Akkermansia muciniphila extracellular vesicles have a protective effect against hypertension.

Akkermansia muciniphila (Am) shows a beneficial role as a probiotic in the treatment of metabolic syndrome. However, the mechanism remains to be elucidated. We tested the hypothesis that Am extracellular vesicles (AmEVs) have a protective effect against hypertension. Extracellular vesicles purified from anaerobically cultured Am were characterized by nanoparticle tracking analysis, transmission electron microscopy, and silver stain after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). AmEVs (1.0 × 1010 log particles/L) or vehicles were added into organ baths to induce vasorelaxation. In addition, AmEVs (1.0 × 108 or 1.0 × 109 particles/kg) or vehicles were injected into the tail veins of Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) weekly for 4 weeks. Peripheral blood mononuclear cells (PBMCs) and splenocytes isolated from both rat strains were analyzed by flow cytometry, RT-qPCR, and western blot. AmEVs affected neither vascular contraction nor endothelial relaxation in thoracic aortas. Moreover, AmEVs protected against the development of hypertension in SHRs without a serious adverse reaction. Additionally, AmEVs increased the population of T regulatory (Treg) cells and tended to reduce proinflammatory cytokines. These results indicate that AmEVs have a protective effect against hypertension without a serious adverse reaction. Therefore, it is foreseen that AmEVs may be utilized as a novel therapeutic for the treatment of hypertension.

Differences in parent and youth perceived neighborhood threat on nucleus accumbens-frontoparietal network resting state connectivity and alcohol sipping in children enrolled in the ABCD study.

Purpose: Evidence has shown neighborhood threat (NT) as a social driver of emotional and brain development. Few studies have examined the relationship between NT and neural function. Altered functional connectivity in the nucleus accumbens (NAcc) with the frontoparietal network (FPN) has been implicated in the development of substance use, however, little is known about perceived NT-related brain function or downstream alcohol sipping during early adolescence. This study examined the longitudinal relationship between youth and combined youth/parent perceived NT, resting state functional connectivity (RSFC) of the NAcc-FPN, and alcohol sipping behavior during late childhood and preadolescence. Methods: This study used data (N = 7,744) from baseline to 2-year follow-up (FU) of the Adolescent Brain Cognitive Development Study (ABCD; Release 4.0). Relationships between youth and combined youth/parent perceive NT, alcohol sipping (baseline to two-year FU), and NAcc-FPN (left/right) connectivity, adjusting for demographics, family/peer history of alcohol use, parental monitoring and warmth, externalizing symptoms, and site, were examined in a mediation model via PROCESS in R. Results: Greater youth-reported NT at baseline was significantly associated with lower RSFC between the right (but not left) NAcc-FPN holding covariates constant (R2 = 0.01, B = -0.0019 (unstandardized), F (12, 7,731) = 8.649, p = 0.0087) and increased odds of alcohol sipping at baseline up to the two-year FU (direct effect = 0.0731, 95% CI = 0.0196, 0.1267). RSFC between the right NAcc-FPN did not significantly predict alcohol sipping at the two-year FU (b = -0.0213, SE = 0.42349, p = 0.9599; 95% CI = -0.8086, 0.8512). No significant relationships were observed for combined youth/parent report predicting alcohol sipping or NAcc-FPN connectivity. Conclusion: Findings suggest notable reporting differences in NT. Combined youth/parent report did not reveal significant findings; youth perceived NT was related to increased likelihood of alcohol sipping and lower neural connectivity between the right NAcc-FPN during late childhood and early adolescence. NT context - and source of reporting - may be crucial in examining links with downstream neuronal function and health behaviors. Future research should investigate reward processing and threat as the cohort ages into later adolescence.

Sertraline associated with gold nanoparticles reduce cellular toxicity and induce sex-specific responses in behavior and neuroinflammation biomarkers in a mouse model of anxiety.

