Combined effect of anthracene and polyethylene microplastics on swimming speed and cytochrome P4501A monooxygenase expression of Java medaka (Oryzias javanicus).

Microplastics have been detected in a variety of aquatic ecosystems, and the combined effect of microplastics and chemical pollutants has become a matter of increasing concern. We conducted a 12-d co-exposure test of anthracene and spherical or fragmented polyethylene microplastics (size 200 µm) on Java medaka (Oryzias javanicus). The accumulation of anthracene in Java medaka muscle reached a plateau on day 5 in all anthracene exposure groups, and no significant differences were detected among the groups (ANT, 20.4 ± 5.5; ANT + SPPE-MP, 24.7 ± 2.7; ANT + FRPE-MP, 24.6 ± 4.7 µg/g). However, co-exposure to anthracene and spherical or fragmented polyethylene microplastics increased the duration of slow swimming in a swimming behavior test (control, 4.1 ± 1.4; ANT, 5.2 ± 2.8; ANT + SPPE-MP, 12.4 ± 3.7; ANT + FRPE-MP, 17.4 ± 5.1 min/30 min), and co-exposure to anthracene and fragmented polyethylene microplastics induced higher cytochrome P4501A monooxygenase (CYP1A) expression in Java medaka livers than the other anthracene exposure groups (ANT, 189 ± 74; ANT + SPPE-MP, 203 ± 75; ANT + FRPE-MP 272 ± 36% of control). Polyethylene microplastics appear to be weak vectors of anthracene at the size tested (200 µm), and the effect of shape (spherical or fragmented) on the vector effect was small. However, the presence of polyethylene microplastics could affect the swimming behavior and CYP1A expression in Java medaka.

Hydroxylated benzo[c]phenanthrene metabolites cause osteoblast apoptosis and skeletal abnormalities in fish.

To study the toxicity of 3-hydroxybenzo[c]phenanthrene (3-OHBcP), a metabolite of benzo[c]phenanthrene (BcP), first we compared it with its parent compound, BcP, using an in ovo-nanoinjection method in Japanese medaka. Second, we examined the influence of 3-OHBcP on bone metabolism using goldfish. Third, the detailed mechanism of 3-OHBcP on bone metabolism was investigated using zebrafish and goldfish. The LC50s of BcP and 3-OHBcP in Japanese medaka were 5.7 nM and 0.003 nM, respectively, indicating that the metabolite was more than 1900 times as toxic as the parent compound. In addition, nanoinjected 3-OHBcP (0.001 nM) induced skeletal abnormalities. Therefore, fish scales with both osteoblasts and osteoclasts on the calcified bone matrix were examined to investigate the mechanisms of 3-OHBcP toxicity on bone metabolism. We found that scale regeneration in the BcP-injected goldfish was significantly inhibited as compared with that in control goldfish. Furthermore, 3-OHBcP was detected in the bile of BcP-injected goldfish, indicating that 3-OHBcP metabolized from BcP inhibited scale regeneration. Subsequently, the toxicity of BcP and 3-OHBcP to osteoblasts was examined using an in vitro assay with regenerating scales. The osteoblastic activity in the 3-OHBcP (10-10 to 10-7 M)-treated scales was significantly suppressed, while BcP (10-11 to 10-7 M)-treated scales did not affect osteoblastic activity. Osteoclastic activity was unchanged by either BcP or 3-OHBcP treatment at each concentration (10-11 to 10-7 M). The detailed toxicity of 3-OHBcP (10-9 M) in osteoblasts was then examined using gene expression analysis on a global scale with fish scales. Eight genes, including APAF1, CHEK2, and FOS, which are associated with apoptosis, were identified from the upregulated genes. This indicated that 3-OHBcP treatment induced apoptosis in fish scales. In situ detection of cell death by TUNEL methods was supported by gene expression analysis. This study is the first to demonstrate that 3-OHBcP, a metabolite of BcP, has greater toxicity than the parent compound, BcP.

