Medicine and Health Sciences Commons^™

Clinically Relevant Intronic Splicing Enhancer Mutation In Myelin Proteolipid Protein Leads To Progressive Microglia And Astrocyte Activation In White And Gray Matter Regions Of The Brain, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, Franca Cambi

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Mutations in proteolipid protein (PLP), the most abundant myelin protein in the CNS, cause the X-linked dysmyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2). Point mutations, deletion, and duplication of the PLP1 gene cause PMD/SPG2 with varying clinical presentation. Deletion of an intronic splicing enhancer (ISEdel) within intron 3 of the PLP1 gene is associated with a mild form of PMD. Clinical and preclinical studies have indicated that mutations in myelin proteins, including PLP, can induce neuroinflammation, but the temporal and spatial onset of the reactive glia response in a clinically relevant mild form of PMD …

Sexual Coercion And Sexual Violence At First Intercourse Associated With Sexually Transmitted Infections, Corrine M. Williams, Emily R. Clear, Ann L. Coker

CRVAW Faculty Journal Articles

BACKGROUND: Violence against women has been associated with subsequent risky sexual behaviors and sexually transmitted infections (STIs). We explored whether sexual coercion or violence at first intercourse was associated with self-reported STIs.

METHODS: Using nationally representative data from the 2006 to 2010 National Survey of Family Growth, we analyzed female respondents aged 18 to 44 (n = 9466) who answered questions on coercion at first intercourse (wantedness, voluntariness, and types of force used) and STIs using logistic regression analyses. We explored degrees of coercion, which we label as neither, sexual coercion (unwanted or nonphysical force), or sexual violence (involuntary or …

Diabetes And Prostate Cancer Screening In Black And White Men, Maureen Sanderson, Jay H. Fowke, Loren Lipworth, Xijing Han, Flora Ukoli, Ann L. Coker, William J. Blot, Margaret K. Hargreaves

CRVAW Faculty Journal Articles

PURPOSE: Prior studies conducted primarily among white men find a reduced risk of prostate cancer associated with time since developing diabetes. While biologic explanations are plausible, the association may in part arise from more frequent prostate cancer screening among those with a diabetes diagnosis. The purpose of the present study was to investigate the association between diabetes and prostate cancer screening.

METHODS: We examined differences in prostate cancer screening (prostate-specific antigen and/or digital rectal examination) testing practices after a diabetes diagnosis among lower-income persons living in the southeastern United States and enrolled in the Southern Community Cohort Study between 2002 …

Circulating Micrornas In Alzheimer's Disease: The Search For Novel Biomarkers, Véronique Dorval, Peter T. Nelson, Sébastien S. Hébert

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly. While advancements have been made in understanding the genetic and molecular basis of AD, the clinical diagnosis of AD remains difficult, and post-mortem confirmation is often required. Furthermore, the onset of neurodegeneration precedes clinical symptoms by approximately a decade. Consequently, there is a crucial need for an early and accurate diagnosis of AD, which can potentially lead to strategies that can slow down or stop the progression of neurodegeneration and dementia. Recent advances in the non-coding RNA field have shown that microRNAs (miRNAs) can function as powerful biomarkers …

Dose- And Time-Dependent Neuroprotective Effects Of Pycnogenol® Following Traumatic Brain Injury, Mubeen A. Ansari, Kelly N. Roberts, Stephen W. Scheff

Sanders-Brown Center on Aging Faculty Publications

After traumatic brain injury (TBI), both primary and secondary injury cascades are initiated, leading to neuronal death and cognitive dysfunction. We have previously shown that the combinational bioflavonoid, Pycnogenol® (PYC), alters some secondary injury cascades and protects synaptic proteins when administered immediately following trauma. The purpose of the present study was to explore further the beneficial effects of PYC and to test whether it can be used in a more clinically relevant fashion. Young adult male Sprague-Dawley rats were subjected to a unilateral moderate/severe cortical contusion. Subjects received a single intravenous (i.v.) injection of PYC (1, 5, or 10 mg/kg) …

