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The current study assessed the risk posed to Iranian consumers by oral exposure to a mixture of 20 pesticides and six metals in 96 fruit juice (FJ) samples (3 batches × 4 brands × 8 types of FJs) collected from Iran market. Concentrations of metals and pesticides in FJs were quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES) and chromatography-mass spectrometry (GC-MS), respectively. The mean concentration of all pesticides was below the maximum residue limits (MRLs) set by the European Union (EU). The calculated target hazard quotients (THQs) and total hazard index (HI) were1.0 for all pesticides residue, indicating no risk. For the carcinogenic metals (As, Ni, and Pb), estimated incremental lifetime cancer risks (ILCRs) at the 50th and 95th centiles were respectively 4.25 × 10

BACKGROUND Bisphenol A (BPA) and its analogue bisphenol S (BPS), widely utilized in numerous fields of industry, may seep into the environment and into human organisms. Hitherto, BPA was regarded as the bisphenol to which people were exposed to the greatest extent. As endocrine disruptors, bisphenols have negative effects on human health. Therefore, defining the levels of human exposure to these compounds is a key issue in toxicology. Hair analysis has been increasingly used for biomonitoring of bisphenols in humans, but information about the coexistence of BPA and BPS in human hair is extremely scarce. The present study aimed to analyze hair samples from 25 individuals from Olsztyn, northeastern Poland, to evaluate the levels of these 2 industrial pollutants. MATERIAL AND METHODS The method used in the research was liquid chromatography with a mass spectrometry technique. RESULTS BPA was found in 72% of samples analyzed and its concentration levels fluctuated from 3.6 to 52.9 ng/g (median 17.7 ng/g). The BPS concentration levels were higher - from 13.4 to 1054.9 ng/g (median 98.7 ng/g). We also found that gender, age, and the presence of artificial hair color (hair dye) did not affect the BPA and BPS levels in the hair. CONCLUSIONS This study has shown that hair samples may be used to measure the levels of bisphenols, and that exposure to BPS may be greater than that to BPA in this area. The investigation also revealed that hair analysis is a useful approach for the biomonitoring of BPA and BPS levels in human organisms.

Graphical abstract, Highlights • mEHP was the most detected compound in amniotic fluid and miBP in urine. • The use of plastics for food storage was associated with high mEHP in urine. • The use of deodorant was associated with higher urinary miBP and mnBP. • A weak association was found between urinary mEHP and lower infant birth length. • The daily intake of phthalates was 5.4 μg/kg bw and the hazard index 0.10., Phthalates are used in industry as plasticizers or additives in everyday products and they have been considered as endocrine disrupting chemicals. Maternal exposure during pregnancy has been associated with neonatal exposure, preterm birth and impacts in the reproductive and respiratory systems. The aim of this study is to determine six phthalate metabolites (mono isobutyl phthalate, miBP, mono n-butyl phthalate, mnBP, mono benzyl phthalate, mBzP, mono ethylhexyl phthalate, mEHP, mono 2-ethyl-5-hydroxyhexyl phthalate, mEHHP, mono 2-ethyl-5-oxohexyl-phthalate, mEOHP) in amniotic fluid and urine from 100 pregnant women. Participants answered questionnaires for the use of plastics and cosmetics, dietary habits, health effects, pregnancy problems, health and infant development. Positive amniotic fluid samples ranged from 1% to 21% and urine from 27% to 54%. The median levels for amniotic fluid were 2.3 μg/L - 10.7 μg/L and for urine 4.9 μg/L - 46.7 μg/L. The major results include significant correlations between urinary phthalates indicating their common sources of exposure, the frequent use of deodorant was significantly associated with higher urinary miBP (p = 0.050) and mnBP (p = 0.028) and a weak inverse association was found for the use of make-up products with mBzP (p = 0.053). The frequent use of plastic food containers was significantly associated with urinary mEHP (p = 0.026), and a positive trend was noticed for mEHP in amniotic fluid (p = 0.093). An association although weak was found between urinary mEHP and lower birth length (rs = 0.396, p = 0.062). No other associations were found for infant health problems or development. The daily intake of the total phthalates was calculated 5.4 μg/kg body weight/day which corresponds to hazard index 0.10 and exposure follows the declining trend that has been observed the last decades.

