Prevalence and correlates of diabetes distress, perceived stress and depressive symptoms among adults with early-onset Type 2 diabetes: cross-sectional survey results from the Danish DD2 study.

AIMS: To establish the prevalence of diabetes distress, perceived stress and depressive symptoms among adults with early-onset Type 2 diabetes, and to examine their association with socio-demographic and clinical characteristics. METHODS: A cross-sectional survey was performed among individuals with Type 2 diabetes aged 20-45 years who were included in the Danish nationwide Danish Center for Strategic Research in Type 2 Diabetes cohort between 2010 and 2016. The survey assessed diabetes distress (20-item Problem Areas in Diabetes Scale), perceived stress (10-item Perceived Stress Scale) and depressive symptoms (10-item short form of the Center for Epidemiological Studies Depression Scale Revised), as well as socio-demographic characteristics. Clinical data were collected from national health registers. RESULTS: In total, 216/460 (47%) individuals (48% women) with Type 2 diabetes completed the survey. The median (IQR) age was 42 (38-44) years and the diabetes duration was 5 (3-7) years. In total, 24% of respondents reported high diabetes distress (Problem Areas in Diabetes Scale ≥ 40), 46% reported high perceived stress (Perceived Stress Scale ≥ 18) and 41% reported elevated symptoms of depression (Center for Epidemiological Studies Depression Scale Revised ≥ 10). The prevalence of emotional problems was higher among women than men. Diabetes distress was higher among those prescribed non-insulin glucose-lowering drugs (vs. no glucose-lowering drugs), but was not associated with other clinical or socio-demographic characteristics. High perceived stress was associated with being unemployed and using antidepressant medication, and elevated depressive symptoms were associated with low education level, unemployment, living alone, having a psychiatric disorder and using antidepressant medication. CONCLUSION: We found a high prevalence of emotional problems among adults with early-onset Type 2 diabetes in Denmark. Health care for this group should focus on both physical health and psychosocial circumstances and should also address general as well as diabetes-specific emotional problems.

Periodic bouncing modes for two uniformly magnetized spheres. II. Scaling.

A uniformly magnetized sphere moves without friction in a plane in response to the field of a second, identical, fixed sphere and makes elastic hard-sphere collisions with this sphere. Numerical simulations of the threshold energies and periods of periodic finite-amplitude nonlinear bouncing modes agree with small-amplitude closed-form mathematical results, which are used to identify scaling parameters that govern the entire amplitude range, including power-law scaling at large amplitudes. Scaling parameters are combinations of the bouncing number, the rocking number, the phase, and numerical factors. Discontinuities in the scaling functions are found when viewing the threshold energy and period as separate functions of the scaling parameters, for which large-amplitude scaling exponents are obtained from fits to the data. These discontinuities disappear when the threshold energy is viewed as a function of the threshold period, for which the large-amplitude scaling exponent is obtained analytically and for which scaling applies to both in-phase and out-of-phase modes.

Periodic bouncing modes for two uniformly magnetized spheres. I. Trajectories.

We consider a uniformly magnetized sphere that moves without friction in a plane in response to the field of a second, identical, fixed sphere, making elastic hard-sphere collisions with this sphere. We seek periodic solutions to the associated nonlinear equations of motion. We find closed-form mathematical solutions for small-amplitude modes and use these to characterize and validate our large-amplitude modes, which we find numerically. Our Runge-Kutta integration approach allows us to find 1243 distinct periodic modes with the free sphere located initially at its stable equilibrium position. Each of these modes bifurcates from the finite-amplitude radial bouncing mode with infinitesimal-amplitude angular motion and supports a family of states with increasing amounts of angular motion. These states offer a rich variety of behaviors and beautiful, symmetric trajectories, including states with up to 157 collisions and 580 angular oscillations per period.

PVC flooring at home and uptake of phthalates in pregnant women.

Phthalates are used as plasticizers in polyvinyl chloride (PVC) materials and it is known that phthalates may migrate into the surrounding environment and then become a source for human uptake. The aim of the study was to investigate whether residential PVC flooring was related to the urinary levels of phthalate metabolites determined in pregnant women. The data were from the Swedish SELMA study where sampling was conducted during the time period 2007-2010. Spot urine samples from 1674 women at the end of the first trimester were analyzed for 14 metabolites from seven phthalates and one phthalate alternative. Data on flooring material in the kitchen and the parents' bedrooms as well as potential confounders were collected by postal questionnaires at the same time as the urine samples were taken. Multiple regression modeling by least square geometric mean and weighted quantile sum regression was applied to log-transformed and creatinine-adjusted phthalate metabolite concentrations adjusted for potential confounders from questionnaire data. This study has found significantly higher urinary levels of the BBzP metabolite (MBzP) in pregnant women living in homes with PVC flooring as compared to homes with other flooring materials.

