Antiplatelet and anticoagulant therapy after coronary-artery stenting

To the Editor: Schömig et al. (April 25 issue) report that they did not observe neutropenia in any of the 257 patients receiving short-term ticlopidine therapy after coronary stenting

Effect of four novel bio-based DES (Deep Eutectic Solvents) on hardwood fractionation

Using the basic principle of construction between a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD), four bio-based deep eutectic solvents (DESs) were prepared in a 1:2 molar ratio of HBA:HBD. 2,3-Dihydroxypropyl-1-triethylammonium chloride ([C9H22N+O2]Cl婨 ) was synthesized from raw glycerol and used as an HBA. Lactic acid, urea, pure glycerol, and ethylene glycol were selected as HBD. Attempts to prepare DESs, using citric acid and benzoic acid as HBDs, were unsuccessful. All these DESs were characterized using FTIR and NMR techniques. Besides, physicochemical parameters such as pH, viscosity, density, and melting point were determined. The behavior of these DES to fractionate olive pomace was studied. Lignin recovery yields spanned between 27% and 39% (w/w) of the available lignin in olive pomace. The best DES, in terms of lignin yield ([C9H22N+O2]Cl婨 -lactic acid), was selected to perform a scale-up lignin extraction using 40 g of olive pomace. Lignin recovery on the multigram scale was similar to the mg scale (38% w/w). Similarly, for the holocellulose-rich fractions, recovery yields were 34% and 45% for mg and multi-gram scale, respectively. Finally, this DES was used to fractionate four fruit pruning samples. These results show that our novel DESs are alternative approaches to the ionic liquid:triethylammonium hydrogen sulfate and the widely used DES: choline chloride:lactic acid (1:10 molar ratio) for biomass processingThis work has been partially funded by the Spanish government (CTQ2015-70982-C3-1-R (MINECO/FEDER)

Critical review of analytical methods for the determination of flame retardants in human matrices

Human biomonitoring is a powerful approach in assessing exposure to environmental pollutants. Flame retardants (FRs) are of particular concern due to their wide distribution in the environment and adverse health effects. This article reviews studies published in 2009-2020 on the chemical analysis of FRs in a variety of human samples and discusses the characteristics of the analytical methods applied to different FR biomarkers of exposure, including polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), novel halogenated flame retardants (NHFRs), bromophenols, incl. tetrabromobisphenol A (TBBPA), and organophosphorous flame retardants (PFRs). Among the extraction techniques, liquid-liquid extraction (LLE) and solid phase extraction (SPE) were used most frequently due to the good efficiencies in the isolation of the majority of the FR biomarkers, but with challenges for highly lipophilic FRs. Gas chromatography-mass spectrometry (GC-MS) is mainly applied in the instrumental analysis of PBDEs and most NHFRs, with recent inclusions of GC-MS/MS and high resolution MS techniques. Liquid chromatography-MS/MS is mainly applied to HBCD, bromophenols, incl. TBBPA, and PFRs (including metabolites), however, GC-based analysis following derivatization has also been used for phenolic compounds and PFR metabolites. Developments are noticed towards more universal analytical methods, which enable widening method scopes in the human biomonitoring of FRs. Challenges exist with regard to sensitivity required for the low concentrations of FRs in the general population and limited sample material for some human matrices. A strong focus on quality assurance/quality control (QA/QC) measures is required in the analysis of FR biomarkers in human samples, related to their variety of physical-chemical properties, low levels in most human samples and the risk of contamination.This study was part of the HBM4EU project receiving funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 733032. The authors acknowledge Berith E. Knudsen for her help with the literature search.S

Organophosphorus Pesticide Exposure at 17 Weeks’ Gestation and Odds of Offspring Attention-Deficit/Hyperactivity Disorder Diagnosis in the Norwegian Mother, Father, and Child Cohort Study

Prenatal organophosphorus pesticides (OPs) are ubiquitous and have been linked to adverse neurodevelopmental outcomes. However, few studies have examined prenatal OPs in relation to diagnosed attention-deficit/hyperactivity disorder (ADHD), with only two studies exploring this relationship in a population primarily exposed through diet. In this study, we used a nested case-control study to evaluate prenatal OP exposure and ADHD diagnosis in the Norwegian Mother, Father, and Child Cohort Study (MoBa). For births that occurred between 2003 and 2008, ADHD diagnoses were obtained from linkage of MoBa participants with the Norwegian Patient Registry (N = 297), and a reference population was randomly selected from the eligible population (N = 552). Maternal urine samples were collected at 17 weeks’ gestation and molar sums of diethyl phosphates (ΣDEP) and dimethyl phosphates metabolites (ΣDMP) were calculated. Multivariable adjusted logistic regression models were used to estimate the association between prenatal OP metabolite exposure and child ADHD diagnosis. Additionally, multiplicative effect measure modification (EMM) by child sex was assessed. In most cases, mothers in the second and third tertiles of ΣDMP and ΣDEP exposure had slightly lower odds of having a child with ADHD, although confidence intervals were wide and included the null. EMM by child sex was not observed for either ΣDMP or ΣDEP. In summary, we did not find evidence that OPs at 17 weeks’ gestation increased the odds of ADHD in this nested case-control study of ADHD in MoBa, a population primarily experiencing dietary exposure

Prenatal Exposure to Organophosphorus Pesticides and Preschool ADHD in the Norwegian Mother, Father and Child Cohort Study

