2 resultados para 464

em DigitalCommons@The Texas Medical Center


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The Personal Response System Program at Huffington Center on Aging, Baylor College of Medicine, provides emergency call systems for elderly people living independently in Houston, Texas. The goal of the project was to complete a formative evaluation of the Personal Response System Program. The specific aims of the evaluation were three-fold. One aim was to evaluate participant health status and level of disability. The second aim was to develop a health care cost estimation strategy. Finally, a preliminary cost-effectiveness analysis was completed to evaluate the program's impact on health care costs and health status among the elderly target population. ^ The evaluation was a longitudinal, randomized experimental design. After the screening of 120 volunteers for eligibility, clients were asked to complete a written questionnaire and a monthly health service contact diary. Volunteers were contacted by telephone interviewers to collect health status information from 100 eligible clients (83%) on three occasions during the six months of follow-up. ^ Initially, volunteers were randomized to two experimental groups. The two groups were found to be comparable at the beginning of the study. No significant differences were detected related to health status, level of disability, or history of physician visits at baseline. However, the group with the Personal Response System (PRS) device had more adverse health events, higher IADL scores, more frequent use of walkers, lower average health status scores, and fewer community volunteers hours than the usual care comparison group. ^ The health care costs were estimated based on an algorithm adapted from the American Medical Association guidelines. Average total health care costs for the group with the PRS device ($912) were greater than the usual care group ($464). However, median health care values for the PRS group ($263) were similar to the usual care comparison group ($234). The preliminary findings indicated that the use of the PRS device was not associated with health care cost savings. ^ In the preliminary cost-effectiveness analysis, use of the personal response system was found to be associated with increased mental health status among elderly clients. The cost-effectiveness evaluation indicated that the associated cost for six months was $710 per unit increase in mental component score when the $150 PRS subscription was included. However, clients with the PRS device were found to have a greater decline in physical health status during the six-month follow-up. The beneficial effect on mental health status was found to be in contrast to negative findings associated with changes in physical health status. The implications for future research relate to the need to identify risk factors among geriatric populations to better target groups that would most likely benefit from PRS Program enrollment. ^

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Normal development and tissue homeostasis requires the carefully orchestrated balance between cell proliferation and cell death. Cell cycle checkpoints control the extent of cell proliferation. Cell death is coordinated through the activation of a cell suicide pathway that results in the morphologically recognizable form of death, apoptosis. Tumorigenesis requires that the balance between these two pathways be disrupted. The tumor suppressor protein Rb has not only been shown to be involved in the enforcement of cell cycle checkpoints, but has also been implicated in playing a role in the regulation of apoptosis. The manner in which Rb enforces cell cycle checkpoints has been well studied; however, its involvement in the regulation of apoptosis is still very unclear. p84N5 is a novel nuclear death domain containing protein that has been shown to interact with the N-terminus of Rb. The fact that it contains a death domain and the fact that it is nuclear localized possibly provides the first known mechanism for apoptotic signaling from the nucleus. The following study tested the hypothesis that the novel exclusively nuclear death domain containing protein p84N5 is an important mediator of programmed cell death and that its apoptotic function is reliant upon its nuclear localization and is regulated by unique functional domains within the p84N5 protein. We identified the p84N5 nuclear localization signal (NLS), eliminated it, and tested the functional significance of nuclear localization by using wild type and mutant sequences fused to EGFP-C1 (Clontech) to create wild type GFPN5 and subsequent mutants. The results of these assays demonstrated exclusive nuclear localization of GFPN5 is required for normal p84N5 induced apoptosis. We further conducted large-scale mutagenesis of the GFPN5 construct to identify a minimal region within p84N5 capable of interacting with Rb. We were able to identify a minimal sequence containing p84N5 amino acids 318 to 464 that was capable of interacting with Rb in co-immunoprecipitation assays. We continued by conducting a structural and functional analysis to identify the region or regions within p84N5 responsible for inducing apoptosis. Point mutations and small-scale deletions within the death domain of p84N5 lessened the effect but did not eliminate p84N5-induced cytotoxicity. Further analysis revealed that the minimal sequence of 318 to 464 of p84N5 was capable of inducing apoptosis to a similar degree as wild-type GFPN5 protein. Since amino acids 318 to 464 of p84N5 are capable of inducing apoptosis and interacting with Rb, we propose possible mechanisms whereby p84N5 may function in a Rb regulated manner. These results demonstrate that p84N5 induced apoptosis is reliant upon its nuclear localization and is regulated by unique functional domains within the p84N5 protein. ^