Soon after the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in December, 2019, numerous research teams, assisted by vast capital investments, achieved vaccine development in a fraction of time. However, almost 8 months following the initiation of the European vaccination programme, the need for prospective monitoring of the vaccine-induced immune response, its determinants and related side-effects remains a priority. The present study aimed to quantify the immune response following full vaccination with the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine by measuring the levels of immunoglobulin G (IgG) titers in healthcare professionals. Moreover, common side-effects and factors associated with IgG titers were identified. For this purpose, blood samples from 517 individuals were obtained and analysed. Blood sampling was performed at a mean period of 69.0±23.5 days following the second dose of the vaccine. SARS-CoV-2 IgG titers had an overall mean value of 4.23±2.76. Females had higher titers than males (4.44±2.70 and 3.89 ±2.84, respectively; P=0.007), while non-smokers had higher titers than smokers (4.48±2.79 and 3.80±2.64, respectively; P=0.003). An older age was also associated with lower antibody titers (P

Background: Early diagnosis of long QT type 3 (LQT3) syndrome during the neonatal period is of paramount clinical importance. LQT3 syndrome results in increased mortality and a mutation-specific response to treatment compared to other more common types of LQT syndrome. Mexiletine, a sodium channel blocker, demonstrates a mutation-specific QTc shortening effect in LQT3 syndrome patients.Case Presentation: A neonate manifested marked QTc prolongation after birth. An electrocardiogram (ECG) recording was performed due to positive family history of genetically confirmed LQT3 syndrome (SCN5A gene missense mutation Tyr1795Cys), and an association with sudden cardiac death was found in family members. The mexiletine QTc normalizing effect (QTc shortening from 537 to 443 ms), practical issues related to oral mexiletine treatment of our young patient, along with a literature review regarding identification and mexiletine treatment in infants with LQT3 syndrome are presented.Conclusions: Mexiletine could be considered in the treatment of high-risk LQT3 patients already in the neonatal period in addition to b-blocker therapy. Availability of standardized commercial mexiletine pediatric formulas, serum mexiletine level analyses, and future prospective studies are needed to evaluate the potential beneficial effect of early mexiletine treatment on the incidence of future acute cardiac events in these high-risk LQT syndrome patients.

This study focused on defining the in vitro behavior of amphiphilic poly-N-vinylpyrrolidone (Amph-PVP) nanoparticles toward whole blood, blood plasma and blood cells in order to assess nanoparticle blood compatibility. In addition, possible effects on endothelium cell growth/viability were evaluated. The Amph-PVP nanoparticles were formed via self-assembling in aqueous media and composed of a hydrophobic alkyl core and a hydrophilic PVP outer shell. Their blood compatibility was evaluated by investigating their effect on red blood cells (RBCs) or erythrocytes, white blood cells (WBCs) or leukocytes, platelets (PLTs) and on complement system activation. Our results clearly demonstrate that the Amph-PVP nanoparticles are stable in presence of blood serum, have no significant effects on the function of RBCs, WBCs, PLTs and complement system activation. The Amph-PVP nanoparticles did not show considerable hemolytic or inflammatory effect, neither influence on platelet aggregation, coagulation process, or complement activation at the tested concentration range of 0.05–0.5 mg/ml. The Amph-PVP nanoparticles did not exhibit any significant effect on HMEC-1 microvascular skin endothelial cells’ growth in in vitro experiments. The excellent blood compatibility of the Amph-PVP nanoparticles and the lack of effect on endothelium cell growth/viability represent a crucial feature dictating their further study as novel drug delivery systems.

Health benefits of fish consumption could be counterbalanced by the intake of contaminants after long term fish consumption, burdened even in trace levels. The presence of the indicator PCBs (NDL-PCBs and PCB 118) in farmed and wild seabream and seabass was evaluated. For the determination of PCB, a GC-MS method was developed and evaluated. The association of PCB accumulation in fish with seasonality, locality, production mode and species was also investigated. A new approach for the risk characterisation after exposure to NDL-PCB through fish consumption in Greece was developed, based on the real exposure and the permitted maximum levels of both aggregated dietary exposure and exposure through fish consumption. PCB levels determined in fish were below established permitted limits (6.24 ng/g 95th percentile), while PCB levels and congener distribution varied significantly between farmed and wild fish (p = 0.001). Seasonality was highlighted as an important factor affecting NDL-PCBs accumulation, with high levels coinciding with the reproduction period of each species. Differences were also depicted for sampling sites, with PCB 118 presenting significantly higher values in open seas while NDL-PCB congeners in closed seas. Risk assessment of NDL-PCB intake through fish consumption corrected for the aggregated exposure revealed no risk for the consumers.