Early-onset type 2 diabetes: Age gradient in clinical and behavioural risk factors in 5115 persons with newly diagnosed type 2 diabetes-Results from the DD2 study.

AIM: To examine the association between early onset of type 2 diabetes mellitus (DM) and clinical and behavioural risk factors for later complications of diabetes. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early onset) with diagnosis age 46 to 55, 56 to 65 (average onset = reference), 66 to 75, and >75 years (late onset). Prevalence ratios (PRs) were computed by using Poisson regression. RESULTS: Poor glucose control, ie, HbA1c ≥ 75 mmol/mol (≥9.0%) in the early-, average-, and late-onset groups was observed in 12%, 7%, and 1%, respectively (PR 1.70 [95% confidence intervals (CI) 1.27, 2.28] and PR 0.17 [95% CI 0.06, 0.45]). A similar age gradient was observed for severe obesity (body mass index > 40 kg/m2 : 19% vs. 8% vs. 2%; PR 2.41 [95% CI 1.83, 3.18] and 0.21 (95% CI 0.08, 0.57]), dyslipidemia (90% vs. 79% vs. 68%; PR 1.14 [95% CI 1.10, 1.19] and 0.86 [95% CI 0.79, 0.93]), and low-grade inflammation (C-reactive protein > 3.0 mg/L: 53% vs. 38% vs. 26%; PR 1.41 [95% CI 1.12, 1.78] and 0.68 [95% CI 0.42, 1.11]). Daily smoking was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2 DM need clinical awareness and support.

Occupational exposure to asphalt mixture during road paving is related to increased mitochondria DNA copy number: a cross-sectional study.

BACKGROUND: Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from hot mix asphalt via both inhalation and dermal absorption. The use of crumb rubber modified (CRM) asphalt may result in higher exposure to PAHs and more adverse effects. Our aim is to assess occupational exposure to PAHs from conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere length. METHODS: We recruited 116 workers paving conventional asphalt, 51 workers paving CRM asphalt and 100 controls in Sweden, all males. A repeated-measures analysis included 31 workers paving both types of asphalt. Urine and blood samples were collected pre-working on Monday morning and post-working on Thursday afternoon after 4 days working. PAH metabolites: 1-hydroxypyrene (1-OH-PYR) and 2-hydroxyphenanthrene (2-OH-PH) were measured in urine by LC-MS/MS. Relative mtDNAcn and telomere length were measured by quantitative PCR. RESULTS: Conventional and CRM asphalt workers showed higher 1-OH-PYR and 2-OH-PH than controls (p < 0.001 for all). Relative mtDNAcn were 0.21 units (p < 0.001) higher in conventional asphalt workers and 0.13 units (p = 0.010) higher in CRM asphalt workers compared to controls. Relative telomere length did not differ across occupational groups, but it was positively associated with increment of 2-OH-PH (ß = 0.075, p = 0.037) in asphalt workers. The repeated-measures analysis showed no difference in either increment of 1-OH-PYP, or changes in effect biomarkers (mtDNAcn or telomere length) between paving with conventional and CRM asphalt. Increment of 2-OH-PH was smaller after paving with CRM asphalt. CONCLUSIONS: Road asphalt paving in open areas resulted in PAHs exposure, as shown by elevation of PAH metabolites in urine. Asphalt workers may experience oxidative stress, evidenced by alternation in mtDNAcn; however the effects could not be fully explained by exposure to PAHs from the asphalt mixture.

Prenatal phthalate exposure was associated with croup in Swedish infants.

AIM: This study examined whether prenatal phthalate exposure was associated with lower or upper airway inflammation in infants. METHODS: From 2007 to 2010, we used liquid chromatography-tandem mass spectrometry, adjusted for creatinine, to analyse 14 phthalate metabolites and one phthalate replacement in the urine of 1062 Swedish mothers at a median of 10 weeks of pregnancy. This was used to determine any associations between prenatal phthalate exposure and croup, wheezing or otitis in their offspring until 12 months of age, using logistic regression, adjusted for potential confounders. RESULTS: There were significant associations between phthalate metabolites of butyl-benzyl phthalate (BBzP) and di-ethyl-hexyl phthalate (DEHP) concentrations in maternal prenatal urine and croup in 1062 infants during the first year of life, when adjusted for potential confounders. A dose-response relationship was found between prenatal phthalates exposure and maternal reported croup in the children, with a significant association in boys. There was no clear indication with regard to associations between prenatal phthalate exposure and wheezing or otitis media in the children during the first year of life. CONCLUSION: Our analysis suggests that exposure to BBzP and DEHP phthalates was associated with maternal reports of croup in infants up to 12 months of age.

