Perfluoroalkyl substances in the meat of Polish farm animals and game - Occurrence, profiles and dietary intake.

Meat from farm animals (pigs, cattle and poultry) and game (wild boar and deer) was analysed in terms of thirteen perfluoroalkyl substances (PFASs). Wild boar muscle tissue was statistically significantly more contaminated than muscle tissue from other animals, and the species order of the lower-bound (LB) sum of four (∑4) PFAS (perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid, perfluorononanoic acid and perfluorohexanesulfonic acid) concentrations was wild boar > cattle > deer > pigs > poultry. None of the samples exceeded the maximum levels set by Commission Regulation (EU) 2023/915. Linear PFOS was the most frequently detected compound (in 21 % of all samples analysed and 100 % of wild boar samples), reaching its highest concentration of 1.87 µg/kg wet weight in wild boar. Dietary intake was estimated on the basis of the average per-serving consumption of pork, beef and poultry, and in the absence of such data for game, a 100 g portion was used for the calculation. Mean LB∑4 PFAS concentrations led to intakes between 0.000 and 1.75 ng/kg body weight (BW) for children and 0.000 and 0.91 ng/kg BW for adults. The potential risk to consumers was assessed in relation to the tolerable weekly intake (TWI) of 4.4 ng/kg BW established by the European Food Safety Authority in 2020. Exposure associated with the consumption of poultry, pork, beef and venison was negligible, being only <1 % of the TWI for children and adults; higher exposure was found to associate with the consumption of wild boar, being 63 % and 21 % of the TWI for children and adults, respectively. The findings of this research suggest that the intake of PFASs through the consumption of meat from Polish livestock and deer is unlikely to be a health concern. However, frequent consumption of wild boar meat could be a significant source of PFASs.

Analytical challenges related to the measurement of chlorothalonil in serum in the perspective of human biomonitoring studies.

Chlorothalonil (CTN) is a popular fungicide widely used in the world. However, its determination in serum samples is highly challenging, preventing a reliable investigation of human CTN internal exposure. We first investigated CTN's behaviour all along this analytical process on spiked serum samples. We used a radiolabelled 14C-CTN standard to monitor CTN in spiked serum samples and observed (1) a complete degradation of CTN in deproteinised serum samples after 4 h of contact; (2) a strong interaction between serum proteins and CTN by-products, with only 20 % of the radioactivity found to be extractable after 24 h of contact and (3) a slightly improved stability of CTN in serum following a first step of acidification or EDTA addition to samples. Using liquid chromatography coupled to high resolution mass spectrometry, 4-hydroxy-2,5,6-trichloroisophthalonitrile (HCTN) was identified as the major serum by-product of CTN. A protocol was developed to monitor both extractable CTN and HCTN from serum. This method was implemented on 36 human adult serum samples from the French "Esteban" Cohort. No free CTN was identified in these serum samples. Conversely, HCTN was detected in all samples at concentrations around 15 ± 2 ng mL-1, corresponding to the extractable fraction of CTN. Thus, HCTN may constitute a relevant biomarker of human internal exposure. Of note, the potential CTN contamination during blood collection could also be a source of HCTN detection in serum samples. Finally, blood sampling in EDTA tubes would seem more appropriate than in dry tubes for any future internal exposure studies on CTN.

Blood levels of persistent organic pollutants among women in France in the 90's: Main profiles and individual determinants.

CONTEXT AND OBJECTIVES: Persistent organic pollutants (POPs) are a group of organic chemical compounds potentially toxic to human health. The objectives of this study were 1) to describe the levels of POPs biomarkers in blood samples from French women collected during the 1990s and to compare them with levels measured in two more recent French studies, 2) to identify POPs exposure profiles, and 3) to explore their main determinants. METHODS: 73 POPs biomarkers were measured in the blood of 468 women from the French E3N cohort (aged 45-73 years), collected between 1994 and 1999: 28 per- and polyfluoroalkyl substances, 27 organochlorine pesticides, 14 polychlorinated biphenyls and 4 polybrominated diphenyl ethers. POPs biomarker levels were described and compared with levels measured in two more recent French studies conducted by the French National Public Health Agency, the ENNS and Esteban studies. Principal component analysis was performed on POPs quantified in at least 75% of samples to identify the main exposure profiles. Linear regression models were used to estimate the associations between anthropometric, socio-demographic and lifestyle characteristics and exposure to these profiles. RESULTS: Among the 73 biomarkers measured, 41 were quantified in more than 75% of samples. Levels of most pollutants that were also measured in the Esteban of ENNS studies have decreased over time. Six POPs exposure profiles were revealed, explaining 62.1% of the total variance. Most of the characteristics studied were associated with adherence to at least one of these profiles. CONCLUSION: This study highlighted that most of the pollutants for which a comparison was possible decreased over the 10 or 20 years following the E3N blood collection, and identified those which, on the contrary, tended to increase. The health effects of the profiles identified could be assessed in future studies. The determinants identified should be confirmed in larger populations.