Persistent organic pollutants (POPs) constitute a wide range of chemicals. Their release into the environment has raised great concern due to their potentially harmful impact in humans and wildlife species. The aim of this current study was to detect selected POPs in hair samples of wild terrestrial mammals from Primorsky Krai, Russia, so as to assess potential environmental exposure. The tested wild species were leopard cat, musk deer, wolf, amur hedgehog, and raccoon dog. The targeted organochlorines were hexachlorobenzene (HCB) and DDTs (opDDE, ppDDE, and opDDD), polychlorinated biphenyl (PCB) congeners (28, 52, 101, 118, 138, 153, and 180), and polycyclic aromatic hydrocarbons (PAHs) (acenaphylene (ACEN), fluorene (FLU), anthracene (ANTH) phenathrene (PHEN), and pyrene (PYR)). The detection of POPs was conducted in hair samples by a one-step hair extraction method, by using a headspace solid-phase microextraction technique (HS-SPME) and analyzed then by GC-MS. The majority of the wild animal hair samples were found positive in all tested pollutants. More specifically, the percentage of positive hair samples for HCB was 93.3% and for DDTs, PCBs, and PAHs, 20.0 to 100.0%, 6.7 to 100.0%, and 75.0 to 100.0%, respectively. DDT, PCB, and PAH detection ranged from 1.26 to 52.06 pg mg−1, 0.73 to 31.34 pg mg−1, and 2.59 to 35.00 pg mg−1, respectively. The highest mean concentration levels of all tested pollutants were found for musk deer (PCBs 12.41 pg mg−1, DDTs 21.87 pg mg−1, PAHs 22.12 pg mg−1) compared to the other wild species. To the best of our knowledge, this is the first study that provides results regarding contamination in different terrestrial mammals by POP exposure. The use of hair as a matrix is proven to be an effective tool for nondestructive biological monitoring of POP contamination in terrestrial ecosystems.

Human exposure to pesticides can be estimated through different approaches. The approach adopted in this study is based on internal dose measures. Studies published during 2001 and 2017 were collected from PubMed and Scopus databases, filtered and organized. The intake of parent compounds is estimated based on the urinary excretion of different OP metabolites applying a mathematical model previously used for similar purposes. Once defined an Estimated Daily Intake (EDI), risk assessment is performed through comparison with specific guideline values and hazard index (HI) is calculated to assess cumulative health risk. The EDI was expressed as malathion, diazinon, parathion, phorate and dimethoate equivalents. Differences in exposure between pregnant women, general population, children and farmers are highlighted and exposures are presented by country and sampling year. Higher exposure to OPs was calculated for farmers, followed by children whereas pregnant women were less exposed. Median HQ values for children ranged between 0.016 and 0.618, for pregnant women 0.005-0.151, for general population 0.008-0.206 and for farmers 0.009-0.979. Combined exposure to dimethoate and phorate was the worst-case scenario. The annual distribution of the urinary DAPs showed that exposure to OPs since 1998 tends to be stable for both children and adults.

Graphical abstract, Highlights • Cretan traditional Medicine, used Opium poppies as sedatives for children. • Poppies’ folk preparations were called Hypnos. • The practice to offer Hypnos to children was alive until the early 20th century. • Iatrosofia are written collections of traditional remedies. • Hypnos related recipes are absent in Cretan Iatrosofia after the 17th century., Opium Poppy (Papaver somniferum L.) is considered as one of the earliest medicinal plants known to mankind. Derived from the Greek name “opos” meaning juice, referring to its psychotropic latex, the plant was known and extensively used since Antiquity during religious rituals and for Medical purposes, mainly as hypnotic and pain reliever agent. In Cretan folk medicine it was recommended along with other poppies until the early 20th century to induce children sedation, by the name: “Hypnos” meaning sleep.

BNN27 is a novel 17‐spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty‐two C57BL/6 mice and 48 Sprague–Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro‐orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography‐mass spectrometry (LC‐MS). Non‐compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant k el = 0.465 h−1 and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (C max) in the retina was detected at 2 h (tCmax) after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC‐MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood–retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease., The pharmacokinetics of the microneurotrophin BNN27, a synthetic DHEA exhibiting neuroprotective actions but lacking endocrinal activity, have been calculated in this study. BNN27 shows a rapid absorption and elimination from the blood of the C57BL/6 mouse after ip administration as expected by its small size and lipophilic nature. Bioavailability in the retina of albino rats was also documented, demonstrating the ability of the molecule to cross blood‐retina barriers (retina data provided in the article)..

