82 resultados para vascular aging
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We examined whether self-ratings of “being active” among older people living in four different settings (major city high and lower density suburbs, a regional city, and a rural area) were associated with out-of-home participation and outdoor physical activity. A mixed-methods approach (survey, travel diary, and GPS tracking over a one-week period) was used to gather data from 48 individuals aged over 55 years. Self-ratings of “being active” were found to be positively correlated with the number of days older people spent time away from home but unrelated to time traveled by active means (walking and biking). No significant differences in active travel were found between the four study locations, despite differences in their respective built environments.The findings suggest that additional strategies to the creation of “age-friendly” environments are needed if older people are to increase their levels of outdoor physical activity. “Active aging” promotion campaigns may need to explicitly identify the benefits of walking outdoors to ambulatory older people as a means of maintaining their overall health, functional ability, and participation within society in the long-term and also encourage the development of community-based programs in order to facilitate regular walking for this group.
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Background The VEGF pathway has become an important therapeutic target in lung cancer, where VEGF has long been established as a potent pro-angiogenic growth factor expressed by many types of tumors. While Bevacizumab (Avastin) has proven successful in increasing the objective tumor response rate and in prolonging progression and overall survival in patients with NSCLC, the survival benefit is however relatively short and the majority of patients eventually relapse. The current use of tyrosine kinase inhibitors alone and in combination with chemotherapy has been underwhelming, highlighting an urgent need for new targeted therapies. In this study, we examined the mechanisms of VEGF-mediated survival in NSCLC cells and the role of the Neuropilin receptors in this process. Methods NSCLC cells were screened for expression of VEGF and its receptors. The effects of recombinant VEGF and its blockade on lung tumor cell proliferation and cell cycle were examined. Phosphorylation of Akt and Erk1/2 proteins was examined by high content analysis and confocal microscopy. The effects of silencing VEGF on cell proliferation and survival signaling were also assessed. A Neuropilin-1 stable-transfected cell line was generated. Cell growth characteristics in addition to pAkt and pErk1/2 signaling were studied in response to VEGF and its blockade. Tumor growth studies were carried out in nude mice following subcutaneous injection of NP1 over-expressing cells. Results Inhibition of the VEGF pathway with anti-VEGF and anti-VEGFR-2 antibodies or siRNA to VEGF, NP1 and NP2 resulted in growth inhibition of NP1 positive tumor cell lines associated with down-regulation of PI3K and MAPK kinase signaling. Stable transfection of NP1 negative cells with NP1 induced proliferation in vitro, which was further enhanced by exogenous VEGF. In vivo, NP1 over-expressing cells significantly increased tumor growth in xenografts compared to controls. Conclusions Our data demonstrate that VEGF is an autocrine growth factor in NSCLC signaling, at least in part, through NP1. Targeting this VEGF receptor may offer potential as a novel therapeutic approach and also support the evaluation of the role of NP1 as a biomarker predicting sensitivity or resistance to VEGF and VEGFR-targeted therapies in the clinical arena.
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In order to evaluate the capability of 1H MRS to monitor longitudinal changes in subjects with probable Alzheimer's disease (AD), the temporal stability of the metabolite measures N-acetylaspartate and N- acetylaspartylglutamate (NA), total Creatine (Cr), myo-Inositol (mI), total Choline (Chol), NA/Cr, mI/Cr, Chol/Cr and NA/mI were investigated in a cohort of normal older adults. Only the metabolite measures NA, mI, Cr, NA/Cr, mI/Cr, and NA/mI were found to be stable after a mean interval of 260 days. Relative and absolute metabolite measures from a cohort of patients with probable AD were subsequently compared with data from a sample of normal older adult control subjects, and correlated with mental status and the degree of atrophy in the localized voxel. Concentrations of NA, NA/Cr, and NA/mI were significantly reduced in the AD group with concomitant significant increases in mI and mI/Cr. There were no differences between the two groups in measures of Cr, Chol, or Chol/Cr. Significant correlations between mental status as measured by the Mini-Mental State Examination and NA/mI, mI/Cr and NA were found. These metabolite measures were also significantly correlated with the extent of atrophy (as measured by CSF and GM composition) in the spectroscopy voxel.
