Abstract  Per- and polyfluoroalkyl substances (PFASs), including fluorotelomer alcohols (FTOHs), perfluoroalkyl sulfonamidoethanols (FOSEs), and perfluoroalkyl sulfonamides (FOSAs), were assessed in 61 residential indoor air and 15 personal air samples collected in Oslo area, Norway. FTOHs were detected in all samples, and the median concentrations in residential indoor air were 2970, 10400, and 3120 pg m-3 for 6:2, 8:2, and 10:2 FTOH, respectively. This is similar to or higher than previously reported in studies from the same geographical area and worldwide. FOSEs and FOSAs were detected in 49-70% and 7-13% of the residential indoor air samples, respectively. The median FTOH concentrations observed in personal air were 1970, 7170, and 1590 pg m-3 for 6:2, 8:2, and 10:2 FTOH, respectively, which is 30 to 50% lower than the median concentrations in residential indoor air. No FOSEs or FOSAs were detected above the method detection limit (MDL) in the personal air samples. Intakes of perfluorohexanoate (PFHxA), perfluoroheptanoate (PFHpA), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and perfluorooctyl sulfonate (PFOS) through inhalation and biotransformation of PFAS precursors in air were estimated. Median intakes of 1.7, 0.17, 5.7, 0.57, 1.8, 0.18, and 2.3 pg kg bw-1 day-1 were obtained in residential indoor air, while 1.0, 0.10, 3.3, 0.33, 0.88, and 0.09 pg kg bw-1 day-1 were found in personal air for PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, and PFOS, respectively. The median PFOA intakes from residential indoor air (5.7 pg kg bw-1 day-1) and personal air (3.3 pg kg bw-1 day-1) were both around 5 orders of magnitude lower than the tolerable daily intake (TDI) reported by the European Food Safety Authority (EFSA).

Abstract  OBJECTIVE: The objective of this research is to determine the association of seven perfluoroalkyl and polyfluoroalkyl substances versus dental caries experience in US children, ages 3-11 years.

METHODS: A cross-sectional study design was used in the analysis of National Health and Nutrition Examination Survey 2013-2014 serological data of perfluoroalkyl and polyfluoroalkyl substances. The seven perfluoroalkyl and polyfluoroalkyl substances were: 2-(N-methyl-perfluorooctane sulfonamide) acetic acid; perfluorodecanoic acid; perfluorononanoic acid; perfluorohexane sulfonic acid; linear isomers of perfluorooctanoate; linear perfluorooctane sulfonate; and monomethyl branched isomers of perfluorooctane sulfonate. Two summative variables were created: monomethyl branch isomers of perfluorooctane sulfonic acid with linear isomer of perfluorooctane and branch isomers of perfluorooctanoate with linear isomer perfluorooctonate.

RESULTS: In unadjusted logistic regression, in which the comparison was between the less than 75th percentile reference group and the 75th and above percentile group, higher perfluorodecanoic acid was associated with dental caries experience [unadjusted odds ratio: 1.79 (95% CI: 1.19, 2.46; P = 0.0069); adjusted odds ratio: 1.54 (95% CI: 1.03, 2.30; P = 0.0385)].

CONCLUSIONS: Of the seven examined perfluoroalkyl and polyfluoroalkyl substances, only perfluorodecanoic acid had an association with dental caries experience in an unadjusted model and adjusted logistic regression model.

Abstract  There is evidence of a positive association between per- and polyfluoroalkyl substances (PFASs) and cholesterol levels in human plasma, which may be due to common reabsorption of PFASs and bile acids (BAs) in the gut. Here we report development and validation of a method that allows simultaneous, quantitative determination of PFASs and BAs in plasma, using 150 μL or 20 μL of sample. The method involves protein precipitation using 96-well plates. The instrumental analysis was performed with ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS), using reverse-phase chromatography, with the ion source operated in negative electrospray mode. The mass spectrometry analysis was carried out using multiple reaction monitoring mode. The method proved to be sensitive, robust, and with sufficient linear range to allow reliable determination of both PFASs and BAs. The method detection limits were between 0.01 and 0.06 ng mL-1 for PFASs and between 0.002 and 0.152 ng mL-1 for BAs, with the exception of glycochenodeoxycholic acid (0.56 ng mL-1). The PFAS measured showed excellent agreement with certified plasma PFAS concentrations in NIST SRM 1957 reference serum. The method was tested on serum samples from 20 healthy individuals. In this proof-of-concept study, we identified significant associations between plasma PFAS and BA levels, which suggests that PFAS may alter the synthesis and/or uptake of BAs. Graphical Abstract.