Background The EUREST-PLUS ITC Europe surveys aim to evaluate the impact of the European Union’s Tobacco Products Directive (EU TPD) implementation within the context of the WHO FCTC. This article describes the methodology of the 2016 (Wave 1) and 2018 (Wave 2) International Tobacco Control 6 European (6E) Country Survey in Germany, Greece, Hungary, Poland, Romania and Spain; the England arm of the 2016 (Wave 1) and 2018 (Wave 2) ITC 4 Country Smoking and Vaping (4CV) Survey; and the 2016 (Wave 10) and 2017 (Wave 11) ITC Netherlands (NL) Survey. All three ITC surveys covering a total of eight countries are prospective cohort studies with nationally representative samples of smokers. Methods In the three surveys across the eight countries, the recruited respondents were cigarette smokers who smoked at least monthly, and were aged 18 and older. At each survey wave, eligible cohort members from the previous waves were retained, regardless of smoking status, and dropouts were replaced by a replenishment sample. Results Retention rates between the two waves of the ITC 6E Survey by country were 70.5% for Germany, 41.3% for Greece, 35.7% for Hungary, 45.6% for Poland, 54.4% for Romania and 71.3% for Spain. The retention rate for England between ITC 4CV1 and ITC 4CV2 was 39.1%; the retention rates for the ITC Netherlands Survey were 76.6% at Wave 10 (2016) and 80.9% at Wave 11 (2017). Conclusion The ITC sampling design and data collection methods in these three ITC surveys allow analyses to examine prospectively the impact of policy environment changes on the use of cigarettes and other tobacco products in each country, to make comparisons across the eight countries.

Physical exercise could be a protective factor against the development of substance use disorders; however, a number of preclinical studies report reward-enhancing effects of exercise for various drugs of abuse. We examined the effects of chronic wheel-running on brain reward sensitivity, reaction to novelty, reward-facilitating and locomotor-stimulating effects of morphine, using the intracranial self-stimulation (ICSS) and the open field test (OFT). Male Sprague-Dawley rats were randomly assigned to a sedentary or exercised group. For the ICSS procedure, rats were implanted with electrodes and trained to respond for electrical stimulation. Several indices were recorded in the training phase to estimate brain reward sensitivity. Once responding was stable, the animals of both groups received systemic injections of morphine and their ICSS thresholds were measured with the curve-shift paradigm. Employing the OFT, basal and morphine-induced locomotor activity was measured. Finally, basal and morphine-evoked tissue levels of dopamine and its metabolites were determined in the striatum using gas chromatography/mass spectrometry. Chronic wheel-running decreased brain reward sensitivity and subsequently increased the reward-facilitating effect of morphine. Exercised animals demonstrated a decreased reaction to novelty and reduced morphine-induced locomotion. Lastly, dopaminergic activity was decreased in the striatum of exercised animals under basal conditions, whereas morphine administration led to an increase in dopamine turnover. These findings indicate that chronic voluntary exercise exerts divergent effects on reward function, psychomotor activity and the reward-facilitating and locomotor-activating effects of opioids during adulthood. Our results provide insights into the increased non-medical use of opioids among young athletes reported in the literature.

Pesticides are widely used in agriculture and their proven high toxicity makes the need of monitoring their presence in food imperative. A multi residue method is applied in apples samples (81) collected from the Greek market for the monitoring of 40 analytes. Pesticides levels were evaluated by gas and liquid chromatography-mass spectrometry using a QuEChERs protocol. Risk for consumers was assessed by a newly developed methodology, employing the source related Hazard Quotient (HQs) and the adversity specific Hazard Index (HIA). The 84% of the apple's samples were positive for at least one pesticide, 21% for one pesticide, 55.6% for two to four pesticide residues and 7.4% for more than 4 pesticide residues. The most frequently detected compound was carbendazim (45.7%) followed by chlorpyrifos (44.4.0%). The mean detected concentration levels varied from 0.169 ppm (fluopyram) to 0.005 ppm (triazophos). 19 of the 40 investigated pesticides were not detected in any apple sample. For all individual pesticides, the source related Hazard Quotient (HQs) was HIA, resulting from the sum of all HQs was found HIA

