614 research outputs found

    Aging and source monitoring: Cognitive processes and neuropsychological correlates.

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    LPS- induced inflammation exacerbates phospho-tau pathology in rTg4510 mice

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    Inflammation and microglial activation are associated with Alzheimer's disease (AD) pathology. Somewhat surprisingly, injection of a prototypical inflammatory agent, lipopolysaccharide (LPS) into brains of amyloid precursor protein (APP) transgenic mice clears some of the pre-existing amyloid deposits. It is less well understood how brain inflammation modulates tau pathology in the absence of Aβ. These studies examined the role of LPS-induced inflammation on tau pathology. We used transgenic rTg4510 mice, which express the P301L mutation (4R0N TauP301L) and initiate tau pathology between 3-5 months of age. First, we found an age-dependent increase in several markers of microglial activation as these rTg4510 mice aged and tau tangles accumulated. LPS injections into the frontal cortex and hippocampus induced significant activation of CD45 and arginase 1 in rTg4510 and non-transgenic mice. In addition, activation of YM1 by LPS was exaggerated in transgenic mice relative to non-transgenic animals. Expression of Ser199/202 and phospho-tau Ser396 was increased in rTg4510 mice that received LPS compared to vehicle injections. However, the numbers of silver-positive neurons, implying presence of more pre- and mature tangles, was not significantly affected by LPS administration. These data suggest that inflammatory stimuli can facilitate tau phosphorylation. Coupled with prior results demonstrating clearance of Aβ by similar LPS injections, these results suggest that brain inflammation may have opposing effects on amyloid and tau pathology, possibly explaining the failures (to date) of anti-inflammatory therapies in AD patients

    Evidence for impaired t cell dna methylation in systemic lupus erythematosus and rheumatoid arthritis

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    Procainamide and hydralazine inhibit T cell DNA methylation and induce autoreactivity in cloned CD4+ T cells. These drugs also induce an autoimmune syndrome, suggesting a possible relationship between DNA hypomethylation, T cell autoreactivity, and certain autoimmune diseases. To test this relationship, DNA methylation was studied in T cells from patients with rheumatoid arthritis and patients with systemic lupus erythematosus, and was found to be impaired. These results support a relationship between DNA hypomethylation and some forms of autoimmune disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37783/1/1780331109_ftp.pd

    Relationship of Sedentary Behavior and Physical Activity to Incident Cardiovascular Disease Results From the Women's Health Initiative

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    ObjectivesThe aim of this study was to examine the independent and joint associations of sitting time and physical activity with risk of incident cardiovascular disease (CVD).BackgroundSedentary behavior is recognized as a distinct construct beyond lack of leisure-time physical activity, but limited data exist on the interrelationship between these 2 components of energy balance.MethodsParticipants in the prospective Women’s Health Initiative Observational Study (n = 71,018), 50 to 79 years of age and free of CVD at baseline (1993 to 1998), provided information on sedentary behavior, defined as hours of sitting/day, and usual physical activity at baseline and during follow-up through September 2010. First CVD (coronary heart disease or stroke) events were centrally adjudicated.ResultsSitting ≥10 h/day compared with ≤5 h/day was associated with increased CVD risk (hazard ratio: 1.18, 95% confidence interval: 1.09 to 1.29) in multivariable models including physical activity. Low physical activity was also associated with higher CVD risk (p for trend < 0.001). When women were cross-classified by sitting time and physical activity (p for interaction = 0.94), CVD risk was highest in inactive women (≤1.7 metabolic equivalent task-h/week) who also reported ≥10 h/day of sitting. Results were similar for coronary heart disease and stroke when examined separately. Associations between prolonged sitting and risk of CVD were stronger in overweight versus normal weight women and women 70 years of age and older compared with younger women.ConclusionsProlonged sitting time was associated with increased CVD risk, independent of leisure-time physical activity, in postmenopausal women without a history of CVD. A combination of low physical activity and prolonged sitting augments CVD risk

    Vitamin D levels and menopause-related symptoms.

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    Objective: To determine whether vitamin D levels are associated with menopause-related symptoms in older women. Methods: A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women’s Health Initiative Calcium and Vitamin D (CaD) trial of postmenopausal women aged 51-80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the CaD trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women [mean age 66.2 years (SD 6.8)] were included in these analyses. Results: There were borderline significant associations between 25(OH)D levels and total number of menopausal symptoms (p values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. There were no associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue (p’s > 0.10 for fully adjusted models). Conclusions: There was no evidence of a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women

    The impact of behavioral and mental health risk assessments on goal setting in primary care

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    Patient-centered health risk assessments (HRAs) that screen for unhealthy behaviors, prioritize concerns, and provide feedback may improve counseling, goal setting, and health. To evaluate the effectiveness of routinely administering a patient-centered HRA, My Own Health Report, for diet, exercise, smoking, alcohol, drug use, stress, depression, anxiety, and sleep, 18 primary care practices were randomized to ask patients to complete My Own Health Report (MOHR) before an office visit (intervention) or continue usual care (control). Intervention practice patients were more likely than control practice patients to be asked about each of eight risks (range of differences 5.3-15.8 %, p < 0.001), set goals for six risks (range of differences 3.8-16.6 %, p < 0.01), and improve five risks (range of differences 5.4-13.6 %, p < 0.01). Compared to controls, intervention patients felt clinicians cared more for them and showed more interest in their concerns. Patient-centered health risk assessments improve screening and goal setting.Trial RegistrationClinicaltrials.gov identifier: NCT01825746
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