Altered Transcriptome Response in PBMCs of Czech Adults Linked to Multiple PFAS Exposure: B Cell Development as a Target of PFAS Immunotoxicity.

While the immunomodulation effects of per- and polyfluoroalkyl substances (PFASs) are described on the level of clinical signs in epidemiological studies (e.g., suppressed antibody response after vaccination), the underlying mechanism has still not been fully elucidated. To reveal mechanisms of PFAS exposure on immunity, we investigated the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMCs) responding to PFAS exposure (specifically, exposure to PFPA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS). Blood samples and the chemical load in the blood were analyzed under the cross-sectional CELSPAC: Young Adults study. The overall aim of the study was to identify sensitive gene sets and cellular pathways conserved for multiple PFAS chemicals. Transcriptome networks related to adaptive immunity were perturbed by multiple PFAS exposure (i.e., blood levels of at least four PFASs). Specifically, processes tightly connected with late B cell development, such as B cell receptor signaling, germinal center reactions, and plasma cell development, were shown to be affected. Our comprehensive transcriptome analysis identified the disruption of B cell development, specifically the impact on the maturation of antibody-secreting cells, as a potential mechanism underlying PFAS immunotoxicity.

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding.

Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.

Enrichment of human nasopharyngeal bacteriome with bacteria from dust after short-term exposure to indoor environment: a pilot study.

BACKGROUND: Indoor dust particles are an everyday source of human exposure to microorganisms and their inhalation may directly affect the microbiota of the respiratory tract. We aimed to characterize the changes in human nasopharyngeal bacteriome after short-term exposure to indoor (workplace) environments. METHODS: In this pilot study, nasopharyngeal swabs were taken from 22 participants in the morning and after 8 h of their presence at the workplace. At the same time points, indoor dust samples were collected from the participants' households (16 from flats and 6 from houses) and workplaces (8 from a maternity hospital - NEO, 6 from a pediatric hospital - ENT, and 8 from a research center - RCX). 16S rRNA sequencing analysis was performed on these human and environmental matrices. RESULTS: Staphylococcus and Corynebacterium were the most abundant genera in both indoor dust and nasopharyngeal samples. The analysis indicated lower bacterial diversity in indoor dust samples from flats compared to houses, NEO, ENT, and RCX (p < 0.05). Participants working in the NEO had the highest nasopharyngeal bacterial diversity of all groups (p < 0.05). After 8 h of exposure to the workplace environment, enrichment of the nasopharynx with several new bacterial genera present in the indoor dust was observed in 76% of study participants; however, no significant changes were observed at the level of the nasopharyngeal bacterial diversity (p > 0.05, Shannon index). These "enriching" bacterial genera overlapped between the hospital workplaces - NEO and ENT but differed from those in the research center - RCX. CONCLUSIONS: The results suggest that although the composition of nasopharyngeal bacteriome is relatively stable during the day. Short-term exposure to the indoor environment can result in the enrichment of the nasopharynx with bacterial DNA from indoor dust; the bacterial composition, however, varies by the indoor workplace environment.

A Critical Review on the Opportunity to Use Placenta and Innovative Biomonitoring Methods to Characterize the Prenatal Chemical Exposome.

Adverse effects associated with chemical exposures during pregnancy include several developmental and reproductive disorders. However, considering the tens of thousands of chemicals present on the market, the effects of chemical mixtures on the developing fetus is still likely underestimated. In this critical review, we discuss the potential to apply innovative biomonitoring methods using high-resolution mass spectrometry (HRMS) on placenta to improve the monitoring of chemical exposure during pregnancy. The physiology of the placenta and its relevance as a matrix for monitoring chemical exposures and their effects on fetal health is first outlined. We then identify several key parameters that require further investigations before placenta can be used for large-scale monitoring in a robust manner. Most critical is the need for standardization of placental sampling. Placenta is a highly heterogeneous organ, and knowledge of the intraplacenta variability of chemical composition is required to ensure unbiased and robust interindividual comparisons. Other important variables include the time of collection, the sex of the fetus, and mode of delivery. Finally, we discuss the first applications of HRMS methods on the placenta to decipher the chemical exposome and describe how the use of placenta can complement biofluids collected on the mother or the fetus.

