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Dr. Dinesh K. Singh, PI, Potentiating an HIV DNA Vaccine with Flagellin at the Cervical/Vaginal Mucosa
AIDS is the number-one killer of African-American women between the ages of 25 and 34 in the United States. This group forms the fastest-growing cluster representing 67 percent of all AIDS cases in US. Currently, a vaccine for HIV/AIDS is not available. Since >90% of HIV transmission takes place at the mucosal surfaces, a vaccine that can elicit a potent mucosal immune response is the need of the hour. Currently, non-infectious DNA molecules are being tested but these molecules are weak sources of antigens and do not elicit a strong immune response at mucosal surfaces. Therefore, the goal of this project is to evaluate flagellin to potentiate a plasmid DNA that expresses env, gag and pol genes of HIV. The central hypothesis is that, since flagellin enhances both innate and adaptive immunity, it can potentiate immunogenicity of this DNA at cervix and vagina. The approach is to use this non-infectious HIV-DNA along with flagellin at cervix and vagina of B ALB/c mice. After two intra-vaginal applications of this DNA-flagellin complex within 21 days interval, both innate and adaptive immunological responses will be evaluated. The NK cell and dendritic cell activities, and vaccine stimulated cytokine production will be analyzed. In our previous studies, this plasmid DNA has been shown to be immunogenic in muscles. However, this DNA has not been tested at mucosal surfaces. The central hypothesis will be tested and the objective of the project will be accomplished by two specific aims. Aim 1 will test the hypothesis that HIV-DNA will be able to generate a strong specific immune response at the reproductive mucosa. Aim 2 will test the adjuvant effect of flagellin at reproductive mucosa. We anticipate that use of an immunogenic plasmid DNA along with a potent adjuvant will mount a strong immune response that will destroy HIV particles present in semen. Since flagellin also activates NK cells and dendritic cells non-specifically, we expect that it will help to destroy cell associated viruses in semen and therefore will assist specific immune responses to prevent virus transmission. It is our expectation that the resultant strategy may prove to be helpful in developing a prophylactic mucosal vaccine for HIV/AIDS thereby reducing chances of virus spread from infected to healthy individuals. Such outcomes will have profound and significant impact on preventing health disparities among minority individuals infected with HIV by providing affordable vaccine and reducing morbidity and mortality associated with HIV and AIDS. Collaborator: Dr. Steven B. Mizel, Wake Forest University School of Medicine
Dr. Azeez A. Aileru, PI, Modulation and Neuroplastic Behavior in Inheritance form of Hypertension
Hypertension affects over 50 million people in the United States and is disturbingly higher in African Americans than in white Americans. Evidence suggests that a genetic predisposition to hypertension may underlie this health disparity. Studies suggest that hypertensive humans and animal models of hypertension exhibit increased peripheral sympathetic nervous system activity (SNA) but the knowledge of the events that lead to elevated SNA and its significance in the genesis and maintenance of elevated blood pressure is rudimentary. Our long-range goal is to understand how alterations in SNA modulate hypertension or vice versa, the mechanism(s) behind it, and how this behavior can be modulated for preventive and therapeutic purposes. The objective is to understand the underlying causes behind the profound changes in the physiology of autonomic synaptic transmission in hypertension. We will use a multifaceted approach to study changes from the cell to the system in a genetic model of hypertension, the (mRen2) 27 transgenic rats. Based on our preliminary data, the central hypotheses is that hypertension in this model arises from altered angiontensin II (All) signaling resulting in: 1) increased sympathetic outflow from sympathetic ganglia such as the superior cervical (SCO); and/or 2) activation of sympathetic nervous system outflow from the central nervous system. Our preliminary data show dramatic changes in the electrophysiological behavior of sympathetic ganglion neurons ranging from alterations