, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong …

Health & Wellness In The Business Context, Michael T. Childress

Issue Brief on Topics Affecting Kentucky’s Economy

No abstract provided.

Activation Of Matrix Metalloproteinases Following Anti-Aβ Immunotherapy; Implications For Microhemorrhage Occurrence, Donna M. Wilcock, Dave Morgan, Marcia N. Gordon, Tiffany L. Taylor, Lisa A. Ridnour, David A. Wink, Carol A. Colton

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD) currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s) by which they occur.

METHODS: We have examined the matrix metalloproteinase (MMP) protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which …

Preventive Medicine Introduction, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Preventive Medicine Introduction, F. Douglas Scutchfield Md

F. Douglas Scutchfield MD

No abstract provided.

Evaluation Of The Global Association Between Cholesterol-Associated Polymorphisms And Alzheimer's Disease Suggests A Role For Rs3846662 And Hmgcr Splicing In Disease Risk, Christopher R. Simmons, Fanggeng Zou, Steven G Younkin, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNP)s that are essentially unequivocally associated with peripheral cholesterol. Since the alleles of the APOE gene, which modulate peripheral cholesterol metabolism, and midlife plasma cholesterol are both associated with Alzheimer's disease (AD) risk, we have evaluated the hypothesis that SNPs associated with plasma cholesterol are also associated with AD.

RESULTS: Seventeen non-APOE SNPs reproducibly associated with cholesterol per GWAS were tested for association with AD in ~2,000 AD and ~4,000 non-AD subjects. As a group, these SNPs are associated with AD. Two SNPs in particular, rs3846662 and rs1532085, are …

Epigenetic Silencing Of Nucleolar Rrna Genes In Alzheimer's Disease, Maciej Pietrzak, Grzegorz Rempala, Peter T. Nelson, Jing-Juan Zheng, Michal Hetman

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer's disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation.

METHODOLOGY/PRINCIPAL FINDINGS: To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter …

Microglial P38Α Mapk Is A Key Regulator Of Proinflammatory Cytokine Up-Regulation Induced By Toll-Like Receptor (Tlr) Ligands Or Beta-Amyloid (Aβ), Adam D. Bachstetter, Bin Xing, Lucia De Almeida, Edgardo R. Dimayuga, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Overproduction of proinflammatory cytokines from activated microglia has been implicated as an important contributor to pathophysiology progression in both acute and chronic neurodegenerative diseases. Therefore, it is critical to elucidate intracellular signaling pathways that are significant contributors to cytokine overproduction in microglia exposed to specific stressors, especially pathways amenable to drug interventions. The serine/threonine protein kinase p38α MAPK is a key enzyme in the parallel and convergent intracellular signaling pathways involved in stressor-induced production of IL-1β and TNFα in peripheral tissues, and is a drug development target for peripheral inflammatory diseases. However, much less is known about the quantitative …

Analyzing The Impact Of 23 Mg/Day Donepezil On Language Dysfunction In Moderate To Severe Alzheimer's Disease, Steven H. Ferris, Frederick A. Schmitt, Judith Saxton, Sharon Richardson, Joan Mackell, Yijun Sun, Yikang Xu

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Progressive language impairment is among the primary components of cognitive decline in Alzheimer's disease (AD). Because expressive and receptive language help to maintain emotional connections to caregivers and support the management of AD patients' functional needs, language plays a critical role in patients' emotional and physical health. Using data from a large prospective clinical trial comparing two doses of donepezil in patients with moderate to severe AD, we performed a post hoc analysis to determine whether a higher dose of donepezil was associated with greater benefits in language function.

METHODS: In the original randomized, double-blind clinical trial, 1,467 patients …

Phssr Research Agenda, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Phssr Research Agenda, F. Douglas Scutchfield Md

F. Douglas Scutchfield MD

No abstract provided.

Gender Differences In Smoking Behaviour And Cessation, Chizimuzo T.C. Okoli, Iris Torchalla, Natalie Hemsing, Lorraine Greaves

Chizimuzo T.C. Okoli

This article reviews the literature to compare differential outcomes among men and women after smoking cessation, assess barriers they may face during cessation and provide recommendation to address gender-specific challenges in smoking cessation interventions. There is some evidence that women achieve lower abstinence rates than men after a quit attempt with nicotine replacement therapy, as well as without pharmacotherapy, and several underlying mechanisms were discussed to account for these findings. These include: (a) women have specific genetic variants that affect pharmacokinetics and pharmacodynamics of the medication, (b) hormonal influences increase nicotine metabolism and withdrawal symptoms, (c) women are more responsive …

A Tale Of Two Cities? The Heterogeneous Impact Of Medicaid Managed Care In Kentucky, James Marton, Aaron Yelowitz, Jeffery C. Talbert

