Moderate agreement between self-reported stroke and hospital-recorded stroke in two cohorts of Australian women: a validation study

Background: Conflicting findings on the validity of self-reported stroke from existing studies creates uncertainty about the appropriateness of using self-reported stroke in epidemiological research. We aimed to compare self-reported stroke against hospital-recorded stroke, and investigate reasons for disagreement. Methods: We included participants from the Australian Longitudinal Study on Women's Health born in 1921-26 (n = 1556) and 1946-51 (n = 2119), who were living in New South Wales and who returned all survey questionnaires over a defined period of time. We determined agreement between self-reported and hospitalised stroke by calculating sensitivity, specificity and kappa statistics. We investigated whether characteristics including age, education, area of residence, country of birth, language spoken at home, recent mental health at survey completion and proxy completion of questionnaire were associated with disagreement, using logistic regression analysis to obtain odds ratios (ORs) with 95% confidence intervals (CIs). Results: Agreement between self-report and hospital-recorded stroke was fair in older women (kappa 0.35, 95% CI 0.25 to 0.46) and moderate in mid-aged women (0.56, 95% CI 0.37 to 0.75). There was a high proportion with unverified self-reported stroke, partly due to: reporting of transient ischaemic attacks; strokes occurring outside the period of interest; and possible reporting of stroke-like conditions. In the older cohort, a large proportion with unverified stroke had hospital records of other cerebrovascular disease. In both cohorts, higher education was associated with agreement, whereas recent poor mental health was associated with disagreement. Conclusion: Among women who returned survey questionnaires within the period of interest, validity of self-reported stroke was fair to moderate, but is probably underestimated. Agreement between self-report and hospital-recorded stroke was associated with individual characteristics. Where clinically verified stroke data are unavailable, self-report may be a reasonable alternative method of stroke ascertainment for some epidemiological studies

Is dietary zinc protective for type 2 diabetes? Results from the Australian longitudinal study on women's health

Background: Animal studies have shown that zinc intake has protective effects against type 2 diabetes, but few studies have been conducted to examine this relationship in humans. The aim of this study is to investigate if dietary zinc is associated with risk of type 2 diabetes in a longitudinal study of mid-age Australian women. Methods: Data were collected from a cohort of women aged 45-50 years at baseline, participating in the Australian Longitudinal Study on Women's Health. A validated food frequency questionnaire was used to assess dietary intake and other nutrients. Predictors of 6-year incidence of type 2 diabetes were examined using multivariable logistic regression. Results: From 8921 participants, 333 incident cases of type 2 diabetes were identified over 6 years of follow-up. After adjustment for dietary and non-dietary factors, the highest quintile dietary zinc intake had almost half the odds of developing type 2 diabetes (OR = 0.50, 95% C.I. 0.32-0.77) compared with the lowest quintile. Similar findings were observed for the zinc/iron ratio; the highest quintile had half the odds of developing type 2 diabetes (OR = 0.50, 95% C.I 0.30-0.83) after multivariable adjustment of covariates. Conclusions: Higher total dietary zinc intake and high zinc/iron ratio are associated with lower risk of type 2 diabetes in women. This finding is a positive step towards further research to determine if zinc supplementation may reduce the risk of developing type 2 diabetes. © 2013 Vashum et al.; licensee BioMed Central Ltd

Miscarriage, Preterm Delivery, and Stillbirth: Large Variations in Rates within a Cohort of Australian Women

Objectives We aimed to use simple clinical questions to group women and provide their specific rates of miscarriage, preterm delivery, and stillbirth for reference. Further, our purpose was to describe who has experienced particularly low or high rates of each event. Methods Data were collected as part of the Australian Longitudinal Study on Women's Health, a national prospective cohort. Reproductive histories were obtained from 5806 women aged 31–36 years in 2009, who had self-reported an outcome for one or more pregnancy. Age at first birth, number of live births, smoking status, fertility problems, use of in vitro fertilisation (IVF), education and physical activity were the variables that best separated women into groups for calculating the rates of miscarriage, preterm delivery, and stillbirth. Results Women reported 10,247 live births, 2544 miscarriages, 1113 preterm deliveries, and 113 stillbirths. Miscarriage was correlated with stillbirth (r = 0.09, P<0.001). The calculable rate of miscarriage ranged from 11.3 to 86.5 miscarriages per 100 live births. Women who had high rates of miscarriage typically had fewer live births, were more likely to smoke and were more likely to have tried unsuccessfully to conceive for ≥12 months. The highest proportion of live preterm delivery (32.2%) occurred in women who had one live birth, had tried unsuccessfully to conceive for ≥12 months, had used IVF, and had 12 years education or equivalent. Women aged 14–19.99 years at their first birth and reported low physical activity had 38.9 stillbirths per 1000 live births, compared to the lowest rate at 5.5 per 1000 live births. Conclusion Different groups of women experience vastly different rates of each adverse pregnancy event. We have used simple questions and established reference data that will stratify women into low- and high-rate groups, which may be useful in counselling those who have experienced miscarriage, preterm delivery, or stillbirth, plus women with fertility intent

The TSC-mTOR pathway regulates macrophage polarization

Macrophages are able to polarize to proinflammatory M1 or alternative M2 states with distinct phenotypes and physiological functions. How metabolic status regulates macrophage polarization remains not well understood, and here we examine the role of mTOR (Mechanistic Target of Rapamycin), a central metabolic pathway that couples nutrient sensing to regulation of metabolic processes. Using a mouse model in which myeloid lineage specific deletion of Tsc1 (Tsc1Δ/Δ) leads to constitutive mTOR Complex 1 (mTORC1) activation, we find that Tsc1Δ/Δ macrophages are refractory to IL-4 induced M2 polarization, but produce increased inflammatory responses to proinflammatory stimuli. Moreover, mTORC1-mediated downregulation of Akt signaling critically contributes to defective polarization. These findings highlight a key role for the mTOR pathway in regulating macrophage polarization, and suggest how nutrient sensing and metabolic status could be “hard-wired” to control of macrophage function, with broad implications for regulation of Type 2 immunity, inflammation, and allergy

Anticholinergic burden in older women: not seeing the wood for the trees?