in the pattern of action potential activity recorded in postganglionic neurons to an enhanced efficacy of synaptic transmission. The rationale for the proposed research is that understanding the mechanisms responsible for alteration of synaptic plasticity in hypertension will lead to new strategies that can be used to prevent and/or treat hypertension, thereby reducing the morbidity and mortality associated with high blood pressure. We propose 4 specific aims to test our hypotheses: Aim 1 will define the efficiency of synaptic transmission in sympathetic ganglia isolated from inherent form of hypertension and investigate the mechanism of the effects of antihypertensive drugs on SNA responses in whole animals; Aim 2 will determine whether biophysical properties, ion channel populations and/or Angll signaling pathways are altered in isolated neurons of the SCG using patch clamping techniques; Aim 3 will test whether alterations in synaptic plasticity in hypertensive rats is due to alteration of presynaptic or postsynaptic mechanisms using an anitsense approach to knock out AT] receptors; and Aim 4 will test whether sympathetic responses to spinal cord stimulation are correlated to alterations in ganglionic transmission by monitoring postganglionic nerve activity and cerebral blood flow responses to electrical stimulation of lower cervical and upper thoracic intermediolateral cell columns in hypertensive rats. Taken together, this proposal will use a broad range of electrophysiological, molecular biological, biochemical and whole-animal physiological techniques to elucidate the causes underlying this genetic form of hypertension. Moreover, the proposed work is innovative because it capitalizes on the autonomic control of hypertension and will use cellular and whole-animal techniques to relate underlying cellular mechanisms to the disease at the organism level. It is our expectation that the resultant approach will lead to a better perception of how autonomic ganglia function to regulate blood pressure. More importantly, knowledge of the mechanisms that are responsible for alteration of synaptic plasticity in hypertension will be significant because this new knowledge will point out novel targets for preventive and therapeutic interventions. Collaborator: Dr. Debra I. Diz, Wake Forest University School of Medicine
Dr. Teresa L. Singleton, PI , Analysis of Intergenic Regions Selected for Insertion by the Retrotransposon, Tfl
An important step in the life cycle of retroviruses and long terminal repeat (LTR) retrotransposons is the ability to replicate a copy of the viral cDNA and insert within the host's chromatin. When accessible, retroviral elements are able to integrate within actively transcribing genes therefore attributing to the appearance of numerous diseases related to health disparities among minorities including, cancer, and AIDS. Our long-range goal is to understand the mechanisms involved during insertion of the LTRretrotransposon, Tf1-a virus with a life-cycle very similar to the human immunodeficiency virus (HIV) that causes AIDS - in Schizosaccharomyces pombe - a strain of yeast that has several biological similarities to higher-order eukaryotes. We plan to test our central hypothesis and accomplish the overall objective of this application by pursuing the following two specific aims: 1) Chromatin analysis of Tf1 transposed and nontransposed yeast cells, and 2) Identify the mechanistic basis for Tf1 target site selection. The rationale for the proposed research is that preferred regions for Tf1 insertion will make possible a clear understanding of target site selection among retroviruses, and will allow the design of additional antiviral agents that will prevent or control the process of integration. It is our expectation that findings from this study will reveal that Tf1 not only targets intergenic regions but there will be a strong correlation in localization with regulatory regions and that the frequency of Tf1 integration is related to the number of original insertion events isolated. The proposed research is significant, because the studies will generate new information concerning target site selection among retroviruses. Target site selection involved during the process of integration will likely predict areas of interception and prevention of diseases (cancer and AIDS) affecting minority health.