Triclosan (TCS) is an organic substance showing antibacterial action, which is commonly used in many branches of industry, including, among others, cosmetics, pharmaceuticals and the food industry. TCS may penetrate into living organisms and negatively affect the health of humans and animals. The majority of previous investigations on TCS biomonitoring in humans have been performed on urine, but currently, studies on hair samples are becoming increasingly important. The aim of this study was to evaluate TCS concentration levels in residents of Olsztyn, a city in northeastern Poland, using a liquid chromatography-mass spectrometry technique. The presence of TCS was observed in 96.7% of samples tested, with concentration levels from 37.9 pg/mg to 3386.5 pg/mg. The mean concentration level of TCS in the present study was 402.6 (±803.6) pg/mg, and the median value was 103.3 pg/mg. Although there were some differences in TCS concentration levels between males and females, humans of various ages and humans with colored and natural hair had no statistically significant differences in TCS concentration levels. The obtained results have clearly indicated that people living in northeastern Poland are exposed to TCS to a large degree, and hair analysis, despite some limitations, is a suitable method for TCS biomonitoring in humans.

Bisphenol A (BPA), triclosan (TCS) and perfluorooctanoic acid (PFOA) are endocrine disruptors linked with negative health effects such as developmental, reproductive and cardiovascular toxicity. The aim of this study was to determine simultaneously the concentration of BPA, TCS and PFOA in hair from children and adults and examine possible associations between biomonitoring data and age, gender, dietary habits and body mass index. Methanolic extraction was applied and the compounds were determined by liquid chromatography-mass spectrometry. Low levels of exposure to PFOA were detected for children and adults at concentrations below limit of quantification. The mean concentration of BPA in children and adults was 20.6 and 16.6 pg mg-1 , while for TCS 275.2 and 687.0 pg mg-1 , respectively. Children were highly exposed to BPA relative to adults (P = .011) although adults had greater exposure to TCS (P = .003). Hair from girls had a greater burden of BPA (P = .06) compared to boys. Moreover, higher TCS levels were depicted for females in both examined groups (children P = .200 and adults P = .213) compared to males, but no statistical differences were observed. Significant differences were also observed between age groups (P = .0007) for TCS. No correlations were found between BPA or TCS levels and body mass index or dietary habits for both children and adults. Children have a greater exposure to BPA compared to adults, whereas exposure of adults to TCS seems to be higher than that in children and elderly people. Exposure to BPA occurs mainly via ingestion whereas exposure to TCS mainly via dermal absorption.

Anabolic agents are doping substances which are commonly used in sports. Stanozolol, a 17α-alkylated derivative of testosterone, has a widespread use among athletes and bodybuilders. Several medical and behavioral adverse effects are associated with anabolic androgenic steroids (AAS) abuse, while the liver remains the most well recognized target organ. In the present study, the hepatic effects of stanozolol administration in rats at high doses resembling those used for doping purposes were investigated, in the presence or absence of exercise. Stanozolol and its metabolites, 16-β-hydroxystanozolol and 3′-hydroxystanozolol, were detected in rat livers using liquid chromatography-mass spectrometry (LC-MS). Telomerase activity, which is involved in cellular aging and tumorigenesis, was detected by examining telomerase reverse transcriptase (TERT) and phosphatase and tensin homolog (PTEN) expression levels in the livers of stanozolol-treated rats. Stanozolol induced telomerase activity at the molecular level in the liver tissue of rats and exercise reversed this induction, reflecting possible premature liver tissue aging. PTEN gene expression in the rat livers was practically unaffected either by exercise or by stanozolol administration.

Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes. For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings. No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p

The substance 4-methylimidazole (4-MEI) has raised several concerns regarding its toxicity to humans, although no harmonized classification has yet been decided. The regulatory limits for food products set by various authorities in Europe and the USA differ considerably. The purpose of the present study is to compare two liquid chromatography techniques in order to determine the levels of 4-MEI in food products from the Greek market and roughly estimate the possible exposure and relevant health risk for the consumers. A total of thirty-four samples (soft drinks, beers, balsamic vinegars, energy drinks and sauces) were collected and analyzed. The quality parameters for both analytical methodologies (linearity, accuracy, inter day precision, recovery) are presented. No detectable levels of 4-MEI are found in beers and soft drink samples, other than cola type. On the other hand, 4-MEI was detected in all cola type soft drinks (15.8–477.0 ng/ml), energy drinks (57.1%, 6.6–22.5 ng/ml) and vinegar samples (66.7%, 9.7–3034.7 ng/ml), while only one of the sauce samples was found to have a detectable level of 17.5 ng/ml 4-MEI.