Spatial and Temporal Trends of Persistent Organic Pollutants across Europe after 15 Years of MONET Passive Air Sampling.

The Global Monitoring Plan of the Stockholm Convention on Persistent Organic Pollutants (POPs) was established to generate long-term data necessary for evaluating the effectiveness of regulatory measures at a global scale. After 15 years of passive air monitoring (2003-2019), MONET is the first network to produce sufficient data for the analysis of continuous long-term temporal trends of POPs in air across the entire European continent. This study reports long-term concentrations of 20 POPs monitored at 32 sites in 27 European countries. As of January 1, 2019, the concentration ranges (pg/m3) were 1.1-52.8 (∑6PCB), 0.3-8.5 (∑12dl-PCB), 0.007-0.175 (∑17PCDD/F), 0.02-2.2 (∑9PBDE), 0.4-24.7 (BDE 209), 0.5-247 (∑6DDT), 1.7-818 (∑4HCH), 15.8-74.7 (HCB), and 5.9-21.5 (PeCB). Temporal trends indicate that concentrations of most POPs have declined significantly over the past 15 years, with median annual decreases ranging from -8.0 to -11.5% (halving times of 6-8 years) for ∑6PCB, ∑17PCDD/F, HCB, PeCB, and ∑9PBDE. Furthermore, no statistically significant differences were observed in either the trends or the concentrations of specific POPs at sites in Western Europe (WEOG) compared to sites in Central and Eastern Europe (CEE), which suggests relatively uniform compound-specific distribution and removal at the continental scale.

Impact of PFAS exposure on prevalence of immune-mediated diseases in adults in the Czech Republic.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are emerging environmental contaminants with multiple hazardous properties including immunomodulation potency. Human exposure to PFASs has been associated with various immune-mediated diseases and outcomes. This study aimed to investigate the association between PFAS exposure and immune-mediated diseases such as allergies, eczemas, and autoimmune diseases in a population of adults in the Czech Republic. METHODS: This study included 309 adults from the Central European Longitudinal Study of Parents and Children: Young Adults (CELSPAC: YA). 12 PFASs were measured in participants' serum by HPLC-MS/MS, 3 PFASs were removed from the subsequent analyses due to low detection frequency. The associations of 9 PFASs with 9 immune-mediated diseases were assessed by logistic regression. Furthermore, Bayesian kernel machine regression (BKMR) was used to estimate the effect of the PFAS mixture on immune-mediated diseases. All analyses were adjusted for sex, age, BMI, smoking, education, and family history of immune-mediated diseases. In cases of a statistically significant interaction of PFASs and sex, stratified analyses were performed for men and women. RESULTS: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) were negatively associated with both atopic eczema (OR per IQR increase 0.58 (95% CI 0.37-0.90) for PFOA and 0.56 (0.32-0.95) for PFOS) and contact dermatitis (0.37 (0.16-0.85) for PFOA and 0.33 (0.11-0.94) for PFOS). Perfluoroundecanoate (PFUnDA) was negatively associated with pollen, dust, and mite allergy (0.62 (0.43-0.89)). BKMR modelling showed a negative tendency in the overall effect of PFAS mixture on immune-health outcomes. Based on the stratified analysis, sex was suggested to be an effect modifier in the association of PFOS and atopic eczema. CONCLUSION: Our results contribute to the body of literature that observes the immunosuppressive effect of PFAS exposure during eczemas and allergies, both for PFASs individually and as a mixture.

Harmonized Quality Assurance/Quality Control Provisions for Nontargeted Measurement of Urinary Pesticide Biomarkers in the HBM4EU Multisite SPECIMEn Study.