Dr. Stephen Aragon, PI , Provider Patient-Centeredness and Disparities Outcome Measurement Initiative
Sustaining NCMHD's mission to improve minority health and reduce disparities, this initiative represents a 5-year life-cycle of empirical research leading to program implementation, which will advance knowledge and increase the prevalence patient-centered providers caring for minority patients. SPECIFIC AIM 1 will test the fractorial and construct validity of patient-centeredness (PC) as a latent trait of healthcare providers. SPECIFIC AIM 2 will test the structural validity of PC's causal influence on minority patient satisfaction, trust, and ratings of quality. SPECIFIC AIM 3, a simulated intervention, will test the invariance of PC and its causal influence across patients, providers, and settings. SPECIFIC AIM 4, an interventional trial, will test the hypothesis that provider PC increases minority diabetic program compliance. SPECIFIC AIMs 5-6-7 will result in the development and implementation of a PC measurement scale, an immersion-based PC Certificate Program, and PC Symposiums for health providers to improve minority health. Concurrently SPECIFIC AIM 8 will enhance junior minority faculty research skills to conduct PC research to improve minority health and reduce disparities. Employing randomly selected test and cross-validation samples from national health secondary datasets, this project will employ advanced psychometric methods, including multigroup structural equation modeling and item response theory, with a clinical trial design. Experimentally designed simulations will test the measurement invariance of PC's effects across groups and against a rival model. Nonparametric bootstrap samples will be generated to further assess the precision and validity of PC and its effects across groups. Also a diabetic program compliance intervention will be tested via a randomized clinical trial. Concerning public health, DHHS published the reality of wide-spread minority health disparities years ago. Now 20 years later, the National Disparities Report states that "disparities related to race, ethnicity, and socioeconomic status STILL PERVADE the American health care system." Given this inertia, the focus of this project is to increase the availability and accessibility of patient-centered healthcare providers to improve minority health and reduce disparities. Collaborators: Dr. Timothy Carey, Cecil G. Sheps Center for Health Services Research; Dr. Lloyd Bond, The Carneige Foundation for the Advnacement of Teaching
Dr. Teresa A. Conner-Kerr, PI, Pilot Project #1, Ethnic Differences in Diabetic and Non-Diabetic Skin From Normal and Inflamed Tissue
Research has demonstrated that African Americans have a 2-fold increased risk for developing foot ulcers and lower extremity amputations as compared to their Non-Hispanic White peers. Exposure of the plantar surface (sole) of the foot to abnormally high pressure forces in the presence of peripheral neuropathy (impaired sensation) and altered biomechanics (decreased range of motion/increased tissue stiffness) is widely accepted as a precursor to diabetic pressure ulcerations in all ethnic groups. However, a number of studies have shown that African Americans exhibit lower plantar pressures than their Non-Hispanic White peers and have more motion in their lower extremity joints. Taken together, these findings point to the existence of other factors that contribute to the increased incidence of diabetic foot ulcerations in African Americans. Therefore, the primary purpose of this proposal is to determine if ethnic differences in 1.) skin structure and function or 2.) fibroblast function exist that may account for the increased incidence of diabetic ulcerations in African Americans with diabetes. The secondary purpose of this proposal is to determine if inflamed skin from African Americans with diabetes responds differently than inflamed skin of Non-Hispanic White Americans. Specific Aims: To determine if mechanical and/or cellular differences exist in the skin of the distal lower extremity between African American and Non-Hispanic White American individuals with and without noninsulin-dependent diabetes and in the presence or absence of inflammation. Collaborators: Dr. Laura E. Edsberg, Daemen College; Dr. Mona M. Baharestani, East Tennessee State University
Ms. Betty Martin-Watson, PI Pilot Project #2, Diabetic Community Based Satellite Center (DCBSC)
Diabetes is the sixth leading cause of death in the United States, and African Americans are 2-3 times more likely to develop diabetes in their lifetime than are their non-Hispanic white counterparts. Research has shown this is primarily the result of educational deficits and barriers of access to healthcare. The eastern part of Forsyth County, North Carolina, has a population of predominantly low-income African Americans that as a community has limited access to healthcare providers, little or no medical insurance, inadequate transportation, and cultural and language barriers that can further impede the provision of care. The purpose of this pilot study is to examine the relationship between increased healthcare education and improved access to healthcare providers on patient management of diabetes. A Diabetic Community-Based Satellite Center will be designed and housed in a church in the heart of a public housing community within a Medically Underserved census tract. The center will allow one-on-one interaction and emphasize instruction on basic topics such as how to select meals at restaurants, regulate caloric consumption, participate in exercise programs that focus on technique and stamina, and arrange a healthy meal in any setting. Based on the success of these basic strategies for prevention, health promotion and illness management, Diabetes Community-Based Satellite Centers will be an effective strategy in reducing health care disparities among an underserved segment of the population.