Female exposure to phthalates and time to pregnancy: a first pregnancy planner study.

STUDY QUESTION: Is female exposure to phthalate metabolites associated with reduced fecundity, as estimated by prolonged time to pregnancy (TTP)? SUMMARY ANSWER: Female exposure to monoethyl phthalate (MEP) but not monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate (MEHP) was associated with a longer TTP. WHAT IS KNOWN ALREADY: Male exposure to phthalates is potentially associated with adverse effects on human fecundity in epidemiological studies, but little is known about the potential effects on female reproduction. STUDY DESIGN SIZE AND DURATION: A cohort study with prospective data based on 229 women from a Danish cohort of 430 first pregnancy planning couples enrolled in 1992-1994. In 2009, urinary analyses of phthalate metabolites were performed on stored urine samples from this cohort. PARTICIPANTS/MATERIALS, SETTING AND METHODS: We analyzed MEP, MBP, MBzP and MEHP in female morning spot urine samples collected daily during the first 10 days of menstrual cycles after discontinuation of contraception. The exposure assessment was based on the mean of two measurements from each woman collected in a period of 6 menstrual cycles. We used Cox regression with discrete time to estimate fecundability ratios (FRs) and 95% CI in relation to the average urine metabolite concentration exposure level, controlled for age and BMI, and the time-varying variables smoking and alcohol. MAIN RESULT AND ROLE OF CHANCE: Urinary concentration of MEP was associated with a decreased fecundity (adjusted FR 0.79; 95% CI: 0.63; 0.99) corresponding to a 21% decreased probability of conception for each natural log (ln) unit increase in MEP. No significant association with TTP was found for MBP, MBzP and MEHP. LIMITATIONS REASONS FOR CAUTION: Subfertile women were overrepresented in the study population due to exclusion of 77 high fertile women who became pregnant in the first cycle when urine collection began. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that female exposure to MEP may have an adverse effect on female fecundity, but these findings need to be replicated in a larger and newer cohort study with sufficient exposure contrast if the use of diethyl phthalate (DEP) and thereby MEP in the future potentially should be regulated in cosmetics and industrial consumer products. STUDY FUNDING/COMPETING INTERESTS: The original data collected were founded by Aarhus University Research Foundation, the Danish Medical Research Council and the Danish Medical Health Insurance Foundation. There are no conflicts of interest to be declared. TRIAL REGISTRATION NUMBER: N/A.

Diverging temporal trends of human exposure to bisphenols and plastizisers, such as phthalates, caused by substitution of legacy EDCs?

Phthalates and phenolic substances were investigated in urine samples from first-time mothers in Uppsala, Sweden, collected between 2009 and 2014. These substances have a comparably fast metabolism and urinary metabolites are predominantly analysed. The main aim was to investigate if measures to decrease production and use of certain phthalates and bisphenol A (BPA) have resulted in decreased human exposure, and to determine if exposures to replacement chemicals have increased. Temporal trends were evaluated for metabolites (n=13) of seven phthalates, a phthalate replacer, four different bisphenols, triclosan, one organophosphate-based flame retardant, and for two pesticides. The results showed downward trends of several phthalates which are in the process of being regulated and phased out. Concomitantly, an increasing trend was seen for a metabolite of the phthalate replacer Di-iso-nonylcyclohexane 1,2-dicarboxylate (DiNCH). Bisphenol A (BPA) showed a downward trend, whereas bisphenol F, identified as one of the substitutes for BPA, showed an increasing trend. The decreasing trend of triclosan is likely due to declining use within the EU. Temporal trend studies of urine samples make it possible to investigate human exposure to rapidly metabolised substances and study how measures taken to regulate and replace problematic chemicals affect human exposure.

Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates.

PURPOSE: Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. METHOD: In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure. RESULTS: No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms. CONCLUSION: Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).

Characterization of Prohibitin 1 as a Host Partner of Vibrio vulnificus RtxA1 Toxin.