Exposure to per- and polyfluorinated alkyl substances in pregnant Brazilian women and its association with fetal growth.

Research pertaining to exposure of humans to per- and polyfluorinated alkyl substances (PFASs) has received considerable public and regulatory attention in recent years. Although several studies have reported exposure to PFASs by populations in North America and western Europe, such information is still scarce in Latin America, including Brazil. In this study, concentrations of thirteen PFASs were determined in whole blood collected during the second trimester from 252 pregnant Brazilian women. This is a nested case-control study within the Brazilian Ribeirao Preto and Sao Luiz Birth Cohort Study (BRISA) with selected birth outcomes cases (n = 63) and matched controls (n = 189). PFASs concentrations were associated with conditions including preeclampsia, birth weight (BW), preterm birth, and intrauterine growth restriction (IUGR). Among PFASs measured, perfluorooctane sulfonate (PFOS) was found at the highest concentration (range: 1.06-106 ng mL-1 with a median value of 3.41 ng mL-1) which was followed by perfluorooctanoic acid (PFOA, range: 0.11-2.77 ng mL-1 with a median value of 0.20 ng mL-1). A significant positive association of PFOS and PFOA concentrations with fetal growth restriction (p < 0.05) was found. This is the first study to assess whole blood concentrations of PFASs and their effect on fetal growth in pregnant Brazilian women.

Perfluoroalkyl substances, bone density, and cardio-metabolic risk factors in obese 8-12 year old children: A pilot study.

BACKGROUND AND OBJECTIVE: Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), have been associated with adverse bone, and metabolic changes in adults. However association of PFASs with bone health in children is understudied. Considering their role as endocrine disruptors, we examined relationships of four PFASs with bone health in children. METHODS: In a cross sectional pilot study, 48 obese children aged 8-12 years were enrolled from Dayton's Children Hospital, Ohio. Anthropometric, clinical and biochemical assessments of serum were completed. Serum PFASs were measured by UPLC-ESI-MS/MS. In a subset of 23 children, bone health parameters were measured using calcaneal quantitative ultrasound (QUS). RESULTS: While PFASs exposure was associated with a consistent negative relationship with bone health parameters, among four PFASs tested, only PFNA showed a significant negative relationship with bone parameter (ß [95% CI], = - 72.7 [- 126.0, - 19.6], p = .010). PFNA was also associated with raised systolic blood pressure (p = .008), low density lipoprotein cholesterol (LDL-C; p < .001), and total cholesterol (TC; p = .014). In addition, both PFOA and PFOS predicted elevation in LDL-C, and PFOA predicted increased TC, as well. In this analysis, PFASs were not strongly related to thyroid hormones, 25-hydroxy vitamin D, liver enzymes, or glucose homeostasis. CONCLUSION: PFASs exposure in obese children may play a role in adverse skeletal and cardiovascular risk profiles.

Urinary levels of triclosan and triclocarban in several Asian countries, Greece and the USA: Association with oxidative stress.

Triclosan (TCS) and Triclocarban (TCC) are widely used as antimicrobial preservatives in personal care products (PCPs). Because of their potential for endocrine disrupting effects, human exposure to these chemicals is a concern. Biomonitoring studies of human exposure to TCS and TCC have shown widespread exposure of populations in western European countries and the USA. However, exposure to TCC and TCS by populations in Asian countries is less well known. In this study, concentrations of TCS and TCC were determined in human urine collected from seven Asian countries (China, India, Korea, Kuwait, Japan, Saudi Arabia, and Vietnam), and Greece and the USA. A total of 430 urine samples were analyzed for TCS and TCC, of which 355 (83%) and 82 (19%), respectively, contained measurable levels of these chemicals. The overall geometric mean [GM] concentrations of TCS and TCC, were 1.36 and 0.03ng/mL, respectively. The highest mean concentration of TCS was found in urine from China (100ng/mL) and the lowest concentration was found in urine from Vietnam (2.34ng/mL). We also analyzed urinary 8-OHdG, a marker of oxidative stress, to elucidate the association with TCS and TCC levels for samples from Saudi Arabia (n=130) and a positive correlation between Ln-transformed TCC levels and 8-OHdG was found, although this was not statistically significant. This is the first study to report urinary levels of TCS and TCC in several Asian countries, especially for Vietnam, Kuwait, and Japan.