A set of quality assurance/quality control (QA/QC) criteria for nontargeted measurement of pesticide exposure markers in a large-scale study of human urine has been proposed and applied across five laboratories within the HBM4EU project. Quality control material, including reference standards and fortified pooled urine samples (QC urine) were prepared in a centralized way and distributed across participants to monitor analytical performance and consistency of the liquid chromatography coupled to high-resolution mass spectrometry data generated with a harmonized workflow. Signal intensities, mass accuracy, and retention times of selected QA/QC markers covering a broad range of physicochemical properties were monitored across QC solvent standards, QC urine samples, study urine samples, and procedural blanks, setting acceptance thresholds for repeatability and accuracy. Overall, results showed high repeatability of the collected data. The RSDs of the signal intensities were typically below 20-30% in QC and study samples, with good stability of the chromatographic separation (retention time drift within 2-4 s intrabatch and 5 s interbatch) and excellent mass accuracy (average error < 2 ppm). The use of the proposed criteria allowed for the identification of handling errors, instrumental issues, and potential batch effects. This is the first elaboration of harmonized QA/QC criteria applied across multiple laboratories to assess the quality of data generated by nontargeted analysis of human samples.

Prenatal psychosocial stress and children's sleep problems: Evidence from the ELSPAC-CZ study.

Prenatal exposure to maternal stress may increase the risk of developing sleep problems in childhood. This study examined the association between prenatal stressful life events (PSLE) and children's sleep problems, taking into consideration their trajectory over time. Data were obtained from the Czech portion of the European Longitudinal Cohort Study of Pregnancy and Childhood (ELSPAC-CZ; N = 4,371 children). Mothers reported PSLE using an inventory of 42 life events and child sleep problems at five time-points (child age of 1.5, 3, 5, 7, and 11 years). The association was tested by a Poisson latent growth model, controlling for maternal and family demographics, birth characteristics, maternal depression, and alcohol use in pregnancy. The average rate of sleep problems was 2.06 (p < 0.001) at the age of 1.5 years and the rate of sleep problems decreased in a linear fashion over time (estimate = -0.118; p < 0.001). A higher number of PSLE was associated with a higher rate of sleep problems at the age of 1.5 years (incidence rate ratio [IRR] per interquartile range = 1.08, 95% confidence interval [CI] 1.05-1.12, p < 0.001) and with a reduced rate of decrease in sleep problems between the ages of 1.5 and 11 years (p < 0.001). Thus, PSLE were associated with chronicity of sleep problems in addition to their amount during early childhood. Prenatal exposure to stress may predispose individuals to the development of sleep problems in later life.

Enhancing Scientific Support for the Stockholm Convention's Implementation: An Analysis of Policy Needs for Scientific Evidence.

The Stockholm Convention is key to addressing the global threats of persistent organic pollutants (POPs) to humanity and the environment. It has been successful in identifying new POPs, but its national implementation remains challenging, particularly by low- and middle-income Parties. Concerted action is needed to assist Parties in implementing the Convention's obligations. This analysis aims to identify and recommend research and scientific support needed for timely implementation of the Convention. We aim this analysis at scientists and experts from a variety of natural and social sciences and from all sectors (academia, civil society, industry, and government institutions), as well as research funding agencies. Further, we provide practical guidance to scientists and experts to promote the visibility and accessibility of their work for the Convention's implementation, followed by recommendations for sustaining scientific support to the Convention. This study is the first of a series on analyzing policy needs for scientific evidence under global governance on chemicals and waste.

Polycyclic aromatic hydrocarbons (PAHs) in human breast milk from Colombia: Spatial occurrence, sources and probabilistic risk assessment.