Dr. Hamdy Radwan, PI, Pilot Project #3, Increasing e-Health Literacy to Decrease Health Disparities: e-CARE Project
The project outcome is that individuals from underserved communities will learn to assume greater responsibility in preventing chronic conditions by reducing risk behaviors and increasing their participation in a healthy lifestyle. The e-CARE research project is being proposed as a campus-community partnership to enhance the access of e-health information. This project will be achieved by engaging faculty, graduate students from the School of Health Sciences and Rehabilitation Studies and community members in educating the local underserved community on how to access and utilize reliable internet resources for health care education. Participants will take part in a train-the-trainer program on accessing reliable and credible e-Health information and on how to convey this information to a community with limited computer literacy skills. To reach the target population, the investigators will utilize up to 13 Winston-Salem State University community-based computer centers described below. The long-term objectives and aims of the projects are to: 1) Train faculty and graduate students of the School of Health Sciences and Rehabilitation Studies on accessing reliable e- Health information; a) how to locate and evaluate reliable internet health care information; b) trained to effectively teach underserved community members how to access e-health information. 2) Teach community
participants how to access and utilize reliable e-health information and demonstrate an understanding of risk factors and healthy behaviors: a) approximately 100 community participants per center will be trained on the use of the e-health information, b) will demonstrate ability to access the e-health information, and c) will have increase understanding of risk health factors and increase participation in healthy behaviors. Research design: A Post-Then-Pre design study will be established to evaluate competency in evaluating and accessing reliable e-health information by faculty and students participating in the train the trainer program. Pre and post tests will be implemented to evaluate community participants in the program to determine: 1) competency in accessing reliable e-Health information, 2) increase knowledge of risk factors, and 3) implementation of healthy behaviors.
Dr. Judy L. Foxworth, PI, Pilot Project #4, Assessing Balance, Gait, and Falls in Elderly African Americans with Hypertension
Normal age related and age associated changes in the cardiovascular system are contributors to hypertensive disease in the elderly. Data from the National Center for Health Statistics (NCHS) shows that elderly African Americans demonstrate a higher occurrence of hypertension (66.9%) as compared to all adults age 65 and older (50.1%). Additionally, these changes contribute to increased fall risk among the elderly such that greater than one-third of those age 65 and older experience falls annually. Blood pressure changes associated with hypertension contribute to decreased brain and muscle tissue perfusion which, in turn, increases the risk for falls in the elderly. OBJECTIVE/PURPOSE: The primary objective of this study is to decrease the number of falls in community dwelling elderly African Americans with hypertension. Our specific aims are: 1) To evaluate balance, leg strength and gait speed of elderly African-Americans with hypertension as compared to those without hypertension: Several factors may contribute to increased fall risk in the elderly. Among these are leg strength, balance, gait, and effects of systemic hypertension, activity status, comorbidities, and others. In order to be able to identify and determine the prevalence of selected fall risk factors in hypertensive and normotensive elderly African Americans who are community dwellers, investigators will administer specific tests and measures to assess balance, postural sway, leg strength, and gait speed. 2) To determine the relationship between falls and hypertension in elderly African Americans: In African Americans, hypertension develops at an earlier age as compared to Whites. In addition, there is a higher rate of stage 3 hypertension among African Americans. These factors contribute to a higher burden of risk for a population who already suffer health disparities and often do not receive treatment until their blood pressure has been elevated for long periods of time. These changes may indicate a higher fall risk in the African American elderly population. 3) To provide pilot data for developing interventions to address fall risk factors in the target population: Use of exercise as an intervention to improve leg strength, balance, and gait has been demonstrated to decrease the negative effect of modifiable fall risk factors in the elderly. We expect to be able to use the outcome data from the selected tests and measures to provide a valid basis for developing interventions that will decrease fall risk factors in the target population. METHODOLOGY: This will be a cross sectional study assessing specific fall risk factors and their association with hypertension as predictors for falls. We will partner with local churches, community centers and senior citizen housing in order to recruit 100 participants for our study. One half of the subjects will have a diagnosis of hypertension and one half will not have a diagnosis of hypertension. The study consists of an assessment phase, including demographic and performance measures, and two follow up telephone surveys to determine post assessment frequency of falls in the target population. We will use the Tinetti Balance Subscale, a hand dynamometer, Gait Speed, and a Balance Platform as our evaluative measures. ANALYSIS: Univariate statistics will be used to describe the distribution of scores for all demographic and performance measures. We will examine relationships among balance, leg strength, and gait speed in those with and without hypertension. We will also compare the frequency of falls and examine relationships between the stated parameters for fallers and non-fallers.