Endocrine disrupting chemicals in seminal plasma and couple fecundity.

Growing evidence supports the importance of men's exposure to non-persistent endocrine disruptors (EDCs) and couple fecundability, as measured by time-to-pregnancy (TTP). This evolving literature contrasts with the largely equivocal findings reported for women's exposures and fecundity. While most evidence relies upon urinary concentrations, quantification of EDCs in seminal plasma may be more informative about potential toxicity arising within the testes. We analyzed 5 chemical classes of non-persistent EDCs in seminal plasma for 339 male partners of couples who were recruited prior to conception and who were followed daily until pregnant or after one year of trying. Benzophenones, bisphenols, parabens, and phthalate metabolites and phthalate diesters were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) except for phthalate diesters, which were analyzed using gas chromatography-mass spectrometry. Cox regression with discrete-time was used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs) for each chemical to estimate the probability of pregnancy. While most EDCs were detected in seminal plasma, concentrations were lower than urinary concentrations previously analyzed for the cohort. None of the EDCs were significantly associated with fecundability even after covariate adjustment, though benzophenones consistently yielded FORs <1.0 (ranging from 0.72 to 0.91) in couple-adjusted models suggestive of diminished fecundity (longer TTP). The findings underscore that a range of EDCs can be quantified in seminal plasma, but the lower concentrations may require a large cohort for assessing couple fecundability, as well as the need to consider other fecundity outcomes such as semen quality.

Preconception seminal plasma concentrations of endocrine disrupting chemicals in relation to semen quality parameters among male partners planning for pregnancy.

BACKGROUND: Some non-persistent endocrine disruptors (EDCs) are adversely associated with semen quality and few studies have measured those EDCs in seminal plasma. OBJECTIVE: To find an association between EDCs in seminal plasma and semen quality parameters. METHODS: Five chemical classes of non-persistent EDCs were quantified in seminal plasma from 339 male partners who participated in a prospective pregnancy study. Bisphenols, benzophenone UV-filters, antimicrobials and phthalate diesters and their monoester metabolites were measured using high performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Semen samples underwent next day analysis using a standardized protocol for the quantification of 35 endpoints. Linear mixed-effects models of EDCs that were log transformed and rescaled by their standard deviations or dichotomized at the 75th percentile for each exposure and outcomes with covariate adjustment were performed. EDCs in seminal plasma were also assessed relative to clinical reference values of semen quality endpoints using logistic regression or generalized estimating equations. RESULTS: The most consistent findings supporting adverse associations between seminal EDCs and semen quality were observed for some phthalate metabolites. For example, seminal plasma mono-ethyl, mono-n-butyl, mono-2-isobutyl and mono-benzyl phthalate concentrations were associated with decreased odds of having semen volume above clinical reference values (mEP: aOR=0.46; 95%CI= 0.32, 0.66; mBP: aOR=0.40; 95%CI= 0.28, 0.57; miBP: aOR=0.39; 95%CI= 0.27, 0.56), and mBzP: aOR= 0.34; 95%CI= 0.24, 0.49). CONCLUSIONS: Environmentally relevant concentrations of specific phthalates in seminal plasma were associated with diminished semen volume, sperm motility, viability, and morphological alterations in sperm heads such that semen volume and sperm viability fall below reference values.

Serum perfluoroalkyl substances in children exposed to the world trade center disaster.

