Cosmetic and personal care product use, urinary levels of parabens and benzophenones, and risk of endometriosis: results from the EndEA study.

AIM: To explore the relationship of urinary concentrations of different congeners of benzophenones and parabens with the utilization of cosmetics and personal care products (PCPs) and their impact on the risk of endometriosis, and to evaluate the influence of oxidative stress on associations found. METHODS: This case-control study comprised a subsample of 124 women (35 cases; 89 controls). Endometriosis was confirmed (cases) or ruled out (controls) by laparoscopy, with visual inspection of the pelvis and biopsy of suspected lesions (histological diagnosis). Urinary concentrations of benzophenone-1 (BP-1), benzophenone-3 (BP-3), 4-hydroxibenzophenone (4-OH-BP), methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butyl-paraben (BuP), and biomarkers of oxidative stress [lipid peroxidation (TBARS) and total antioxidant power (TAP)] were quantified. Information was gathered on the frequency of use of cosmetics and PCPs. Associations between the frequency of cosmetics/PCP use, urinary concentrations of benzophenones and parabens, oxidative stress, and endometriosis risk were explored in logistic and linear multivariable regression analyses. RESULTS: The frequency of utilization of certain cosmetics and PCPs was significantly associated with urinary concentrations of benzophenones and parabens. After adjustment for potential confounders, the risk of endometriosis was increased in women in the second versus first terciles of MeP (OR = 5.63; p-value<0.001), BP-1 (OR = 5.12; p-value = 0.011), BP-3 (OR = 4.98; p-value = 0.008), and Æ©BPs (OR = 3.34; p-value = 0.032). A close-to-significant relationship was observed between TBARS concentrations and increased endometriosis risk (OR = 1.60, p-value = 0.070) and an inverse association between TAP concentrations and this risk (OR = 0.15; p-value = 0.048). Oxidative stress results did not modify associations observed between benzophenone/paraben exposure and endometriosis risk. CONCLUSIONS: Our findings indicate that the frequency of cosmetics and PCP utilization is a strong predictor of exposure to certain benzophenone and paraben congeners. These compounds may increase the risk of endometriosis in an oxidative stress-independent manner. Further studies are warranted to corroborate these findings.

Determination of bisphenol A and bisphenol S concentrations and assessment of estrogen- and anti-androgen-like activities in thermal paper receipts from Brazil, France, and Spain.

Bisphenol A (BPA) is a high-production-volume chemical with endocrine disrupting properties commonly used as color developer in thermal paper. Concerns about the potential hazards of human BPA exposure have led to the increasing utilization of alternatives such as bisphenol S (BPS) and bisphenol F (BPF). This study was designed to assess: (i) BPA, BPS, and BPF concentrations in 112 thermal paper receipts from Brazil, France, and Spain by liquid chromatography coupled to mass spectrometry (LC-MS); and (ii) hormone-like activities of these receipts using two receptor-specific bioassays, the E-Screen for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity. BPA was present in 95.3% of receipts from Spain, 90.9% of those from Brazil, and 51.1% of those from France at concentrations up to 20.27 mg/g of paper. Only two samples from Brazil, two from Spain, and ten from France had a BPS concentration ranging from 6.46 to 13.29 mg/g; no BPA or BPS was detected in 27.7% of French samples. No BPF was detected in any receipt. Estrogenic activity was observed in all samples from Brazil and Spain and in 74.5% of those from France. Anti-androgenic activity was observed in > 90% of samples from Brazil and Spain and in 53.2% of those from France. Only 25.5% of French samples were negative for both estrogenic and anti-androgenic activity. Estrogenic and anti-androgenic activities per gram of paper were up to 1.411 µM estradiol (E2) equivalent units (E2eq) and up to 359.5 mM procymidone equivalent units (Proceq), respectively. BPA but not BPS concentrations were positively correlated with both estrogenic and anti-androgenic activities. BPA still dominates the thermal paper market in Brazil and Spain, and BPS appears to be one of the main alternatives in France. There is an urgent need to evaluate the safety of alternatives proposed to replace BPA as developer in thermal printing. The large proportion of samples with hormonal activity calls for the adoption of preventive measures.

Radiofrequency exposure in the Neonatal Medium Care Unit.