Development Of Novel In Vivo Chemical Probes To Address Cns Protein Kinase Involvement In Synaptic Dysfunction, D Martin Watterson, Valerie L. Grum-Tokars, Saktimayee M. Roy, James P. Schavocky, Brinda Desai Bradaric, Adam D. Bachstetter, Bin Xing, Edgardo Dimayuga, Faisal Saeed, Hong Zhang, Agnieszka Staniszewski, Jeffrey C. Pelletier, George Minasov, Wayne F. Anderson, Ottavio Arancio, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Serine-threonine protein kinases are critical to CNS function, yet there is a dearth of highly selective, CNS-active kinase inhibitors for in vivo investigations. Further, prevailing assumptions raise concerns about whether single kinase inhibitors can show in vivo efficacy for CNS pathologies, and debates over viable approaches to the development of safe and efficacious kinase inhibitors are unsettled. It is critical, therefore, that these scientific challenges be addressed in order to test hypotheses about protein kinases in neuropathology progression and the potential for in vivo modulation of their catalytic activity. Identification of molecular targets whose in vivo modulation can attenuate synaptic …

Intracranial Injection Of Gammagard, A Human Ivig, Modulates The Inflammatory Response Of The Brain And Lowers AΒ In App/Ps1 Mice Along A Different Time Course Than Anti-AΒ Antibodies, Tiffany L. Sudduth, Abigail Greenstein, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Gammagard IVIg is a therapeutic approach to treat Alzheimer's disease currently in phase 3 clinical trials. Despite the reported efficacy of the approach the mechanism of action is poorly understood. We have previously shown that intracranial injection of anti-Aβ antibodies into the frontal cortex and hippocampus reveals important information regarding the time course of events once the agent is in the brain. In the current study we compared IVIg, mouse-pooled IgG, and the anti-Aβ antibody 6E10 injected intracranially into the frontal cortex and hippocampus of 7-month-old APP/PS1 mice. We established a time course of events ranging from 1 …

Comprehensive Behavioral Characterization Of An App/Ps-1 Double Knock-In Mouse Model Of Alzheimer's Disease, Scott J. Webster, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Despite the extensive mechanistic and pathological characterization of the amyloid precursor protein (APP)/presenilin-1 (PS-1) knock-in mouse model of Alzheimer's disease (AD), very little is known about the AD-relevant behavioral deficits in this model. Characterization of the baseline behavioral performance in a variety of functional tasks and identification of the temporal onset of behavioral impairments are important to provide a foundation for future preclinical testing of AD therapeutics. Here we perform a comprehensive behavioral characterization of this model, discuss how the observed behavior correlates with the mechanistic and pathological observations of others, and compare this model with other commonly used …

An Ehealth System Supporting Palliative Care For Patients With Non-Small Cell Lung Cancer: A Randomized Trial, David H. Gustafson, Lori L. Dubenske, Kang Namkoong, Robert Hawkins, Ming-Yuan Chih, Amy K. Atwood, Roberta Johnson, Abhik Bhattacharya, Cindy L. Carmack, Anne M. Traynor, Toby C. Campbell, Mary K. Buss, Ramaswamy Govindan, Joan H. Schiller, James F. Cleary

Community & Leadership Development Faculty Publications

BACKGROUND: In this study, the authors examined the effectiveness of an online support system (Comprehensive Health Enhancement Support System [CHESS]) versus the Internet in relieving physical symptom distress in patients with non-small cell lung cancer (NSCLC).

METHODS: In total, 285 informal caregiver-patient dyads were assigned randomly to receive, for up to 25 months, standard care plus training on and access to either use of the Internet and a list of Internet sites about lung cancer (the Internet arm) or CHESS (the CHESS arm). Caregivers agreed to use CHESS or the Internet and to complete bimonthly surveys; for patients, these tasks …

Intracranial Injection Of Aav Expressing Nep But Not Ide Reduces Amyloid Pathology In App+Ps1 Transgenic Mice, Nikisha Carty, Kevin R. Nash, Milene Brownlow, Dana Cruite, Donna M. Wilcock, Maj-Linda B. Selenica, Daniel C. Lee, Marcia N. Gordon, Dave Morgan

Sanders-Brown Center on Aging Faculty Publications

The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer's disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry …

