Is outdoor recreational activity an independent predictor of cardiovascular disease mortality - NHANES III?

BACKGROUND AND AIMS: To investigate if frequency of outdoor recreational activity (ORA) predicts cardiovascular disease (CVD) mortality, independent of serum 25(OH)D concentration. METHODS AND RESULTS: Baseline data on ORA and serum 25(OH)D, collected from 11,746 participants aged 30-90 years in the Third National Health and Nutrition Examination Survey during 1988-1994, were linked to the National Death Index for assessment of CVD deaths from baseline through December 2006. CVD mortality as a primary cause of death was assessed during a mean follow up of 12.9 (SD, 4.2) years. There were 1519 CVD deaths during follow up. A strong positive association was observed between frequency of ORA in the last month and serum 25(OH)D (p < 0.001). Compared to participants who did no ORA in the last month, the hazard ratio (HR) of CVD mortality was 0.72 (95% confidence interval 0.58-0.90) for those doing ORA 1-4 times, 0.64 (0.47-0.89) for 5-12 times, 0.70 (0.56-0.89) for 13-30 times and 0.63 (0.47-0.84) for ≥30 times (p-trend < 0.001), in a Cox proportional hazards regression model which included 25(OH)D and CVD risk factors. Serum 25(OH)D was inversely associated with CVD mortality (p-trend, 0.01) in this same model. CONCLUSIONS: An inverse association between ORA and CVD mortality was observed independent of 25(OH)D. The underlying mechanism for this association may not involve 25(OH)D hence, further studies are warranted to confirm and investigate the underlying mechanism.

Associations of progesterone receptor polymorphisms with age at menarche and menstrual cycle length.

BACKGROUND: Age at menarche and menstrual cycle characteristics are indicators of endocrine function and may be risk factors for diseases such as reproductive cancers. The progesterone receptor gene (PGR) has been identified as a candidate gene for age at menarche and menstrual function. METHODS: Women office workers ages 19-41 self-reported age at menarche and participated in a prospective study of menstrual function and fertility. First-morning urine was used as the DNA source. 444 women were genotyped for a functional variant in PGR, rs1042838 (Val660Leu), and 264 women were also genotyped for 29 other SNPs across the extended gene region. RESULTS: Genetic variation across PGR was associated with age at menarche using a global score statistic (p = 0.03 among non-Hispanic whites). Women carrying two copies of the Val660Leu variant experienced menarche 1 year later than women carrying one or no copies of the variant (13.6 ± 0.5 vs. 12.6 ± 0.1; p = 0.03). The Val660Leu variant was also associated with decreased odds of short menstrual cycles (17-24 days) (OR, 95% CI: 0.54 [0.36, 0.80]; p = 0.002). CONCLUSION: Genetic variation in PGR was associated with age at menarche and menstrual cycle length in this population. Further investigation of these associations in a replication dataset is warranted.

Examination of reproductive aging milestones among women who carry the FMR1 premutation.

BACKGROUND: The fragile X premutation is characterized by a large CGG repeat track (55-199 repeats) in the 5' UTR of the FMR1 gene. This X-linked mutation leads to an increased risk for premature ovarian failure; interestingly, the association of repeat size with risk is non-linear. We hypothesize that the premutation-associated ovarian insufficiency is due to a diminished oocyte pool and examined reproductive aging milestones by repeat size group to determine if the same non-linear association is observed. METHODS: We analyzed cross-sectional reproductive history questionnaire data from 948 women with a wide range of repeat sizes. RESULTS: We have confirmed the non-linear relationship among premutation carriers for ovarian insufficiency. The mid-range repeat size group (80-100 repeats), not the highest group, had an increased risk for: altered cycle traits (shortened cycle length, irregular cycles and skipped cycles), subfertility and dizygotic twinning. Smoking, a modifiable risk, decreased the reproductive lifespan of women with the premutation by about 1 year, similar to its effect on non-carriers. As expected, premutation carriers were found to be at an increased risk for osteoporosis. CONCLUSIONS: Possible molecular mechanisms to explain the non-linear repeat size risk for ovarian insufficiency are discussed.

Effects of PEGylation on the preservation of cationic lipid/DNA complexes during freeze-thawing and lyophilization.

The incorporation of components with covalently attached polyethylene glycol (PEG) into nonviral vectors has been shown to prevent aggregation in serum and extend the circulating half-life of lipid/DNA complexes (lipoplexes) in vivo. The tendency of synthetic vectors to aggregate during processing and storage also represents a significant obstacle in the development of lipoplexes as marketable pharmaceutical products. The extreme instability of lipoplexes formulated as aqueous suspensions has generated interest in preserving nonviral vectors as frozen or lyophilized formulations. Previous work has demonstrated that stabilizing excipients are capable of protecting lipoplexes during freezing and lyophilization, but there is little known about the ability of PEGylation to protect vectors during these stresses. This study incorporates up to 10% by weight dioleoyl phosphatidylethanolamine conjugated to PEG-2000 and PEG-5000 into lipoplexes and assesses the maintenance of particle size and transfection after agitation, freeze-thawing, and lyophilization. Our results indicate that the incorporation of PEGylated components alone (up to 10% by weight) is insufficient to preserve particle size during these stresses. However, when sucrose was employed in combination with PEGylated components, a small protective effect of PEGylation was observed.