The aims of this study were to characterize electromagnetic fields of radiofrequency (RF-EMF) levels generated in a Neonatal Medium Care Unit and to analyze RF-EMF levels inside unit's incubators. Spot and long-term measurements were made with a dosimeter. The spot measurement mean was 1.51±0.48V/m. Higher values were found in the proximity to the window and to the incubator evaluated. Mean field strength for the entire period of 17h was 0.81 (±0.07)V/m and the maximum value was 1.58V/m for long-term RF-EMF measurements in the incubator. Values found during the night period were higher than those found during the day period. It is important to consider RF-EMF exposure levels in neonatal care units, due to some evidence of adverse health effects found in children and adults. Characterization of RF-EMF exposure may be important to further investigate the mechanisms and underlying effects of electromagnetic fields (EMF) on infant health. A prudent avoidance strategy should be adopted because newborns are at a vulnerable stage of development and the actual impact of EMF on premature infants is unknown.

Assumed non-persistent environmental chemicals in human adipose tissue; matrix stability and correlation with levels measured in urine and serum.

The aim of this study was to (1) optimize a method for the measurement of parabens and phenols in adipose tissue, (2) evaluate the stability of chemical residues in adipose tissue samples, and (3) study correlations of these compounds in urine, serum, and adipose tissue. Samples were obtained from adults undergoing trauma surgery. Nine phenols and seven parabens were determined by isotope diluted TurboFlow-LC-MS/MS. The analytical method showed good accuracy and precision. Limits of detection (LOD) for parabens and phenols ranged from 0.05 to 1.83ng/g tissue. Good recovery rates were found, even when biological samples remained defrosted up to 24h. Benzophenone-3 (BP-3; range of values: 70% of adipose tissue samples, while bisphenol-A (BPA; 40% of adipose tissue samples. In general, levels were similar between adipose tissue and serum, while a correlation between adipose tissue and urine was only found for BP-3. In conclusion, adipose tissue samples in this study were found to contain environmental chemicals considered to be non-persistent, whose levels were weakly or not at all correlated with the urine burden. Therefore, adipose tissue may potentially provide additional information to that obtained from other biological matrices. Further investigations are warranted to explore whether adipose tissue might be a suitable matrix for assessment of the consequences for human health of mid/long-term exposure to these chemicals.

Compensated reduction in Leydig cell function is associated with lower semen quality variables: a study of 8182 European young men.

STUDY QUESTION: Is the Leydig cell function of young European men associated with semen quality? SUMMARY ANSWER: Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. WHAT IS ALREADY KNOWN: Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below and within the WHO reference range. STUDY DESIGN, SIZE AND DURATION: A coordinated, cross-sectional population-based study of 8182 men undertaken in 1996-2010. PARTICIPANTS, SETTING AND METHOD: Young men (median age 19.1 years) were investigated in centres in Denmark, Estonia, Finland, Germany Latvia, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone, and ratios between serum testosterone and LH were determined. MAIN RESULT AND ROLE OF CHANCE: Serum testosterone levels were not associated with sperm concentrations, total sperm counts, or percentage of motile or morphologically normal spermatozoa. There was an inverse association between the semen parameters and serum LH levels, and accordingly a positive association to testosterone/LH ratio and calculated-free-testosterone/LH ratio. LIMITATIONS, REASON FOR CAUTION: The size of the study mitigates the intra-individual variability concern. The distinction between different sub-categories of sperm motility and sperm morphology is subjective despite training. However, inter-observer variation would tend towards non-differential misclassification and would decrease the likelihood of detecting associations between reproductive hormone levels and semen variables, suggesting that the presented associations might in reality be even stronger than shown. Although we adjusted for confounders, we cannot of course exclude that our results can be skewed by selection bias or residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. This is apparent even within the WHO reference range of semen quality. It is unknown whether impaired Leydig cell function in young men may confer an increased risk of acquired testosterone deficiency later in life. STUDY FUNDING/COMPETING INTERESTS: Support from The Research Fund of Rigshospitalet (grant no. R42-A1326) to N.J. made this study possible. The background studies of young men have been supported economically by several grants. ITALIC! Denmark: The European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603 and most recently FP7/2007-2013, DEER Grant agreement no. 212844), The Danish Research Council (grants nos. 9700833 2107-05-0006), The Danish Agency for Science, Technology and Innovation (Grant no. 271070678), Rigshospitalet (Grant no. 961506336), The University of Copenhagen (Grant no. 211-0357/07-3012), The Danish Ministry of Health and the Danish Environmental Protection Agency, A.P. Møller and wife Chastine McKinney Møllers foundation, and Svend Andersens Foundation. ITALIC! Finland: European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT- 2002-00603 and most recently FP7/2008-2012, DEER Grant agreement no. 212844), The Academy of Finland, Turku University Hospital Funds, Sigrid Juselius Foundation. ITALIC! Estonia, Latvia and Lithuania: European Union (QLRT-2001-02911), the Estonian Science Foundation, grant number 2991, Lithuanian Foundation for Research, Organon Agencies B.V. and the Danish Research Council, grant no. 9700833. ITALIC! Germany: European Union (contract numbers QLK4-CT-2002-00603). ITALIC! Spain: European Commission QLK4-1999-01422. M.F. received support from the Spanish Ministry of Science and Innovation (Program Ramon y Cajal). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. None of the authors have any competing interests to declare.