Objectives: To identify medicines contributing to and describe predictors of anticholinergic burden among community-dwelling older Australian women. Design, setting and participants: Retrospective longitudinal analysis of data from the Australian Longitudinal Study on Women's Health linked to Pharmaceutical Benefits Scheme medicines data from 1 January 2008 to 30 December 2010; for 3694 women born in 1921–1926. Main outcome measures: Anticholinergic burden calculated from Anticholinergic Drug Scale (ADS) scores derived from ADS levels (0 to 3) for all medicines used by each woman, summed over each 6-month period (semester), medicines commonly used by women with high semester ADS scores (defined as 75th percentile of scores). Results: 1126 women (59.9%) used at least one medicine with anticholinergic properties. The median ADS score was 4 or 5 across all semesters. Most anticholinergic medicines used by women who had a high anticholinergic burden (ADS score, = 9) had a low anticholinergic potency (ADS level 1). Increasing age, cardiovascular disease, and number of other medicines used were predictive of a higher anticholinergic burden. Conclusions: A high anticholinergic medicines burden in this group was driven by the use of multiple medicines with lower anticholinergic potency rather than the use of medicines with higher potency. This is a novel and important finding for clinical practice as doctors would readily identify the risk of a high anticholinergic burden for patients using high potency medicines, but may be less likely to identify this risk for users of multiple medicines with low anticholinergic potency

mTORC1 suppresses PIM3 expression via miR-33 encoded by the SREBP loci

The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth that is often aberrantly activated in cancer. However, mTORC1 inhibitors, such as rapamycin, have limited effectiveness as single agent cancer therapies, with feedback mechanisms inherent to the signaling network thought to diminish the anti-tumor effects of mTORC1 inhibition. Here, we identify the protein kinase and proto-oncogene PIM3 as being repressed downstream of mTORC1 signaling. PIM3 expression is suppressed in cells with loss of the tuberous sclerosis complex (TSC) tumor suppressors, which exhibit growth factor-independent activation of mTORC1, and in the mouse liver upon feeding-induced activation of mTORC1. Inhibition of mTORC1 with rapamycin induces PIM3 transcript and protein levels in a variety of settings. Suppression of PIM3 involves the sterol regulatory element-binding (SREBP) transcription factors SREBP1 and 2, whose activation and mRNA expression are stimulated by mTORC1 signaling. We find that PIM3 repression is mediated by miR-33, an intronic microRNA encoded within the SREBP loci, the expression of which is decreased with rapamycin. These results demonstrate that PIM3 is induced upon mTORC1 inhibition, with potential implications for the effects of mTORC1 inhibitors in TSC, cancers, and the many other disease settings influenced by aberrant mTORC1 signaling

Which aspects of socio-economic status are related to health in mid-aged and older women?

A population-based study was conducted to validate gender- and age-specific indexes of socio-economic status (SES) and to investigate the associations between these indexes and a range of health outcomes in 2 age cohorts of women. Data from 11,637 women aged 45 to 50 and 9,510 women aged 70 to 75 were analyzed. Confirmatory factor analysis produced four domains of SES among the mid-aged cohort (employment, family unit, education, and migration) and four domains among the older cohort (family unit, income, education, and migration). Overall, the results supported the factor structures derived from another population-based study (Australian Bureau of Statistics, 1995), reinforcing the argument that SES domains differ across age groups. In general, the findings also supported the hypotheses that women with low SES would have poorer health outcomes than higher SES women, and that the magnitude of these effects would differ according to the specific SES domain and by age group, with fewer and smaller differences observed among older women. The main exception was that in the older cohort, the education domain was significantly associated with specific health conditions. Results suggest that relations between SES and health are highly complex and vary by age, SES domain, and the health outcome under study.<br /

The Impact of Education and Lifestyle Factors on Disability-Free Life Expectancy From Mid-Life to Older Age: A Multi-Cohort Study

Objectives: Low education and unhealthy lifestyle factors such as obesity, smoking, and no exercise are modifiable risk factors for disability and premature mortality. We aimed to estimate the individual and joint impact of these factors on disability-free life expectancy (DFLE) and total life expectancy (TLE). Methods: Data (n = 22,304) were from two birth cohorts (1921-26 and 1946-51) of the Australian Longitudinal Study on Women's Health and linked National Death Index between 1996 and 2016. Discrete-time multi-state Markov models were used to assess the impact on DFLE and TLE. Results: Compared to the most favourable combination of education and lifestyle factors, the least favourable combination (low education, obesity, current/past smoker, and no exercise) was associated with a loss of 5.0 years TLE, 95% confidence interval (95%CI): 3.2-6.8 and 6.4 years DFLE (95%CI: 4.8-7.8) at age 70 in the 1921-26 cohort. Corresponding losses in the 1946-51 cohort almost doubled (TLE: 11.0 years and DFLE: 13.0 years). Conclusion: Individual or co-ocurrance of lifestyle risk factors were associated with a significant loss of DFLE, with a greater loss in low-educated women and those in the 1946-51 cohort.Md. Mijanur Rahman, Carol Jagger, Lucy Leigh, Elizabeth Holliday, Emily Princehorn, Deb Loxton, Paul Kowal, John Beard, and Julie Byle

Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation