A pooled analysis of 10 case–control studies of melanoma and oral contraceptive use

Data regarding the effects of oral contraceptive use on women's risk of melanoma have been difficult to resolve. We undertook a pooled analysis of all case–control studies of melanoma in women completed as of July 1994 for which electronic data were available on oral contraceptive use along with other melanoma risk factors such as hair colour, sun sensitivity, family history of melanoma and sun exposure. Using the original data from each investigation (a total of 2391 cases and 3199 controls), we combined the study-specific odds ratios and standard errors to obtain a pooled estimate that incorporates inter-study heterogeneity. Overall, we observed no excess risk associated with oral contraceptive use for 1 year or longer compared to never use or use for less than 1 year (pooled odds ratio (pOR)=0.86; 95% CI=0.74–1.01), and there was no evidence of heterogeneity between studies. We found no relation between melanoma incidence and duration of oral contraceptive use, age began, year of use, years since first use or last use, or specifically current oral contraceptive use. In aggregate, our findings do not suggest a major role of oral contraceptive use on women's risk of melanoma

Different patterns of brisk walking are equally effective in decreasing postprandial lipaemia.

OBJECTIVE: To compare the effects of different patterns of brisk walking on day-long plasma triacylglycerol concentrations in sedentary adults. DESIGN: A three-trial, repeated measures design in which subjects were studied in the fasted state and throughout a day during which they consumed three standardized, mixed meals. On different occasions, subjects undertook no exercise (control), walked briskly for 10 min before each meal (short walks) or walked briskly for 30min before breakfast (long walk). SUBJECTS: Seven postmenopausal sedentary women and three sedentary men aged between 34 and 66y, with body mass index between 24 and 35 kg/m2. MEASUREMENTS: Plasma concentrations of triacylglycerol, non-esterified fatty acids, glucose and insulin, metabolic rate and whole-body substrate oxidation in the fasted state and at hourly intervals for 3 h after each meal. RESULTS: Postprandial plasma triacylglycerol concentrations were lower (P= 0.009) during the walking trials than during the control trial (average values: control 2.08 +/- 0.28 mmol/l; short walks 1.83 +/- 0.22mmol/l; long walk 1.84 +/- 0.22mmol/l (mean+/-s.e.) but did not differ between the two patterns of walking. The difference between control and walking trials increased as successive meals were consumed (interaction of trial x meal P= 0.03). Plasma triacylglycerol concentration increased during the 3 h after breakfast, changed little after lunch and decreased after the evening meal (interaction of meal x time P=0.001). When both walking trials were treated as one condition, walking increased postprandial fat oxidation (average values: control, 0.066 +/- 0.009 g/min;walking 0.074 +/- 0.008 g/min; P < 0.01). CONCLUSIONS: Thirty minutes of brisk walking, undertaken in one session or accumulated throughout a day, reduces postprandial plasma triacylglycerol concentrations and increases fat oxidation

Telomeres in ICF syndrome cells are vulnerable to DNA damage due to elevated DNA:RNA hybrids

DNA:RNA hybrids, nucleic acid structures with diverse physiological functions, can disrupt genome integrity when dysregulated. Human telomeres were shown to form hybrids with the lncRNA TERRA, yet the formation and distribution of these hybrids among telomeres, their regulation and their cellular effects remain elusive. Here we predict and confirm in several human cell types that DNA:RNA hybrids form at many subtelomeric and telomeric regions. We demonstrate that ICF syndrome cells, which exhibit short telomeres and elevated TERRA levels, are enriched for hybrids at telomeric regions throughout the cell cycle. Telomeric hybrids are associated with high levels of DNA damage at chromosome ends in ICF cells, which are significantly reduced with overexpression of RNase H1. Our findings suggest that abnormally high TERRA levels in ICF syndrome lead to accumulation of telomeric hybrids that, in turn, can result in telomeric dysfunction