Practical aspects of factor concentrate use in patients with von Willebrand disease undergoing invasive procedures: a European survey.

INTRODUCTION: The bleeding propensity in von Willebrand disease (VWD) is usually moderate or mild and patients with VWD do not need continuous treatment, but do require extra increased haemostatic cover when undergoing dental or surgical procedures. Desmopressin can be effective in certain patient groups and this has been considered in a previous publication. AIM: This paper now seeks to evaluate current knowledge and practice in the use of factor concentrate in the management of VWD patients undergoing invasive procedures. METHODS: A literature search was performed on the use of factor concentrates to cover invasive procedures and a survey of current practice in a number of specialist haematology centres across Europe represented by the European Haemophilia Strategy Board was conducted. RESULTS: Our review of the literature and the results of the survey showed considerable heterogeneity in treatment regimens, and a lack of consistency in reporting of the variables that determine factor concentrate dosing and monitoring. CONCLUSION: By analysing the literature, examining guidelines and using consensus deliberation, this survey allowed the group to develop recommendations for management of VWD patients undergoing invasive procedures.

Practical aspects of DDAVP use in patients with von Willebrand Disease undergoing invasive procedures: a European survey.

INTRODUCTION: Desamino D-arginine vasopressin (DDAVP or desmopressin) is a useful and effective haemostatic treatment for patients with von Willebrand Disease (VWD). However, there are still issues regarding in which subtypes of VWD DDAVP is appropriate and little consensus on its use in different surgical settings. We also lack information concerning the appropriate laboratory parameters that should be monitored. AIM: The European Haemophilia Therapy Strategy Board (EHTSB) wished to investigate published information and clinical use of DDAVP in VWD patients. METHODS: We conducted a literature survey on management of VWD during surgical interventions and undertook a survey of specialist haematologist centres across Europe to assess current management of VWD patients. RESULTS: DDAVP is ineffective in type 3 VWD and its use in type 2B remains controversial due to the possibility of thrombocytopenia. It can, however, be used effectively to cover minor surgery and dental procedures in most other VWD patients. For major surgery there is wider use of factor concentrate in preference to DDAVP depending on the subtype of VWD. We give consensus recommendations on the use of DDAVP for surgical interventions in VWD including laboratory parameters that denote an adequate response and contraindications to its use. CONCLUSIONS: DDAVP can be recommended to cover invasive procedure in selected patients with VWD, however, we need more information and systematic recording of adverse events associated with DDAVP use in VWD. A companion paper will be published covering the use of factor concentrates in VWD patients.

Efficacy and safety of pegylated full-length recombinant factor VIII with extended half-life for perioperative haemostasis in haemophilia A patients.

INTRODUCTION: BAX 855 is a pegylated full-length recombinant factor VIII (rFVIII) with an extended half-life, built on a licensed rFVIII (ADVATE(®) ). BAX 855 demonstrated efficacy and safety in prophylaxis and the treatment of bleeding episodes in previously treated patients (PTPs) with severe haemophilia A. AIM: This phase 3 surgery study evaluates the haemostatic efficacy and safety of BAX 855 for perioperative haemostasis in PTPs with severe haemophilia A undergoing surgery. METHODS: Elective procedures were prospectively classified as major or minor. The dose and frequency of BAX 855 administered perioperatively were to be guided by each patient's pharmacokinetic profile for major procedures or BAX 855 incremental recovery for minor procedures. Haemostatic efficacy was evaluated using a predefined scale. Blood loss was compared to the expected average and maximum blood loss predicted preoperatively. RESULTS: A total of 15 male patients (aged 19-52 years) underwent 15 procedures (11 major and four minor). The overall intra- and perioperative haemostatic efficacy of BAX 855 was 'excellent' in all 15 subjects (100%). Postoperatively, evaluated at postoperative Day 1, all treatments were 'excellent' except for one minor (dental) procedure which was rated 'good'. No related adverse events, allergic reactions, thrombotic events, nor signs of immunogenicity in terms of induction of binding antibodies to FVIII, PEG or PEG-VIII, or FVIII inhibitors were observed. CONCLUSION: These results demonstrate that BAX 855 is safe and haemostatically effective in patients with severe haemophilia A undergoing surgery.