The World Trade Center (WTC) disaster released large amounts of various chemical substances into the environment, including perfluoroalkyl substances (PFASs). Yet, no studies have examined exposures in children living or attending schools near the disaster site. We measured serum PFASs in WTC Health Registry (WTCHR) respondents who were ≤8 years of age on September 11, 2001 and a sociodemographically-matched comparison group. We also examined the relationship of PFASs levels with dust cloud exposure; home dust exposure, and with traumatic exposure, the latter to take into account differences related to possible mental health consequences and associated behavioral problems. Serum samples, collected between 2014 and 2016, were analyzed from 123 WTCHR participants and from 185 participants in the comparison group. In the WTCHR group, median perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels were 1.81ng/mL and 3.72ng/mL, respectively. Controlling for sex, caloric intake, race/ethnicity, and date of birth, significant increases among WTCHR participants compared with the matched comparison group were detected for perfluorohexanesulfonate (0.23ng/mL increase or 0.24log unit increase, p=0.006); PFOS (0.86ng/mL increase or 0.16log unit increase, p=0.011); PFOA (0.35ng/mL increase or 0.18log unit increase, p<0.001); perfluorononanoic acid (0.12ng/mL increase or 0.17log unit increase, p=0.003); perfluorodecanoic acid (0.06ng/mL increase or 0.42log unit increase, p<0.001); and perfluoroundecanoic acid (0.03ng/mL increase or 0.32log unit increase, p=0.019). Stronger associations were identified for home dust exposures and traumatic exposures than dust cloud. These findings highlight the importance of conducting longitudinal studies in this population to assess possible cardiometabolic and renal consequences related to these exposures.

Contaminants in Liquid Organic Fertilizers Used for Agriculture in Japan.

To provide an overview of anthropogenic contaminants in liquid organic fertilizers (LOFs), products from four biogas plants in Kyushu, Japan, were analyzed for a wide range of contaminants, including copper, cadmium, tributyltin (TBT), dibutyltin (DBT), perfluorooctane sulfonate, 952 semi-volatile organic compounds, and 89 antibiotics. The highest concentrations of copper (31.1 mg/L) and cadmium (0.08 mg/L) were found in LOFs from the Hita biogas plant. Only ofloxacin and sulfapyridine were detected in total 89 antibiotics screened. TBT, DBT, and perfluorooctane sulfonate were present at low concentrations in the LOFs from all four locations. Among the 952 semi-volatile organic compounds, 78 compounds were detected in at least one sample and were present at concentrations between 1.2 and 139.6 mg/L. On the basis of comparisons with previous studies and quality standards for the use of organic fertilizers, the concentrations of contaminants in the studied LOFs indicate that they might be safe for agricultural purposes.

Urinary paracetamol and time-to-pregnancy.

