Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors

Objective To estimate the percentage reduction in incidence of dementia that would be obtained if specific risk factors were eliminated

Metabolic Syndrome and Onset of Depressive Symptoms in the Elderly: Findings from the Three-City Study

OBJECTIVE-Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and the onset of depressive symptoms according to different age-groups in a large, general elderly population.RESEARCH DESIGN AND METHODS-This was a prospective cohort study of 4,446 men and women aged 65-91 years who were free of depression or depressive symptoms at baseline (the Three-City Study, France). MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. New onset of depressive symptoms (the Center for Epidemiologic Studies Depression Scale score >= 16 and use of antidepressant treatment) was assessed at 2- and 4-year follow-ups.RESULTS-After adjusting for a large range of potential confounders, we observed MetS to be associated with 1.73-fold (95% CI 1.02-2.95) odds for new-onset depressive symptoms in the youngest age-group (65-70 years at baseline), independently of cardiovascular diseases. No such association was seen in older age-groups.CONCLUSIONS-Our findings suggest that the link between MetS and depressive symptoms evidenced until now in middle-aged people can be extended to older adults but not to the oldest ones. Additional research is needed to examine if a better management of MetS prevents depressive symptoms in people aged 65-70 years. Diabetes Care 34:904-909, 201

Search for new resonant states in 10C and 11C and their impact on the cosmological lithium problem

The observed primordial 7Li abundance in metal-poor halo stars is found to be lower than its Big-Bang nucleosynthesis (BBN) calculated value by a factor of approximately three. Some recent works suggested the possibility that this discrepancy originates from missing resonant reactions which would destroy the 7Be, parent of 7Li. The most promising candidate resonances which were found include a possibly missed 1- or 2- narrow state around 15 MeV in the compound nucleus 10C formed by 7Be+3He and a state close to 7.8 MeV in the compound nucleus 11C formed by 7Be+4He. In this work, we studied the high excitation energy region of 10C and the low excitation energy region in 11C via the reactions 10B(3He,t)10C and 11B(3He,t)11C, respectively, at the incident energy of 35 MeV. Our results for 10C do not support 7Be+3He as a possible solution for the 7Li problem. Concerning 11C results, the data show no new resonances in the excitation energy region of interest and this excludes 7Be+4He reaction channel as an explanation for the 7Li deficit.Comment: Accepted for publication in Phys. Rev. C (Rapid Communication

Search for resonant states in 10C and 11C and their impact on the primordial 7Li abundance

The cosmological 7Li problem arises from the significant discrepancy of about a factor 3 between the predicted primordial 7Li abundance and the observed one. The main process for the production of 7Li during Big-Bang nucleosynthesis is the decay of 7Be. Many key nuclear reactions involved in the production and destruction of 7Be were investigated in attempt to explain the 7Li deficit but none of them led to successful conclusions. However, some authors suggested recently the possibility that the destruction of 7Be by 3He and 4He may reconcile the predictions and observations if missing resonant states in the compound nuclei 10C and 11C exist. Hence, a search of these missing resonant states in 10C and 11C was investigated at the Orsay Tandem-Alto facility through 10B(3He,t)10C and 11B(3He,t)11C charge-exchange reactions respectively. After a short overview of the cosmological 7Li problem from a nuclear physics point of view, a description of the Orsay experiment will be given as well as the obtained results and their impact on the 7Li problem

Study of the 26Al(n,p)26Mg and 26Al(n,α)23Na reactions using the 27Al(p,p')27Al inelastic scattering reaction

26Al was the first cosmic radioactivity ever detected in the galaxy as well as one of the first extinct radioactivity observed in refractory phases of meteorites. Its nucleosynthesis in massive stars is still uncertain mainly due to the lack of nuclear information concerning the 26Al(n,p)26Mg and 26 Al(n,α)23Na reactions. We report on a single and coincidence measurement of the 27Al(p,p')27Al(p)26Mg and 27Al(p,p')27Al(α)23Na reactions performed at the Orsay TANDEM facility aiming at the spectroscopy study of 27Al above the neutron threshold. Fourteen states are observed for the first time within 350 keV above the 26Al+n threshold

Reprogramming Primordial Germ Cells into Pluripotent Stem Cells

Background: Specification of primordial germ cells (PGCs) results in the conversion of pluripotent epiblast cells into monopotent germ cell lineage. Blimp1/Prmt5 complex plays a critical role in the specification and maintenance of the early germ cell lineage. However, PGCs can be induced to dedifferentiate back to a pluripotent state as embryonic germ (EG) cells when exposed to exogenous signaling molecules, FGF-2, LIF and SCF. Methodology and Principal Findings: Here we show that Trichostatin A (TSA), an inhibitor of histone deacetylases, is a highly potent agent that can replace FGF-2 to induce dedifferentiation of PGCs into EG cells. A key early event during dedifferentiation of PGCs in response to FGF-2 or TSA is the down-regulation of Blimp1, which reverses and apparently relieves the cell fate restriction imposed by it. Notably, the targets of Blimp1, which include c-Myc and Klf-4, which represent two of the key factors known to promote reprogramming of somatic cells to pluripotent state, are up-regulated. We also found early activation of the LIF/Stat-3 signaling pathway with the translocation of Stat-3 into the nucleus. By contrast, while Prmt5 is retained in EG cells, it translocates from the nucleus to the cytoplasm where it probably has an independent role in regulating pluripotency. Conclusions/Significance: We propose that dedifferentiation of PGCs into EG cells may provide significant mechanistic insights on early events associated with reprogramming of committed cells to a pluripotent state

Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

BackgroundCigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause.Methods and findingsA total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (ConclusionsThe probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

Background: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E e4 allele (APOE*4) carrier status were associated with decline. Methods and findings: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42, 170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval CI] -0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI -0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI -0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI -0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI 0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI 0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI -0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI -0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. Conclusions: Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data