This study aimed to evaluate the effects of sertraline associated with gold nanoparticles (AuNPs) in vitro cell viability and in vivo behavior and inflammatory biomarkers in a mouse model of anxiety. Sertraline associated with AuNPs were synthesized and characterized. For the in vitro study, NIH3T3 and HT-22 cells were treated with different doses of sertraline, AuNPs, and sertraline + AuNPs and their viability was evaluated using the MTT assay. For the in vivo study, pregnant Swiss mice were administered a single dose of lipopolysaccharide (LPS) on the ninth day of gestation. The female and male offspring were divided into five treatment groups on PND 60 and administered chronic treatment for 28 days. The animals were subjected to behavioral testing and were subsequently euthanized. Their brains were collected and analyzed for inflammatory biomarkers. Sertraline associated with AuNPs exhibited significant changes in surface characteristics and increased diameters. Different doses of sertraline + AuNPs showed higher cell viability in NIH3T3 and HT-22 cells compared with sertraline alone. The offspring of LPS-treated dams exhibited anxiety-like behavior and neuroinflammatory biomarker changes during adulthood, which were ameliorated via sertraline + AuNPs treatment. The treatment response was sex-dependent and brain region-specific. These results suggest that AuNPs, which demonstrate potential to bind to other molecules, low toxicity, and reduced inflammation, can be synergistically used with sertraline to improve drug efficacy and safety by decreasing neuroinflammation and sertraline toxicity.

A Randomized, Self-Controlled Case Series Evaluating Core Osteostixis of Osseous Cyst-Like Lesions of the Navicular Bone to Improve Lameness in Horses with Podotrochlear Syndrome.

Introduction: Podotrochlear syndrome is a common cause of lameness in Quarter Horses involving both soft tissue and bony structures within the heel region. Current surgical treatment of podotrochlear syndrome addresses pathological changes affecting the soft tissue structures of the navicular region but does not address either edema or cyst-like lesions of the navicular bone. Objective: The objective of this randomized, self-controlled case series was to determine whether core osteostixis improved lameness in Quarter Horses with podotrochlear syndrome characterized by bilateral magnetic resonance imaging (MRI) findings of osseous cyst-like lesions of the navicular bone. Methods: Seven Quarter Horses that had not responded to standard medical management were included. Each horse had an affected forefoot randomly assigned to surgical treatment with navicular bursoscopy and core osteostixis; the contralateral limb was assigned to navicular bursoscopy only. Video recordings were used to assign lameness scores and make comparisons of each limb at baseline and 24 weeks post-operatively by an observer blinded to the surgical treatment. A second MRI was performed 24 weeks after surgery to reevaluate navicular bone edema, osseous cyst-like lesions of the navicular bone, and tears of the deep digital flexor tendon (DDFT). Results: Reduction of lameness score from baseline was significantly (P = 0.0254) greater for the limbs treated with core osteostixis than limbs treated with bursoscopy. New DDFT tears were noted in 3 of 7 limbs treated with core osteostixis and in 1 of 7 bursoscopy limbs. Conclusion: Results of this study suggest that core osteostixis of the navicular bone combined with navicular bursoscopy can improve lameness in horses with osseous cyst-like lesions. Further evaluation of this technique is warranted.

CD5L as an Extracellular Vesicle-Derived Biomarker for Liquid Biopsy of Lung Cancer.

Cancer screening and diagnosis can be achieved by analyzing specific molecules within serum-derived extracellular vesicles (EVs). This study sought to profile EV-derived proteins to identify potential lung cancer biomarkers. EVs were isolated from 80 serum samples from healthy individuals and cancer patients via polyethylene glycol (PEG)-based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM. Proteomic analysis was performed using 2-D gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The expression of proteins that were differentially upregulated in the EVs or tissue of lung cancer samples was validated by Western blotting. The area under the curve (AUC) was calculated to assess the predictability of each differentially expressed protein (DEP) for lung cancer. A total of 55 upregulated protein spots were selected, seven of which (CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3) were found to be expressed at high levels in patient-derived EVs by Western blotting. Meanwhile, only the expression of EV CD5L correlated with that in cancer tissues. CD5L also demonstrated the highest AUC value (0.943) and was found to be the core regulator in a pathway related to cell dysfunction. Cumulatively, these results show that EV-derived CD5L may represent a potential biomarker-detected via a liquid biopsy-for the noninvasive diagnosis of lung cancer.