STUDY QUESTION: Is preconception urinary paracetamol (acetaminophen) associated with time-to-pregnancy (TTP)? SUMMARY ANSWER: Higher urinary paracetamol concentrations among male partners were associated with a longer TTP. WHAT IS KNOWN ALREADY: Paracetamol is a commonly used analgesic among women and men of all ages. As metabolites of select chemicals used in the manufacturing of polyurethane foam, dyes and various industrial products, as well as a common medicinal product, paracetamol and its primary metabolite p-aminophenol, are ubiquitous in the environment. Studies investigating the relationship between adult urinary concentrations of paracetamol and TTP are lacking. STUDY DESIGN, SIZE, DURATION: This prospective cohort included 501 couples discontinuing contraception for the purposes of attempting conception during the years 2005-2009 and residing in Michigan or Texas, USA. PARTICIPANTS/MATERIALS, SETTING, METHODS: Total urinary paracetamol, its metabolite para-aminophenol (p-aminophenol), and a summary measure of both urinary biomarkers were quantified by ultra-performance liquid chromatography coupled with an electrospray triple quadrupole mass spectrometry (UPLC-ESI-MS/MS). Female partners used the Clearblue® digital home test to confirm pregnancy. Cox's proportional odds models for discrete survival time were used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs), adjusting for age, body mass index (BMI), urinary creatinine, preconception smoking status, race/ethnicity and household income. Models were further adjusted for hypothyroidism and hypertension as an attempt to account for possible indications of paracetamol medication use. FOR estimates <1.0 denote a longer TTP (diminished fecundity). Models were performed to examine urinary concentrations of paracetamol as a continuous and variable or categorized into quartiles. In light of TTP being a couple-dependent outcome, models were first performed for females and males, modeled separately, and then modeled for couples with each partner's concentrations being adjusted for the other. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 501 enrolled couples, 347 (69%) had an human chorionic gonadotrophin confirmed pregnancy. Urinary concentrations of paracetamol were lowest among females and males who achieved pregnancy and p-aminophenol concentrations were lowest among those not achieving pregnancy. Urinary paracetamol concentrations were higher among female than male partners (Median = 26.6 and 13.2 ng/ml, respectively; P < 0.0001). After adjustment for age, BMI, urinary creatinine, preconception smoking status, race/ethnicity and household income, the highest quartile of male urinary paracetamol was associated with a longer TTP [FOR = 0.67; 95% CI = (0.47, 0.95)]. This association remained after adjustment for chronic health conditions, hypothyroidism and hypertension and female partner's urinary paracetamol concentration [FOR = 0.65; 95% CI = (0.45, 0.94)]. No associations were observed between female or male partners' urinary concentrations of paracetamol or of its metabolite p-aminophenol when urinary concentrations were modeled continuously. LIMITATIONS, REASONS FOR CAUTION: Only a single spot urine was available for analysis despite the short-lived nature of paracetamol. Additionally, participants were not asked to provide information on indication of use for paracetamol medications; any underlying conditions for the paracetamol use would have been potential confounders. WIDER IMPLICATIONS OF THE FINDINGS: If corroborated with more robust studies, findings from our exploratory analysis may have both clinical and public health relevance among reproductive aged individuals, including those trying for pregnancy, given the prevalent use of paracetamol/acetaminophen medications and the ubiquitous nature of paracetamol in the environment. STUDY FUNDING/COMPETING INTERESTS: This research was supported by the National Institutes of Health, Intramural Research Program, and Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-3-3355; N01-HD-3-3356; NOH-HD-3-3358; HHSN27500001/HHSN27500001). None of the authors have any conflicts to declare.

Identification of perfluorooctane sulfonate binding protein in the plasma of tiger pufferfish Takifugu rubripes.

It is well known that perfluorooctane sulfonate (PFOS) preferentially accumulates in the plasma of wildlife and humans. Although earlier studies have suggested that this was due to binding of PFOS to a plasma protein, definite characterization of the protein in in vivo exposure studies was not conducted thus far. In this study, we conducted both in vitro and in vivo experiments to identify PFOS binding protein in the plasma of fish. For the in vivo studies, PFOS was administered intraperitoneally to tiger pufferfish, Takifugu rubripes, and the plasma was separated by ammonium sulfate fractionation. High concentrations of PFOS were found in the 65-70 percent ammonium sulfate fraction (190ng/mL). After SDS-PAGE and N-terminal amino acid sequence analysis, the PFOS-binding protein was identified as an apolipoprotein A-I, which was confirmed on the basis of a significant correlation to the PFOS concentration in each fraction. The plasma samples fractionated by ammonium sulfate from untreated pufferfish were subjected to PFOS binding assay by the equilibrium dialysis method. The results further confirmed that the 60-65 percent ammonium sulfate fraction showed a high PFOS-binding ratio, similar to that found from in vivo studies. We demonstrated that PFOS is likely bound to an apolipoprotein A-I in the plasma of tiger pufferfish in in vivo and in vitro studies.

Tablet-Based Cognitive and Eye Movement Measures as Accessible Tools for Schizophrenia Assessment: Multisite Usability Study.

