The prevalence of diabetes and its complications has increased among older adults, and new models of care are needed to combat this trend among vulnerable populations. According to the Chronic Care Model (CCM), optimal chronic illness care requires linkages with community-based resources. Research based upon the CCM suggests that self-management support for older adults with diabetes may be bolstered by linkages between primary care providers and senior centers, but studies of such linkages are rare.

TxBiomed is measuring the Cytokines in both Merocel Spear Eluates and Cervicovaginal Lavages in order to establish reasonable baselines across National Primate Centers.

Periodontal infection has been shown to increase the incidence and severity of atherosclerosis, which is now the number one cause of morbidity and mortality in the United States. Furthermore there is increasing evidence linking obesity, which is a major risk factor of atherosclerosis, to periodontal disease. In atherosclerosis, the earliest lesions contain macrophages that have phagocytized and accumulated modified lipoproteins. The continued monocyte recruitment and cholesterol accumulation in the vessel wall facilitates chronic disease progression.

Depression is a severe and common mental disorder and often coexists with metabolic disorders such as diabetes. Therefore, the identification and characterization of therapeutic targets that are potentially beneficial for the treatment of both depression and diabetes would be of great clinical significance. Adiponectin, a hormone secreted almost exclusively by white adipose tissue, is well recognized as an anti-diabetic adipokine. We have demonstrated that adiponectin insufficiency increases susceptibility to depression-like symptoms.

The ultimate goal of this Program Project is to develop novel therapeutic approaches for advanced childhood sarcoma. While over 70% of children with sarcoma are considered cured, the outcome is still poor for those with advanced or metastatic disease. Specifically, the 5-year event free survival rates are 30 percent or less in children with advanced or metastatic Ewing sarcoma, osteosarcoma or rhabdomyosarcoma and intensive chemo-radiotherapy has not significantly altered this outcome.

The long-term goal of this research project is to understand the role of scaffolding proteins in the regulation of nociceptor plasticity. Dynamic changes to proteins expressed in primary afferent terminals significantly alter pain sensation. For instance, ion channel phosphorylation can modulate channel activity, thereby affecting acute nocifensive responses to noxious stimuli. However, states of persistent pain likely rely on multiple mechanisms of dynamic protein modifications to maintain peripheral nociceptor sensitization.

The applicant's career goal is to become a physician-scientist studying translational research in age- related neurodegeneration. A comprehensive training plan with a team of mentors of diverse backgrounds will ensure the applicant's career development. The proposed studies will address the mechanism of Amyloid-beta mediated mTOR dysregulation in neurodegeneration. Alzheimer's disease (AD) is the most common cause of age-related neurodegeneration and is the sixth leading cause of death in the U.S.

Steadily decreasing rates of cardiovascular disease (CVD) in the US threaten to be reversed because of rapid increases in obesity and diabetes. The proposed study will take advantage of the Strong Heart Study data in American Indians to further our understanding of CVD and its risk factors, especially diabetes and obesity, which will lead to more effective prevention and therapy and reduce the burden of CVD morbidity and mortality.

There is a continual need to explore alternative approaches to treat cancer to improve patient outcome and reduce the dreadful side-effects of some of the therapies available. While specific bacteria have shown a natural propensity to target tumors in animal models and have been engineered for drug delivery, targeting in human trials was essentially ineffective. To date, while antibody based targeting has been employed to deliver radio- or chemo- active compounds to destroy the tumor, it has so far not been fully explored to deliver bacteria.

Methamphetamine (METH) addiction currently presents an enormous public health issue, and yet no therapeutic agent is currently approved for its treatment. Psychostimulant addiction is a chronic, progressive disease driven by numerous persistent neurophysiological adaptations. METH self-administration increases input of the neuropeptide neurotensin onto dopamine (DA) neurons in the ventral tegmental area (VTA), which are extensively implicated in drug reward processes.