Efficacy and safety of long-acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery.

INTRODUCTION: Recombinant factor IX fusion protein (rIX-FP) has been developed to improve the pharmacokinetic (PK) profile of factor IX (FIX), allowing maintenance of desired FIX activity between injections at extended intervals, ultimately optimizing haemophilia B treatment. AIM: To determine the efficacy and safety of rIX-FP in the perioperative setting. METHODS: Subjects were adult and paediatric patients with severe to moderately severe haemophilia B (FIX ≤ 2%) participating in three Phase III clinical trials and undergoing a surgical procedure. PK profiles were established prior to surgery for each patient. Haemostatic efficacy was assessed by the investigator for up to 72 h after surgery. Safety measurements during the study included adverse events and inhibitors to FIX. FIX activity was monitored during and after surgery to determine if repeat dosing was required. RESULTS: Twenty-one, both major and minor, surgeries were performed in 19 patients. Haemostatic efficacy was rated as excellent (n = 17) or good (n = 4) in all surgeries. A single preoperative dose maintained intraoperative haemostasis in 20 of 21 surgeries. Nine major orthopaedic surgeries were conducted in eight patients with a mean of 7 (range: 6-12) rIX-FP injections during surgery and the 14-day postoperative period. Median rIX-FP consumption for orthopaedic surgeries was 87 IU kg(-1) preoperatively and 375 IU kg(-1) overall. No subject developed inhibitors to FIX or antibodies to rIX-FP. CONCLUSION: Recombinant factor IX fusion protein was well tolerated and effectively maintained haemostasis during and after surgery. Stable FIX activity was achieved with a prolonged dosing interval and reduced consumption compared to conventional or currently available long-acting recombinant FIX.

In vitro antiviral activity of Lactobacillus casei and Bifidobacterium adolescentis against rotavirus infection monitored by NSP4 protein production.

AIMS: The aim of this study was to determine the antiviral activity of four probiotic metabolites (Lactobacillus and Bifidobacetrium species) against rotavirus in vitro infection monitored by the NSP4 protein production and Ca(2+) release. METHODS AND RESULTS: The antiviral effect of the metabolites was performed due a comparison between a blocking model and an intracelullar model on MA104 cells, with the response of NSP4 production and Ca(2+) liberation measured by flow cytometry. Significant results were obtained with the metabolites of Lactobacillus casei, and Bifidobacterium adolescentis in the reduction of the protein production (P = 0·04 and P = 0·014) and Ca(2+) liberation (P = 0·094 and P = 0·020) in the intracellular model, which suggests a successful antiviral activity against RV infection. CONCLUSIONS: This study demonstrates that probiotic metabolites were able to interfere with the final amount of intracellular NSP4 protein and a successful Ca(2+) regulation, which suggests a new approach to the mechanism exerted by probiotics against the rotavirus infection. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel anti-rotaviral effect exerted by probiotic metabolites monitored by the NSP4 protein during the RV in vitro infection and the effect on the Ca(2+) release is reported; suggesting a reduction on the impact of the infection by decreasing the damage of the cells preventing the electrolyte loss.

Outdoor characterization of radio frequency electromagnetic fields in a Spanish birth cohort.