The diet is the main route that polycyclic aromatic hydrocarbons (PAHs) enter the body and measuring breast milk is one of the best ways to understand the maternal body burden and can be passed on to infants. In this study, it was determinate the concentrations of 23 PAHs in 60 milk samples taken from 3 cities in Colombia and to determine the potential routes of exposure and risk to human health. On average, concentration for the ∑PAHs across all locations was 186.6 ng g-1, lipid mass (LM), with city means of 260.1, 175.7, and 123.9 ng g-1 LM for Cartagena, Bogota and Medellin, respectively. Monte Carlo simulations were used to estimate the hazard quotient (HQ) and incremental lifetime cancer risk (ILCR) for infant dietary exposure to PAHs. HQs were below the safe thresholds (HQ = 1) while ILCRs were greater than the reference value equal to 10-6 (mg kg-1day-1). Dietary source assessment indicated that fish is a significant source of PAHs, with mothers that consumed fish at least once per week having ∼2.5 times greater PAH milk concentrations than other groups. While a disparity was also observed among consumers of exclusively marine (∑PAHs 198.5 ng g-1 LM) or freshwater fish (∑PAHs 85.7 ng g-1 LM). However, geographical considerations can be significant in this finding.

Personal care product use and lifestyle affect phthalate and DINCH metabolite levels in teenagers and young adults.

Humans are widely exposed to phthalates and their novel substitutes, and considering the negative health effects associated with some phthalates, it is crucial to understand population levels and exposure determinants. This study is focused on 300 urine samples from teenagers (aged 12-17) and 300 from young adults (aged 18-37) living in Czechia collected in 2019 and 2020 to assess 17 plasticizer metabolites as biomarkers of exposure. We identified widespread phthalate exposure in the study population. The diethyl phthalate metabolite monoethyl phthalate (MEP) and three di (2-ethylhexyl) phthalate metabolites were detected in the urine of >99% of study participants. The highest median concentrations were found for metabolites of low-molecular-weight (LMW) phthalates: mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) and MEP (60.7; 52.6 and 17.6 µg/L in young adults). 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) metabolites were present in 68.2% of the samples with a median of 1.24 µg/L for both cohorts. Concentrations of MnBP and MiBP were similar to other European populations, but 5-6 times higher than in populations in North America. We also observed large variability in phthalate exposures within the study population, with 2-3 orders of magnitude differences in urinary metabolites between high and low exposed individuals. The concentrations varied with season, gender, age, and lifestyle factors. A relationship was found between high levels of MEP and high overall use of personal care products (PCPs). Cluster analysis suggested that phthalate exposures depend on season and multiple lifestyle factors, like time spent indoors and use of PCPs, which combine to lead to the observed widespread presence of phthalate metabolites in both study populations. Participants who spent more time indoors, particularly noticeably during colder months, had higher levels of high-molecular weight phthalate metabolites, whereas participants with higher PCP use, particularly women, tended to have higher concentration of LMW phthalate metabolites.

Trends of Diverse POPs in Air and Water Across the Western Atlantic Ocean: Strong Gradients in the Ocean but Not in the Air.

Oceans have remained the least well-researched reservoirs of persistent organic pollutants (POPs) globally, due to their vast scale, difficulty of access, and challenging (trace) analysis. Little data on POPs exists along South America and the effect of different currents and river plumes on aqueous concentrations. Research cruise KN210-04 (R/V Knorr) offered a unique opportunity to determine POP gradients in air, water, and their air-water exchange along South America, covering both hemispheres. Compounds of interest included polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenylethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs). Remote tropical Atlantic Ocean atmospheric concentrations varied little between both hemispheres; for HCB, BDEs 47 and 99, they were ∼5 pg/m3, PCBs were ∼1 pg/m3, α-HCH was ∼0.2 pg/m3, and phenanthrene and other PAHs were in the low 100s pg/m3. Aqueous concentrations were dominated by PCB 52 (mean 4.1 pg/L), HCB (1.6 pg/L), and ß-HCH (1.9 pg/L), with other compounds <1 pg/L. Target PCBs tended to undergo net volatilization from the surface ocean, while gradients indicated net deposition for a-HCH. In contrast to atmospheric concentrations, which were basically unchanged between hemispheres, we detected strong gradients in aqueous POPs, with mostly nondetects in the tropical western South Atlantic. These results highlight the importance of currents and loss processes on ocean scales for the distribution of POPs.