The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis.

Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting glucose (FG), hs-CRP, ferritin, diastolic BP and steatosis improved significantly, independent of diabetes status: most patients with prediabetes returned to normal FG levels. Significant adiponectin increases correlated with hepatic and CMH marker improvement; patients had an average weight gain of 2.5 kg, with 49% gaining ≥2.5% weight. Therapeutic benefits were similar regardless of weight change. Here, we show that effects of lanifibranor on liver histology in MASH are accompanied with CMH improvement, indicative of potential cardiovascular clinical benefits.

Perfluoroalkyl substances (PFAS) occurrence, concentrations and spatial distribution along the French Mediterranean coast and lagoons, based on active biomonitoring.

Tracking PFAS in ecosystems is challenging. In this context, monitoring programs are crucial to fill data gaps, especially in marine environments, which are the ultimate outlets for these forever chemicals. The 2021 chemical contamination monitoring campaign along the French Mediterranean coast established a baseline for PFAS concentrations in mussels, with 90 % of measurements below quantification limits. When detected, long-chain PFCA's were predominant. Spatial distribution patterns suggested continuous PFAS inputs and complex dynamics, shaped by the influence of large watersheds and rivers (Rhône, Aude, Huveaune). Lapeyrade shallow lagoon stood out as the most contaminated site. Similar PFAS profiles in connected sites implied shared sources but raised questions about accumulation processes in mussels. While certain sites had evident sources (e.g., military airbase for Palo lagoon), others remained uncertain (e.g., Toulon bay). Coastal stations (Banyuls, Cap Agde, Brégançon, Pampelonne) showed PFAS contamination without clear onshore sources, possibly due to insufficient transportation process understanding.

Quantification of chlorinated paraffins by chromatography coupled to high-resolution mass spectrometry - Part A: Influence of gas chromatography and ionisation source parameters.

The analysis of chlorinated paraffins (CPs) has become a major analytical challenge. GC-ECNI-HRMS coupling is often used to analyse and quantify them. However, the influence of certain GC and ECNI parameters on the responses of polychlorinated n-alkanes (PCAs), the dominant components of CPs, has hardly been studied. In this paper, we investigated not only the influence of GC column characteristics, but also oven, GC inlet and source temperatures for simultaneous analysis of PCAs with chain-length ranging from 10 up to 20 carbon atoms (PCAs-C10-20). Particular attention was paid to the absolute response and PCA homologue group pattern obtained for a CP technical mixture. The optimum conditions for a wide homologue group determination were GC inlet, final gradient and ion source temperatures set at 220-240 °C, 340 °C and 200 °C. At the same time, a higher response was obtained with the Optima 5HT column compared to Optima 1 column, and with a length and film thickness of 12.5 m and 0.25 µm, respectively. The homologue group pattern of the technical mixture studied was significantly modified as a function of the source and GC inlet temperatures, film thickness and composition of the stationary phase. Here we recommend conditions that will improve the overall PCA pattern, in order to better characterise their occurrence in future environmental monitoring and exposure assessment.

Quantification of chlorinated paraffins by chromatography coupled to high-resolution mass spectrometry - Part B: Influence of liquid chromatography separation.