Neurotoxic chemicals including several pesticides have been suggested to play a role in the etiology of amyotrophic lateral sclerosis (ALS). We investigated the relation between organochlorine pesticides and their metabolites (OCPs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in the etiology of sporadic ALS, determining for the first time their levels in cerebrospinal fluid as indicator of antecedent exposure. We recruited 38 ALS patients and 38 controls referred to an Italian clinical center for ALS care, who underwent a lumbar puncture for diagnostic purposes between 1994-2013, and had 1mL of cerebrospinal fluid available for the determination of OCPs, PCBs and PAHs. Many chemicals were undetectable in both case and control CSF samples, and we found little evidence of any increased disease risk according to higher levels of exposure. Among males >60 years, we found a slight but statistically very unstable increased ALS risk with higher levels of the congener PCB 28 and the OCP metabolite p,p'-DDE. Overall, these results do not suggest an involvement of the neurotoxic chemicals investigated in this study in disease etiology, although small numbers limited the precision of our results.

Polymeric nanoparticles were prepared from self-assembled amphiphilic N-vinylpyrrolidone polymers in aqueous media and evaluated as novel carriers of indomethacin, a non-steroidal, anti-inflammatory drug. It was determined that these nanoparticles could be created in spherical morphologies with sizes less than 100nm, narrow size distributions and high indomethacin contents(up to 35%) combined with high drug loading efficiencies(up to 95%). In cytotoxicity tests using the human embryonic stem cell derived fibroblasts (EBF-H9) and hepatocellular carcinoma cells (HepG2), the indomethacin-loaded polymeric nanoparticles showed higher cell viability compared to that of free indomethacin at the same concentration. The median LD50 values, determined by the Litchfield-Wilcoxon method, were 55-70mg/kg body weight depending on the polymer molecular design in both mice and rats. Based on the acquired results, these novel amphiphilic poly-N-vinylpyrrolidone nanoparticles can be considered as potential carriers for new, highly efficient, injectable drug delivery systems for hydrophobic drugs such as indomethacin.

Background and Objectives The purpose of this study was to evaluate the extent of short-term memory impairment and schizophrenia-like symptoms in heavy and systematic cannabis users and the association between the severity of abuse and the longevity of its persistent symptoms after refraining from such use. Methods A complete psychiatric examination and a psychometric evaluation were performed in 48 solely cannabis users. Additionally, head hair samples were analyzed and the detected cannabinoids levels were correlated with the psychometric findings. Results A total of 33.3% (n = 16) of the total examined cannabis users were currently imprisoned. The years of abuse ranged from 1 to 35 years and the median daily dose was 5.84.4 gr and 4.84.0 gr for prisoners (n = 16) and non prisoners (n = 32), respectively. A total of 39.6% of the users experienced hallucinations (mostly auditory), 54.2% experienced delusions (mostly ideas of reference and persecution), 85.4% had organic brain dysfunction in a test addressing visual-motor functioning and visual perception skills, and all users (100%) were found to have organic brain dysfunction in a test of visual memory immediate recall. The cannabinoid metabolite levels in the hair samples were consistent with the reported history of substance abuse and total grams of consumption for the participants below 35 years old (p

A novel Liposome Aggregate Platform (LAP) system for prolonged retention of drugs in the posterior eye segment after intravitreal injection (IVT) was developed and evaluated. Calcein, FITC-dextran-4000 (FD4) and Flurbiprofen (FLB), were encapsulated in negatively charged liposomes, and mixed with protamine to produce the LAP. The lipid/protamine ratio was fixed, in order to have a convenient aggregation rate permitting IVT injection and also a sustained release of liposome-entrapped molecules (in vitro) from LAP. In vitro release studies confirmed the potential of LAP system consisted of HPC/DPPG/Chol liposomes and protamine (at 1:1 w/w to lipid), to delay calcein, FD4 and FLB release, compared to free liposomes. In vivo studies demonstrated increased vitreous retention of liposomes and LAP for all molecules, compared to the corresponding solutions; however the retention of FD4 is similar for non-aggregated liposomes and LAP, and calcein retention is only slightly increased by LAP compared to liposomes. The later result may be connected with the visible ocular inflammation caused by both dyes; interestingly inflammation was moderately reduced when dyes were entrapped in liposomes and even more when in LAP. No visible inflammation was demonstrated for FLB, and the LAP system significantly increased the retention of FLB in the ocular tissues (compared to non-aggregated liposomes). Taking into account the capability of the novel LAP system to decrease inflammatory reactions towards calcein and FD4, and prolong the retention of FLB in ocular tissues, it is concluded that such systems, after further optimization, may be considered as promising effective and safe approaches for treatment of posterior segment ocular pathologies.