RtxA1 toxin, which results in cytoskeletal rearrangement, contact cytotoxicity, hemolysis, tissue invasion, and lethality in mice, is the most potent cytotoxic virulence factor of Vibrio vulnificus. Bioinformatics analysis of rtxA1 predicted 4 functional domains that presumably performed discrete functions during host cell killing. V. vulnificus RtxA1 has a unique domain designated as RtxA1-D2, corresponding to amino acids 1951-2574, which is absent in Vibrio cholerae multifunctional-autoprocessing repeats-in-toxin, suggesting that this domain confers specific biological functions to V. vulnificus RtxA1. HeLa cells expressing green fluorescent protein-RtxA1-D2 became round and lost their viability. A yeast 2-hybrid system identified prohibitin (PHB) 1 as the host partner of RtxA1-D2. The specific interaction of RtxA1-D2 with PHB1 was confirmed by performing immunoprecipitation. Interestingly, V. vulnificus RtxA1 up-regulated PHB1 expression on the cytoplasmic membrane of host cells. Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways were confirmed as being important in the up-regulation of PHB1 by using inhibitors. Down-regulation of PHB1 by small interfering RNAs decreased the cytotoxicity of RtxA1-D2 against HeLa cells. The pretreatment of an anti-PHB1 antibody impaired the cytotoxicity of V. vulnificus RtxA1. These results suggest that the involvement PHB1 in the RtxA1 cytotoxicity has significant implications for the pathogenesis of V. vulnificus infections.

Cotinine Validation of Self-Reported Smoking During Pregnancy in the Swedish Medical Birth Register.

INTRODUCTION: Self-reported data on smoking during pregnancy from the Medical Birth Register of Sweden (MBR) are widely used. However, underreporting of such behavior may occur, leading to biases. It is of importance to validate the smoking data in the MBR. The main objective was to investigate the agreement between self-reported smoking data from the MBR and cotinine levels in maternal serum among women from the general population in the region of Skåne, Sweden. We also estimated the transfer of cotinine from mother to fetus. METHODS: From a cohort used previously to investigate the relationship between intrauterine environmental exposures and offspring neuropsychiatric outcomes, there were 204 control children retrieved from the MBR with data on maternal smoking in early pregnancy registered. Data on maternal and umbilical cord cotinine at delivery were available for these children from a regional biobank. RESULTS: There was a high agreement between cotinine levels and MBR smoking data (κ = 0.82) and a high correlation between cotinine levels in maternal and umbilical cord serum (r s = 0.90, P < .001). Of the self-reported nonsmokers, 95% (95% confidence interval: 89% to 97%) were classified as nonsmokers after cotinine measurements. CONCLUSION: In these data, we found that the agreement between mothers' self-reported smoking habits during pregnancy and their levels of serum cotinine was high, as was the transfer of cotinine from mother to fetus. This indicates that birth register data on pregnancy smoking in Sweden could be considered a valid measure.

A systematic review and meta-analysis of music therapy for the older adults with depression.

OBJECTIVES: To determine the efficacy of music therapy in the management of depression in the elderly. METHOD: We conducted a systematic review and meta-analysis of randomized controlled trials. Change in depressive symptoms was measured with various scales. Standardized mean differences were calculated for each therapy-control contrast. RESULTS: A comprehensive search yielded 2,692 citations; 19 articles met inclusion criteria. Meta-analysis suggests that music therapy plus standard treatment has statistical significance in reducing depressive symptoms among older adults (standardized mean differences = 1.02; 95% CI = 0.87, 1.17). CONCLUSIONS: This systematic review and meta-analysis suggests that music therapy has an effect on reducing depressive symptoms to some extent. However, high-quality trials evaluating the effects of music therapy on depression are required. Copyright © 2016 John Wiley & Sons, Ltd.

Targeted proteomic analyses of nasal lavage fluid in persulfate-challenged hairdressers with bleaching powder-associated rhinitis.

Hairdressers have an increased risk for developing airway symptoms, for example, asthma and rhinitis. Persulfates, which are oxidizing agents in bleaching powder, are considered important causal agents for these symptoms. However, the underlying mechanisms are unclear. The aim was therefore to measure proteomic changes in nasal lavage fluid from persulfate-challenged subjects to identify proteins potentially involved in the pathogenesis of bleaching powder-associated rhinitis or candidate effect biomarkers for persulfate. Also, oxidized peptides were measured to evaluate their usefulness as biomarkers for persulfate exposure or effect, for example, oxidative stress. Samples from hairdressers with and without bleaching powder-associated rhinitis were analyzed with liquid chromatography tandem mass spectrometry using selected reaction monitoring to target 246 proteins and five oxidized peptides. Pathway analysis was applied to obtain a functional overview of the proteins. Several proteins involved in biologically meaningful pathways, functions, or disorders, for example, inflammatory responses, oxidative stress, epithelium integrity, and dermatological disorders, changed after the persulfate challenge. A list with nine proteins that appeared to be affected by the persulfate challenge and should be followed up was defined. An albumin peptide containing oxidized tryptophan increased 2 h and 5 h after the challenge but not after 20 min, which indicates that such peptides may be useful as oxidative stress biomarkers.

