Medical Specialties Commons^™

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 …

Calpain 1 Knockdown Improves Tissue Sparing And Functional Outcomes After Spinal Cord Injury In Rats, Chen Guang Yu, Yanzhang Li, Kashif Raza, Xin Xin Yu, Sarbani Ghoshal, James W. Geddes

Spinal Cord and Brain Injury Research Center Faculty Publications

To evaluate the hypothesis that calpain 1 knockdown would reduce pathological damage and functional deficits after spinal cord injury (SCI), we developed lentiviral vectors encoding calpain 1 shRNA and eGFP as a reporter (LV-CAPN1 shRNA). The ability of LV-CAPN1 shRNA to knockdown calpain 1 was confirmed in rat NRK cells using Northern and Western blot analysis. To investigate the effects on spinal cord injury, LV-CAPN1shRNA or LV-mismatch control shRNA (LV-control shRNA) were administered by convection enhanced diffusion at spinal cord level T10 in Long-Evans female rats (200–250 g) 1 week before contusion SCI, 180 kdyn force, or sham surgery at …

The Young And Suicide, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Deficiency In P38Β Mapk Fails To Inhibit Cytokine Production Or Protect Neurons Against Inflammatory Insult In In Vitro And In Vivo Mouse Models, Bin Xing, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

The p38 MAPK pathway plays a key role in regulating the production of proinflammatory cytokines, such as TNFα and IL-1β, in peripheral inflammatory disorders. There are four major isoforms of p38 MAPK (p38α, β, δ, γ), with p38α and p38β the targets of most p38 MAPK inhibitor drugs. Our previous studies demonstrated that the p38α MAPK isoform is an important contributor to stressor-induced proinflammatory cytokine up-regulation and neurotoxicity in the brain. However, the potential role of the p38β MAPK isoform in CNS proinflammatory cytokine overproduction and neurotoxicity is poorly understood. In the current studies, we used primary microglia from wild …

Imatinib Reverses Doxorubicin Resistance By Affecting Activation Of Stat3-Dependent Nf-Κb And Hsp27/P38/Akt Pathways And By Inhibiting Abcb1, Jonathan T. Sims, Sourik S. Ganguly, Holly Bennett, J. Woodrow Friend, Jessica Tepe, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

Despite advances in cancer detection and prevention, a diagnosis of metastatic disease remains a death sentence due to the fact that many cancers are either resistant to chemotherapy (conventional or targeted) or develop resistance during treatment, and residual chemoresistant cells are highly metastatic. Metastatic cancer cells resist the effects of chemotherapeutic agents by upregulating drug transporters, which efflux the drugs, and by activating proliferation and survival signaling pathways. Previously, we found that c-Abl and Arg non-receptor tyrosine kinases are activated in breast cancer, melanoma, and glioblastoma cells, and promote cancer progression. In this report, we demonstrate that the c-Abl/Arg inhibitor, …

Carrots, Sticks And False Carrots: How High Should Weight Control Wellness Incentives Be? Findings From A Population-Level Experiment, Harald Schmidt

Frontiers in Public Health Services and Systems Research

Employers are increasingly using wellness incentives, including penalties for unhealthy behavior. Survey data suggests that people are willing to accept the principle of penalizing those perceived to take health risks, but the equally relevant question of the magnitude of acceptable penalties is unclear.

While the principle of penalizing overweight and obese people has some support, findings from a population-level experiment (n=1,000) suggest that the acceptable size of penalties is comparatively small, around $50: more than 10-fold below levels favored by advocates. Reward-based incentives are favored over penalty-based ones by a factor of 4. Of two different ways of framing penalty …

Soluble Human Epidermal Growth Factor Receptor 2 (Sher2) As A Potential Risk Assessment, Screening, And Diagnostic Biomarker Of Lung Adenocarcinoma, Abby L. Cosentino-Boehm, Jacqueline M. Lafky, Tammy M. Greenwood, Kimberly D. Kimbler, Marites C. Buenafe, Yuxia Wang, Adam J. Branscum, Ping Yang, Nita J. Maihle, Andre T. Baron

Obstetrics and Gynecology Faculty Publications

Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2) for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC) using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma …

Lifelong Bilingualism Maintains Neural Efficiency For Cognitive Control In Aging, Brian T. Gold, Chobok Kim, Nathan F. Johnson, Richard J. Kryscio, Charles D. Smith

Neuroscience Faculty Publications

Recent behavioral data have shown that lifelong bilingualism can maintain youthful cognitive control abilities in aging. Here, we provide the first direct evidence of a neural basis for the bilingual cognitive control boost in aging. Two experiments were conducted, using a perceptual task-switching paradigm, including a total of 110 participants. In Experiment 1, older adult bilinguals showed better perceptual switching performance than their monolingual peers. In Experiment 2, younger and older adult monolinguals and bilinguals completed the same perceptual task-switching experiment while functional magnetic resonance imaging (fMRI) was performed. Typical age-related performance reductions and fMRI activation increases were observed. However, …