Levels of dialkylphosphate (DAP) metabolites were measured in hair and urine of children that lived close to intensively farmed areas of Almeria (Southeast Spain). The levels were used as proxies for exposure of these children to organophosphate pesticides (OPs). Determinants of exposure to DAPs were also examined. Urine and hair samples were collected from 222 children aged 3–11 years and information on lifestyle and dietary habits was collected from questionnaires administered to mothers. Urinary DAPs were analyzed by ultra-high performance liquid-chromatography coupled to triple-quadrupole tandem mass-spectrometry (UHPLC-QqQ-MS/MS) and hair DAPs by gas-chromatography coupled to mass spectrometry (GC–MS). Detection rates ranged from 21.8% for diethylphosphate (DEP) and diethylthiophosphate (DETP) to 35.9% for dimethylphosphate (DMP) in urine; and from 42.3% for DETP to 92.8% for DMP in hair. Diethyldithiophosphate (DEDTP) was detected in 0.5% of urine samples (one child), and in 26.6% of children's hair samples. A lack of correlation was observed for individual DAP metabolites and ΣDAPs between urine and hair samples, except for DEDTP. Urinary DAP levels of our child population were lower than those reported for children from other countries, including NHANES 1999–2000 data., This study was partially funded by the Ministry of Economy, Innovation, Science and Employment, Government of Andalucia (reference number P08-CTS-04313, FEDER funds).

Flavours play a major role in facilitating smoking initiation and in sustaining long-term use of tobacco, the leading cause of preventable morbidity and mortality in Europe. The European Union’s Tobacco Product Directive prohibits cigarettes and roll-your-own tobacco products with a characterising flavour. A ‘characterising flavour’ is defined by the TPD as a clearly noticeable smell or taste other than one of tobacco, resulting from an additive or a combination of additives, including, but not limited to, fruit, spice, herbs, alcohol, candy, menthol or vanilla, which is noticeable before or during the consumption of the tobacco product. The main objective of the EUREST-FLAVOURS project is provide services to the European Commission to facilitate the implementation of the ban on characterising flavours. Specifically, the objectives are to carry out the practical sensory and chemical assessments of tobacco products, to specify the methods for sensory analysis of tobacco products, and to assist in decisions whether tobacco products impart a characterising flavour other than tobacco. The methodology to support the decision whether a tobacco product has a characterising flavour is based on a comparison of smelling properties of test products and reference products, as well as complemented, as appropriate, by a chemical assessment of the product composition. The culminating work of EUREST-FLAVOURS is to support implementation of the EU’s ban on characterising flavours, and ultimately to contribute to the protection of public health in the EU.

Persistent organic pollutants are synthetic chemicals highly resistant to degradation with strong tendency to bioaccumulation. Assessment of human exposure to these compounds is crucial for public health protection, especially during vulnerable periods. The aim of the present cohort study was to evaluate the level of contamination to PCBs, o,p’- and p,p’-DDE, o,p’ and p,p’-DDD, o,p’ and p,p’-DDT and HCB in pregnant women. Hair, amniotic fluid and serum samples were collected and analyzed by HS-SPME-GCMS. The most detected analytes in amniotic fluids were p,p’-DDE, p,p’-DDD, o,p’-DDE and PCB101, in serum p,p’-DDE, HCB and PCB101 and in hair p,p’-DDE, HCB and PCB101. The levels of HCB and PCB101 in amniotic fluids were positively correlated with those in hair. Higher levels of DDDs and DDTs in hair samples and PCB28 in amniotic fluids were observed in smoker pregnant women. Gestation age was inversely proportional with the detected levels of PCB101 in all tested samples.

ObjectiveTo evaluate electronic cigarette (e-cigarette) product compliance with European regulations (Tobacco Products Directive (TPD), Implementing Decisions), with a focus on labelling/packaging practices and technical design/safety features.MethodsBefore the implementation of the TPD, in early 2016, we randomly selected e-cigarette refill liquids from the five top-selling companies in France, Poland, Germany, Netherlands, UK, Spain, Romania, Hungary and Greece. Identical products were purchased after the implementation of the TPD (early 2018) and assessment of compliance was performed on self-matched samples (n=107) using a prospective cohort design. Compliance with the Classification, Labelling and Packaging (CLP) regulations was also evaluated.ResultsFollowing the implementation of the TPD, improvements were noted with regards to the existence of text-only warnings (32.7% pre vs 86.0% post, pConclusionsThis is the first study to evaluate the level of implementation of the e-cigarette regulations in nine EU member states. Our results indicate that refill liquids had substantial but not full compliance in most of the characteristics evaluated. Further effort is needed to ensure complete compliance.