The analysis of chlorinated paraffins (CPs) is today an analytical challenge. Indeed, it is still impractical to describe their real composition in terms of polychlorinated alkanes (PCAs) homologue groups, which dominate technical mixtures. The co-elution of PCA congeners generates interferences due to the competition phenomena which occur during the ionisation process as well as to the dependence of the ionisation sources on the PCA chemistry. Therefore, the aim of this study was to investigate the influence of chromatographic separation, by LC-ESI-HRMS coupling, on the PCA homologue group pattern and, eventually, on their determination in food samples from interlaboratory studies. For this, three different mobile phases and six LC chromatographic columns were studied in order to optimise the analysis of CP mixtures. The first results showed that the use of a MeOH/H2O mobile phase reveals more appropriately the higher chlorinated PCAs. However, using ACN/H2O led to less ion species, with almost exclusively [M + Cl]- adducts, formed using post-column dichloromethane addition. Regarding the choice of the stationary phases, Hypercarb column provided a completely different homologue group pattern from the other chromatographic columns, in relation with the stronger retention of PCAs. Among the other columns, the C30 column better highlighted the short-chain PCAs compared to the C18 column conventionally used. Because the regulations now concern short-chain CPs, the quantification of food samples was then carried out on the C30 column. The optimised LC-ESI-HRMS conditions using C30 column and MeOH/H2O solvent mixture led to a quantification of PCAs in samples from interlaboratory studies with satisfactory accuracy (|Z-score| ≤ 2) and precision (<15%).

A comprehensive multiplatform metabolomic analysis reveals alterations of 2-hydroxybutyric acid among women with deep endometriosis related to the pesticide trans-nonachlor.

BACKGROUND: Exposure to persistent organic pollutants (POPs) has been related to the risk of endometriosis however the mechanisms remain unclear. The objective of the present study was to characterize the metabolic profiles underpinning the associations between POPs and endometriosis risk. METHODOLOGY: A hospital-based case-control study was conducted in France to recruit women with and without surgically confirmed deep endometriosis. Women's serum was analyzed using gas and liquid chromatography coupled to high-resolution mass spectrometry (HRMS) to measure the levels of polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and per-/polyfluoroalkyl substances (PFAS). A comprehensive metabolomic profiling was conducted using targeted HRMS and 1H nuclear magnetic resonance (1H NMR) to cover polar and non-polar fractions. A "meet-in-the-middle" statistical framework was applied to identify the metabolites related to endometriosis and POP levels, using multivariate linear and logistic regressions adjusting for confounding variables. RESULTS: Fourteen PCBs, six OCPs and six PFAS were widely found in almost all serum samples. The pesticide trans-nonachlor was the POP most strongly and positively associated with deep endometriosis risk, with odds ratio (95 % confidence interval) of 2.42 (1.49; 4.12), followed by PCB180 and 167. Women with endometriosis exhibited a distinctive metabolic profile, with elevated serum levels of lactate, ketone bodies and multiple amino acids and lower levels of bile acids, phosphatidylcholines (PCs), cortisol and hippuric acid. The metabolite 2-hydroxybutyrate was simultaneously associated to endometriosis risk and exposure to trans-nonachlor. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive metabolome-wide association study of endometriosis, integrating ultra-trace profiling of POPs. The results confirmed a metabolic alteration among women with deep endometriosis that could be also associated to the exposure to POPs. Further observational and experimental studies will be required to delineate the causal ordering of those associations and gain insight on the underlying mechanisms.

Polychlorinated Naphthalenes in Foods from the French Market: Occurrence, Dietary Exposure, and Evaluation of Relative Contributions to Dioxin-like Contaminants.

Despite the growing interest in PCNs and the dioxin-like toxicity exhibited by a number of congeners, a comprehensive assessment of their contribution to the cocktail of dioxin-like contaminants is still lacking. To address such a shortcoming, this study investigated the PCN contamination in foodstuffs recently acquired in France, together with that of the regulatory polychlorinated dibenzodioxins/furans (PCDD/Fs) and polychlorinated biphenyls (PCBs). PCNs were ubiquitous at levels (∑70 PCNs = 2.5-150 pg g-1 wet weight) similar to those reported in other countries, with maximum concentrations observed in fish and fishery products from the North-East Atlantic Ocean. Their congener patterns further suggested unintentional releases of PCNs, while those of the other foodstuffs were correlated to the historical PCN profiles. Low risk from dietary exposure was estimated (∑70 PCNs-EDIs of 60-360 pg kg-1 bw d-1, ∑24 PCNs-TEQ-EDIs of 8 × 10-3-2.2 × 10-2 pg TEQ kg-1 bw d-1), with milk and dairy products being the highest contributors, followed by meat and meat products. Finally, the rather high contributions of PCNs to the total PCNs+PCDD/Fs+PCBs concentrations (0.9-50%, average of 9%) and the toxic equivalents (0.2-24%, average of 5%) show that these substances are not minor components of the PCNs+PCDD/Fs+PCBs cocktail.