Low-cost exercise interventions improve long-term cardiometabolic health independently of a family history of type 2 diabetes: a randomized parallel group trial.

INTRODUCTION: To investigate the effect of an exercise prescription and a 1-year supervised exercise intervention, and the modifying effect of the family history of type 2 diabetes (FH), on long-term cardiometabolic health. RESEARCH DESIGN AND METHODS: For this prospective randomized trial, we recruited non-diabetic participants with poor fitness (n=1072, 30-70 years). Participants were randomly assigned with stratification for FH either in the exercise prescription group (PG, n=144) or the supervised exercise group (EG, n=146) group and compared with a matched control group from the same population study (CON, n=782). The PG and EG received exercise prescriptions. In addition, the EG attended supervised exercise sessions two times a week for 60 min for 12 months. Cardiometabolic risk factors were measured at baseline, 1 year, 5 years, and 6 years. The CON group received no intervention and was measured at baseline and 6 years. RESULTS: The EG reduced their body weight, waist circumference, diastolic blood pressure, and low-density lipoprotein-cholesterol (LDL-C) but not physical fitness (p=0.074) or insulin or glucose regulation (p>0.1) compared with the PG at 1 year and 5 years (p≤0.011). The observed differences were attenuated at 6 years; however, participants in the both intervention groups significantly improved their blood pressure, high-density lipoprotein-cholesterol, and insulin sensitivity compared with the population controls (p≤0.003). FH modified LDL-C and waist circumference responses to exercise at 1 year and 5 years. CONCLUSIONS: Low-cost physical activity programs have long-term beneficial effects on cardiometabolic health regardless of the FH of diabetes. Given the feasibility and low cost of these programs, they should be advocated to promote cardiometabolic health. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT02131701.

Periodic bouncing modes for two uniformly magnetized spheres. II. Scaling.

A uniformly magnetized sphere moves without friction in a plane in response to the field of a second, identical, fixed sphere and makes elastic hard-sphere collisions with this sphere. Numerical simulations of the threshold energies and periods of periodic finite-amplitude nonlinear bouncing modes agree with small-amplitude closed-form mathematical results, which are used to identify scaling parameters that govern the entire amplitude range, including power-law scaling at large amplitudes. Scaling parameters are combinations of the bouncing number, the rocking number, the phase, and numerical factors. Discontinuities in the scaling functions are found when viewing the threshold energy and period as separate functions of the scaling parameters, for which large-amplitude scaling exponents are obtained from fits to the data. These discontinuities disappear when the threshold energy is viewed as a function of the threshold period, for which the large-amplitude scaling exponent is obtained analytically and for which scaling applies to both in-phase and out-of-phase modes.

Periodic bouncing modes for two uniformly magnetized spheres. I. Trajectories.

We consider a uniformly magnetized sphere that moves without friction in a plane in response to the field of a second, identical, fixed sphere, making elastic hard-sphere collisions with this sphere. We seek periodic solutions to the associated nonlinear equations of motion. We find closed-form mathematical solutions for small-amplitude modes and use these to characterize and validate our large-amplitude modes, which we find numerically. Our Runge-Kutta integration approach allows us to find 1243 distinct periodic modes with the free sphere located initially at its stable equilibrium position. Each of these modes bifurcates from the finite-amplitude radial bouncing mode with infinitesimal-amplitude angular motion and supports a family of states with increasing amounts of angular motion. These states offer a rich variety of behaviors and beautiful, symmetric trajectories, including states with up to 157 collisions and 580 angular oscillations per period.

Prevalence and correlates of diabetes distress, perceived stress and depressive symptoms among adults with early-onset Type 2 diabetes: cross-sectional survey results from the Danish DD2 study.