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We present global and regional rates of brain atrophy measured on serially acquired Tl-weighted brain MR images for a group of Alzheimer's disease (AD) patients and age-matched normal control (NC) subjects using the analysis procedure described in Part I. Three rates of brain atrophy: the rate of atrophy in the cerebrum, the rate of lateral ventricular enlargement and the rate of atrophy in the region of temporal lobes, were evaluated for 14 AD patients and 14 age-matched NC subjects. All three rates showed significant differences between the two groups. However, the greatest separation of the two groups was obtained when the regional rates were combined. This application has demonstrated that rates of brain atrophy, especially in specific regions of the brain, based on MR images can provide sensitive measures for evaluating the progression of AD. These measures will be useful for the evaluation of therapeutic effects of novel therapies for AD.
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In the prospect of limited energy resources and climate change, effects of alternative biofuels on primary emissions are being extensively studied. Our two recent studies have shown that biodiesel fuel composition has a significant impact on primary particulate matter emissions. It was also shown that particulate matter caused by biodiesels was substantially different from the emissions due to petroleum diesel. Emissions appeared to have higher oxidative potential with the increase in oxygen content and decrease of carbon chain length and unsaturation levels of fuel molecules. Overall, both studies concluded that chemical composition of biodiesel is more important than its physical properties in controlling exhaust particle emissions. This suggests that the atmospheric aging processes, including secondary organic aerosol formation, of emissions from different fuels will be different as well. In this study, measurements were conducted on a modern common-rail diesel engine. To get more information on realistic properties of tested biodiesel particulate matter once they are released into the atmosphere, particulate matter was exposed to atmospheric oxidants, ozone and ultra-violet light; and the change in their properties was monitored for different biodiesel blends. Upon the exposure to oxidative agents, the chemical composition of the exhaust changes. It triggers the cascade of photochemical reactions resulting in the partitioning of semi-volatile compounds between the gas and particulate phase. In most of the cases, aging lead to the increase in volatility and oxidative potential, and the increment of change was mainly dependent on the chemical composition of fuels as the leading cause for the amount and the type of semi-volatile compounds present in the exhaust.
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Introduction: The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptor molecules. High concentrations of three of its putative proinflammatory ligands, S100A8/A9 complex (calprotectin), S100A8, and S100A12, are found in rheumatoid arthritis (RA) serum and synovial fluid. In contrast, soluble RAGE (sRAGE) may prevent proinflammatory effects by acting as a decoy. This study evaluated the serum levels of S100A9, S100A8, S100A12 and sRAGE in RA patients, to determine their relationship to inflammation and joint and vascular damage. Methods: Serum sRAGE, S100A9, S100A8 and S100A12 levels from 138 patients with established RA and 44 healthy controls were measured by ELISA and compared by unpaired t test. In RA patients, associations with disease activity and severity variables were analyzed by simple and multiple linear regressions. Results: Serum S100A9, S100A8 and S100A12 levels were correlated in RA patients. S100A9 levels were associated with body mass index (BMI), and with serum levels of S100A8 and S100A12. S100A8 levels were associated with serum levels of S100A9, presence of anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF). S100A12 levels were associated with presence of ACPA, history of diabetes, and serum S100A9 levels. sRAGE levels were negatively associated with serum levels of C-reactive protein (CRP) and high-density lipoprotein (HDL), history of vasculitis, and the presence of the RAGE 82Ser polymorphism. Conclusions: sRAGE and S100 proteins were associated not just with RA inflammation and autoantibody production, but also with classical vascular risk factors for end-organ damage. Consistent with its role as a RAGE decoy molecule, sRAGE had the opposite effects to S100 proteins in that S100 proteins were associated with autoantibodies and vascular risk, whereas sRAGE was associated with protection against joint and vascular damage. These data suggest that RAGE activity influences co-development of joint and vascular disease in rheumatoid arthritis patients.