Abstract  The fluorescence solvatochromism of p-phenylenediamine-derived carbon dots (CDs) was modulated through surface modification with decanoic acid or perfluorodecanoic acid. This is attributed to the adjustment of the dipole interaction between solvent molecules and the CD surface in terms of steric hindrance of a surface modifier and polarization of the modified CD surface.

Abstract  The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances (PFASs) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFASs: PFOA, PFNA, PFHxS and PFOS. These made up half of the lower bound (LB) exposure to those PFASs with available occurrence data, the remaining contribution being primarily from PFASs with short half‐lives. Equal potencies were assumed for the four PFASs included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL10 of 17.5 ng/mL for the sum of the four PFASs in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake (TWI) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI, which is of concern.

Abstract  Multiparous female Long-Evans rats, 20 months or older, were seen to progress from irregular estrous cycles to a constant-estrous syndrome to a series of irregular pseudopregnancies to an anestrous state. An animal in constant estrus was characterized by ovaries with well developed and sometimes cystic follicles, no corpora lutea, an estrogen-stimulated uterus, and an anterior pituitary that appeared normal. Repeatedly pseudopregnant rats had long diestrous periods of variable length, ovaries with many corpora lutea, uteri with numerous secretory glands, and anterior pituitaries that often showed hemorrhagic or small tumorous areas. Anestrous rats had small, atrophic ovaries with no obvious follicular or luteal elements, atrophic uteri, and large pituitary tumors. Twice-daily injections of L-dopa induced the resumption of regular or irregular estrous cycles in most constant-estrous but not in pseudopregnant or anestrous rats.

Abstract  Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age, causing a range of reproductive, metabolic and endocrine defects including anovulation, infertility, hyperandrogenism, obesity, hyperinsulinism, and an increased risk of type 2 diabetes and cardiovascular disease. Hyperandrogenism is the most consistent feature of PCOS, but its etiology remains unknown, and ethical and logistic constraints limit definitive experimentation in humans to determine mechanisms involved. In this study, we provide the first comprehensive characterization of reproductive, endocrine, and metabolic PCOS traits in 4 distinct murine models of hyperandrogenism, comprising prenatal dihydrotestosterone (DHT, potent nonaromatizable androgen) treatment during days 16-18 of gestation, or long-term treatment (90 days from 21 days of age) with DHT, dehydroepiandrosterone (DHEA), or letrozole (aromatase inhibitor). Prenatal DHT-treated mature mice exhibited irregular estrous cycles, oligo-ovulation, reduced preantral follicle health, hepatic steatosis, and adipocyte hypertrophy, but lacked overall changes in body-fat composition. Long-term DHT treatment induced polycystic ovaries displaying unhealthy antral follicles (degenerate oocyte and/or > 10% pyknotic granulosa cells), as well as anovulation and acyclicity in mature (16-week-old) females. Long-term DHT also increased body and fat pad weights and induced adipocyte hypertrophy and hypercholesterolemia. Long-term letrozole-treated mice exhibited absent or irregular cycles, oligo-ovulation, polycystic ovaries containing hemorrhagic cysts atypical of PCOS, and displayed no metabolic features of PCOS. Long-term dehydroepiandrosterone treatment produced no PCOS features in mature mice. Our findings reveal that long-term DHT treatment replicated a breadth of ovarian, endocrine, and metabolic features of human PCOS and provides the best mouse model for experimental studies of PCOS pathogenesis.