Introduction The European Union (EU) Tobacco Product Directive (TPD) bans tobacco products with characterising flavours. The objective of the EUREST-FLAVOURS project is to support the European Commission in the specification of the methodology to support the decision on whether a tobacco product has a characterising flavour– based on a comparison with reference products. The aim of the current analysis was to propose a list of potential tobacco products, to be considered as part of a ‘reference’ group of products. Methods We used a combination of data sources, including but not limited to commercial sales data and data submitted via the EU Common Entry Gate (EU-CEG) and applied a random sampling among strata approach. Results The identified list of potential reference tobacco products includes leading and non-leading brands representing a broad geographical distribution of products across the EU. The potential reference products further cover a wide range of tobacco product characteristics. Conclusions Using a robust methodology, we proposed two separate lists (boxed cigarettes and RYO tobacco) of potential reference products. The final list of reference products will be a valid and comprehensive representation of tobacco products currently sold on the EU-market that are currently considered as not imparting a characterising flavour.

Introduction Data on the flavors and additives content of the electronic cigarette liquids are scarce. This study aimed to identify, record and evaluate flavor and additive content of e-liquids. Methods Within the Horizon2020, EUREST-PLUS study and during the post TPD sample selection period, we purchased in total 137 e-liquids from France, Poland, Germany, the Netherlands, United Kingdom, Spain, Romania, Hungary and Greece. These products included all e-liquids selected in the pre TPD period still available in the market and all the products that were in the top rank during the post TPD period. A quantitative and qualitative chemical analysis was performed using a head space solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GCMS) and liquid chromatography-mass spectrometry method. Results The GCMS analysis using two mass spectral libraries (NIST, WILEY) revealed that more than 247 compounds were present in the examined e-liquid samples. The chemical compounds most frequently detected were: menthol (57.66%), nonanal (53.28%), ethyl maltol (35.77%), linalool (25.55%) beta damascene (24.09%) and ethyl vanillin (24.09%). From the quantitative analysis of the flavor, the mean % w/w content for menthol was 0.0474, for linalool 0.0121, for beta damascene 0.0082, b-ionone 0.003, for a-ionone 0.0037, for ethyl hexanoate 0.0041, alpha damascene 0.0043, for limonene 0.0019 , for a-terpinolene 0.0005 , for methyl cyclopentanolone 0,1536, for acetyl pyrazine 0,0207, for 2,5 dimethylpyrazine for 0,0027, for ethyl maltol for 0,2979, for 3,4 dimethoxy benzaldehyde 0,0116 and for ethyl vanillin 0,1646. Conclusions Our evaluation revealed that after the implementation of TPD and specifically Article 18 where it is clearly stated that additives that increase carcinogenic, mutagenic and reprotoxic properties in unburnt form, addictiveness and toxicity should also be prohibited, stricter policies and monitoring on the flavors and additives are still necessary.

Male infertility is a major problem with important socioeconomic consequences. It is associated with several pathological factors, including but not limited to endocrine disruption as a result of environmental pollution and the alarming decline in sperm count over the decades is indicative of involvement of many environmental and lifestyle changes around the globe. Organochlorine pollutants such as dichlorodiphenyltrichlorethanes (DDTs), polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) disrupt male reproductive system but the exact effect of environmental exposure on semen parameters in human is still not clear. This study was designed to monitor PCBs, DDTs and HCB in hair, urine and serum samples of infertile and healthy fertile men. Solid-phase microextraction gas chromatography-mass spectrometry (SPME/GC-MS) was used to monitor analytes. All tested compounds were detected, indicating recent use/persistent accumulation. Hair samples revealed no significant association with serum/urine concentrations of the analytes, while serum/urine concentrations were significantly correlated positively. Concentrations were higher in serum compared to other samples. The levels of organochlorine pollutants were higher in infertile men compared to controls with few exceptions. Among PCBs, and DDTs, PCB-153 and pp'-DDT were detected in highest concentrations, respectively. op'-DDT and pp'-DDT levels were significantly higher in infertile men compared to controls. HCB was significantly correlated negatively with sperm motility in all samples. Serum concentrations of all compounds were higher in men with defective semen parameters compared to normospermics. Serum was the best biological sample for assessing health outcomes in relation to exposure levels.