Dr. Cynthia Williams Brown, PI, Pilot Project #5, Intervention Strategies for Obesity in Young Women at Risk for Type II Diabetes
Physical inactivity and poor nutrition are strongly correlated with development of obesity and subsequently Type II diabetes, hypertension, and heart disease. While these conditions are becoming widespread in Americans, they are very prevalent in African Americans and contribute to the disparities in health outcomes seen between white and African Americans. The ultimate goal of the proposed project is to reduce Type II Diabetes risk factors in African American women by implementation of a long-term intervention designed to reduce body fat, improve physical activity levels and eating habits, increase knowledge and change health behavior. The following objectives will guide program development, implementation, and evaluation: 1) increase knowledge of obesity and diabetes prevention and the control the individuals have over their own risk; 2) evaluate the short term and long-term impact of a lifestyle intervention program on percentage of body, physical activity (walking) and nutrition (fat and calorie intake), thus reducing the risk for diabetes; and 3) develop a culturally relevant model program that can be disseminated and implemented on other campuses and in communities through recreation centers and churches. The intervention project will focus on first year female African American college students, age 18-24, who will fully engage the intervention model and then be evaluated for changes in the key outcome measures: knowledge, physical activity, nutrition, diabetes risk factors, and weight at four time periods: pre-intervention, immediate-post-intervention, 3-months-postintervention, and 6-months-post-intervention. Key strategies of the intervention include the development, implementation, and assessment of a culturally sensitive, educational and age-appropriate health education curriculum focused on individual responsibility; implementation of a comprehensive screening program aimed at early identification of diabetes risk; implementation of a progressive walking program and nutrition choice program; design and implementation of healthy lifestyle; and development and testing of a model for knowledge and behavior change that can be implemented in community based settings. The proposed project is a comprehensive multidisciplinary effort that will establish partnerships between the Winston-Salem State University Department of Human Performance and Sport Sciences (HPSS), School of Health Sciences (SHS) and the Division of Institutional Planning, Assessment, and Research (IPAR). In addition, the project will collaborate with community organizations and institutional programs within the Division of Student Affairs.
Dr. Cecile Yancu, PI, Pilot Project #6, The Impact of Chronic Daily Stress on Obesity-Related Health Disparities
This study will examine the relationship between chronic daily stress and weight gain to further what is known about the etiology of the obesity epidemic and the health disparities embedded within it. The prevalence of overweight and obesity continues to increase dramatically (USPSTF, 2003) leading to an increase in morbidity and all-cause mortality (Strum & Wells, 2001). Although obesity risk factors are complex, the basic mechanics of weight control amounts to balancing calories consumed against calories burned (Nawaz & Katz, 2001). We argue that although poor eating behaviors and low exercise motivation contribute to obesity, there is no clear evidence that diet and fitness counseling alone has curtailed the problem. Moreover, African Americans are significantly more likely than other racial groups to be obese and experience weight-related health problems (MMWR, 2005; Mokdad et al., 2001). Preliminary studies demonstrate a complex relationship between stress and obesity (McEwen, 1998). Sapolsky (2005) suggests that although humans are well equipped to cope with acute stress, our bodies are poor at handling chronic daily stress. We hypothesize that chronic daily stress mediates the relationship between poor quality calorie intake and obesity. More specifically, although overweight/obese individuals self-medicate with food, drink and sedentary activities to manage chronic stress (Bossolo & Dobbins, 2006), for minorities, stressors such as racism may increase negative health behaviors and exacerbate health disparities. A total of 150 African American and Caucasian students will be recruited from WSSU (n=75) and UNC-G (n=75) as participants. Researchers will conduct interviews to gather psychosocial and perceived chronic daily stress data, measure body fat (i.e., waist-to-hip ratio), and use diaries to assess diet and exercise patterns. A 2006 WSSU alumna will collect the UNC-G data as part of her graduate studies. Potential Pitfalls and Suggested Corrective Measures: In that this is a non-random, student-based sample the generalizability of the findings may be limited. However, we intend to replicate this study in a randomized community sample. Additionally, to control for the effects of negative stress associated with group membership among Caucasians attending an HBCU, we have included a comparative sample from a PWI.