Short-term functional outcomes of robotic-assisted TKA are better with functional alignment compared to adjusted mechanical alignment.

INTRODUCTION: Ligament balancing is essential to the functional outcome of total knee arthroplasty (TKA). The optimal method of alignment remains a controversial issue. The primary objective was to compare the clinical outcomes of TKA between functional and adjusted mechanical alignment techniques. The secondary objectives were to compare bone resection, robotic alignment, and radiological assessment. MATERIALS AND METHODS: This was a retrospective case-control series comparing TKA performed with functional alignment (FA) and adjusted mechanical alignment (aMA). Sixty-four FA subjects were matched with 64 aMA controls. These two groups were matched for age, gender, body mass index (BMI), surgeon, and type of frontal deformity. Both surgical procedures were performed using the MAKO® haptic robotic system. Functional scores (Forgotten Joint Score (FJS), Knee Society Score (KSS), and Oxford Knee Score (OKS)) were measured at the final postoperative follow-up. A radiographic evaluation was performed at the same time. RESULTS: Mean FJS were respectively 63.4 ± 25.1 [0-100] and 51.2 ± 31.8 [0-100] in FA versus aMA group (p = 0.034). Mean OKS were respectively 40.8 ± 6.3 [21-48] and 34.9 ± 11.8 [3-48] in FA versus aMA group (p = 0.027). Mean KSS were respectively 184.9 ± 17.0 [126-200] and 175.6 ± 23.1 [102-200] in FA versus aMA group (p = 0.02). The main residual symptom was "none" for 73.0% versus 57.8%, "instability" for 6.4% versus 21.9%, "Pain" for 19.1% versus 12.5%, and "effusion" for 1.6% and 7.8% respectively for FA and aMA group (p = 0.016). There were 4 complications in the FA group versus 5 in the aMA group (p > 0.999). Mean postoperative hip-knee-ankle (HKA) robotic assessment were respectively 177.3° ± 2.0 [172-180] and 178.2° ± 2.0 [173-180] for FA and aMA group (p = 0.018). The median difference between HKA robotic and HKA radiological was -3.0° (IQR = 3.0; p < 0.001). CONCLUSION: With greater residual deformity and without release, functional alignment showed a statistically significantly better short-term clinical outcome than adjusted mechanical alignment. This difference may not be clinically significant.

First Observations of a Potential Association Between Accumulation of Per- and Polyfluoroalkyl Substances in the Central Nervous System and Markers of Alzheimer's Disease.

The entire human population is exposed to persistent organic pollutants throughout their lives. Among them, per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in industrial and consumer products that are known to exert adverse effects on human health. As they bioaccumulate in the human brain and are known to be neurotoxic in experimental models, they are assumed to be involved in neurodegenerative processes. In this proof-of-concept study, we measured the level of 18 PFAS in cerebrospinal fluid (CSF) from 8 patients hospitalized with suspected normal pressure hydrocephalus. We then analyzed whether PFAS levels could be related to both biological and clinical markers of Alzheimer's disease. We showed that PFAS and perfluorooctanesulfonate were found in all CSF samples from a French region without fluorochemical industries. Moreover, we observed a significant difference between the levels of PFAS and perfluorooctanesulfonate in the CSF of patients with both Alzheimer's disease markers and cognitive impairment compared with those with only 1 or neither. Two previous studies have shown that PFAS levels in human CSF increase with age and are linked to impaired blood-brain barrier integrity. Our results provide the first evidence of a link between PFAS accumulation in the central nervous system and clinical and biological markers of Alzheimer's disease.

Exposure of the general French population to herbicides, pyrethroids, organophosphates, organochlorines, and carbamate pesticides in 2014-2016: Results from the Esteban study.