Temporal Trends of Persistent Organic Pollutants across Africa after a Decade of MONET Passive Air Sampling.

The Global Monitoring Plan of the Stockholm Convention on Persistent Organic Pollutants (POPs) was established to generate long-term data necessary for evaluating the effectiveness of regulatory measures at a global scale. After a decade of passive air monitoring (2008-2019), MONET is the first network to produce sufficient data for the analysis of long-term temporal trends of POPs in the African atmosphere. This study reports concentrations of 20 POPs (aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, endosulfan, HBCDD, HCB, HCHs, heptachlor, hexabromobiphenyl, mirex, PBDEs, PCBs, PCDDs, PCDFs, PeCB, PFOA, and PFOS) monitored in 9 countries (Congo, Ghana, Ethiopia, Kenya, Mali, Mauritius, Morocco, Nigeria, and Sudan). As of January 1, 2019, concentrations were in the following ranges (pg/m3): 0.5-37.7 (∑6PCB), 0.006-0.724 (∑17PCDD/F), 0.05-5.5 (∑9PBDE), 0.6-11.3 (BDE 209), 0.1-1.8 (∑3HBCDD), 1.8-138 (∑6DDT), 0.1-24.3 (∑3endosulfan), 0.6-14.6 (∑4HCH), 9.1-26.4 (HCB), 13.8-18.2 (PeCB). Temporal trends indicate that concentrations of many POPs (PCBs, DDT, HCHs, endosulfan) have declined significantly over the past 10 years, though the rate was slow at some sites. Concentrations of other POPs such as PCDD/Fs and PBDEs have not changed significantly over the past decade and are in fact increasing at some sites, attributed to the prevalence of open burning of waste (particularly e-waste) across Africa. Modeled airflow back-trajectories suggest that the elevated concentrations at some sites are primarily due to sustained local emissions, while the low concentrations measured at Mt. Kenya represent the continental background level and are primarily influenced by long-range transport.

Tracing the movement of persistent organic pollutants at a high-mountain sampling site by chemometric assessment.

The main objective of the present study was to determine and differentiate the concentration levels, to define the probable sources of persistent organic pollutants (POPs) pollution in the atmospheric air and their seasonal variations in Bulgaria, on the high mountain peak Moussala, Rila Mountain. The study was based on the obtained results from the passive monitoring of POPs in 2014-2017. During this period, the measurements of POPs were performed with passive samplers, advanced instrumental methods analytically determined the concentrations of PAHs, and the analysis of the obtained data was performed by the multivariate statistical analysis (cluster, factor and time-series analysis). It is shown that the POPs species could be correctly classified according to their chemical nature into several patterns of similarity and their concentration profile depends on the annual season.

Global intercomparison of polyurethane foam passive air samplers evaluating sources of variability in SVOC measurements.