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Background Bloodstream infections resulting from intravascular catheters (catheter-BSI) in critical care increase patients' length of stay, morbidity and mortality, and the management of these infections and their complications has been estimated to cost the NHS annually £19.1–36.2M. Catheter-BSI are thought to be largely preventable using educational interventions, but guidance as to which types of intervention might be most clinically effective is lacking. Objective To assess the effectiveness and cost-effectiveness of educational interventions for preventing catheter-BSI in critical care units in England. Data sources Sixteen electronic bibliographic databases – including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health Literature (CINAHL), NHS Economic Evaluation Database (NHS EED), EMBASE and The Cochrane Library databases – were searched from database inception to February 2011, with searches updated in March 2012. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify any additional references. Review methods References were screened independently by two reviewers using a priori selection criteria. A descriptive map was created to summarise the characteristics of relevant studies. Further selection criteria developed in consultation with the project Advisory Group were used to prioritise a subset of studies relevant to NHS practice and policy for systematic review. A decision-analytic economic model was developed to investigate the cost-effectiveness of educational interventions for preventing catheter-BSI. Results Seventy-four studies were included in the descriptive map, of which 24 were prioritised for systematic review. Studies have predominantly been conducted in the USA, using single-cohort before-and-after study designs. Diverse types of educational intervention appear effective at reducing the incidence density of catheter-BSI (risk ratios statistically significantly < 1.0), but single lectures were not effective. The economic model showed that implementing an educational intervention in critical care units in England would be cost-effective and potentially cost-saving, with incremental cost-effectiveness ratios under worst-case sensitivity analyses of < £5000/quality-adjusted life-year. Limitations Low-quality primary studies cannot definitively prove that the planned interventions were responsible for observed changes in catheter-BSI incidence. Poor reporting gave unclear estimates of risk of bias. Some model parameters were sourced from other locations owing to a lack of UK data. Conclusions Our results suggest that it would be cost-effective and may be cost-saving for the NHS to implement educational interventions in critical care units. However, more robust primary studies are needed to exclude the possible influence of secular trends on observed reductions in catheter-BSI.
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This paper presents a literature review and indicative findings that are part of ongoing research into aging and technology. The review finds that research on older technology users has contributed valuable information on the impact of age-related changes on technology use, as well as older adults’ acceptance and adoption of contemporary technologies. However, the majority of the research has been conducted from the perspective of age-related differences in use and performance, or it is medically-focused, examining the potential of technology to improve an individual’s quality of life (QoL), for example. Research on older people and technology does not adequately address the integration of technology into the everyday lives of older people. This paper identifies that there is substantial opportunity to examine older users’ everyday information and communication technology (ICT) use, and to inform technology design beyond measures of performance, usability and adoption.
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TERMINAL EAR1-like (TEL) genes encode putative RNA-binding proteins only found in land plants. Previous studies suggested that they may regulate tissue and organ initiation in Poaceae. Two TEL genes were identified in both Populus trichocarpa and the hybrid aspen Populus tremula × P. alba, named, respectively, PoptrTEL1-2 and PtaTEL1-2. The analysis of the organisation around the PoptrTEL genes in the P. trichocarpa genome and the estimation of the synonymous substitution rate for PtaTEL1-2 genes indicate that the paralogous link between these two Populus TEL genes probably results from the Salicoid large-scale gene-duplication event. Phylogenetic analyses confirmed their orthology link with the other TEL genes. The expression pattern of both PtaTEL genes appeared to be restricted to the mother cells of the plant body: leaf founder cells, leaf primordia, axillary buds and root differentiating tissues, as well as to mother cells of vascular tissues. Most interestingly, PtaTEL1-2 transcripts were found in differentiating cells of secondary xylem and phloem, but probably not in the cambium itself. Taken together, these results indicate specific expression of the TEL genes in differentiating cells controlling tissue and organ development in Populus (and other Angiosperm species).
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Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10 -7. In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10 -11) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10 -11). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10 -7) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10 -7); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.
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Percutaneous coronary interventions have increased 50% in Australia, yet vascular and cardiac complications remain ongoing outcome issues for patients. Managing complications is confounded by reduced length of patient stay, yet is an integral component of a cardiac nurses’ scope of practice. The aim of this study was to highlight in and out of hospital vascular and cardiac complications, for twelve months post patient discharge after PCI. Prospective data was collected from the hospital angioplasty database from 1089 consecutive patients who had PCI procedures from 1 January 2005 to 31 December 2006. In hospital vascular complications were reported by 391 (35%) of the 1089 patients, following PCI. Of these, 22.4% had haemorrhage only, 7.1% haematoma only. Cardiac complications in hospital were, one death (0.09%) following PCI, three deaths (0.27%) during the same admission and no incidence of myocardial infarction or bypass surgery. Patients who had PCI in 2005 (525) were telephone followed up after discharge at one and twelve months. Surprisingly, ongoing vascular outcomes were noted, with a 2.5% incidence at one month and 4% at 12 months. Cardiac complications were also identified, 51 (9.7%) patients requiring readmission for repeat angiogram, 19 (3.6%) a repeat PCI and 7 (1.3%) patients undergoing bypass surgery. This review highlights that vascular and cardiac problems are ongoing issues for PCI patients both in and out of hospital. The results suggest that cardiac nurses focus more on improving the monitoring and discharge care of patients and families for recovery after PCI.