Esteban is a nationwide cross-sectional study conducted in France in 2014-2016, including 2503 adults aged 18-74 years old and 1104 children aged 6-17 years old, as part of the French Human Biomonitoring programme. The present paper describes the biological levels of five families of pesticides analysed on random sub-samples of 900 adults and 500 children for urine concentrations, and 759 adults and 255 children for serum concentrations, and the determinants of exposure. Organophosphates, carbamates and herbicides were measured in urine by UPLC-MS/MS; chlorophenols and pyrethroids were measured in urine by GC-MS/MS; specific organochlorines were measured in serum by GC-HRMS. Multivariate analyses were performed to identify the determinants of exposure using a generalized linear model. Pyrethroid metabolites were quantified in 99% of adults and children, with the exeption of F-PBA, which was quantified in 31% of adults and 27% of children, respectively. Carbamates and some specific organophosphates were barely or not quantified. DMTP was quantified in 82% of adults and 93% of children, and γ-HCH (lindane) was quantified in almost 50% of adults and children. Concentration levels of pesticide biomarkers were consistent with comparable international studies, except for ß-HCH, DMTP, and the deltamethrin metabolite Br2CA, whose levels were sometimes higher in France. Household insecticide use and smoking were also associated with higher levels of pyrethroids. All pyrethroids concentration levels were below existing health-based HBM guidance values, HBM-GVsGenPop, except for 3-PBA, for which approximately 1% and 10% of children were above the lower and upper urine threshold values of 22 µg/L and 6.4 µg/L, respectively. Esteban provides a French nationwide description of 70 pesticide biomarkers for the first time in children. It also describes some pesticide biomarkers for the first time in adults, including glyphosate and AMPA. For the latter, urine concentration levels were overall higher in children than in adults. Our results highlight a possible beneficial impact of existing regulations on adult exposure to organochlorine and organophosphate pesticides between 2006 and 2016, as concentration levels decreased over this period.

Associations between perfluoroalkyl substances and the severity of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide and the determinants driving its severity remain to be elucidated. Perfluoroalkyl substances (PFAS) are synthetic chemical compounds. They are used in commonplace products and persistent in water, soil and the human body. In vitro and animal studies suggest a pathogenic role for PFAS in metabolic diseases such as NAFLD. OBJECTIVES: We aimed to evaluate the association between NAFLD severity and serum PFAS concentrations in humans. METHODS: One hundred biopsy-proven NAFLD patients were included with a well-balanced distribution between the different stages of severity: 25 patients with simple steatosis, 25 with early non-alcoholic steatohepatitis (NASH and F0-F1 fibrosis), 33 with fibrotic NASH (NASH and F2-F3 fibrosis), and 17 with cirrhotic NASH (NASH and F4 fibrosis). Liver histological features were evaluated according to the NASH Clinical Research Network classification. Seventeen PFAS were measured by high-performance liquid chromatography coupled with tandem mass spectrometry on serum samples stored at -80 °C. RESULTS: The median age was 60 years, 61 % of patients were male, 46 % had diabetes and the median body mass index (BMI) was 32 kg/m2. Long-chain PFAS were associated with steatosis grade (p = 0.03). Among the nine PFAS detected in > 50 % of the patients, Perfluoro-n-heptanoic acid (PFHpA) showed significantly higher concentrations in grade 3 steatosis versus grade 1 (p = 0.02). Perfluoro-n-dodecanoic acid (PFDoA) concentrations were higher in patients with significant fibrosis (p = 0.04) and PFHpA in patients with advanced fibrosis (p = 0.02). The association between PFHpA and steatosis grade remained significant in multivariate analysis adjusted for age, gender, BMI, diabetes presence and dyslipidemia (p = 0.004). DISCUSSION: Our study showed a significant association between PFHpA and liver steatosis in NAFLD. According to data available in the literature, PFHpA could be implicated in liver steatosis through ß-oxidation and biosynthesis of fatty acids.

A percutaneous ultrasound-guided iliotibial band release technique reduces surgical time and costs compared to an endoscopic technique.

PURPOSE: External snapping hip is caused by the iliotibial band snapping from the greater trochanter during hip movement. The aim of this study was to compare a technique of ultrasound-guided iliotibial band release versus a similar endoscopic technique. METHODS: An anatomical study was performed on 10 cadavers i.e. 20 hips. The same operator performed ultrasound-guided and endoscopic iliotibial band release on either side of each specimen. An independent operator performed an open control to verify the outcome measures. The primary outcome was iliotibial cutting percentage, defined as the ratio of the transversal cut distance and the width of the iliotibial at the most prominent portion of the great trochanter. Secondary outcomes included nerve injuries. The surgical time was assessed and disposable medical supplies costs were estimated. RESULTS: The average cutting percentage was 95% ± 8 by ultrasound, compared with 91% ± 11 by endoscopy (n.s.). No iatrogenic lesions were found, particularly nerve damage. The average duration of the ultrasound procedure was 12.3 minutes ± 6 compared to 21 minutes ± 10.7 for endoscopy (p=0.04), with a 3-fold decrease between the first and last procedure, regardless of the technique. The ultrasound procedure was 3 times less expensive in terms of disposable medical supplies (120.5€ versus 353.5€). CONCLUSION: This technique of ultrasound-guided iliotibial band release appears to be as effective and safe as a similar endoscopic technique. The surgical time is reasonable for a surgeon trained in ultrasound, with lower disposable supplies costs. A comparative clinical study is further needed to assess the actual benefits of each technique.