AIMS: To establish the prevalence of diabetes distress, perceived stress and depressive symptoms among adults with early-onset Type 2 diabetes, and to examine their association with socio-demographic and clinical characteristics. METHODS: A cross-sectional survey was performed among individuals with Type 2 diabetes aged 20-45 years who were included in the Danish nationwide Danish Center for Strategic Research in Type 2 Diabetes cohort between 2010 and 2016. The survey assessed diabetes distress (20-item Problem Areas in Diabetes Scale), perceived stress (10-item Perceived Stress Scale) and depressive symptoms (10-item short form of the Center for Epidemiological Studies Depression Scale Revised), as well as socio-demographic characteristics. Clinical data were collected from national health registers. RESULTS: In total, 216/460 (47%) individuals (48% women) with Type 2 diabetes completed the survey. The median (IQR) age was 42 (38-44) years and the diabetes duration was 5 (3-7) years. In total, 24% of respondents reported high diabetes distress (Problem Areas in Diabetes Scale ≥ 40), 46% reported high perceived stress (Perceived Stress Scale ≥ 18) and 41% reported elevated symptoms of depression (Center for Epidemiological Studies Depression Scale Revised ≥ 10). The prevalence of emotional problems was higher among women than men. Diabetes distress was higher among those prescribed non-insulin glucose-lowering drugs (vs. no glucose-lowering drugs), but was not associated with other clinical or socio-demographic characteristics. High perceived stress was associated with being unemployed and using antidepressant medication, and elevated depressive symptoms were associated with low education level, unemployment, living alone, having a psychiatric disorder and using antidepressant medication. CONCLUSION: We found a high prevalence of emotional problems among adults with early-onset Type 2 diabetes in Denmark. Health care for this group should focus on both physical health and psychosocial circumstances and should also address general as well as diabetes-specific emotional problems.

PVC flooring at home and uptake of phthalates in pregnant women.

Phthalates are used as plasticizers in polyvinyl chloride (PVC) materials and it is known that phthalates may migrate into the surrounding environment and then become a source for human uptake. The aim of the study was to investigate whether residential PVC flooring was related to the urinary levels of phthalate metabolites determined in pregnant women. The data were from the Swedish SELMA study where sampling was conducted during the time period 2007-2010. Spot urine samples from 1674 women at the end of the first trimester were analyzed for 14 metabolites from seven phthalates and one phthalate alternative. Data on flooring material in the kitchen and the parents' bedrooms as well as potential confounders were collected by postal questionnaires at the same time as the urine samples were taken. Multiple regression modeling by least square geometric mean and weighted quantile sum regression was applied to log-transformed and creatinine-adjusted phthalate metabolite concentrations adjusted for potential confounders from questionnaire data. This study has found significantly higher urinary levels of the BBzP metabolite (MBzP) in pregnant women living in homes with PVC flooring as compared to homes with other flooring materials.

Effects of Mongolian Warm Acupuncture on iNOS/NO and Inflammatory Cytokines in the Hippocampus of Chronic Fatigue Rats.

The inducible nitric oxide synthase/nitric oxide (iNOS/NO) signaling pathway and inflammatory cytokines play important roles in the pathogenesis of exercise-induced fatigue. Studies have found that Mongolian warm acupuncture (WA) could alleviate exercise-induced fatigue. However, the exact mechanisms underlying its effects remain unclear. In the present study, we investigated the effects of Mongolian WA on iNOS/NO signaling pathway and proinflammatory cytokines in a chronic exhaustive swimming-induced fatigue rat model. Animals were randomly divided into Control group, Ctrl + WA group, Model group, and Model + WA group. The body weight, exhaustive swimming time test, and Morris water maze test were performed before and after the chronic exhaustive swimming. The serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and iNOS were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-1ß, IL-6, TNF-α, IFN-γ, and iNOS in the hippocampus were measured by real-time polymerase chain reaction (RT-PCR). Moreover, the protein expression of iNOS in the hippocampus was measured by western blot, and the NO productions in the serum and hippocampus were detected by Griess reaction system. Chronic exhaustive exercise significantly reduced the body weight and exhaustive swimming time, and induced impairment in learning and memory, and which were reversed by WA treatment. Chronic exhaustive exercise also increased the expressions of iNOS and proinflammatory cytokines, while WA treatment significantly decreased the level of iNOS and proinflammatory cytokines. However, chronic exhaustive exercise did not affect the NO production. These findings demonstrated that WA could alleviate the chronic exhaustive swimming-induced fatigue and improve the learning and memory ability, and the actions might be related to the reduction of inflammatory response and iNOS expression.

Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case-Control Study.

The period of the first to second trimester transition in human pregnancy represents a sensitive window for fetal organogenesis, particularly in regard to the development of the male reproductive system. This is a time of relative analytical inaccessibility. We have used a large national biobank of amniotic fluid samples collected at routine amniocentesis to determine the impacts of exogenous endocrine disruptor load on specific fetal biomarkers at this critical time. While adrenal and testicular steroids are highly correlated, they are also mostly positively influenced by increasing phthalate load, represented by the metabolites 7cx-MMeHP and 5cx-MEPP, by perfluorooctane sulfonate (PFOS) exposure, and by smoking, suggesting an adrenal stress response. In contrast, the testis specific biomarkers insulin-like peptide 3 (INSL3) and androstenedione are negatively impacted by the phthalate endocrine disruptors. Using a case-control design, we show that cryptorchidism and hypospadias are both significantly associated with increased amniotic concentration of INSL3 during gestational weeks 13-16, and some, though not all steroid biomarkers. Cases are also linked to a specifically increased variance in the Leydig cell biomarker INSL3 compared to controls, an effect exacerbated by maternal smoking. No influence of phthalate metabolites or PFOS was evident on the distribution of cases and controls. Considering that several animal and human studies have shown a negative impact of phthalate load on fetal and cord blood INSL3, respectively, the present results suggest that such endocrine disruptors may rather be altering the relative dynamics of testicular development and consequent hormone production, leading to a desynchronization of tissue organization during fetal development. Being born small for gestational age appears not to impact on the testicular biomarker INSL3 in second trimester amniotic fluid.

Occupational exposure to asphalt mixture during road paving is related to increased mitochondria DNA copy number: a cross-sectional study.

BACKGROUND: Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from hot mix asphalt via both inhalation and dermal absorption. The use of crumb rubber modified (CRM) asphalt may result in higher exposure to PAHs and more adverse effects. Our aim is to assess occupational exposure to PAHs from conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere length. METHODS: We recruited 116 workers paving conventional asphalt, 51 workers paving CRM asphalt and 100 controls in Sweden, all males. A repeated-measures analysis included 31 workers paving both types of asphalt. Urine and blood samples were collected pre-working on Monday morning and post-working on Thursday afternoon after 4 days working. PAH metabolites: 1-hydroxypyrene (1-OH-PYR) and 2-hydroxyphenanthrene (2-OH-PH) were measured in urine by LC-MS/MS. Relative mtDNAcn and telomere length were measured by quantitative PCR. RESULTS: Conventional and CRM asphalt workers showed higher 1-OH-PYR and 2-OH-PH than controls (p < 0.001 for all). Relative mtDNAcn were 0.21 units (p < 0.001) higher in conventional asphalt workers and 0.13 units (p = 0.010) higher in CRM asphalt workers compared to controls. Relative telomere length did not differ across occupational groups, but it was positively associated with increment of 2-OH-PH (ß = 0.075, p = 0.037) in asphalt workers. The repeated-measures analysis showed no difference in either increment of 1-OH-PYP, or changes in effect biomarkers (mtDNAcn or telomere length) between paving with conventional and CRM asphalt. Increment of 2-OH-PH was smaller after paving with CRM asphalt. CONCLUSIONS: Road asphalt paving in open areas resulted in PAHs exposure, as shown by elevation of PAH metabolites in urine. Asphalt workers may experience oxidative stress, evidenced by alternation in mtDNAcn; however the effects could not be fully explained by exposure to PAHs from the asphalt mixture.

Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function: a Systematic Review of Human Evidence.