Abstract  In the present paper we describe changes of anatomical parameters in inbred Lewis strain rats, namely their body weight, body weight gain per week, absolute and relative heart, thyroid gland and skeletal muscle weights, that are assumed to reflect experimentally altered thyroid status. The hyperthyroid state was induced by DL-thyroxine or Na 3,3',5-triiodo-L-thyronine, while methimazole was employed for inducing hypothyroidism. We have found that when compared to euthyroid rats, hypothyroidism resulted in a significantly lower body weight gain, absolute and relative heart weight and, in contrast, in a significant increase of absolute and relative thyroid gland weight. On the other hand, hyperthyroidism led to a significant increase of absolute and relative heart weight and to a significant reduction of absolute and relative thyroid gland weight. However, the body mass was not significantly altered in hyperthyroidism as compared with euthyroid rats. We conclude that our protocol leads to chronic hyper- or hypothyroidism as demonstrated by body, heart and thyroid gland weight changes. These anatomical data can thus be utilized as supplemental criteria for the assessment of the thyroid state of experimental rats.

Abstract  Allergic responses are the result of the activation of mast cells and basophils, and the subsequent release of vasoactive and proinflammatory mediators. Exposure to an allergen in a sensitized individual can result in clinical symptoms that vary from minor erythema to life threatening anaphylaxis. In the laboratory, various animal models have been developed to understand the mechanisms driving allergic responses. Herein, we describe a detailed method for measuring changes in vascular permeability to quantify localized allergic responses. The local anaphylaxis assay was first reported in the 1920s, and has been adapted from the technique published by Kojima et al. in 2007(1). In this assay, mice sensitized to OVA are challenged in the left ear with vehicle and in the right ear with OVA. This is followed by an intravenous injection of Evans Blue dye. Ten min after injecting Evans Blue, the animal is euthanized and the dye that has extravasated into the ears is extracted overnight in formamide. The absorbance of the extracted dye is then quantified with a spectrophotometer. This method reliably results in a visual and quantifiable manifestation of a local allergic response.

Abstract  Ethnopharmacological relevance: Curine is a bisbenzylisoquinoline alkaloid and the major constituent isolated from Chondrodendron platyphyllum, a plant that is used to treat inflammatory diseases in Brazilian folk medicine. This study investigates the effectiveness of curine on mast cell-dependent responses in mice.Materials and methods: To induce mast cell-dependent responses, Swiss mice were subcutaneously sensitized with ovalbumin (OVA-12 mu g/mouse) and Al(OH)(3) in a 0.9% NaCl solution. Fifteen days later, the animals were challenged with OVA through different pathways. Alternatively, the animals were injected with compound 48/80 or histamine, and several parameters, including anaphylaxis, itching, edema and inflammatory mediator production, were analyzed. Promethazine, cromoglycate, and verapamil were used as control drugs, and all of the treatments were performed 1 h before the challenges.Results: Curine pre-treatment significantly inhibited the scratching behavior and the paw edema induced by either compound 48/80 or OVA, and this protective effect was comparable in magnitude with those associated with treatment with either cromoglycate or verapamil. In contrast, curine was a weak inhibitor of histamine-induced paw edema, which was completely inhibited by promethazine. Curine and verapamil significantly inhibited pleural protein extravasations and prostaglandin D-2 (PGD(2)) and cysteinyl leukotrienes (CysLTs) production following allergen-induced pleurisy. Furthermore, like verapamil, curine inhibited the anaphylactic shock caused by either compound 48/80 or an allergen. In in vitro settings, these treatments also inhibited degranulation as well as PGD(2) and CysLT production through IgE-dependent activation of the mast cell lineage RBL-2H3.Conclusion: Curine significantly inhibited immediate allergic reactions through mechanisms more related to mast cell stabilization and activation inhibition than interference with the pro-inflammatory effects of mast cell products. These findings are in line with the hypothesis that the alkaloid curine may be beneficial for the treatment of allergic disorders. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Abstract  Background: Hypercholesterolemia is a major cardiovascular risk factor, and cholesterol awareness is important in both clinical practice and in public health. We evaluated the validity of self-reported hypercholesterolemia and identified determinants of validity.Methods: The study design was a cross-sectional survey, from 1988 to 1994, of adult participants (N=8236) from the Third National Health and Nutrition Examination Survey for whom self-report of hypercholesterolemia and serum measurement were available. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for self-reported hypercholesterolemia were calculated using total cholesterol greater than or equal to5.17 mmol/L (200 mg/dL) and/or taking cholesterol-lowering medication as the criterion standard.Results: Overall test characteristics for self-report were sensitivity, 51%; specificity, 89%; PPV, 87%; and NPV, 55%. Sensitivity of self-report was higher among older subjects and non-Hispanic whites, specificity was higher among subjects with >12 years of education, PPV was higher in older subjects, and NPV was higher in younger subjects and in those with >12 years of education. Using higher cholesterol thresholds to define hypercholesterolemia led to higher sensitivity, lower specificity, lower PPV, and higher NPV. Sociodemographic and anthropometric predictors of validity were identified by logistic regression.Conclusions: Due to low sensitivity, self-reported hypercholesterolemia should be used with caution, both during the patient encounter and for surveillance of trends in hypercholesterolemia in the absence of measured cholesterol levels. Specificity is consistently much higher than sensitivity. The high PPV may be of use in certain clinical situations. Such validation studies should form the foundation for future research based on self-report.

