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Objectives: Both pre-frailty and frailty are linked with impaired executive function (EF) but the mechanism underlying this relationship is not known. Williams and colleagues' model posits EF affects health outcomes via stress regulation. This model was utlized to test indicators of stress regulation as mediators of the relationship between EF and pre-frailty in older adults. Design: Cross-sectional. Setting: Academic general clinical research centers. Participants: 690 community-dwelling older adults ≥ 50 years of age. Measurements: Pre-frailty was measured using a modified form of the Fried Frailty measure. EF was assessed via telephone-based neurocognitive assessments. Indicators of stress regulation included: stress exposure (measured by perceived stress), reactivity and recovery (measured by heart rate) and restoration (measured by serum interleukin-6 and sleep quality). Results: 396 individuals were classified as non-frail, 277 as pre-frail, and 17 as frail. Pre-frail and non-frail individuals were included in data analyses. Compared to non-frail individuals, pre-frail were older and exhibited poorer EF, higher levels of stress exposure and poorer stress restoration. Poorer EF was associated with greater stress exposure, less stress reactivity, longer stress recovery and poorer stress restoration. The total effect of the relationship between EF and pre-frailty was significant with significant indirect effects supporting stress exposure and restoration as mediators of the relationship. Conclusion: Stress exposure and restoration appear to mediate the relationship between EF and pre-frailty. Longitudinal studies are needed to clarify the direction of causality and determine whether stress regulation processes are appropriate targets for interventions aiming to prevent declines in EF and the development of pre-frailty. [ABSTRACT FROM AUTHOR]

Nature exposure has been linked to a plethora of health benefits, but the mechanism for this effect is not well understood. We conducted two studies to test a new model linking the health benefits of nature exposure to reduced impulsivity in decision-making (as measured by delay discounting) via psychologically expanding space perception. In study 1 we collected a nationwide U.S. sample (n = 609) to determine whether nature exposure was predictive of health outcomes and whether impulsive decision-making mediated the effect. Results indicated that Nature Accessibility and Nature Exposure From Home significantly predicted reduced scores on the Depression, Anxiety, Stress Scales (DASS) (p < .001, p = .03, respectively) and improved general health and wellbeing (p < .001, p < .01, respectively). Nature Accessibility also predicted reduced impulsive decision-making (p < .01), and Nature Accessibility showed significant indirect effects through impulsive decision-making on both the DASS (p = .02) and general health and wellbeing (p = .04). In Study 2, a lab-based paradigm found that nature exposure expanded space perception (p < .001), and while the indirect effect of nature exposure through space perception on impulsive decision-making did not meet conventional standards of significance (p < .10), the pattern was consistent with hypotheses. This combination of ecologically-valid and experimental methods offers promising support for an impulsivity-focused model explaining the nature-health relationship., Competing Interests: The authors have declared that no competing interests exist.

Background: The BRCA1 and BRCA2 genes confer increased susceptibility to breast and ovarian cancer and to a spectrum of other cancers. There is controversy regarding the risk of colorectal cancer conferred by germline mutations in these two genes., Methods: We followed 7015 women with a BRCA mutation for new cases of colorectal cancer. Incidence rates in carriers were compared with population-specific incidence rates, and standardised incidence ratios (SIRs) were estimated. The expected numbers of cancers were computed by multiplying person-years at risk by the appropriate age-, sex- and country-specific incidence rates from the five countries., Results: Twenty-one incident colorectal cancer cases were observed among all mutation carriers, compared with 23.6 cases expected. The SIR for BRCA1 carriers was 0.92 (95% confidence interval (CI), 0.54-1.40, P=0.7) and for BRCA2 carriers was 0.82 (95% CI, 0.30-1.81, P=0.7). The SIR for colon cancer was 3.81 (95% CI 1.77-7.23) for women below the age of 50 years (both genes combined) and was 0.60 (95% CI 0.33-1.00) for women aged 50 years and above., Conclusion: The risk of colorectal cancer is increased in female carriers of BRCA1 mutations below the age of 50 years but not in women with BRCA2 mutations or in older women.

Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).