Polyurethane foam passive air samplers (PUF-PAS) are the most common type of passive air sampler used for a range of semi-volatile organic compounds (SVOCs), including regulated persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs), and emerging contaminants (e.g., novel flame retardants, phthalates, current-use pesticides). Data from PUF-PAS are key indicators of effectiveness of global regulatory actions on SVOCs, such as the Global Monitoring Plan of the Stockholm Convention on Persistent Organic Pollutants. While most PUF-PAS use similar double-dome metal shielding, there is no standardized dome size, shape, or deployment configuration, with many different PUF-PAS designs used in regional and global monitoring. Yet, no information is available on the comparability of data from studies using different PUF-PAS designs. We brought together 12 types of PUF-PAS used by different research groups around the world and deployed them in a multi-part intercomparison to evaluate the variability in reported concentrations introduced by different elements of PAS monitoring. PUF-PAS were deployed for 3 months in outdoor air in Kjeller, Norway in 2015-2016 in three phases to capture (1) the influence of sampler design on data comparability, (2) the influence of analytical variability when samplers are analyzed at different laboratories, and (3) the overall variability in global monitoring data introduced by differences in sampler configurations and analytical methods. Results indicate that while differences in sampler design (in particular, the spacing between the upper and lower sampler bowls) account for up to 50 % differences in masses collected by samplers, the variability introduced by analysis in different laboratories far exceeds this amount, resulting in differences spanning orders of magnitude for POPs and PAHs. The high level of variability due to analysis in different laboratories indicates that current SVOC air sampling data (i.e., not just for PUF-PAS but likely also for active air sampling) are not directly comparable between laboratories/monitoring programs. To support on-going efforts to mobilize more SVOC data to contribute to effectiveness evaluation, intercalibration exercises to account for uncertainties in air sampling, repeated at regular intervals, must be established to ensure analytical comparability and avoid biases in global-scale assessments of SVOCs in air caused by differences in laboratory performance.

Assessing Stress in Pregnancy and Postpartum: Comparing Measures.

INTRODUCTION: Measuring early-life psychosocial stress is complicated by methodological challenges. This paper compares three survey instruments for the assessment of life in pregnancy/postpartum and investigates the effects of the timing of early-life stress for emotional/behavioral difficulties (EBD) of offspring during mid/late childhood and adolescence. METHODS: Observational data were obtained from the European Longitudinal Cohort Study of Pregnancy and Childhood (ELSPAC-CZ), which included 4811 pregnancies in two Czech metropolitan areas. We used data collected between 1991 and 2010 at 20 weeks of pregnancy (T1), after delivery (T2), at 6 months postpartum (T3), and at child's age of 7 years (T4), 11 years (T5), 15 years (T6), and 18 years (T7). Life stress was assessed with (1) the Edinburgh Postnatal Depression Scale (EPDS), (2) a stressful life events (SLE) count based on 42-item inventory, and (3) the SLE measure weighted by perceived stressfulness (PS). Each stress measure was administered at T1, T2, and T3. Child's EBD were assessed with the Strengths and Difficulties Questionnaire at T4, T5, T6, and T7. RESULTS: Each stress measure independently predicted long-term EBD. The best data fit was obtained in a model combining EPDS and SLE. Effect sizes for SLEs decreased between the first half of pregnancy and postpartum, while the effect of EPDS increased. DISCUSSION: SLE-based methods capture an aspect of perinatal stress not adequately assessed by EPDS. Combination of psychological distress measures and SLE-based measures is optimal in predicting EBD of the child. Stress measures based on SLE are suitable for early pregnancy, while self-reports of depressive symptoms may perform better in postpartum.

Childhood Sleep Functioning as a Developmental Precursor of Adolescent Adjustment Problems.

Sleep has been linked to adjustment difficulties in both children and adolescents; yet little is known about the long-term impact of childhood sleep on subsequent development. This study tested whether childhood sleep problems, sleep quantity, and chronotype predicted internalizing and externalizing problems during adolescence. Latent Growth Modeling using the Czech portion of the European Longitudinal Study of Pregnancy and Childhood (N = 4393) was utilized to test the developmental trajectories of sleep characteristics (from 1.5 to 7 years) as predictors of adjustment problems trajectories (from 11 to 18 years). Findings provided evidence that children with higher levels of sleep problems at 1.5 years (and throughout childhood) reported higher levels of internalizing and externalizing problems at age 11. Additionally, greater eveningness at age 1.5 predicted a greater increase in externalizing problems from ages 11 to 18 years. The results emphasize the importance of childhood sleep problems in evaluating the risk of future adjustment difficulties.

Multiplex Assay for Quantification of Acute Phase Proteins and Immunoglobulin A in Dried Blood Spots.