Amniotic fluid phthalate levels and male fetal gonad function.

BACKGROUND: Prenatal exposure to phthalates may pose a threat to human male reproduction. However, additional knowledge about the in vivo effect in humans is needed, and reported associations with genital abnormalities are inconclusive. We aimed to study prenatal di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP) exposure in relation to cryptorchidism, hypospadias, and human fetal Leydig cell function. METHODS: We studied 270 cryptorchidism cases, 75 hypospadias cases, and 300 controls. Second-trimester amniotic fluid samples were available from a Danish pregnancy-screening biobank (n = 25,105) covering 1980-1996. We assayed metabolites of DEHP and DiNP (n = 645) and steroid hormones (n = 545) by mass spectrometry. We assayed insulin-like factor 3 by immunoassay (n = 475) and analyzed data using linear or logistic regression. RESULTS: Mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP, DEHP metabolite) was not consistently associated with cryptorchidism or hypospadias. However, we observed an 18% higher (95% confidence interval [CI] = 5%-33%) testosterone level, and a 41% lower (-56% to -21%) insulin-like factor 3 level in the highest 5cx-MEPP tertile compared with the lowest. Mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP, DiNP metabolite) showed elevated odds ratio point estimates for having cryptorchidism (odds ratio = 1.28 [95% CI = 0.80 to 2.01]) and hypospadias (1.69 [0.78 to 3.67]), but was not consistently associated with the steroid hormones or insulin-like factor 3. CONCLUSIONS: Data on the DEHP metabolite indicate possible interference with human male fetal gonadal function. Considering the DiNP metabolite, we cannot exclude (nor statistically confirm) an association with hypospadias and, less strongly, with cryptorchidism.

Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.

Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to <5ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose-response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting "sneezing", the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity.

Exposure of hairdressers to ortho- and meta-toluidine in hair dyes.

BACKGROUND: Carcinogenic aromatic amines derived from hair dyes have recently received new attention. One of these is ortho (o)-toluidine, which is classified as carcinogenic to humans. OBJECTIVES: To clarify exposure of hairdressers to potentially carcinogenic aromatic amines, including o-toluidine. METHODS: We measured eight potentially carcinogenic aromatic amines in the blood of 295 hairdressers, 32 users of hair dyes and 60 controls. The study was restricted to female non-smokers. Lifestyle data were collected for all participants using self-administered questionnaires. Blood samples were taken for analysis of ortho-, meta (m)- and para (p)-toluidine; 2-, 3- and 4-ethylaniline, 2,3- and 3,4-dimethylaniline as haemoglobin adducts. The samples were analysed with gas chromatography-tandem mass spectrometry. RESULTS: Generally, adduct concentrations were in the range of 0-200 pg/g haemoglobin. A comparison of the adduct concentrations found in hairdressers, consumers and controls showed no statistically significant differences. However, for hairdressers, o- and m-toluidine concentrations increased significantly with the weekly number of hair waving (p=0.020) and permanent hair dyeing treatments (p=0.026), respectively. o-Toluidine and m-Toluidine concentrations also tended (p=0.076 and 0.080, respectively) to increase with the frequency of light-colour permanent hair dye treatments. CONCLUSIONS: Hairdressers who use light-colour permanent hair dyes, other permanent hair dyes and hair waving treatments seem to be exposed to o- and m-toluidine as indicated by associations with the number of treatments performed. Analyses of hair waving and hair dye products should be performed to identify the possible sources of exposure to o- and m-toluidine.

Phthalates, perfluoroalkyl acids, metals and organochlorines and reproductive function: a multipollutant assessment in Greenlandic, Polish and Ukrainian men.