Abstract  Per- and polyfluoroalkyl substances (PFASs) are a group of persistent contaminants detected in firefighting foam impacted waters. Previous studies have performed suspect and non-target screening by high-resolution mass spectrometry (HRMS) to determine the composition of PFAS contamination and to discover unknown PFASs. Here, we performed a profile analysis with suspect screening against two lists in the NORMAN Suspect List Exchange in firefighting foam impacted environmental and drinking water (n = 18) collected in Okinawa, Japan, in April 2019. Samples were analyzed by liquid chromatography (LC) quadrupole time-of-flight (QTOF) MS in electron spray ionization mode. Suspect screening returned 116 candidate PFASs with their molecular weights, functional groups, and perfluoroalkyl chain lengths. Long-chain perfluoroalkyl acids (PFAAs) and some of their precursors were specifically found around the firefighting training area. Short-chain PFAAs were assumed to be formed from precursors by environmental processes. Perfluoroalkyl sulfonamide precursors were found to be transformed to perfluoroalkyl sulfonic acids (PFSAs) in the drinking water treatment process. In contrast, biological activated carbon filtration formed perfluoroalkyl carboxylic acids (PFCAs). The PFAS profile showed that a large number of different substances needs to be considered.

Abstract  In in vitro cell assays, nominal concentrations of a test chemical are most frequently used in the description of its dose-response curves. Although the biologically effective concentration (BEC) is considered as the most relevant dose metric, in practice, it is very difficult to measure. In this work, we attempted to determine the BEC of long-chain perfluoroalkyl carboxylic acids (PFCAs) in peroxisome proliferator-activated receptor γ (PPARγ) activity assays. In both adipogenesis and transcriptional activity assays with human and mouse cells, PPARγ activity of 7 PFCAs first increased and then decreased with their carbon chain length. The binding affinity of these PFCAs with the ligand-binding domain of PPARγ was measured by fluorescence competitive binding assay and showed very poor correlation with their receptor activity (r2 = 0.002-0.047). Internal concentrations of the PFCAs in the cells were measured by LC-MS/MS. Although their correlation with the receptor activity increased significantly, it is still low (r2 = 0.41-0.82). Using the binding affinity constant, internal concentration, and PPARγ concentration measured by immunoassays, concentrations of receptor-bound PFCAs in cells were calculated, which exhibited excellent correlation with PPARγ activity in both adipogenesis and transcriptional activity assays (r2 = 0.91-0.93). These results demonstrate that the concentration of receptor-bound PFCA is the BEC that dictates its activity on human and mouse PPARγ in cell assays. In the absence of any direct detection method, our approach can be used to calculate the target-site concentration of other ligands.

Abstract  BACKGROUND: Childhood obesity is a national public health issue with increasing prevalence. It has been linked to diet, lack of physical activity, and genetic susceptibility, with more recent evidence that it could also result from environmental factors. Studies linking it to environmental factors are limited, unsystematic, incomprehensive, and inconclusive.