Characterization of pregnant women exposure to halogenated parabens and bisphenols through water consumption.

Exposure of pregnant women to endocrine disruptor compounds, such as parabens and bisphenol A is of concern for fetal transition. Their halogenated degradation products, mainly coming from water treatment plans, could be problematic as well, depending on their occurrence in drinking water in the first place. Thus, 25 halogenated compounds were synthesised in order to investigate 60 substances (Bisphenols, parabens and their degradation products) in 325 drinking water samples coming from a French cohort study of pregnant women. Analysis was performed by tandem mass spectrometry coupled to gas chromatography (GC-MS/MS) after SPE extraction and derivation of the contaminants. Results indicate that parabens (methylparaben, n-propylparaben, ethylparaben and n-butylparaben), bisphenols S, A and F, and their degradation product, 4-hydroxybenzoic acid, were detected up to several hundred ng/L in drinking water, with detection frequencies between 16% and 88%. Regarding halogenated degradation products, the highest detection frequencies were found for monochlorinated products (about 50% for 2-chlorobisphenol A), which were quantified up to several tens of ng/L. Such analytical approaches with broader spectrum of monitoring (i.e. chemical hazards and their degradation products) constitute in the beginning of a solution to exhaustively answer the questions related to the characterization of the human chemical exposome.

Persistent organochlorine pesticides in periprostatic adipose tissue from men with prostate cancer: Ethno-geographic variations, association with disease aggressiveness.

Although several studies have examined the relationship between organochlorine pesticides (OCPs) and prostate cancer (PCa) risk, no data are available concerning the association between OCPs concentrations in periprostatic adipose tissue (PPAT), which reflects cumulative exposure, and PCa aggressiveness. Moreover, no previous study has compared OCPs exposure in two distinct ethno-geographical populations. The objectives were to analyze OCPs in PPAT of PCa patients from either Mainland France or French West Indies in correlation with features of tumor aggressiveness, after adjusting for potential confounders such age, BMI, and polyunsaturated fatty acid (PUFA) content of PPAT. PPAT was analyzed in 160 patients (110 Caucasians and 50 African-Caribbeans), 80 with an indolent tumor (ISUP group 1 + pT2), and 80 with an aggressive tumor (ISUP group more than 3 + pT3). The concentrations of 29 OCPs were measured in PPAT concomitantly with the characterization of PUFA content. Exposure patterns of OCPs differed according to the ethno-geographical origin. Most OCPs were found at higher concentration in Caucasian patients, whereas pp'-DDE content was twice as high in African-Caribbeans. Chlordecone was only detected in PPAT from African-Caribbean patients. Most OCP concentrations were positively correlated with age, and some with BMI. After adjusting for age, BMI, and PUFA composition of PPAT, no significant association was found between OCPs content and risk of aggressive disease, except of mirex which appeared inversely associated with aggressive features of PCa in Caucasian patients. These results highlight a significant ethno-geographic variation in internal exposure to OCPs, which likely reflects differences in consumption patterns. The inverse relationship observed between mirex concentration and markers of PCa aggressiveness need to be further investigated.

Mixtures of persistent organic pollutants and ovarian function in women undergoing IVF.

