Medicine and Health Sciences Commons^™

Chess Improves Cancer Caregivers' Burden And Mood: Results Of An Ehealth Rct, Lori L. Dubenske, David H. Gustafson, Kang Namkoong, Robert P. Hawkins, Amy K. Atwood, Roger L. Brown, Ming-Yuan Chih, Fiona Mctavish, Cindy L. Carmack, Mary K. Buss, Ramaswamy Govindan, James F. Cleary

Community & Leadership Development Faculty Publications

OBJECTIVE: Informal caregivers (family and friends) of people with cancer are often unprepared for their caregiving role, leading to increased burden or distress. Comprehensive Health Enhancement Support System (CHESS) is a Web-based lung cancer information, communication, and coaching system for caregivers. This randomized trial reports the impact on caregiver burden, disruptiveness, and mood of providing caregivers access to CHESS versus the Internet with a list of recommended lung cancer websites.

METHODS: A total of 285 informal caregivers of patients with advanced nonsmall cell lung cancer were randomly assigned to a comparison group that received Internet or a treatment group that …

Calcineurin And Glial Signaling: Neuroinflammation And Beyond, Jennifer L. Furman, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Similar to peripheral immune/inflammatory cells, neuroglial cells appear to rely on calcineurin (CN) signaling pathways to regulate cytokine production and cellular activation. Several studies suggest that harmful immune/inflammatory responses may be the most impactful consequence of aberrant CN activity in glial cells. However, newly identified roles for CN in glutamate uptake, gap junction regulation, Ca²⁺ dyshomeostasis, and amyloid production suggest that CN's influence in glia may extend well beyond neuroinflammation. The following review will discuss the various actions of CN in glial cells, with particular emphasis on astrocytes, and consider the implications for neurologic dysfunction arising with aging, injury, …

Obesity And Diabetes Cause Cognitive Dysfunction In The Absence Of Accelerated Β-Amyloid Deposition In A Novel Murine Model Of Mixed Or Vascular Dementia, Dana M. Niedowicz, Valerie L. Reeves, Thomas L. Platt, Katharina Kohler, Tina L. Beckett, David K. Powell, Tiffany L. Lee, Travis R. Sexton, Eun Suk Song, Lawrence D. Brewer, Caitlin S. Latimer, Susan D. Kraner, Kara L. Larson, Sabire Özcan, Christopher M. Norris, Louis B. Hersh, Nada M. Porter, Donna M. Wilcock, Michael Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased risk for Alzheimer's disease (AD), though the underlying mechanisms are unknown. We have created a novel mouse model that recapitulates features of T2DM and AD by crossing morbidly obese and diabetic db/db mice with APP^ΔNL/ΔNLx PS1^P264L/P264L knock-in mice. These mice (db/AD) retain many features of the parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of β-amyloid (Aβ)). The combination of the two diseases led to additional pathologies-perhaps most striking of which was the presence of severe cerebrovascular pathology, including aneurysms and small …

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 …

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 …

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 …

Transforming The Healthcare Response To Intimate Partner Violence And Taking Best Practices To Scale, Michele R. Decker, Shannon Frattaroli, Brigid Mccaw, Ann L. Coker, Elizabeth Miller, Phyllis Sharps, Wendy G. Lane, Mahua Mandal, Kelli Hirsch, Donna M. Strobino, Wendy L. Bennett, Jacquelyn Campbell, Andrea Gielen

CRVAW Faculty Journal Articles

BACKGROUND: Intimate partner violence (IPV) is prevalent among adolescent and adult women, with significant physical, sexual, and mental health consequences. In 2011, the Institute of Medicine's Clinical Preventive Services for Women consensus report recommended universal screening for violence as a component of women's preventive services; this policy has been adopted by the Health Resources and Services Administration (HRSA). These policy developments require that effective clinic-based interventions be identified, easily implemented, and taken to scale.

METHODS: To foster dialogue about implementing effective interventions, we convened a symposium entitled "Responding to Violence Against Women: Emerging Evidence, Implementation Science, and Innovative Interventions," on …

Practice Effects In A Longitudinal, Multi-Center Alzheimer's Disease Prevention Clinical Trial, Erin L. Abner, Brandon C. Dennis, Melissa J. Mathews, Marta S. Mendiondo, Allison Caban-Holt, Richard J. Kryscio, Frederick A. Schmitt, John J. Crowley

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Practice effects are a known threat to reliability and validity in clinical trials. Few studies have investigated the potential influence of practice on repeated screening measures in longitudinal clinical trials with a focus on dementia prevention. The current study investigates whether practice effects exist on a screening measure commonly used in aging research, the Memory Impairment Screen (MIS).

METHODS: The PREADViSE trial is a clinical intervention study evaluating the efficacy of vitamin E and selenium for Alzheimer's disease prevention. Participants are screened annually for incident dementia with the MIS. Participants with baseline and three consecutive follow-ups who made less …

Perlecan Domain V Induces Vegf Secretion In Brain Endothelial Cells Through Integrin Α5Β1 And Erk-Dependent Signaling Pathways, Douglas N. Clarke, Abraham Al Ahmad, Boyeon Lee, Christi Parham, Lisa Auckland, Andrezj Fertala, Michael Kahle, Courtney S. Shaw, Jill Roberts, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction …

Lithium Treatment Of Appswdi/Nos2−/− Mice Leads To Reduced Hyperphosphorylated Tau, Increased Amyloid Deposition And Altered Inflammatory Phenotype, Tiffany L. Sudduth, Joan G. Wilson, Angela Everhart, Carol A. Colton, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3β). We recently developed a mouse model that progresses from amyloid pathology to tau pathology and neurodegeneration due to the genetic deletion of NOS2 in an APP transgenic mouse; the APPSwDI/NOS2-/- mouse. Because this mouse develops tau pathology, amyloid pathology and neuronal loss we were interested in the effect anti-tau therapy would have on amyloid pathology, learning and memory. We administered lithium in the diets of APPSwDI/NOS2-/- mice for a period of eight months, followed by water maze …