OBJECTIVE: To conduct an environment-wide association study (EWAS) to comprehensively investigate all the environmental factors available in a nationally representative sample of children to determine factors associated with childhood obesity.

METHODS: We utilized the 1999-2016 National Health and Nutrition Examination Survey (NHANES) datasets and included all children/adolescents (6-17 years). Obesity was measured using body mass index and waist to height ratio. A multinomial and binary logistic regression were used adjusting for age, sex, race/ethnicity, creatinine, calorie intake, physical activity, screen time, limitation to physical activities, and socioeconomic status. We then controlled for multiple hypothesis testing and validated our findings on a different cohort of children.

RESULTS: We found that metals such as beryllium (OR: 3.305 CI: 1.460-7.479) and platinum (OR: 1.346 CI: 1.107-1.636); vitamins such as gamma-tocopherol (OR: 8.297 CI: 5.683-12.114) and delta-tocopherol (OR: 1.841 CI:1.476-2.297); heterocyclic aromatic amines such as 2-Amino-9H-pyrido (2,3-b) indole (OR: 1.323 CI: 1.083-1.617) and 2-Amino-3-methyl-9H-pyriodo(2,3-b)indole (OR: 2.799 CI: 1.442-5.433); polycyclic aromatic amines such as 9- fluorene (OR: 1.509 CI: 1.230-1.851) and 4-phenanthrene (OR: 2.828 CI: 1.632-4.899); and caffeine metabolites such as 1,3,7-trimethyluric acid (OR: 1.22 CI: 1.029-1.414) and 1,3,7-trimethylxanthine (OR: 1.258 CI: 1.075-1.473) were positively and significantly associated with childhood obesity.

CONCLUSION: Following the unique concept of EWAS, certain environmental factors were associated with childhood obesity. Further studies are required to confirm these associations while investigating their mechanisms of action.

Abstract  Perfluorocarboxylic acids (PFCAs) are environmental contaminants that are highly persistent, and many are bio-accumulative and have been detected along with their atmospheric precursors far from emission sources. The overall importance of precursor emissions as an indirect source of PFCAs to the environment is uncertain. Previous studies have estimated the atmospheric source of PFCAs using models and degradation pathways of differing complexities, leading to quantitatively different results. We present results from simulations of atmospheric PFCA formation and fate using the chemical transport model GEOS-Chem. We simulate the most up-to-date chemistry available to our knowledge for the degradation of the precursors fluorotelomer alcohol (FTOH), fluorotelomer olefin (FTO), and fluorotelomer iodide (FTI), as well as the deposition and transport of the precursors, intermediates and end-products of the formation chemistry. We calculate yields of C3-C13 PFCAs formed from 4 : 2 to 12 : 2 fluorotelomer precursors and their deposition to the surface. We find that the ratio of long-chain to short-chain PFCAs increases strongly with distance from source regions. We compare our model results to remote deposition measurements and mid-latitude rainwater measurements. The model captures the observed relationship between rainwater abundance and PFCA chain length, as well as the average deposition rates at mid-latitude and Arctic sites, but underestimates the deposition of PFDoA, PFDA, and TFA at mid-latitudes and PFNA at the Devon Ice Cap. We provide estimates of cumulative PFCA deposition globally. We find that given the most recent emission inventory, the atmospheric source of PFCAs is 6-185 tonnes per year globally and 0.1-2.1 tonnes per year to the Arctic.

Abstract  BACKGROUND/OBJECTIVE: Per- and polyfluoroalkyl substances (PFAS) display neurobehavioral toxicity in laboratory animal studies. We examined associations of modeled prenatal maternal exposure to PFAS with child diagnosis of autism spectrum disorder (ASD).

METHODS: Participants were 453 mother-child pairs from CHARGE (CHildhood Autism Risk from Genetics and Environment), a population-based case-control study. Children underwent psychometric testing and were clinically confirmed for ASD (n = 239) or typical development (TD, n = 214). At the end of the clinic visit, maternal blood specimens were collected. We quantified nine PFAS in maternal serum samples collected when their child was 2-5 years old. As surrogate in utero exposure, we used a model built from external prospective data in pregnancy and 24 months post-partum and then reconstructed maternal PFAS serum concentrations during pregnancy in this case-control sample. We used logistic regression to evaluate associations of modeled prenatal maternal PFAS concentrations with child ASD.