Bapineuzumab Alters Aβ Composition: Implications For The Amyloid Cascade Hypothesis And Anti-Amyloid Immunotherapy, Alex E. Roher, David H. Cribbs, Ronald C. Kim, Chera L. Maarouf, Charisse M. Whiteside, Tyler A. Kokjohn, Ian D. Daugs, Elizabeth Head, Carolyn Liebsack, Geidy Serrano, Christine Belden, Marwan N. Sabbagh, Thomas G. Beach

Sanders-Brown Center on Aging Faculty Publications

The characteristic neuropathological changes associated with Alzheimer's disease (AD) and other lines of evidence support the amyloid cascade hypothesis. Viewing amyloid deposits as the prime instigator of dementia has now led to clinical trials of multiple strategies to remove or prevent their formation. We performed neuropathological and biochemical assessments of 3 subjects treated with bapineuzumab infusions. Histological analyses were conducted to quantify amyloid plaque densities, Braak stages and the extent of cerebral amyloid angiopathy (CAA). Amyloid-β (Aβ) species in frontal and temporal lobe samples were quantified by ELISA. Western blots of amyloid-β precursor protein (AβPP) and its C-terminal (CT) fragments …

Using Risk And Participatory Communication To Support Community-Based Decisions: The Paducah Gaseous Diffusion Plant Future Vision Project, Anna G. Hoover

Anna G. Hoover

No abstract provided.

The Impact Of The Internet On The Sexual Health Of Adolescents: A Brief Review, Julia Springate, Hatim A. Omar

Pediatrics Faculty Publications

The object of this review is to summarize the impact of the Internet on the sexual health of adolescents. This article examines the use of websites, blogs and chat rooms as sources for sexual health information for adolescents. The influence of Internet pornography on sexual behaviors and attitudes is addressed. The use of the Internet as a place to find sexual partners is also assessed. During a time of great physical, emotional and sexual change, the Internet is playing a huge role in the decisions adolescents are making, both positive and negative.

Comparing Clinical Profiles In Alzheimer's Disease And Parkinson's Disease Dementia, Martin R. Farlow, Frederick A. Schmitt, Dag Aarsland, George T. Grossberg, Monique Somogyi, Xiangyi Meng

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) may improve the interpretation of drug effects and the design of future studies.

METHODS: This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD). Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, 10-item Neuropsychiatric Inventory (NPI-10) and the ADCS-Clinical Global Impression of Change (CGIC) was compared [standardized difference (Cohen's d), similar if <0.1].

RESULTS: Patients with AD or PDD had similar levels …

Conviction Celerity, Punishment Severity, And Treatment Compliance As Predictors Of Dui Recidivism: Mediation And Moderation Models Of Deterrence, Megan F. Dickson

Theses and Dissertations--Sociology

Driving under the influence (DUI) is one of the most frequently committed offenses in the United States and approximately one-third of DUI offenders are recidivists. Researchers have evaluated multiple DUI prevention approaches, most of which have been rooted in deterrence theory. Recently, the criminal justice system has moved away from deterrence-based approaches and begun employing various forms of rehabilitation to reduce DUI recidivism. This shift in the criminal justice system has lead researchers to begin exploring the effects of rehabilitation on DUI offenders, including an examination of offender compliance with rehabilitation programs. Although each of these areas has been investigated …

Untangling Neoliberalism’S Gordian Knot: Cancer Prevention And Control Services For Rural Appalachian Populations, George F. Bills

Theses and Dissertations--Sociology

In eastern Kentucky, as in much of central Appalachia, current local storylines narrate the frictions and contradictions involved in the structural transition from a post-WWII Fordist industrial economy and a Keynesian welfare state to a Post-Fordist service economy and Neoliberal hollow state, starving for energy to sustain consumer indulgence (Jessop, 1993; Harvey, 2003; 2005). Neoliberalism is the ideological force redefining the “societal infrastructure of language” that legitimates this transition, in part by redefining the key terms of democracy and citizenship, as well as valorizing the market, the individual, and technocratic innovation (Chouliaraki & Fairclough, 1999; Harvey, 2005). This project develops …