Conformational Altered P53 As An Early Marker Of Oxidative Stress In Alzheimer's Disease, Laura Buizza, Giovanna Cenini, Cristina Lanni, Giulia Ferrari-Toninelli, Chiara Prandelli, Stefano Govoni, Erica Buoso, Marco Racchi, Maria Barcikowska, Maria Styczynska, Aleksandra Szybinska, D. Allan Butterfield, Maurizio Memo, Daniela Uberti

Sanders-Brown Center on Aging Faculty Publications

In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut …

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 …

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 …

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 …

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 …

Deficient Liver Biosynthesis Of Docosahexaenoic Acid Correlates With Cognitive Impairment In Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Nicole C. Berchtold, Vinh Q. Nguyen, Daniel L. Gillen, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer's disease, compared to control subjects (P = 0.007). Mini Mental State Examination (MMSE) scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P = 0.005) and mid-frontal cortex (P = 0.018), but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer's …

Omega-3 Fatty Acids: Potential Role In The Management Of Early Alzheimer's Disease, Gregory A. Jicha, William R. Markesbery

Sanders-Brown Center on Aging Faculty Publications

Omega-3 fatty acids are essential for brain growth and development. They play an important role throughout life, as critical modulators of neuronal function and regulation of oxidative stress mechanisms, in brain health and disease. Docosahexanoic acid (DHA), the major omega-3 fatty acid found in neurons, has taken on a central role as a target for therapeutic intervention in Alzheimer's disease (AD). A plethora of in vitro, animal model, and human data, gathered over the past decade, highlight the important role DHA may play in the development of a variety of neurological and psychiatric disorders, including AD. Cross sectional and prospective …

Sexuality And Persons With Down Syndrome. A Study From Brazil, Bruna Marques Bononi, Maria José Carvalho Sant'anna, André Chao Vasconcellos De Oliveira, Tadeu Silveira Renattini, Carla Franchi Pinto, Maria Lúcia Passarelli, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

In recent years, important gains and changes have been observed in the life of teenagers with Down syndrome (DS) with increased inclusion into society. This review will discuss adolescence and sexuality in teenagers with DS from a descriptive study of 50 patients with DS between the ages of 10 and 20 years. The mean age was 13.5 years, 50% females; 86% went to school with 62.2% in school for over six years. Of the patients that attended school, 60% went to special education school and only 10% read and wrote correctly. In an evaluation of autonomy, 66% took showers, 78% …

Neuropathological Findings Processed By Artificial Neural Networks (Anns) Can Perfectly Distinguish Alzheimer's Patients From Controls In The Nun Study, Enzo Grossi, Massimo P. Buscema, David Snowdon, Piero Antuono

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover …

Pregnant Teenager Involvement In Sexual Activity And The Social Context, Maria José Carvalho Sant'anna, Júlia Kerr Catunda, Kepler Alencar Mendes Carvalho, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

Pregnancy during adolescence represents a challenge to society as a whole. Its incidence is increasing and brings about social and medical consequences to both the teen mothers and their children. The purpose of this study was to evaluate pregnant teenager involvement in sexual activity and the social context. The group studied comprised 152 pregnant teenagers attending the Department of Pediatrics, Santa Casa de Sao Paulo (SCSP) General Hospital. All information was analyzed. The age at first intercourse was 14.2 years and the average period between first intercourse and pregnancy was 1.4 years. Most pregnancies (75%) were neither planned nor wanted, …

Depression, Sensation Seeking, And Maternal Smoking As Predictors Of Adolescent Cigarette Smoking, Judy Van De Venne, Kay Bradford, Catherine A. Martin, Megan Cox, Hatim A. Omar

Family Sciences Faculty Publications

The purpose of this study was to examine maternal and adolescent depression, maternal and teen sensation seeking, and maternal smoking, and their associations with adolescent smoking. Data were collected from a sample of 47 male and 66 female adolescents (ages 11-18 years) and their mothers from three different health clinics. The findings indicated that maternal sensation seeking was linked indirectly with adolescent smoking through teen sensation seeking, both of which were significantly associated with teen smoking (β = 0.29, p < 0.001 and β = 0.32, p < 0.001, respectively). Teen depression was associated positively with teen smoking (β = 0.24, p < 0.01) when controlling for sensation seeking behaviors. Maternal smoking was also directly linked to adolescent smoking (β = 0.20, p < 0.05). These findings underscore a potentially important role of sensation seeking in the origins of adolescent smoking, and clarify pathways of influence with regard to maternal attitudes and behaviors in subsequent teenage nicotine use.

Parenting Adolescents, Sandra L. D'Angelo, Hatim A. Omar

Pediatrics Faculty Publications

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included.

Intimate Partner Violence Among Men And Women In South Carolina, 1998, Ann L. Coker, Christina Derrick, Julia L. Lumpkin, Robert Oldendick, R H. Potter

CRVAW Faculty Journal Articles

Few studies provide population-based estimates of intimate partner violence (IPV) for men and women, especially at the state level. IPV may result in adverse health effects for victims and perpetrators (1-3). To estimate the lifetime incidence of IPV by type of violence (e.g., physical, sexual, and perceived emotional abuse) and to explore demographic correlates of reporting IPV among men and women, the South Carolina Department of Health and Environmental Control and the University of South Carolina conducted a population-based random-digit-dialed telephone survey of adults in the state. This report summarizes the results of the survey, which indicated that approximately 25% …