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

Toxoplasma gondii Activates Hypoxia-inducible Factor (HIF) by Stabilizing the HIF-1α Subunit via Type I Activin-like Receptor Kinase Receptor Signaling*

Toxoplasma gondii is an intracellular protozoan parasite that can cause devastating disease in fetuses and immune-compromised individuals. We previously reported that the α subunit of the host cell transcription factor, hypoxia-inducible factor-1 (HIF-1), is up-regulated by infection and necessary for Toxoplasma growth. Under basal conditions, HIF-1α is constitutively expressed but rapidly targeted for proteasomal degradation after two proline residues are hydroxylated by a family of prolyl hydroxylases (PHDs). The PHDs are α-ketoglutarate-dependent dioxygenases that have low Km values for oxygen, making them important cellular oxygen sensors. Thus, when oxygen levels decrease, HIF-1α is not hydroxylated, and HIF-1 is activated. How Toxoplasma activates HIF-1 under normoxic conditions remains unknown. Here, we report that Toxoplasma infection increases HIF-1α stability by preventing HIF-1α prolyl hydroxylation. Infection significantly decreases PHD2 abundance, which is the key prolyl hydroxylase for regulating HIF-1α. The effects of Toxoplasma on HIF-1α abundance and prolyl hydroxylase activity require activin-like receptor kinase signaling. Finally, parasite growth is severely diminished when signaling from this family of receptors is inhibited. Together, these data indicate that PHD2 is a key host cell factor for T. gondii growth and represent a novel mechanism by which a microbial pathogen subverts host cell signaling and transcription to establish its replicative niche