RESULTS: Modeled prenatal maternal perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) were borderline associated with increased odds of child diagnosis of ASD (per nanogram per milliliter increase: odds ratio [OR] = 1.46; 95% confidence interval [CI]: 0.98, 2.18 for PFHxS, OR = 1.03; 95% CI: 0.99, 1.08 for PFOS). When compared to the lowest quartile (reference category), the highest quartile of modeled prenatal maternal PFHxS was associated with increased odds of child diagnosis of ASD (OR = 1.95; 95% CI: 1.02, 3.72).

CONCLUSIONS: In analyses where modeled prenatal maternal PFAS serum concentrations served as in utero exposure, we observed that prenatal PFHxS and PFOS exposure, but not other PFAS, were borderline associated with increased odds of child diagnosis of ASD. Further studies in which PFAS concentrations are prospectively measured in mothers and children at a range of developmental stages are needed to confirm these findings.

Abstract  Chicken, duck, egg, and duck egg samples from the Yangtze River Delta and Pearl River Delta regions in China were analyzed for 17 perfluorinated compounds (PFCs). The concentrations of PFCs in chicken and duck livers ranged from

Abstract  Commercial, untreated cotton fabrics have been directly silver coated using one-step electroless deposition and, subsequently, conformally encapsulated with a thin layer of poly(perfluorodecylacrylate) (PFDA) using initiated chemical vapor deposition (iCVD). The surface of these PFDA encapsulated fabrics are notably water-repellent while still displaying a surface resistance as low as 0.2 Ω cm-1, making them suitable for incorporation into launderable wearable electronics. X-ray photoelectron spectroscopy confirms that the PFDA encapsulation prevents oxidation of the silver coating, whereas unencapsulated samples display detrimental silver oxidation after a month of air exposure. The wash stability of PFDA-encapsulated, silver-coated cotton is evaluated using accelerated laundering conditions, following established AATCC protocols, and the samples are observed to withstand up to twenty home laundering cycles without notable mechanical degradation of the vapor-deposited PFDA encapsulation. As a proof-of-concept, PFDA-Ag cotton is employed as a top and bottom electrode in a layered, all-fabric triboelectric generator that produces voltage outputs as high as 25 V with small touch actions, such as tapping. © 2019 The Royal Society of Chemistry.

Abstract  I would certainly never have predicted that I would become the director of the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program (NTP) when I was a Jewish girl growing up in Teaneck, New Jersey. My family stressed the importance of education. Yet for a girl there were many not-so-subtle suggestions that the appropriate careers were in teaching or nursing, and the most important thing was to be a wife and mother. Well, I can't disagree with the latter, although I would have to add grandmother to that list of achievements. My parents were both college graduates, but my mom only taught high school English for one year before leaving the field to start our family. My dad returned from World War II and joined his brother in accounting. After my first sister was born, my father joined my mother's family jewelry business and helped to open a second retail store. My mother helped my dad out during the busy times-Christmas and wedding season-but otherwise focused on our growing family of three girls and one boy. This became increasingly challenging when it became clear that my little brother was severely retarded and would require extra care.

Abstract  The rat Reuber hepatoma cell cell line, H4IIEC3, has been used in gene transfection studies to study the molecular mechanisms of induction of the acyl CoA oxidase gene, the first and rate-limiting enzyme of the peroxisomal fatty acid beta-oxidation spiral. cDNAs encoding the peroxisome proliferator activated receptor and the 9-cis retinoic acid receptor were transfected into the cells, either in the presence or absence of their cognate ligands (Wy-14,643 and 9-cis retinoic acid respectively), in addition to the acyl CoA oxides promoter linked to a chloramphenicol acetyltransferase reporter gene construct. The above experimental approach has confirmed that the 9-cis retinoic acid receptor acts cooperatively with the peroxisome receptor in mediating activation of the acyl CoA oxidase gene. In addition, in vivo experiments have demonstrated that treatment of rats with peroxisome proliferators substantially increase the hepatic levels of the peroxisome receptor mRNA itself. Taken collectively, the above data provides a wealth of molecular and mechanistic information on perioxisome proliferation in the rat and is discussed in terms of the safety assessment of peroxisome proliferators in man. © 1994 Springer-Verlag.