PURPOSE OF REVIEW: The purpose of this review is to systematically review the literature linking di-2-ethylhexyl phthalate (DEHP) exposure with effects on reproductive health in adult males. RECENT FINDINGS: Thirty-three papers were included of which 28 were cross-sectional. Twenty-one papers investigated semen samples, 18 investigated reproductive hormones, and three studies investigated time to pregnancy. Studies revealed some but inconsistent indications that higher urinary DEHP metabolite levels are associated with an increase in the proportion of spermatozoa with damaged DNA and to a decrease in sperm concentration and motility. A negative association between DEHP metabolites and testosterone levels was more consistent. DEHP metabolites do not seem to be associated with a delay in time to pregnancy, but data are sparse. The studies on DEHP exposure and reproductive biomarkers in men converge to support the hypothesis that DEHP exposure is related to impaired male reproductive function. Longitudinal studies are needed to establish if the observed associations are causal.

Prenatal phthalate exposure was associated with croup in Swedish infants.

AIM: This study examined whether prenatal phthalate exposure was associated with lower or upper airway inflammation in infants. METHODS: From 2007 to 2010, we used liquid chromatography-tandem mass spectrometry, adjusted for creatinine, to analyse 14 phthalate metabolites and one phthalate replacement in the urine of 1062 Swedish mothers at a median of 10 weeks of pregnancy. This was used to determine any associations between prenatal phthalate exposure and croup, wheezing or otitis in their offspring until 12 months of age, using logistic regression, adjusted for potential confounders. RESULTS: There were significant associations between phthalate metabolites of butyl-benzyl phthalate (BBzP) and di-ethyl-hexyl phthalate (DEHP) concentrations in maternal prenatal urine and croup in 1062 infants during the first year of life, when adjusted for potential confounders. A dose-response relationship was found between prenatal phthalates exposure and maternal reported croup in the children, with a significant association in boys. There was no clear indication with regard to associations between prenatal phthalate exposure and wheezing or otitis media in the children during the first year of life. CONCLUSION: Our analysis suggests that exposure to BBzP and DEHP phthalates was associated with maternal reports of croup in infants up to 12 months of age.

Early-onset type 2 diabetes: Age gradient in clinical and behavioural risk factors in 5115 persons with newly diagnosed type 2 diabetes-Results from the DD2 study.

AIM: To examine the association between early onset of type 2 diabetes mellitus (DM) and clinical and behavioural risk factors for later complications of diabetes. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early onset) with diagnosis age 46 to 55, 56 to 65 (average onset = reference), 66 to 75, and >75 years (late onset). Prevalence ratios (PRs) were computed by using Poisson regression. RESULTS: Poor glucose control, ie, HbA1c ≥ 75 mmol/mol (≥9.0%) in the early-, average-, and late-onset groups was observed in 12%, 7%, and 1%, respectively (PR 1.70 [95% confidence intervals (CI) 1.27, 2.28] and PR 0.17 [95% CI 0.06, 0.45]). A similar age gradient was observed for severe obesity (body mass index > 40 kg/m2 : 19% vs. 8% vs. 2%; PR 2.41 [95% CI 1.83, 3.18] and 0.21 (95% CI 0.08, 0.57]), dyslipidemia (90% vs. 79% vs. 68%; PR 1.14 [95% CI 1.10, 1.19] and 0.86 [95% CI 0.79, 0.93]), and low-grade inflammation (C-reactive protein > 3.0 mg/L: 53% vs. 38% vs. 26%; PR 1.41 [95% CI 1.12, 1.78] and 0.68 [95% CI 0.42, 1.11]). Daily smoking was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2 DM need clinical awareness and support.

Prenatal and Postnatal PCB-153 and p,p'-DDE Exposures and Behavior Scores at 5­9 Years of Age among Children in Greenland and Ukraine.