There is considerable public concern in many countries about the possible adverse effects of exposure to non-ionizing radiation electromagnetic fields, especially in vulnerable populations such as children. The aim of this study was to characterize environmental exposure profiles within the frequency range 100kHz-6GHz in the immediate surrounds of the dwellings of 123 families from the INMA-Granada birth cohort in Southern Spain, using spot measurements. The arithmetic mean root mean-square electric field (ERMS) and power density (SRMS) values were, respectively, 195.79mV/m (42.3% of data were above this mean) and 799.01µW/m(2) (30% of values were above this mean); median values were 148.80mV/m and 285.94µW/m(2), respectively. Exposure levels below the quantification limit were assigned a value of 0.01V/m. Incident field strength levels varied widely among different areas or towns/villages, demonstrating spatial variability in the distribution of exposure values related to the surface area population size and also among seasons. Although recorded values were well below International Commission for Non-Ionizing Radiation Protection reference levels, there is a particular need to characterize incident field strength levels in vulnerable populations (e.g., children) because of their chronic and ever-increasing exposure. The effects of incident field strength have not been fully elucidated; however, it may be appropriate to apply the precautionary principle in order to reduce exposure in susceptible groups.

Serum and adipose tissue as matrices for assessment of exposure to persistent organic pollutants in breast cancer patients.

The aim of this study was to assess differences between two biological matrices (serum and breast adipose tissue) in the evaluation of persistent organic pollutant (POP) exposure in breast cancer patients. The study population consisted of 103 women undergoing surgery for newly diagnosed breast carcinoma in a public hospital in Granada, Southern Spain. Independent variables were gathered from questionnaires and clinical records. POP concentrations were quantified in breast adipose tissue and serum samples. Spearman correlation tests were performed between pairs of POP concentrations and stepwise multivariable linear regression analyses were conducted to assess predictors of concentrations in the two matrices. p,p'- Dichlorodiphenyldichloroethylene (p,p'-DDE) showed the the highest median concentration in both matrices (194.34 and 173.84 ng/g lipid in adipose tissue and serum, respectively). Median wet-basis adipose tissue:serum ratios ranged from 109.34 to 651.62, while lipid-basis ratios ranged from 0.88 to 4.34. In general, we found significant positive correlation coefficients between pairs of POPs in adipose tissue and in serum, which were always higher in adipose tissue. We found positive and statistically significant correlations between serum and adipose tissue concentrations of p,p'-DDE and hexachlorobenzene (HCB) but not of polychlorinated biphenyls (PCBs). Age was positively associated with most POPs in adipose tissue and serum, while the body mass index was positively associated with adipose tissue HCB concentrations and negatively associated with serum PCB-153 and PCB-138 concentrations. Recent weight loss was inversely associated with POP residues in adipose tissue and positively associated with POP residues in serum. Serum HCB and PCB-180 concentrations were lower in patients who had received preoperative chemotherapy. According to our results, serum and adipose tissue POP concentrations in breast cancer patients may be differentially affected by external predictors. Taken together, these findings indicate the need to take account of the individual POP(s) under study and the biological matrix used when relating internal POP exposure to breast cancer disease and to make a careful selection of covariates for adjusting the model.

Adherence to reporting guidelines in observational studies concerning exposure to persistent organic pollutants and effects on semen parameters.

STUDY QUESTION: Are studies on semen quality in men exposed to persistent pesticides reported according to the 'strengthening the reporting of observational studies in epidemiology' (STROBE) recommendations and the guidelines for the appraisal of semen quality studies (SEMQUA)? SUMMARY ANSWER: Most studies of the impact of pesticides on semen quality do not follow the STROBE and SEMQUA guidelines, thus adherence is low, especially in methodological aspects. WHAT IS KNOWN ALREADY: Much of the controversy about reduced semen quality in recent decades arises from a lack of standardization in the methodology applied, despite the existence of several validated instruments for evaluating the quality of reporting. Indeed, SEMQUA was purpose-designed for the particular characteristics of semen quality studies. STUDY DESIGN, SIZE, DURATION: A structured literature search identified eligible articles reporting on persistent pesticides and human semen quality, published in English before 1 September 2012. Opinion articles and reviews were excluded. We assessed the adherence to reporting guidelines of the articles, using and comparing the STROBE statement and the SEMQUA guidelines, in both cases with indicators relevant to observational studies of semen quality. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comprehensive bibliographic search in various electronic literature databases using the key words 'sperm' and 'pesticide' obtained 1179 papers, of which 46 were valid for our purposes. The papers examined occupational (26) and environmental exposure (20). Two of the present authors independently piloted the data extraction form for this review. The articles were then evaluated by two researchers using the STROBE and SEMQUA checklists. MAIN RESULTS AND THE ROLE OF CHANGE: Although no significant differences were found between the overall degree of compliance with STROBE and SEMQUA (47.0 ± 18.5% versus 43.1 ± 11.6%), there were significant differences when only methodological aspects were considered (48.4 ± 21.0% versus 39.5 ± 17.4%; P < 0.001). We observed an increase over time in the degree of compliance, for SEMQUA (r = 0.61 and P < 0.001) and STROBE (r = 0.45 and P < 0.01). The papers that reported a negative effect of exposure to persistent pesticides on sperm concentration presented a lower level of compliance to SEMQUA (42.1 ± 18.3% versus 57.6 ± 14.2%; P < 0.01) and STROBE (40.2 ± 10.3% versus 49.5 ± 11.6%; P < 0.05) than those which recorded no such influence. The year of publication and the observed effect on sperm concentration were the only candidate variables included in the model of stepwise multiple regression model for the 'degree of compliance' variables of SEMQUA and STROBE. LIMITATIONS, REASONS FOR CAUTION: Other characteristics of reporting quality, such as legibility, were not evaluated. WIDER IMPLICATIONS OF THE FINDINGS: The low degree of compliance observed is consistent with that observed in other studies of reproductive medicine and highlights the need to improve the design of studies of semen quality. SEMQUA proved to be a more specific tool than STROBE for the field of semen quality. Editors, reviewers and authors should be aware of SEMQUA and apply it when assessing papers on semen quality. STUDY FUNDING/COMPETING INTEREST(S): No research funding was received and none of the authors have any conflict of interests.