BACKGROUND: Schizophrenia is a complex mental disorder characterized by significant cognitive and neurobiological alterations. Impairments in cognitive function and eye movement have been known to be promising biomarkers for schizophrenia. However, cognitive assessment methods require specialized expertise. To date, data on simplified measurement tools for assessing both cognitive function and eye movement in patients with schizophrenia are lacking. OBJECTIVE: This study aims to assess the efficacy of a novel tablet-based platform combining cognitive and eye movement measures for classifying schizophrenia. METHODS: Forty-four patients with schizophrenia, 67 healthy controls, and 41 patients with other psychiatric diagnoses participated in this study from 10 sites across Japan. A free-viewing eye movement task and 2 cognitive assessment tools (Codebreaker task from the THINC-integrated tool and the CognitiveFunctionTest app) were used for conducting assessments in a 12.9-inch iPad Pro. We performed comparative group and logistic regression analyses for evaluating the diagnostic efficacy of the 3 measures of interest. RESULTS: Cognitive and eye movement measures differed significantly between patients with schizophrenia and healthy controls (all 3 measures; P<.001). The Codebreaker task showed the highest classification effectiveness in distinguishing schizophrenia with an area under the receiver operating characteristic curve of 0.90. Combining cognitive and eye movement measures further improved accuracy with a maximum area under the receiver operating characteristic curve of 0.94. Cognitive measures were more effective in differentiating patients with schizophrenia from healthy controls, whereas eye movement measures better differentiated schizophrenia from other psychiatric conditions. CONCLUSIONS: This multisite study demonstrates the feasibility and effectiveness of a tablet-based app for assessing cognitive functioning and eye movements in patients with schizophrenia. Our results suggest the potential of tablet-based assessments of cognitive function and eye movement as simple and accessible evaluation tools, which may be useful for future clinical implementation.

Growth-phase dependent variation in photosynthetic activity and cellular protein expression profile in the harmful raphidophyte Chattonella antiqua.

This study investigated temporal variations in the potential maximum quantum yield of photosystem II (F(v)/F(m) ratio) and growth-phase dependent cellular protein expressions of Chattonella antiqua under laboratory conditions. Despite the culture conditions, significant positive correlations between the F(v)/F(m) ratio and daily growth rate were observed. Threshold F(v)/F(m) ratios associated with positive cell growth were calculated to be >0.44, >0.44, and >0.37, and those associated with active cell growth (growth rate >0.5 div. d(-1)) were >0.58, >0.60, and >0.49 under control culture, low nutrient and intense light conditions, respectively. Proteome profiles obtained by two-dimensional gel electrophoresis (2-DE) indicated that 42 protein spots were differentially expressed at various growth phases of C. antiqua, which indicates changes in cellular physiological status throughout the growth cycle, and suggests that oxygen evolving enhancer 1 and 2-cysteine peroxiredoxin play roles in maintaining the positive growth of C. antiqua.

Accumulation of organotins in wharf roach (Ligia exotica Roux) and its ability to serve as a biomonitoring species for coastal pollution.

In this study, we measured the accumulation of tributyltin (TBT) in wharf roach (Ligia exotica Roux) and examined the species' ability to be used for TBT biomonitoring in coastal environments. In an exposure test, wharf roach were exposed to TBT via diet for 2d. TBT was accumulated in wharf roach, and its metabolite dibutyltin was detected. The concentrations of these compounds gradually decreased during the depuration period, but they were still detected 12d after exposure ceased (TBT 290±140ng/g; dibutyltin 1280±430ng/g). The biological half-life of TBT in wharf roach was estimated to be about 4d. In a field study conducted in 2011-2012, wharf roach were collected from 15 coastal sites in Japan and 3 sites in Manado, Indonesia. TBT was detected in both Japanese and Indonesian samples. The highest concentration of TBT was found in wharf roach collected at Bitung ferry port, Manado (57.9±16.5ng/g), which is close to a shipyard, and the highest concentration at a Japanese site was 12.3±6.2ng/g. Thus, we were able to detect organotins in the coastal environments by testing wharf roach, suggesting that L. exotica might serve as a good bioindicator for monitoring organotin pollution.

Size effect of polystyrene microplastics on the accumulation of anthracene for Java medaka (Oryzias javanicus).

