Beyond the genetics of HDL:why is HDL cholesterol inversely related to cardiovascular disease?

There is unequivocal evidence that high-density lipoprotein (HDL) cholesterol levels in plasma are inversely associated with the risk of cardiovascular disease (CVD). Studies of families with inherited HDL disorders and genetic association studies in general (and patient) population samples have identified a large number of factors that control HDL cholesterol levels. However, they have not resolved why HDL cholesterol and CVD are inversely related. A growing body of evidence from nongenetic studies shows that HDL in patients at increased risk of CVD has lost its protective properties and that increasing the cholesterol content of HDL does not result in the desired effects. Hopefully, these insights can help improve strategies to successfully intervene in HDL metabolism. It is clear that there is a need to revisit the HDL hypothesis in an unbiased manner. True insights into the molecular mechanisms that regulate plasma HDL cholesterol and triglycerides or control HDL function could provide the handholds that are needed to develop treatment for, e.g., type 2 diabetes and the metabolic syndrome. Especially genome-wide association studies have provided many candidate genes for such studies. In this review we have tried to cover the main molecular studies that have been produced over the past few years. It is clear that we are only at the very start of understanding how the newly identified factors may control HDL metabolism. In addition, the most recent findings underscore the intricate relations between HDL, triglyceride, and glucose metabolism indicating that these parameters need to be studied simultaneously

Quantification of ETS exposure in hospitality workers who have never smoked

<p>Abstract</p> <p>Background</p> <p>Environmental Tobacco Smoke (ETS) was classified as human carcinogen (K1) by the German Research Council in 1998. According to epidemiological studies, the relative risk especially for lung cancer might be twice as high in persons who have never smoked but who are in the highest exposure category, for example hospitality workers. In order to implement these results in the German regulations on occupational illnesses, a valid method is needed to retrospectively assess the cumulative ETS exposure in the hospitality environment.</p> <p>Methods</p> <p>A literature-based review was carried out to locate a method that can be used for the German hospitality sector. Studies assessing ETS exposure using biological markers (for example urinary cotinine, DNA adducts) or questionnaires were excluded. Biological markers are not considered relevant as they assess exposure only over the last hours, weeks or months. Self-reported exposure based on questionnaires also does not seem adequate for medico-legal purposes. Therefore, retrospective exposure assessment should be based on mathematical models to approximate past exposure.</p> <p>Results</p> <p>For this purpose a validated model developed by Repace and Lowrey was considered appropriate. It offers the possibility of retrospectively assessing exposure with existing parameters (such as environmental dimensions, average number of smokers, ventilation characteristics and duration of exposure). The relative risk of lung cancer can then be estimated based on the individual cumulative exposure of the worker.</p> <p>Conclusion</p> <p>In conclusion, having adapted it to the German hospitality sector, an existing mathematical model appears to be capable of approximating the cumulative exposure. However, the level of uncertainty of these approximations has to be taken into account, especially for diseases with a long latency period such as lung cancer.</p

Longevity in mice: is stress resistance a common factor?

A positive relationship between stress resistance and longevity has been reported in a multitude of studies in organisms ranging from yeast to mice. Several mouse lines have been discovered or developed that exhibit extended longevities when compared with normal, wild-type mice of the same genetic background. These long-living lines include the Ames dwarf, Snell dwarf, growth hormone receptor knockout (Laron dwarf), IGF-1 receptor heterozygote, Little, α-MUPA knockout, p66shc knockout, FIRKO, mClk-1 heterozygote, thioredoxin transgenic, and most recently the Klotho transgenic mouse. These mice are described in terms of the reported extended lifespans and studies involving resistance to stress. In addition, caloric restriction (CR) and stress resistance are briefly addressed for comparison with genetically altered mice. Although many of the long-living mice have GH/IGF-1/insulin signaling-related alterations and enhanced stress resistance, there are some that exhibit life extension without an obvious link to this hormone pathway. Resistance to oxidative stress is by far the most common system studied in long-living mice, but there is evidence of enhancement of resistance in other systems as well. The differences in stress resistance between long-living mutant and normal mice result from complex interrelationships among pathways that appear to coordinate signals of growth and metabolism, and subsequently result in differences in lifespan

Anthropogenic intensification of short-duration rainfall extremes

Short- duration (1-3 h) rainfall extremes can cause serious damage to societies through rapidly developing (flash) flooding and are determined by complex, multifaceted processes that are altering as Earth's climate warms. In this Review, we examine evidence from observational, theoretical and modelling studies for the intensification of these rainfall extremes, the drivers and the impact on flash flooding. Both short- duration and long- duration (\textgreater1 day) rainfall extremes are intensifying with warming at a rate consistent with the increase in atmospheric moisture (~7% K-1), while in some regions, increases in short- duration extreme rainfall intensities are stronger than expected from moisture increases alone. These stronger local increases are related to feedbacks in convective clouds, but their exact role is uncertain because of the very small scales involved. Future extreme rainfall intensification is also modulated by changes to temperature stratification and large- scale atmospheric circulation. The latter remains a major source of uncertainty. Intensification of short- duration extremes has likely increased the incidence of flash flooding at local scales and this can further compound with an increase in storm spatial footprint to considerably increase total event rainfall. These findings call for urgent climate change adaptation measures to manage increasing flood risks