Diagnosis of inherited von Willebrand disease: comparison of two methodologies and analysis of the discrepancies.

Diagnostics of von Willebrand disease (VWD) includes assessment of factor VIII (FVIII) coagulant activity, von Willebrand factor (VWF) antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo), and more specific tests as multimeric and genetic analyses are necessary for the correct VWD classification. The ACL AcuStar analyzer introduces chemiluminescence (CL) technology in detection of VWD with automated VWF:Ag and VWF:RCo assays. Compare VWF:Ag-ELISA and VWF:RCo by aggregometry conventional assays with new CL VWF:Ag-IL and VWF:RCo-IL assays, investigate the ability to make accurate VWD diagnosis and concordance with multimeric and genetic analyses. 146 patients with congenital VWD (51 Type 1; 34 Type 2A; 16 Type 2B; 31 Type 2M; 5 Type 2N; 9 Type 3) and 30 healthy normal subjects were included. A comparison was made between CL and conventional methods. Diagnostic evaluation included: VWF:RCo/VWF:Ag ratio, multimeric distribution (sodium dodecyl sulfate [SDS]-agarose gel) of VWF and genetic analysis in 110 of 146 patients. CL and conventional methods revealed good correlation. Kappa test agreement diagnosis was >0.8. CL diagnostic sensitivity was 100% and specificity 97%. Multimeric and genetic analysis were of help in clarifying 13 discrepancies of diagnosis between methods, of which six discrepancies were explained by lack of conventional methods' sensibility. CL methodology can detect VWD and discriminate between type 1, 3 and variant forms and offers an automated, faster, sensitive and less cumbersome method when compared to conventional assays, in particular VWF:RCo by aggregometry. In some cases, even with all phenotype and genetic analyses, discrepancies exist in the classification of VWD.

Proposal of guidelines for the appraisal of SEMen QUAlity studies (SEMQUA).

STUDY QUESTION: Is there a need for a specific guide addressing studies of seminal quality? SUMMARY ANSWER: The proposed guidelines for the appraisal of SEMinal QUAlity studies (SEMQUA) reflect the need for improvement in methodology and research on semen quality. WHAT IS KNOWN ALREADY: From an examination of other instruments used to assess the quality of diagnostic studies, there was no guideline on studies of seminal quality. STUDY DESIGN, SIZE AND DURATION: Through systematic bibliographic search, potential items were identified and grouped into four blocks: participants, analytical methods, statistical methods and results. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Our findings were presented to a panel of experts who were asked to identify opportunities for improvement. Then, a checklist was designed containing the questions generated by the items that summarize the essential points that need to be considered for the successful outcome of a SEMQUA. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen items were identified, from which 19 questions, grouped into four blocks, were generated to constitute the final checklist. An explanation for the inclusion of each item was provided and some examples found in the bibliographic search were cited. LIMITATIONS AND REASONS FOR CAUTION: We consider that not all items are equally applicable to all study designs, and so the hypothetical results are not comparable. For that reason, a score would not be fair to critically appraise a study. This checklist is presented as an instrument for appraising SEMQUAs and therefore remains open to constructive criticism. It will be further developed in the future, in parallel with the continuing evolution of SEMQUAs. WIDER IMPLICATIONS OF THE FINDINGS: The final configuration of the SEMQUA is in the form of a checklist, and includes the items generally considered to be essential for the proper development of a SEMQUA. The final checklist produced has various areas of application; for example, it would be useful for designing and constructing a SEMQUA, for reviewing a paper on the question, for educational purposes or as an instrument for appraising the quality of research articles in this field. STUDY FUNDING/COMPETING INTEREST(S): None.