Pollution by microplastics in aquatic ecosystems is a worldwide problem, and the role of microplastics as vectors of pollutants has been a concern. Although small microplastics are thought to have a greater effect than large microplastics as vectors of pollutants, the impact of the size of microplastics on their ability to serve as vectors of pollutants has not been quantified. In this study, we conducted the 14-day experiment (7 days of exposure and 7 days of depuration) with polystyrene microplastics (2-µm or 10-µm diameter) and anthracene. On the last day of the exposure period, the concentration of anthracene in the muscle of Java medaka exposed to both anthracene and 2-µm polystyrene microplastics was the highest (47.4 ± 15.2 µg/g-muscle) of any group, followed by the group exposed to both anthracene and 10-µm polystyrene microplastics (23.0 ± 4.2 µg/g-muscle) and the group exposed to only anthracene (11.2 ± 2.2 µg/g-muscle). These results demonstrated that the size of microplastics was a critical determinant of their ability to serve as vectors of anthracene. The concentrations of anthracene and fine microplastics in the environment are sufficiently low that the effect of microplastics as vectors of anthracene may be observed only under experimental conditions that are unlikely to occur in the present environment. However, because pollution by plastics is expected to become more serious in the future, careful thought and proactive action will be needed to ensure that the impact of microplastics as vectors of pollutants does not become demonstrable under future environmental conditions.

An adverse outcome pathway-based approach to assess the neurotoxicity by combined exposure to current-use pesticides.

Exposure to multiple pesticides in daily life has become an important public health concern. However, the combined effects of pesticide mixtures have not been fully elucidated by the conventional toxicological testing used for individual chemicals. Grouping of chemicals by mode of action using common key events (KEs) in the adverse outcome pathway (AOP) as endpoints could be applied for efficient risk assessment of combined exposure to multiple chemicals. The purpose of this study was to investigate whether exposure to multiple pesticides has synergistic neurotoxic effects on mammalian nervous systems. According to the AOP-based approach, we evaluated the effects of 10 current-use pesticides (4 neonicotinoids, 4 pyrethroids and 2 phenylpyrazoles) on the common KEs in AOPs for neurotoxicity, such as KEs involving mitochondrial and proteolytic functions, in a mammalian neuronal cell model. Our data showed that several pyrethroids and phenylpyrazoles partly shared the effects on several common KEs, including decreases in mitochondrial membrane potential and proteasome activity and increases in autophagy activity. Furthermore, we also found that combined exposure to a type-I pyrethroid permethrin or a type-II pyrethroid deltamethrin and the phenylpyrazole fipronil decreased the cell viability and the benchmark doses much more than either single exposure, indicating that the pair exhibited synergistic effects, since the combination indexes were less than 1. These findings revealed that novel pairs of different classes of pesticides with similar effects on common KEs exhibited synergistic neurotoxicity and provide new insights into the risk assessment of combined exposure to multiple chemicals.

The Validation of Automated Social Skills Training in Members of the General Population Over 4 Weeks: Comparative Study.