BACKGROUND: Studies have reported some evidence of adverse effects of organochlorine exposures on child development, but the results have been inconsistent, and few studies have evaluated associations with child behavior. OBJECTIVE: We investigated the association between prenatal and early-life exposures to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) and behaviors in children between 5 and 9 y of age. METHODS: In the Biopersistent organochlorines in diet and human fertility: Epidemiologic studies of time to pregnancy and semen quality in Inuit and European populations (INUENDO) cohort, consisting of mother-child pairs from Greenland and Ukraine (n=1,018), maternal serum PCB-153 and p,p'-DDE concentrations were measured during pregnancy, and cumulative postnatal exposures during the first 12 months after delivery were estimated using a pharmacokinetic model. Parents completed the Strengths and Difficulties Questionnaire (SDQ), and children's behaviors were dichotomized as abnormal (high) versus normal/borderline for five SDQ subscales and the total difficulties score. RESULTS: The total difficulties score, an overall measure of abnormal behavior, was not clearly associated with pre- or postnatal exposures to PCB-153 or to p,p'-DDE. However, pooled adjusted odds ratios (ORs) for high conduct problem scores with a doubling of exposure were 1.19 (95% CI: 0.99, 1.42) and 1.16 (95% CI: 0.96, 1.41) for pre- and postnatal PCB-153, respectively, and 1.25 (95% CI: 1.04, 1.51) and 1.24 (95% CI: 1.01, 1.51) for pre- and postnatal p,p'-DDE, respectively. Corresponding ORs for high hyperactivity scores were 1.24 (95% CI: 0.94, 1.62) and 1.08 (95% CI: 0.81, 1.45) for pre- and postnatal PCB-153, respectively, and 1.43 (95% CI: 1.06, 1.92) and 1.27 (95% CI: 0.93, 1.73) for pre- and postnatal p,p'-DDE, respectively. CONCLUSION: Prenatal and early postnatal exposures to p,p'-DDE and PCB-153 were associated with a higher prevalence of abnormal scores for conduct and hyperactivity at 5­9 y of age in our study population. These findings provide further support for the importance of minimizing organochlorine exposures to young children and to women of childbearing age. https://doi.org/10.1289/EHP553.

Concentration of perfluorinated compounds and cotinine in human foetal organs, placenta, and maternal plasma.

BACKGROUND: Perfluoroalkyl substances (PFASs) are bio-accumulative pollutants, and prenatal exposure to PFASs is believed to impact human foetal development and may have long-term adverse health effects later in life. Additionally, maternal cigarette smoking may be associated with PFAS levels. Foetal exposure has previously been estimated from umbilical cord plasma, but the actual concentration in foetal organs has never been measured. OBJECTIVES: The concentrations of 5 PFASs and cotinine - the primary metabolite of nicotine - were measured in human foetuses, placentas, and maternal plasma to evaluate to what extent these compounds were transferred from mother to foetus and to determine if the PFAS concentrations were associated with maternal cigarette smoking. METHODS: Thirty-nine Danish women who underwent legal termination of pregnancy before gestational week 12 were included; 24 maternal blood samples were obtained together with 34 placental samples and 108 foetal organs. PFASs and cotinine were assayed by liquid chromatography/triple quadrupole mass spectrometry. RESULTS: In foetal organs, the average concentrations of perfluorooctanesulphonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDa), and perfluorodecanoic acid (PFDA) were 0.6ng/g, 0.2ng/g, 0.1ng/g, 0.1ng/g, and 0.1ng/g, respectively. A significant positive correlation was found between the exposure duration, defined as foetal age, and foetal to maternal ratio for all five PFASs and cotinine. Smokers presented 99ng/g cotinine in plasma, 108ng/g in placenta, and 61ng/g in foetal organs. No correlation between the maternal cotinine concentrations and PFAS concentrations was found. CONCLUSIONS: PFASs were transferred from mother to foetus, however, with different efficiencies. The concentrations of PFOS, PFOA, PFNA, PFUnDA, and PFDA in foetal organs were much lower than the maternal concentrations. Furthermore, a significant correlation between the exposure duration and all of the evaluated PFASs was found. The health-compromising concentrations of these substances during foetal development are unknown.

Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates.

PURPOSE: Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. METHOD: In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure. RESULTS: No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms. CONCLUSION: Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).