University of Kentucky Center for Poverty Research Discussion Paper Series

Does managed care produce lower health care utilization and costs through better aligned financial incentives and alternative delivery methods (the “pure” HMO effect) or by attracting more healthy enrollees (enrollee selection)? The purpose of this paper is to shed new light on this fundamental question using a quasi-experimental approach that exploits the timing and county specific implementation of Medicaid managed care plans in two distinct sub-sets of Kentucky counties in the late 1990s. We find large differences in the relative success of each region in reducing utilization that are likely driven by important differences in plan design. Asthmatic children enrolled …

Rheumatoid Arthritis-Associated Polymorphisms Are Not Protective Against Alzheimer's Disease, Christopher R. Simmons, Fanggeng Zou, Steven G Younkin, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Rheumatoid arthritis (RA) and Alzheimer's disease (AD) are inversely associated. To test the hypothesis that genetic elements associated with increased RA risk are associated with decreased AD risk, we evaluated RA genetic risk factors recently identified in genome-wide association studies (GWAS) for their association with AD in a two-stage, case-control analysis.

RESULTS: In our Stage 1 analysis of ~800 AD and ~1,200 non-AD individuals, three of seventeen RA-associated SNPs were nominally associated with AD (p < 0.05) with one SNP, rs2837960, retaining significance after correction for multiple testing (p = 0.03). The rs2837960_G (minor) allele, which is associated with increased RA risk, was associated with increased AD risk. Analysis of these three SNPs in a Stage 2 population, consisting of ~1,100 AD and ~2,600 non-AD individuals, did not confirm their association with AD. Analysis of Stage 1 and 2 combined suggested that rs2837960 shows a trend for association with AD. When the Stage 2 population was age-matched for the Stage 1 population, rs2837960 exhibited a non-significant trend with AD. Combined analysis of Stage 1 and the age-matched Stage 2 subset showed a significant association of rs2837960 with AD (p = 0.002, OR 1.24) that retained significance following correction for age, sex and APOE (p = 0.02, OR = 1.20). Rs2837960 is near BACE2, which encodes an aspartic protease capable of processing the AD-associated amyloid precursor protein. Testing for an association between rs2837960 and the expression of BACE2 isoforms in human brain, we observed a trend between rs2837960 and the total expression of BACE2 and the expression of a BACE2 transcript lacking exon 7 (p = 0.07 and 0.10, respectively).

CONCLUSIONS: RA-associated SNPs are generally not associated with AD. Moreover, rs2837960_G is associated with increased risk of both RA and, in individuals less than …

Public Health Finance Management Needs And How Public Health Agencies Are Funded., F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Public Health Finance Management Needs And How Public Health Agencies Are Funded., F. Douglas Scutchfield Md

F. Douglas Scutchfield MD

No abstract provided.

A Brief History Of Phssr: The National Coordinating Center. Lessons From History, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

A Brief History Of Phssr: The National Coordinating Center. Lessons From History, F. Douglas Scutchfield Md

F. Douglas Scutchfield MD

No abstract provided.

Cx3cl1 Reduces Neurotoxicity And Microglial Activation In A Rat Model Of Parkinson's Disease, Mibel M. Pabon, Adam D. Bachstetter, Charles E. Hudson, Carmelina Gemma, Paula C. Bickford

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease. Microglia are capable of producing neuronal damage through the production of bioactive molecules such as cytokines, as well as reactive oxygen species (ROS), and nitric oxide (NO). The inflammatory response in the brain is tightly regulated at multiple levels. One form of immune regulation occurs via neurons. Fractalkine (CX3CL1), produced by neurons, suppresses the activation of microglia. CX3CL1 …

Public Health Services And Systems Research: A Common Meeting Ground, F. Douglas Scutchfield Md

F. Douglas Scutchfield MD

No abstract provided.

Public Health Services And Systems Research: A Common Meeting Ground, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

No Significant Change In Sexual Behavior In Association With Human Papilloma Virus Vaccination In Young Girls, Wafa R.R. Al Romaih, Archana Srinivas, Said Shahtahmasebi, Hatim A. Omar

Pediatrics Faculty Publications

The first human Papilloma virus (HPV) vaccine was approved in the United States in 2006 with the potential to reduce cervical cancer and genital warts. Since then, its efficacy in preventing HPV-related cancers in both males and females has been promising. Despite CDC recommendations, opponents of the vaccine assert that vaccinating pre-adolescents and adolescents will increase their sexual activity, as well as overtly condone risky sexual behavior. We analyzed clinic data of 499 adolescents with a mean age of 16 years to explore whether vaccination led to change in sexual behavior after one year. Our results showed no statistically significant …

Teens Texting And Consequences: A Brief Review, Archana Srinivas, Megan White, Hatim A. Omar

Pediatrics Faculty Publications

The aim of this paper is to summarize the current literature on texting use amongst adolescents. A brief overview will be presented on the prevalence of texting among teenagers, the use of texting for sexting and cyberbullying as well as the dangers of texting while driving. This paper will serve as a brief overview of these topics in order to bring to light the emerging challenges that texting presents to the mental and physical well-being of adolescents in an effort to evoke further discussion regarding the need for increasing awareness and education to parents, educators, law makers and health care …