ning 11 and The Weldox GroupWe investigated airborne and internal exposure to manganese (Mn) and iron (Fe) among welders. Personal sampling of welding fumes was carried out in 241 welders during a shift. Metals were determined by inductively coupled plasma mass spectrometry. Mn in blood (MnB) was analyzed by graphite furnace atom absorption spectrometry. Determinants of exposure levels were estimated with multiple regression models. Respirable Mn was measured with a median of 62 (inter-quartile range (IQR) 8.4 --320) mg/m 3 and correlated with Fe (r ¼ 0.92, 95% CI 0.90 --0.94). Inhalable Mn was measured with similar concentrations (IQR 10 --340 mg/m 3 ). About 70% of the variance of Mn and Fe could be explained, mainly by the welding process. Ventilation decreased exposure to Fe and Mn significantly. Median concentrations of MnB and serum ferritin (SF) were 10.30 mg/l (IQR 8.33 --13.15 mg/l) and 131 mg/l (IQR 76 --240 mg/l), respectively. Few welders were presented with low iron stores, and MnB and SF were not correlated (r ¼ 0.07, 95% CI À0.05 to 0.20). Regression models revealed a significant association of the parent metal with MnB and SF, but a low fraction of variance was explained by exposure-related factors. Mn is mainly respirable in welding fumes. Airborne Mn and Fe influenced MnB and SF, respectively, in welders. This indicates an effect on the biological regulation of both metals. Mn and Fe were strongly correlated, whereas MnB and SF were not, likely due to higher iron stores among welders.

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The current gold standard for the diagnosis of bladder cancer is cystoscopy, which is invasive and painful for patients. Therefore, noninvasive urine cytology is usually used in the clinic as an adjunct to cystoscopy; however, it suffers from low sensitivity. Here, a novel noninvasive, label-free approach with high sensitivity for use with urine is presented. Coherent anti-Stokes Raman scattering imaging of urine sediments was used in the first step for fast preselection of urothelial cells, where high-grade urothelial cancer cells are characterized by a large nucleus-to-cytoplasm ratio. In the second step, Raman spectral imaging of urothelial cells was performed. A supervised classifier was implemented to automatically differentiate normal and cancerous urothelial cells with 100% accuracy. In addition, the Raman spectra not only indicated the morphological changes that are identified by cytology with hematoxylin and eosin staining but also provided molecular resolution through the use of specific marker bands. The respective Raman marker bands directly show a decrease in the level of glycogen and an increase in the levels of fatty acids in cancer cells as compared to controls. These results pave the way for "spectral" cytology of urine using Raman microspectroscopy.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in our environment and can cause cancer. Exposure to PAHs can be assessed by protein adduct dosimetry using benzo[a]pyrene (B[a]P) as a model compound. We present an overview of analytical methods to detect B[a]P- derived protein adducts in humans, their uses in exposure assessment, and recommendations for future research. Two major methodologies, enzyme-linked immunosorbent assay (ELISA) and chemical-specific assays, could be traced in the literature but there remains limitations with both assays. ELISA is nonspecific due to cross-reactivity of the antibody with other PAHs and results are better interpreted in terms of PAH exposure. ELISA is unable to distinguish between exposed and nonexposed persons in the majority of studies. Adduct concentrations are higher by several orders of magnitude compared to those determined by chemical-specific methods. The latter methods mostly analyzed protein adducts derived by (+)-anti-B[a]P-diol epoxide. For this purpose, gas or liquid chromatography in combination with mass spectrometry or fluorescence detection were used. However, the prevalence of positive samples remained low when chemical- specific assays were used mainly due to the lack of sensitivity. Overall, data on B[a]P-derived protein adducts in humans remain inconclusive. Future research should focus on the development and standardization of a sensitive and specific method for B[a]P-derived protein adducts prior to its use in field studies. Finally, exposures of B[a]P at the workplace and via diet, a major route of exposure of the general population, can be studied. The results will contribute to the understanding of B[a]P-induced cancer and will allow for health preventive measures.

Urothelial cancer (UCa) is the most predominant cancer of the urinary tract and noninvasive diagnosis using hypermethylation signatures in urinary cells is promising. Here, we assess gender differences in a newly identified set of methylation biomarkers. UCa‐associated hypermethylated sites were identified in urine of a male screening cohort (n = 24) applying Infinium‐450K‐methylation arrays and verified in two separate mixed‐gender study groups (n = 617 in total) using mass spectrometry as an independent technique. Additionally, tissue samples (n = 56) of mixed‐gender UCa and urological controls (UCt) were analyzed. The hypermethylation signature of UCa in urine was specific and sensitive across all stages and grades of UCa and independent on hematuria. Individual CpG sensitivities reached up to 81.3% at 95% specificity. Albeit similar methylation differences in tissue of both genders, differences were less pronounced in urine from women, most likely due to the frequent presence of squamous epithelial cells and leukocytes. Increased repression of methylation levels was observed at leukocyte counts ≥500/μl urine which was apparent in 30% of female and 7% of male UCa cases, further confirming the significance of the relative amounts of cancerous and noncancerous cells in urine. Our study shows that gender difference is a most relevant issue when evaluating the performance of urinary biomarkers in cancer diagnostics. In case of UCa, the clinical benefits of methylation signatures to male patients may outweigh those in females due to the general composition of women's urine. Accordingly, these markers offer a diagnostic option specifically in males to decrease the number of invasive cystoscopies.