Gleevec, An Abl Family Inhibitor, Produces A Profound Change In Cell Shape And Migration, Zaozao Chen, Elizabeth Lessey, Matthew E. Berginski, Li Cao, Jonathan Li, Xavier Trepat, Michelle Itano, Shawn M. Gomez, Maryna Kapustina, Cai Huang, Keith Burridge, George Truskey, Ken Jacobson

Markey Cancer Center Faculty Publications

The issue of how contractility and adhesion are related to cell shape and migration pattern remains largely unresolved. In this paper we report that Gleevec (Imatinib), an Abl family kinase inhibitor, produces a profound change in the shape and migration of rat bladder tumor cells (NBTII) plated on collagen-coated substrates. Cells treated with Gleevec adopt a highly spread D-shape and migrate more rapidly with greater persistence. Accompanying this more spread state is an increase in integrin-mediated adhesion coupled with increases in the size and number of discrete adhesions. In addition, both total internal reflection fluorescence microscopy (TIRFM) and interference reflection …

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 …

A Feasibility Study Using Tomodirect For Craniospinal Irradiation, Ulrich W. Langner, Janelle A. Molloy, John F. Gleason Jr., Jonathan M. Feddock

Radiation Medicine Faculty Publications

The feasibility of delivering craniospinal irradiation (CSI) with TomoDirect is investigated. A method is proposed to generate TomoDirect plans using standard three-dimensional (3D) beam arrangements on Tomotherapy with junctioning of these fields to minimize hot or cold spots at the cranial/spinal junction. These plans are evaluated and compared to a helical Tomotherapy and a three-dimensional conformal therapy (3D CRT) plan delivered on a conventional linear accelerator (linac) for CSI. The comparison shows that a TomoDirect plan with an overlap between the cranial and spinal fields might be preferable over Tomotherapy plans because of decreased low dose to large volumes of …

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.

Chiral Polarization Scale Of Qcd Vacuum And Spontaneous Chiral Symmetry Breaking, Andrei Alexandru, Ivan Horváth

Anesthesiology Faculty Publications

It has recently been found that dynamics of pure glue QCD supports the low energy band of Dirac modes with local chiral properties qualitatively different from that of a bulk: while bulk modes suppress chirality relative to statistical independence between left and right, the band modes enhance it. The width of such chirally polarized zone – chiral polarization scale Λch – has been shown to be finite in the continuum limit at fixed physical volume. Here we present evidence that Λch remains non–zero also in the infinite volume, and is therefore a dynamical scale in the theory. Our experiments in …

An Exploratory Study Of User-Centered Indexing Of Published Biomedical Images, Sujin Kim

Pathology and Laboratory Medicine Faculty Publications

User-centered image indexing—often reported in research on collaborative tagging, social classification, folksonomy, or personal tagging—has received a considerable amount of attention [1-7]. The general themes in more recent studies on this topic include user-centered tagging behavior by types of images, pros and cons of user-created tags as compared to controlled index terms; assessment of the value added by user-generated tags, and comparison of automatic indexing versus human indexing in the context of web digital image collections such as Flickr. For instance, Golbeck's finding restates the importance of indexer experience, order, and type of images [8]. Rorissa has found a significant …

Peripheral T-Cell Lymphoma With Aberrant Expression Of Cd19, Cd20, And Cd79a: Case Report And Literature Review, Rahul G. Matnani, Rachel L. Stewart, Joseph Pulliam, Chester D. Jennings, Melissa Kesler

Pathology and Laboratory Medicine Faculty Publications

A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a), which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV) or Human Herpes Virus 8 (HHV-8). At the time …

A New Millennium: A New Age Of Behavioral Disorders?, Artemis Tsitsika, Mari Janikian, Donald E. Greydanus, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

The internet has become one of the most widely accessible media and is a significant part of everyday life in adolescence, offering opportunities for social networking and communication, education and entertainment. However, over the past decade a specific behavioral pattern has been researched in respect to Internet use, leading to isolation and neglect of everyday activities, social life –even personal health in general. The phenomenon has received increasing attention from the scientific community, describing it in various terms such as “excessive”, “problematic”, “pathological”, “addictive” use among others.

European research on Internet addictive behavior have been conducted in the past years …

Redox-Regulated Relb-Ar Axis Mediates Prostate Specific Antigen Expression: Insight In Prostate Cancer Response To Radiation Therapy, Lu Miao

Theses and Dissertations--Toxicology and Cancer Biology

Although the prostate specific antigen (PSA) test is widely used in clinical settings for prostate cancer (PCa) diagnosis and post-treatment follow-up monitoring, false positive PSA test results, which contribute to over-diagnosis of PCa, and false negative results, which miss some patients with aggressive PCa, remain problems of clinical importance.