RESEARCH QUESTION: Do internal levels of persistent organic pollutants (POP) in serum and follicular fluid affect ovarian function of women attending IVF? DESIGN: This cohort study included 136 women undergoing IVF in the assisted reproductive technology (ART) service of University Hospital from Nantes (France). Representative POP were measured using gas and liquid chromatography coupled with tandem mass spectrometry. Polyfluoroalkylated and perfluoroalkylated substances were measured in serum and polychlorinated biphenyls and organochlorinated pesticides in follicular fluid. Statistical associations between POP and ovarian reserve markers (anti-Müllerian Hormone [AMH] and antral follicle count [AFC], and ovarian responsiveness markers (Ovarian Sensitivity Index [OSI] and Follicular Output RaTe [FORT]), were explored in single and multipollutant regression models. RESULTS: Twenty-seven out of 53 POP congeners were frequently detected in almost all women attending IVF. Adjusted models did not show statistically significant associations between POP and ovarian reserve markers. Positive associations were found between some POP, i.e. hexachlorobenzene with FORT (ß 0.42, 95% CI 0.13 to 0.71, P = 0.005) or PCB52 with Ovarian Sensitivity Index (ß 0.22; 95% CI, 0.07 to 0.38, P = 0.005). Negative associations between some polyfluoroalkylated and perfluoroalkylated substances, PCB189 and trans-nonachlor with AFC and AMH were found among current smokers. CONCLUSIONS: Globally, associations between POP and the markers of ovarian function or responsiveness were lacking. Nonetheless, the stratification analysis suggested that current smoking could be a risk modifier, and extension of the study to a larger population sample size is needed.

Varus stem positioning does not affect long-term functional outcome in cementless anatomical total hip arthroplasty.

INTRODUCTION: Varus positioning is the most common femoral malposition in total hip arthroplasty (THA). We compared the long-term outcomes of an anatomical cementless femoral stem positioned in varus versus neutral alignment. MATERIALS AND METHODS: Data were retrospectively reviewed for all patients receiving a cementless anatomical femoral stem in THA for osteoarthritis between 1998 and 2008. Exclusion criteria were complex cases, incomplete data or follow-up < 1 year. Primary outcome was survival rate with complications and secondary outcomes were clinical scores, thigh pain, radiological score, cortical hypertrophy and filling rate. RESULTS: Of the 283 included patients, 127 stems were classified as varus and 156 neutral. Mean follow-up was 10 years. Femoral stem size was smaller in the varus group (4.1 vs. 4.4, p = 0.047). A stem-filling rate < 80% was more frequent in the varus group (p < 0.001). The long-term survival rate without any revision procedure was 94.8% ± 2.3% (95%CI 88.4-98.7) in the varus group and 94.1% ± 2.0% (95%CI 91.3-99.1) in the neutral group (p = 0.55). There was no difference in clinical scores, thigh pain or complication occurrence between groups. The Engh-Massin score was lower in the varus group (p < 0.01) and cortical hypertrophy was higher (p < 0.001). CONCLUSIONS: A varus alignment of a cementless anatomic femoral stem does not affect survivorship, clinical outcomes or complication rate on an average follow-up of 10 years, despite increasing stress-shielding rates.

Health risk assessment to polychlorinated naphthalenes dioxin-like compounds in French sea food consumers.

There has been a recent revival of interest in some historical contaminants such as polychlorinated naphthalenes (PCNs). However, occurrence data are still lacking in some countries although industrial production of PCNs has been reported. This observation led to the first ever assessment of their presence in fish and seafood products in France in the present work. Their analysis was integrated in an already validated method applied for polychlorinated dibenzodioxins/furans (PCDD/Fs) and polychlorinated biphenyls (PCBs), based on the structural similarity existing between these POPs. Performances of the method (LODs in the range 0.10-0.28 pg g-1 wet weight (ww), LOQs in the range 0.33-0.93 pg g-1 ww), enabled monitoring 69 di-to octachlorinated congeners in a large representative set of fish and seafood samples collected in 2005 in four coastal areas of the French mainland (n > 30). Their systematic presence was demonstrated in all the investigated seafood products, with levels (ΣPCNs in the range 2-440 pg g-1 wet weight) close to those already reported in other European fish and seafood sampled at a similar period. In addition, the robust measurement of almost all possible PCNs (69/75) allowed a fine interpretation of the observed profiles, highlighting in particular the specificities between species and fishing areas. Compared to the PCDD/Fs, PCBs, and polybrominated diphenylethers levels also measured for this set of samples, PCNs were observed as minor contributors to total concentrations (0.05-3.2%). The specific PCN related dietary dioxin-like exposure could be evaluated at 0.028-0.051 pg of toxic equivalent (TEQ) per kg of body weight per week for an adult, based on fish and seafood consumption only. Overall, this study provides the first baseline data on the occurrence of a large number of PCNs in France, which will allow future evaluation of temporal trends and associated risks.