Abstract  The complete nucleotide sequence has been determined for three newly cloned evolutionary variants from two different independently generated evolutionary series (1100 and 2100 series) of simian virus 40 (SV40). These naturally arising variants, designated ev-1110, ev-2102, and ev-2114, were isolated after five high multiplicity serial passages. The structure of the variants consists of a monomeric unit tandemly repeated four times (ev-2102 and ev-2114) or six times (ev-1110) in the variant genome; the variants have four or six copies, respectively, of the viral origin signal for DNA replication. The DNA content in the three variants is vastly different in that the genome of variant ev-2114 contains only rearranged viral sequences, while variant ev-2102 contains a substitution with monkey DNA sequences consisting of a nearly complete dimeric unit of Alu family sequences as well as less repetitive sequences and variant ev-1110 contains monkey DNA sequences derived solely from repetitive alpha-component DNA. Recombination events, cellular sequences, and structural features of these and other naturally arising SV40 variants are compared.

Abstract  Per- and poly-fluoroalkyl substances (PFAS) raised increasing concerns over the past years due to their persistence and global distribution. Understanding their occurrence in the environment and their disruptive effect on the physiology of humans and wildlife remains a major challenge in ecotoxicological studies. Here, we investigate the occurrence of several carboxylic and sulfonic PFAS in 105 individuals of three seabird species (27 great black-backed gull Larus marinus; 44 lesser black-backed gull Larus fuscus graellsii; and 34 European herring gull Larus argentatus) from South western France. We further estimated the relationship between plasma concentrations of PFAS and i) the body condition of the birds and ii) plasma concentrations of thyroid hormone triiodothyronine (TT3). We found that great and lesser black-backed gulls from South Western France are exposed to PFAS levels comparable to highly contaminated species from other geographical areas, although major emission sources (i.e. related to industrial activities) are absent in the region. We additionally found that PFAS are negatively associated with the body condition of the birds in two of the studied species, and that these results are sex-dependent. Finally, we found positive associations between exposure to PFAS and TT3 in the great black-backed gull, suggesting a potential disrupting mechanism of PFAS exposure. Although only three years of data have been collected, we investigated PFAS trend over the study period, and found that great black-backed gulls document an increasing trend of plasma PFAS concentration from 2016 to 2018. Because PFAS might have detrimental effects on birds, French seabird populations should be monitored since an increase of PFAS exposure may impact on population viability both in the short- and long-term.

Abstract  Background: Previous studies have reported a positive association of perfluoralkyl acids (PFAAs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), with hyperuricemia. The objective of the study is to investigate whether there is an association between concurrent serum levels of several PFAAs and gout, serum uric acid (SUA) or hyperuricemia in the U.S. adult population as represented by the National Health and Nutrition Examination Survey (NHANES) 2009e2014 sample (n ¼ 4917). The PFAAs investigated include PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS) and PFOS. Methods: This cross-sectional study used multivariate logistic regressions to analyze the association of single PFAAs with hyperuricemia and self-reported gout; the association with SUA was analyzed by multivariate linear regression. Analyses were adjusted for race/ethnicity, age, sex, education, alcohol consumption, smoking, serum cotinine, BMI, diabetes, hypertension, chronic kidney disease, and SUA (for gout only). Results: Higher quartile values of serum PFOA and PFHxS were associated with increased odds of selfreported gout. There was a positive association of SUA with increased levels of PFOA, PFNA, PFOS, PFHxS and PFDA. Higher quartile values of PFOA, PFNA, and PFHxS were associated with higher odds of hyperuricemia. Conclusions: In this population-based cross-sectional analysis, we found an association between selected PFAAs and self-reported gout. We also confirmed previous reports of an association between several PFAAs and hyperuricemia. Our study suggests that exposure to PFAAs may be a risk factor for hyperuricemia and gout.