Placental concentrations of heavy metals in a mother-child cohort.

Heavy metals are environmental contaminants with properties known to be toxic for wildlife and humans. Despite strong concerns about their harmful effects, little information is available on intrauterine exposure in humans. The aim of this study was to evaluate prenatal exposure to As, Cd, Cr, Hg, Mn, and Pb and its association with maternal factors in a population-based mother-child cohort in Southern Spain. Between 2000 and 2002, 700 pregnant women were recruited and 137 placentas from the cohort were randomly selected and analyzed for the selected metals by atomic absorption. Maternal sociodemographic and lifestyle factors were obtained by questionnaire after delivery. Bivariate analysis and multivariate linear regression were performed. Cd and Mn concentrations were detected in all placentas, while Cr, Pb, and Hg were found in 98.5%, 35.0%, and 30.7% of samples, respectively. The highest concentrations were observed for Pb (mean: 94.80 ng/g wet weight of placenta), followed by Mn (63.80 ng/g), Cr (63.70 ng/g), Cd (3.45 ng/g), and Hg (0.024 ng/g). Arsenic was not detected in any sample. Gestational age and smoking during pregnancy were associated with placental Cd concentrations, while no factor appeared to influence concentrations of Cr, Hg, Mn, or Pb. In comparison to results of European studies, these concentrations are in a low-intermediate position. Studies are required to investigate the factors contributing to early exposure to heavy metals and to determine how placental transfer of these toxic compounds may affect children's health.

Cell cycle, apoptosis, cell differentiation, and lipid metabolism gene expression in endometriotic tissue and exposure to parabens and benzophenones.

AIM: To describe the expression profile in endometriotic tissue of genes involved in four signaling pathways related to the development and progression of endometriosis (cell cycle, apoptosis, cell differentiation and lipid metabolism) and to explore its relationship with the women exposure to chemicals with hormonal activity released from cosmetics and personal care products (PCPs). METHODS: This cross-sectional study, encompassed within the EndEA study, comprised a subsample of 33 women with endometriosis. Expression levels of 13 genes (BMI1, CCNB1, CDK1, BAX, BCL2L1, FOXO3, SPP1, HOXA10, PDGFRA, SOX2, APOE, PLCG1 and PLCG2) in endometriotic tissue and urinary concentrations of 4 paraben (PB) and 3 benzophenone (BP) congeners were quantified. Bivariate linear and logistic regression analyses were performed to explore the associations between exposure and gene expression levels. RESULTS: A total of 8 out 13 genes (61.5 %) were expressed in >75 % of the samples. Exposure to congeners of PBs and/or BPs was associated with the overexpression of CDK1 gene (whose protein drives cells through G2 phase and mitosis), HOXA10 and PDGFRA genes (whose proteins favor pluripotent cell differentiation to endometrial cells), and APOE (whose protein regulates the transport and metabolism of cholesterol, triglycerides and phospholipids in multiple tissues) and PLCG2 genes (whose protein creates 1D-myo-inositol 1,4,5-trisphosphate and diacylglycerol, two important second messengers). CONCLUSIONS: Our findings suggest that women exposure to cosmetic and PCP-released chemicals might be associated with the promotion of cell cycle and cell differentiation as well as with lipid metabolism disruption in endometriotic tissue, three crucial signaling pathways in the development and progression of endometriosis. However, further studies should be accomplished to confirm these preliminary data.

Semen quality and reproductive hormone levels in men from Southern Spain.