Dr. Jeffery Meixner, PI, Pilot Project #7, Molecular Epidemiology of Candida Albicans in Ethnically Diverse Groups
Candida albicans, a member of the normal flora, is the most important opportunistic fungal pathogen of humans, responsible for both superficial and systemic infections. There is high incidence of candidiasis among African Americans, diabetics, neonates, cancer patients and HIV infected people. The mortality rate approaches 50% with bloodstream and disseminated infection. Molecular epidemiologic studies have shown that C. albicans occurs within five major genetic populations that are geographically distributed (I, II, III, SA and E). Group SA is specific to South Africa, group E to Europe and groups I, II, and III are most prevalent in the USA with the exception of the southwest portion of the USA in which the group II is absent. Molecular genomic characterization provides insight into the genetic diversity of a species as well as the mechanisms underlying the acquisition of such diversity. The genetic mechanisms that underlie these microevolutions and their role in the diversification of C. albicans within ethnic populations have not been investigated. American ethnic populations, who emigrated from diverse geographic locations, have a higher incidence of diabetes, infant mortality, HIV infection and cancer death rates. Since most C. albicans infections are endogenous in origin we propose to use molecular techniques to characterize the distribution of genetic populations of C. albicans associated with ethnic diversity. The phylogenetic based populations of C. albicans will be determined by sequence analysis of the ADP-ribosylation factor, delta-9-fatty acid desaturase and alpha-tubulin genes. As a control, the ITS and D1-D2 regions of the 18s rRNA and 26s rRNA gene, respectively, will be sequenced. Invasive candidiasis is a large burden on health care expenditure in the United States, especially with regard to ethnic groups, in which the incidence of systemic disease is higher. We believe that understanding the genetic populations of this pathogen in ethnic groups will result in better surveillance, diagnosis and management strategies based upon a clearer understanding of host-pathogen interactions associated with ethnicity and yeast populations.
Dr. Fannie Gaston-Johansson, PI, Dr. Bobbie Reddick, Co-PI, Pilot Project #8, Symptom Prevention and Management in African American Women with Breast Cancer
The purpose of this pilot study is to describe the prevalence and severity of pain and other cancer-related symptoms (fatigue, nausea, depression, anxiety, and sleep disturbances), coping strategies (including religious coping) and quality of life in African American women with breast cancer during chemotherapy. Another expected outcome is the development of a core of independent researchers in the faculty of the Division of Nursing at Winston-Salem State University by increasing their knowledge of community-based research and the design, implementation and evaluation of community-based interventions. The study will use a descriptive correlational, predictive design in a convenience sample of 25 African American women with breast cancer scheduled for chemotherapy after breast cancer surgery. After obtaining informed consent, the following symptoms will be measured using the specific instruments listed: pain, Pain-O-Meter; fatigue and nausea: Quality of Life Questionnaire (QLQ-C30); depression and anxiety; Hospital Anxiety and Depression Scale; sleep disturbances; Insomnia Severity Index; coping: Coping Strategy Questionnaire (CSQ); religious coping: BriefRCOPE; and quality of life: Functional Assessment of Cancer Therapy - Breast (FACT-B) scale. Data will be collected in person or by telephone using the following schedule: 1) at baseline prior to start of chemotherapy, 2) at the midpoint of chemotherapy, and 3) after completion of chemotherapy. Statistical analyses will include descriptive statistics, ANOVA and MANOVA tests, and multiple regression analysis. Expected outcomes of the study are: a) a description of the prevalence and severity of the symptom experience in African American women during chemotherapy, b) the role of coping in managing symptom distress, and c) an identification of the symptoms that are predictors of health status. This knowledge gained from this study will help us to develop culturally appropriate interventions to prevent, manage and alleviate symptom distress in African American women undergoing chemotherapy for breast cancer.
Acknowledgment and Disclaimer
"The projects described were supported by Award Number P20MD002303 from the National Center On Minority Health And Health Disparities. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center On Minority Health And Health Disparities or the National Institutes of Health."
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