Environmental impacts of the foot and mouth disease outbreak in Great Britain in 2001: the use of risk analysis to manage the risks in the countryside.

Restrictions imposed for more than ten months throughout Great Britain in 2001 to control and eradicate foot and mouth disease (FMD) had a damaging effect on tourism and rural businesses. Risk assessment can play a valuable role in ensuring that the action taken is proportionate to the risk, and that countryside activities are allowed to resume when this can be done without compromising the objective of controlling and eradicating the disease. A risk assessment unit was established at the commencement of the epidemic to consider the risks posed by particular activities, to identify ways of managing those risks, and to make recommendations which could be used by policy makers when deciding what action to take. The assessments produced by the unit were published and the scientific rationale which supported policy and procedural changes was thereby exposed to public scrutiny and criticism. The author lists the activities subjected to veterinary risk assessments and describes how the process was used to consider public access to the countryside, leading to policy changes which within nine months resulted in the reopening of more than 96% of footpaths and bridleways without causing new outbreaks of FMD. A completed risk assessment is also included.

4-nitroimidazole binding to horse metmyoglobin: evidence for preferential anion binding.

The ionization of 4-nitroimidazole to 4-nitroimidazolate was investigated as a function of ionic strength. The apparent pKa varies from 8.99 to 9.50 between 0.001 and 1.0 M ionic strength, respectively, at 25 degrees C. The ionic strength dependence of this ionization is anomalous. The binding of 4-nitroimidazole by horse metmyoglobin was studied between pH 5.0 and 11.5 and as a function of ionic strength between 0.01 and 1.0 M. The association rate constant is pH-dependent, varying from 24 M(-1)s(-1) at pH 5 to a maximum value of 280 M(-1)s(-1) at pH 9.5 and then decreasing to 10 M(-1)s(-1) at pH 11.5 in 0.1 M ionic strength buffers. The dissociation rate constant has a much smaller pH dependence, varying from 0.082 s(-1) at low pH to 0.035 s(-1) at high pH, with an apparent pKa of 6.5. The binding affinity of 4-nitroimidazole to horse metmyoglobin is about 2.5 orders of magnitude stronger than that for imidazole and this increased affinity is attributed to the much slower dissociation rate for 4-nitroimidazole compared to that of imidazole. Although the ionic strength dependence of the binding rate is small and secondary kinetic salt effects can account for the ionic strength dependence of the association rate constant, the pH dependence of the rate constants and microscopic reversibility arguments indicate that the anionic form of the ligand binds more rapidly to all forms of metmyoglobin than does the neutral form of the ligand. However, the spectrum of the complex is similar to model complexes involving neutral imidazole and not imidazolate. The latter observation suggests that the initial metmyoglobin/4-nitroimidazolate complex rapidly binds a proton and the neutral form of the bound ligand is stabilized, probably through hydrogen binding with the distal histidine.

Purification of a Zn-binding phloem protein with sequence identity to chitin-binding proteins.

In citrus blight, a decline disorder of unknown etiology, the tree canopy exhibits symptoms of Zn deficiency while Zn accumulates in the trunk phloem. We have purified a Zn-binding protein (ZBP) from phloem tissue of healthy and blight-affected citrus (Citrus sinensis [L.] Osbeck on Citrus jambhiri [L.]). The molecular weight of the ZBP was estimated to be 5000 by size-exclusion chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Ion-exchange chromatography at pH 8.0 demonstrated the 5-kD ZBP to be anionic. A partial N-terminal amino acid sequence revealed a cysteine-, glycine-rich domain with 45 to 80% identity with the chitin-binding domain of hevein, wheat germ agglutinin, and several class I chitinases. That the abundance of this protein increased 2.5-fold in association with Zn accumulation in the phloem is characteristic of citrus blight. Tissue mass changes of the phloem suggests that altered tissue structure accompanies blight. Phloem accumulation of the 5-kD ZBP may be in response to wounding or other stress of blight-affected citrus.

The Accumulation Record from the GISP2 Core as an Indicator of Climate Change Throughout the Holocene.

A depth-age scale and an accumulation history for the Holocene have been established on the Greenland Ice Sheet Project 2 (GISP2) deep core, providing the most continuously dated record of annual layer accumulation currently available. The depth-age scale was obtained with the use of various independent techniques to count annual layers in the core. An annual record of surface accumulation during the Holocene was obtained by correcting the observed layer thicknesses for flow-thinning. Fluctuations in accumulation provide a continuous and detailed record of climate variability over central Greenland during the Holocene. Climate events, including "Little Ice Age" type events, are examined.

Changes in Atmospheric Circulation and Ocean Ice Cover over the North Atlantic During the Last 41,000 Years.

High-resolution, continuous multivariate chemical records from a central Greenland ice core provide a sensitive measure of climate change and chemical composition of the atmosphere over the last 41,000 years. These chemical series reveal a record of change in the relative size and intensity of the circulation system that transported air masses to Greenland [defined here as the polar circulation index (PCI)] and in the extent of ocean ice cover. Massive iceberg discharge events previously defined from the marine record are correlated with notable expansions of ocean ice cover and increases in PCI. During stadials without discharge events, ocean ice cover appears to reach some common maximum level. The massive aerosol loadings and dramatic variations in ocean ice cover documented in ice cores should be included in climate modeling.