In North European countries, a significant difference in semen quality among young men has been shown. Men from the western countries, Denmark, Germany and Norway, have lower semen quality than men from the eastern countries Finland, Estonia and Lithuania. Similarly, men in the western countries have a higher risk of testicular cancer. According to the testicular dysgenesis syndrome (TDS) concept that suggests a link between risk of impaired semen quality and increased risk of testicular cancer, Spanish men would be expected to have a semen quality at a normal level because of their very low testis cancer risk. We therefore investigated 273 men from the Almeria region in the Southern Spain to test this hypothesis. The men delivered semen samples, underwent physical examinations, had a blood sample drawn and provided information on lifestyle and reproductive health parameters. The investigations took place from November 2001 to December 2002. Adjusting for effects of confounders, the median sperm concentration and total sperm count were 62 (95% confidence interval 47-82) million/mL and 206 (153-278) million, respectively. The median numbers of motile and morphologically normal spermatozoa assessed according to strict criteria were 59% (57-62%) and 9.4% (8.6-10.0%), respectively. The median total testosterone and calculated free androgen index were 28 nm (26-30) and 95 (88-103), respectively. Assuming that the investigated men, to a large extent, are representative of the population of young men the Southern Spain, the results show that these have normal semen quality and reproductive hormone levels as expected in a population with a low incidence of testicular cancer.

Concentrations of organochlorine pesticides and polychlorinated biphenyls in human serum and adipose tissue from Bolivia.

Organochlorine pesticides and polychlorinated biphenyls (PCBs) are synthetic chemicals that are highly resistant to biodegradation and have proven adverse health effects. The objectives of this study were to determine concentrations of three selected organochlorine pesticides (p,p'-DDT, p,p'-DDE, HCB) and three specific PCB congeners (PCB 138, 153, 180) in adipose tissue and serum samples from an urban adult population (n=112) in the city of Santa Cruz de la Sierra, Bolivia, and to investigate their relationships within and between the two matrices and with selected socio-demographic characteristics. The percentages of samples positive for these compounds ranged from 40% for PCB 180 to 100% for p,p'-DDE in adipose tissue, and from 21% for HCB to 93% for p,p'-DDE in serum. Median number of residues per sample was five for adipose tissue and three for serum. Geometric mean concentrations indicate a considerable historical and recent exposure to organochlorine pesticides and PCBs in this population. Adipose tissue:serum ratios ranged from 149.3 to 590.3 (wet basis) and from 0.9 to 3.5 (lipid basis). We found positive and statistically significant correlations between adipose tissue and serum concentrations only in p,p'-DDE and HCB. This novel study in Bolivia underlines the need for human biomonitoring to assess exposure to environmental pollutants in South America.

Biomonitoring bisphenols, parabens, and benzophenones in breast milk from a human milk bank in Southern Spain.

BACKGROUND: Human breast milk is considered the optimal source of nutrition for infants. Milk from breast milk banks offers an alternative to infant formulas for vulnerable hospitalized neonates most likely to benefit from exclusive human milk feeding. However, breast milk can also be a source of exposure to environmental contaminants, including endocrine-disrupting chemicals (EDCs). AIM: To evaluate concentrations of phenolic EDCs, including bisphenols, parabens (PBs), and benzophenones (BPs), in samples from a human milk bank in Granada, Southern Spain and to explore sociodemographic, reproductive, and lifestyle factors related to their concentrations in the milk. METHODS: Concentrations of three bisphenols [bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS)], four PBs [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP), and butyl-paraben (n-BuP)], and six BPs [BP-1, BP-2, BP-3, BP-6, BP-8, and 4-hydroxy-BP] were determined in milk samples from 83 donors. Information on potential explanatory variables was gathered using the milk bank donor form and an ad hoc questionnaire. Multiple linear and logistic regression models were fitted. RESULTS: Detectable concentrations were found of at least one of the analyzed compounds in all donor breast milk samples and at least five compounds in one-fifth of them. The most frequently detected compounds were MeP (90.5%), BP-3 (75.0%), EtP (51.2%), n-PrP (46.4%), and BPA (41.7%). Median concentrations ranged between <0.10 ng/mL (n-PrP, n-BuP, BP-1) and 0.59 ng/mL (BP-3). No sample contained detectable concentrations of BPF, BPS, or most BPs (BP-2, BP-6, BP-8, and 4- hydroxy-BP). Breast milk phenol concentrations were associated with parity, the utilization of deodorants, mouthwash, skin care products, and cosmetics, and the intake of nutritional supplements. CONCLUSIONS: Results reveal the widespread presence of BPA, PBs, and BP-3 in donor breast milk samples, highlighting the need for preventive measures to enhance the benefits of breast milk from milk banks and from breastfeeding women in general.