Our study demonstrates that radiation therapy, which is widely used for treatment of localized PCa, generates TNF-α in tumor cells and stromal fibroblasts, redox dependently. Interestingly, TNF-α rapidly and transiently triggers the RelA-mediated NF-κB canonical pathway, but its effect on RelB expression is more robust and long lasting, which leads to …

The Impairment Of Macrophage-To-Feces Reverse Cholesterol Transport During Inflammation Does Not Depend On Serum Amyloid A, Maria C. De Beer, Joanne M. Wroblewski, Victoria P. Noffsinger, Ailing Ji, Jason M. Meyer, Deneys R. Van Der Westhuyzen, Frederick C. De Beer, Nancy R. Webb

Saha Cardiovascular Research Center Faculty Publications

Studies suggest that inflammation impairs reverse cholesterol transport (RCT). We investigated whether serum amyloid A (SAA) contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT) mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO) were injected intraperitoneally with ³H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. ³H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of ^{3 …}

United States: Mental Health Issues In An Adolescent Medicine Clinic Patient Population, Abdel Salous, Linah Al-Alem, Hatim A. Omar

Pharmacology and Nutritional Sciences Faculty Publications

The correlation between exposure to forms of violence and development of mental disorders in victims is well established. The purpose of this chapter was to identify mental health problems in an adolescent medicine clinic population in Lexington, Kentucky and to investigate potential correlation of mental disorders with psychosocial factors. Data were gathered from the charts of 169 adolescent clinic patients (age 10-22) seen in the clinic for mental health care and analyzed using Excel. Of the patient population, 68% were urban, whereas 32% were rural. In terms of gender, 40% of the patients were male and 60% were female, 80% …

Internet Addiction, Media Use, And Difficulties Associated With Sleeping In Adolescents, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

The objective of this review article is to summarize the current literature regarding Internet addiction; media use, and sleep disruption in adolescents. Design: Systematic review of current literature. Methods: The data was obtained through literature review of articles published in the last 10 years. Conclusion: Internet addiction and media use have the power to have great influence over the sleep of children and adolescents and it is important to take advantage of the positive effects of media while minimizing the potentially negative, but severe, consequence of sleep disruption.

Cyberbullying: A Brief Review, Amy L. Burnett, John A. Yozwiak, Hatim A. Omar

Pediatrics Faculty Publications

The objective of this review is to summarize the prevalence of Internet use among the adolescent population and the growing threat of cyberbullying. This manuscript also addresses the difference between cyberbullying and traditional bullying and the negative psychological effects that result from cyberbullying. Important intervention and prevention strategies for parents and school officials are noted as well.

Military Tobacco Dependence Treatment: Implications Of Treatment Type On Abstinence And Weight Management Ability, Bradley A. Briscoe

DNP Projects

Military readiness, employer productivity and individual health are all significantly impacted by high rates of tobacco use. Current research, to date, suggests that use of brief, individually tailored behavioral modification strategies through group therapy may be most effective in smoking cessation. The objective of this Practice Inquiry Project was to explore aspects of tobacco use the U.S. military population and examine potential relationships between type of treatment, smoking abstinence, and maintenance of body weight (e.g. avoid weight gain) among those seeking tobacco use cessation. The findings of this project can provide guidance on enhancing current tobacco cessation efforts to enable …

Doxorubicin-Induced, Tnf-Α-Mediated Brain Oxidative Stress, Neurochemical Alterations, And Cognitive Decline: Insights Into Mechanisms Of Chemotherapy Induced Cognitive Impairment And Its Prevention, Jeriel T. Keeney

Theses and Dissertations--Chemistry

The works presented in this dissertation provide insights into the mechanisms of chemotherapy-induced cognitive impairment (CICI or “ChemoBrain”) and take steps toward outlining a preventive strategy. CICI is now widely recognized as a complication of cancer chemotherapy experienced by a large percentage of cancer survivors. Approximately fifty percent of existing FDA-approved anti-cancer drugs generate reactive oxygen species (ROS). Doxorubicin (Dox), a prototypical ROS-generating chemotherapeutic agent, produces the reactive superoxide radical anion (O₂^-•) in vivo. Dox treatment results in oxidation of plasma proteins, including ApoA-I, leading to TNF-α-mediated oxidative stress in plasma and brain. TNF-α elevation in brain …

The Role Of Bridging Therapy In Hepatocellular Carcinoma, Roberto Galuppo, Angie Mccall, Roberto Gedaly