BACKGROUND: Social skills training by human trainers is a well-established method of teaching appropriate social and communication skills and strengthening social self-efficacy. Specifically, human social skills training is a fundamental approach to teaching and learning the rules of social interaction. However, it is cost-ineffective and offers low accessibility, since the number of professional trainers is limited. A conversational agent is a system that can communicate with a human being in a natural language. We proposed to overcome the limitations of current social skills training with conversational agents. Our system is capable of speech recognition, response selection, and speech synthesis and can also generate nonverbal behaviors. We developed a system that incorporated automated social skills training that completely adheres to the training model of Bellack et al through a conversational agent. OBJECTIVE: This study aimed to validate the training effect of a conversational agent-based social skills training system in members of the general population during a 4-week training session. We compare 2 groups (with and without training) and hypothesize that the trained group's social skills will improve. Furthermore, this study sought to clarify the effect size for future larger-scale evaluations, including a much larger group of different social pathological phenomena. METHODS: For the experiment, 26 healthy Japanese participants were separated into 2 groups, where we hypothesized that group 1 (system trained) will make greater improvement than group 2 (nontrained). System training was done as a 4-week intervention where the participants visit the examination room every week. Each training session included social skills training with a conversational agent for 3 basic skills. We evaluated the training effect using questionnaires in pre- and posttraining evaluations. In addition to the questionnaires, we conducted a performance test that required the social cognition and expression of participants in new role-play scenarios. Blind ratings by third-party trainers were made by watching recorded role-play videos. A nonparametric Wilcoxson Rank Sum test was performed for each variable. Improvement between pre- and posttraining evaluations was used to compare the 2 groups. Moreover, we compared the statistical significance from the questionnaires and ratings between the 2 groups. RESULTS: Of the 26 recruited participants, 18 completed this experiment: 9 in group 1 and 9 in group 2. Those in group 1 achieved significant improvement in generalized self-efficacy (P=.02; effect size r=0.53). We also found a significant decrease in state anxiety presence (P=.04; r=0.49), measured by the State-Trait Anxiety Inventory (STAI). For ratings by third-party trainers, speech clarity was significantly strengthened in group 1 (P=.03; r=0.30). CONCLUSIONS: Our findings reveal the usefulness of the automated social skills training after a 4-week training period. This study confirms a large effect size between groups on generalized self-efficacy, state anxiety presence, and speech clarity.

Differences in microplastic degradation in the atmosphere and coastal water environment from two island nations: Japan and New Zealand.

Microplastics are subject to environmental forces that can change polymer organization on a molecular scale. However, it is not clear to what extent these changes occur in the environment and whether microplastics in the atmospheric and water environment differ. Here we identify structural differences between microplastics in the atmosphere and water environment from Japan and New Zealand, representing two archipelagos differing in their proximity to nearby countries and highly populated areas. We first highlight the propensity for smaller microplastics to arrive via air masses from the Asian continent to the Japan Sea coastal area, while New Zealand received larger, locally derived microplastics. Analyses of polyethylene in the Japanese atmosphere indicate that microplastics transported to the Japanese coastal areas were more crystalline than polyethylene particles in the water, suggesting that the plastics arriving by air were relatively more aged and brittle. By contrast, polypropylene particles in New Zealand waters were more degraded than the microplastic particles in the air. Due to the lack of abundance, both polyethylene and polypropylene could not be analyzed for both countries. Nevertheless, these findings show the structural variation in microplastics between environments in markedly different real-world locations, with implications for the toxic potential of these particles.

Correlation between Polycyclic Aromatic Hydrocarbons in Wharf Roach (Ligia spp.) and Environmental Components of the Intertidal and Supralittoral Zone along the Japanese Coast.

Polycyclic aromatic hydrocarbon (PAH) concentrations in wharf roach (Ligia spp.), as an environmental indicator, and in environmental components of the intertidal and supralittoral zones were determined, and the PAH exposure pathways in wharf roach were estimated. Wharf roaches, mussels, and environmental media (water, soil and sand, and drifting seaweed) were collected from 12 sites in Japan along coastal areas of the Sea of Japan. PAH concentrations in wharf roaches were higher than those in mussels (median total of 15 PAHs: 48.5 and 39.9 ng/g-dry weight (dw), respectively) except for samples from Ishikawa (wharf roach: 47.9 ng/g-dw; mussel: 132 ng/g-dw). The highest total PAH concentration in wharf roach was from Akita (96.0 ng/g-dw), followed by a sample from Niigata (85.2 ng/g-dw). Diagnostic ratio analysis showed that nearly all PAHs in soil and sand were of petrogenic origin. Based on a correlation analysis of PAH concentrations between wharf roach and the environmental components, wharf roach exposure to three- and four-ring PAHs was likely from food (drifting seaweed) and from soil and sand, whereas exposure to four- and five-ring PAHs was from several environmental components. These findings suggest that the wharf roach can be used to monitor PAH pollution in the supralittoral zone and in the intertidal zone.