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Older adults report a desire to remain within the preferred environment for as long as possible. This desire is referred to as aging-in-place. Aging-in-place integrates housing and care options. Factors affecting the ability to remain within the preferred environment include current home designs, access to housing choices, social support networks, and community services, to name a few. Research supports physical and psychosocial benefits of aging-in-place for the individual. Home modifications have the potential to influence the quality of life in a number of positive directions that range from personal mobility to community engagement. Modifications range from minor to significant. Financial resources, contractor interest and expertise, consumer awareness and consumer opportunity affect the degree of change. Increasingly, construction professionals express an interest in learning more about aging-in place. Queries ranged from obtaining a greater understanding of the meaning of the concept, impact of demographic change on housing stock, and increased awareness of universal design features. This paper presents findings from a survey administered to current members of the Canadian Home Builders’ Association – Calgary Regional Office. Within this presentation, we report findings on members understanding of demographic change and the effect of this change on the current and future housing stock. We discuss perceived barriers and benefits of the development of business models to support aging-in-place. Finally, we conclude with discussion of educational support to enhance the understanding of aging-in-place.
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This project has investigated how the architecture of the blood vessels supplying nutrients to skeletal muscles is affected by muscle contusion injuries, and how it changes during healing with or without initial treatment of the injury by icing. In order to do this, we used contrast agents to visualise blood vessels in 3D with micro-computed tomography imaging. This research significantly contributes to the fields of orthopaedics, traumatology and sports medicine, as it improves our understanding of muscle contusion injuries. Furthermore, the methods developed in this thesis may help to improve the diagnosis and monitoring of these injuries.
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Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic protein suspected to be involved in the pathogenesis of endometriosis by establishing a new blood supply to the human exfoliated endometrium. Several transcription factor-binding sites are found in the VEGF 5'-untranslated region and variation within the region increases the transcriptional activity. Six previous studies which tested between one and three single nucleotide polymorphisms (SNPs) in samples comprising 105-215 cases and 100-219 controls have produced conflicting evidence for association between the SNPs in the VEGF region and endometriosis. To further investigate the reported association between VEGF variants and endometriosis, we tested the four VEGF polymorphisms (-2578 A/C, rs699947; -460 T/C, rs833061; +405 G/C, rs2010963 and +936 C/T, rs3025039) in a large Australian sample of 958 familial endometriosis cases and 959 controls. We also conducted a literature-based review of all relevant association studies of these VEGF SNPs in endometriosis and performed a meta-analysis. There was no evidence for association between endometriosis and the VEGF polymorphisms genotyped in our study. Combined association results from a meta-analysis did not provide any evidence for either genotypic or allelic association with endometriosis. Our detailed review and meta-analysis of the VEGF polymorphisms suggests that genotyping assay problems may underlie the previously reported associations between VEGF variants and endometriosis.
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It is crucial to advance understanding of the concept of successful aging at work to guide rigorous future research and effective practice. Drawing on the gerontology and life-span developmental literatures, I recently proposed a definition and theoretical framework of successful aging at work that revolve around employees increasingly deviating from average developmental trajectories across the working life span. Based on sustainability, person–job fit, and proactivity theories, Kooij suggested an alternative perspective that emphasizes the active role of employees for successful aging at work. In this article, I compare the 2 approaches and attempt a partial integration. I highlight the importance of a precise definition, comprehensive model, and critical discussion of successful aging at work. Furthermore, I suggest that person–environment fit variables other than person–job fit (e.g., person–organization fit) and adapting to person–environment misfit may also contribute to successful aging at work. Finally, I argue that proactive behaviors must have age-differential effects on work outcomes to be considered personal resources for successful aging at work.