OBJECTIVES: Numerous environmental contaminants have been linked to adverse reproductive health outcomes. However, the complex correlation structure of exposures and multiple testing issues limit the interpretation of existing evidence. Our objective was to identify, from a large set of contaminant exposures, exposure profiles associated with biomarkers of male reproductive function. METHODS: In this cross-sectional study (n=602), male partners of pregnant women were enrolled between 2002 and 2004 during antenatal care visits in Greenland, Poland and Ukraine. Fifteen contaminants were detected in more than 70% of blood samples, including metabolites of di(2-ethylhexyl) and diisononyl phthalates (DEHP, DiNP), perfluoroalkyl acids, metals and organochlorines. Twenty-two reproductive biomarkers were assessed, including serum levels of reproductive hormones, markers of semen quality, sperm chromatin integrity, epididymal and accessory sex gland function, and Y:X chromosome ratio. We evaluated multipollutant models with sparse partial least squares (sPLS) regression, a simultaneous dimension reduction and variable selection approach which accommodates joint modelling of correlated exposures. RESULTS: Of the over 300 exposure-outcome associations tested in sPLS models, we detected 10 associations encompassing 8 outcomes. Several associations were notably consistent in direction across the three study populations: positive associations between mercury and inhibin B, and between cadmium and testosterone; and inverse associations between DiNP metabolites and testosterone, between polychlorinated biphenyl-153 and progressive sperm motility, and between a DEHP metabolite and neutral α-glucosidase, a marker of epididymal function. CONCLUSIONS: This global assessment of a mixture of environmental contaminants provides further indications that some organochlorines and phthalates adversely affect some parameters of male reproductive health.

Prenatal phthalate exposure and reproductive function in young men.

BACKGROUND: Prenatal exposure to phthalates is suggested to negatively impact male reproductive function, but human data are lacking. OBJECTIVES: To study associations between prenatal exposure to diethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP), and reproductive parameters of adolescent men. METHODS: Using linear regression models adjusted for potential confounders, we studied associations between levels of DEHP- and DiNP metabolites in maternal sera from mean 12 weeks of pregnancy, and testicular size, semen quality and reproductive hormones in 112 adolescent sons, recruited from the general population. RESULTS: Men in the highest exposure tertile of one DiNP metabolite [mono-(carboxy-iso-octyl) phthalate], compared with men in the lowest tertile had: 4.3mL (95% CI: 0.89, 7.6mL; p<0.001) lower total testicular volume; 30% (95% CI: 3.6, 63%; p=0.02) higher levels of follicle-stimulating hormone; and 0.87mL (95% CI: 0.28, 1.5mL; p=0.004) lower semen volume. Men in the highest exposure tertile of one DEHP metabolite [mono-(2-ethyl-5-hydroxylhexyl) phthalate] had 0.70mL (95% CI: 0.090, 1.3mL; p=0.03) lower semen volume than men in the lowest exposure tertile. The levels of two DiNP metabolites [mono-(hydroxy-iso-nonyl) phthalate and mono-(oxo-iso-nonyl) phthalate] were linearly associated with luteinizing hormone (p<0.01). CONCLUSION: Prenatal levels of some metabolites of DEHP and DiNP seemed negatively associated with reproductive function of adolescent men.

Levels of perfluoroalkyl substances and risk of coronary heart disease: Findings from a population-based longitudinal study.

BACKGROUND: Cross-sectional studies have shown an association between exposure to perfluoroalkyl substances (PFASs) and coronary heart disease (CHD). These findings need to be evaluated in longitudinal settings. OBJECTIVES: To investigate the risk of CHD in relation to PFAS levels in a longitudinal setting among Swedish rural residents. METHODS: In a population-based prospective cohort of male farmers and rural residents recruited in 1990-1991, all men who received a CHD diagnosis between 1992 and 2009 were identified from national registers (n=253). For each CHD case, one control, matched for age, was chosen randomly from the cohort. For all cases and controls, levels of eight PFASs at baseline were measured in stored blood samples. In addition, for a subsample, PFAS levels were also measured in serum samples collected at a follow-up in 2002-2003. RESULTS: There were no statistically significant associations between levels of seven of the eight PFASs at baseline and risk for developing CHD. There was a significant association between perfluoroheptanoic acid (PFHpA) and CHD (OR=2.72; 95% CI: 1.52, 4.84) for the 3rd quartile and (OR=2.45; 95% CI: 1.40, 4.29) for the 4th quartile compared to the lowest quartile. Changes in levels of PFCs between baseline and follow-up did not differ systematically between cases and controls. CONCLUSIONS: This longitudinal study does not lend support to the previously reported cross-sectional relationship between PFAS levels and CHD risk. We found a significant association with PFHpA, but this could be a chance finding, considering its chemical resemblance to other PFASs.