Surgery Faculty Publications

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver accounting for 7% of all cancers worldwide. Most cases of HCC develop within an established background of chronic liver disease. For that reason, liver resection is only possible in selected patients. Liver transplantation has become the treatment of choice in patients with HCC, end-stage liver disease, and significant portal hypertension. Shortage of organ donors has resulted in overall increase of waiting list time with increased risk of dropout due to tumor progression. Neoadjuvant therapies have emerged as an alternative to control tumor growth in patients while waiting. The …

Evaluation Of Echo Ps Positioning System In A Porcine Model Of Simulated Laparoscopic Ventral Hernia Repair, Erin M. Hanna, Guy R. Voeller, J. Scott Roth, Jeffrey R. Scott, Darcy H. Gagne, David A. Iannitti

Surgery Faculty Publications

Purpose. Operative efficiency improvements for laparoscopic ventral hernia repair (LVHR) have focused on reducing operative time while maintaining overall repair efficacy. Our objective was to evaluate procedure time and positioning accuracy of an inflatable mesh positioning device (Echo PS Positioning System), as compared to a standard transfascial suture technique, using a porcine model of simulated LVHR. Methods. The study population consisted of seventeen general surgeons (n = 17) that performed simulated LVHR on seventeen (n = 17) female Yorkshire pigs using two implantation techniques: (1) Ventralight ST Mesh + Echo PS Positioning System (Echo PS) and …

A 22-Year-Old Female With Invasive Epithelioid Angiomyolipoma And Tumor Thrombus Into The Inferior Vena Cava: Case Report And Literature Review, Campbell Grant, John M. Lacy, Stephen E Strup

Surgery Faculty Publications

A 22-year-old female presented with back pain and was discovered to have a right-sided abdominal mass. Computed tomography (CT) scan revealed a 9 cm enhancing right upper pole renal mass with suspicion for tumor thrombus into the right renal vein and possibly the inferior vena cava (IVC). Magnetic resonance imaging (MRI) confirmed tumor thrombus into the inferior vena cava approximately 3 cm below the hepatic venous confluence. Open right radical nephrectomy with inferior vena cava thrombectomy was performed with removal of right kidney and tumor thrombus en bloc. Pathology revealed malignant epithelioid angiomyolipoma (EAML or PEComa). Epithelioid angiomyolipoma is a …

The Health Consequences And Healthcare-Seeking Strategies For South American Immigrant Careworkers In Genoa, Italy, Patti A. Meyer

Theses and Dissertations--Anthropology

This research on healthcare strategies of home-based, low-wage, immigrant careworkers contributes to the ways medical anthropology, migration studies and social science understand human-economy-family care relationships and health and carework as commodities in today's global economy. It reveals the consequences for workers as they defray the costs of care for the Italian government and contribute to their home economies. This research was conducted in Genoa, Italy, which has the largest percentage of people over the age of 70 in any city of its size in the world and a tradition of sending and receiving immigrant workers. The main question was: Under …

Successfully Climbing The "Stairs": Surmounting Failed Translation Of Experimental Ischemic Stroke Treatments, Michael Kahle, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

The Stroke Therapy Academic Industry Roundtable (STAIR) provided initial (in 1999) and updated (in 2009) recommendations with the goal of improving preclinical stroke therapy assessment and to increase the translational potential of experimental stroke treatments. It is important for preclinical stroke researchers to frequently consider and revisit these concepts, especially since promising experimental stroke treatments continue to fail in human clinical trials. Therefore, this paper will focus on considerations for several key aspects of preclinical stroke studies including the selection and execution of the animal stroke model, drug/experimental treatment administration, and outcome measures to improve experimental validity and translation potential. …

Global Profiling Of Alternative Splicing Events And Gene Expression Regulated By Hnrnph/F, Erming Wang, Vahid Aslanzadeh, Filomena Papa, Haiyan Zhu, Pierre De La Grange, Franca Cambi

Neurology Faculty Publications

In this study, we have investigated the global impact of heterogeneous nuclear Ribonuclear Protein (hnRNP) H/F-mediated regulation of splicing events and gene expression in oligodendrocytes. We have performed a genome-wide transcriptomic analysis at the gene and exon levels in Oli-neu cells treated with siRNA that targets hnRNPH/F compared to untreated cells using Affymetrix Exon Array. Gene expression levels and regulated exons were identified with the GenoSplice EASANA algorithm. Bioinformatics analyses were performed to determine the structural properties of G tracts that correlate with the function of hnRNPH/F as enhancers vs. repressors of exon inclusion. Different types of alternatively spliced events …

Effects Of Exercise On Ampk Signaling And Downstream Components To Pi3k In Rat With Type 2 Diabetes, Shicheng Cao, Bowen Li, Xuejie Yi, Bo Chang, Beibei Zhu, Zhenzhen Lian, Zhaoran Zhang, Gang Zhao, Huili Liu, He Zhang

Barnstable Brown Diabetes Center Faculty Publications

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague-Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and …