Inflammation is the first line defense mechanism against infection, tissue damage, or cancer development. However, inappropriate inflammatory response may also trigger diseases. The quantification of inflammatory proteins is essential to distinguish between harmful and beneficial immune response. Currently used immunoanalytical assays may suffer specificity issues due to antigen-antibody interaction and possible cross-reactivity of antibody with other protein species. In addition, immunoanalytical assays typically require invasive blood sampling and additional logistics; they are relatively costly and highly challenging to multiplex. We present a multiplex assay based on selected reaction monitoring (SRM) for quantification of seven acute-phase proteins (i.e., SAA1, SAA2-isoform1, SAA4, CRP, A1AT-isoform1, A1AG1, A1AG2) and the adaptive immunity effector IGHA1 in dried blood spots. This type of sample is readily available from all human subjects including newborns. The study utilizes proteotypic isotopically labeled peptides with trypsin-cleavable tag and presents optimized and reproducible workflow and several important practical remarks regarding quantitative SRM assays development. The panel of inflammatory proteins was quantified with sequence specificity capable to differentiate protein isoforms with intra- and interday precision (<16.4% coefficient of variation (CV) and <14.3% CV, respectively). Quantitative results were correlated with immuno-nephelometric assay (typically greater than 0.9 Pearson's R).

Environmental ototoxicants, a potential new class of chemical stressors.

Hearing loss is an injury that can develop over time, and people may not even be aware of it until it becomes a severe disability. Ototoxicants are substances that may damage the inner ear by either affecting the structures in the ear itself or by affecting the nervous system. We have examined the possibility that ototoxicants may present a health hazard in association with environmental exposures, adding to existing knowledge of their proven hazards under medical therapeutic conditions or occupational activities. In addition to the already described human environmental ototoxicants, mainly organochlorines such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), hexachlorocyclohexane (HCH) and hexachlorobenzene (HCB), we have examined the ubiquitous chemical stressors phthalates, bisphenol A/S/F/, PFCs, flame retardants (FRs) and cadmium for potential ototoxic properties, both as single substances or as chemical mixtures. Our literature review confirmed that these chemicals may disturb thyroid hormones homeostasis, activate aryl hydrocarbon receptor (AhR), and induce oxidative stress, which in turn may initiate a chain of events resulting in impairment of cochlea and hearing loss. With regard to auditory plasticity, diagnostics of a mixture of effects of ototoxicants, potential interactions of chemical and physical agents with effects on hearing, parallel deterioration of hearing due to chemical exposures and ageing, metabolic diseases or obesity, even using specific methods as brainstem auditory evoked potentials (BAEP) or otoacoustic emissions (OAEs) registration, may be difficult, and establishment of concentration-response relationships problematic. This paper suggests the establishment of a class of environmental oxotoxicants next to the established classes of occupational and drug ototoxicants. This will help to properly manage risks associated with human exposure to chemical stressors with ototoxic properties and adequate regulatory measures.

Sleep Quantity and Problems as Mediators of the Eveningness-Adjustment Link during Childhood and Adolescence.

Chronotype, or morningness/eveningness, has been associated with adjustment in both children and adolescents. Specifically, eveningness has been linked to adjustment difficulties; however, the mechanism underlying this association is poorly understood. The purpose of this study was to test whether the associations between eveningness and adjustment difficulties could be explained by an unfavorable impact of eveningness on sleep. Links from chronotype to internalizing problems and problem behaviors via sleep quantity and sleep problems were tested in a sample from the European Longitudinal Study of Pregnancy and Childhood (N = 3485; 48.8% female), both when the participants were children (7 years at T1, 11 at T2) and when they were adolescents (15 years at T1, 18 at T2). The findings provided evidence that eveningness predicted greater sleep problems and lower sleep quantity; however, only sleep problems predicted internalizing problems and problem behaviors. Sleep quantity did not mediate the eveningness-adjustment link, and sleep problems did so only in children. The findings show that sleep problems appear to be more important in explaining the eveningness-adjustment link rather than altered sleep quantity, commonly associated with eveningness.