Prenatal organophosphorus pesticide (OPP) exposure has been associated with child attention-deficit/hyperactivity disorder (ADHD) in agricultural communities and those that are exposed to residentially applied insecticides. To examine this association in populations that are exposed primarily through diet, we estimate the associations between prenatal OPP exposure and preschool ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa), and describe modification by paraoxonase 1 (PON1) gene variants. We used participants from the MoBa Preschool ADHD Sub-study (n = 259 cases) and a random sample of MoBa sub-cohort participants (n = 547) with birth years from 2004 to 2008. Prenatal urinary dialkylphosphate (DAP) metabolites (total diethylphosphate [∑DEP] and total dimethylphosphate [∑DMP]) were measured by an ultra-performance liquid chromatography-time-of-flight system and summed by molar concentration. Maternal DNA was genotyped for coding variants of PON1 (Q192R and L55M). We used a multivariable logistic regression to calculate the odds ratios (OR) and 95% confidence intervals, adjusted for maternal education, parity, income dependency, age, marital status, ADHD-like symptoms, pesticide use, produce consumption, and season. We found no associations between DAP metabolite concentrations and preschool ADHD. The adjusted ORs for exposure quartiles 2–4 relative to 1 were slightly inverse. No monotonic trends were observed, and the estimates lacked precision, likely due to the small sample size and variation in the population. We found no evidence of modification by PON1 SNP variation or child sex. Maternal urinary DAP concentrations were not associated with preschool ADHD

Identifying human exposure pathways to flame retardants

El principal objetiu d'aquesta tesi consisteix en millorar la comprensió de com i en quina mesura els retardants de flama (RF), tant els heretats com els emergents, que estan incorporats en articles d'ús diari i materials de construcció, entren en els éssers humans. Per això, un grup de 48 mares i els seus fills/es (6-12 anys), residents a l'área metropolitana d'Oslo (Noruega), van participar en l'estudi. Es van recollir mostres biològiques, de sang (només de les mares) i orina, i mostres de pols i aire de l'interior de les viviendes. Per a la determinació de RF persistents en sang es va desenvolupar un mètode basat en GC-MS i un segon mètode, basat en UPLC-TOF, per a la determinació de metabòlits dels RFs excretats en l'orina. Els principals RF persistents detectats en sang van ser: anti-Dechlorane Plus (0.85 ng/g lípid) > BDE -153 (0.82 ng/g lípid) > BDE -47 (0.49 ng/g lípid) > syn-Dechlorane Plus (0.45 ng/g lípid). La suma dels RF emergents va resultar en concentracions comparables a la suma dels difenil èters polibromats, essent els productes alimentaris una de las fonts més importants de RF en aquest estudi. Els dos principals metabòlits detectats en l'orina dels fills/es i les mares van ser el difenil fosfat (1 ng/ml) i el bis(1,3-dicloro-2-propil) fosfat (0.2-0.3 ng/ml). Es va trobar una estreta relació entre les concentracions d'aquests dos metabòlits en l'orina dels fills/es i les concentracions dels RF a l'aire i la pols de las vivendes. Aquest descobriment suggereix que l'ambient interior influeix més significativament en els nivells d'organofosfats en els fills/es que altres fonts com podrien ser els productes alimentaris.El objetivo principal de esta tesis consiste en mejorar la comprensión de cómo y en qué medida los retardantes de llama (FR), tanto los heredados como los emergentes, que están incorporados en los artículos de uso diario y materiales de construcción, entran en los seres humanos. Para ello, un grupo de 48 madres y sus hijos/as (6-12 años), resididentes en el área metropolitana de Oslo (Noruega), participaron en el estudio. Se recogieron muestras biológicas de sangre (sólo de las madres) y orina, y muestras de polvo y aire del interior de las viviendas. Para la determinación de FR persistentes en sangre se desarrollló un método basado en GC-MS y un segundo método basado en UPLC-TOF para la determinación de metabolitos de los FRs excretados en la orina. Los principales FR persistentes detectados en sangre fueron: anti-Dechlorane Plus (0.85 ng/g lípido) > BDE -153 (0.82 ng/g lípido) > BDE -47 (0.49 ng/g lípido) > syn-Dechlorane Plus (0.45 ng/g lípido). La suma de los FR emergentes resultó en concentraciones comparables a la suma de los difenil éteres polibromados, siendo los productos alimentarios una de las fuentes más importantes de FR en este estudio. Los dos principales metabolitos detectados en la orina de los hijos/as y las madres fueron difenil fosfato (1 ng/ml) y bis(1,3-dicloro-2-propil) fosfato (0.2-0.3 ng/ml). Se encontró una estrecha relación entre las concentraciones de estos dos metabolitos en la orina de los niños y las concentraciones de los FR en el aire y el polvo de las viviendas. Este hallazgo sugiere que el ambiente interior contribuye de manera más significativa en los niveles de organofosfatos en los hijos/as que otras fuentes, como podrían ser los productos alimentarios.The main research goal of this thesis is to further understanding of how and to what extent flame retardant (FR) chemicals, both legacy and emerging, which are present in every-day consumer goods and construction materials enter in humans. To do so, a cohort of 48 mothers and their offspring (6-12 years) were recruited in the greater area of Oslo (Norway) and samples of blood (only from the mothers), urine, and samples of indoor dust and air were collected. For the determination of persistent FR in blood a method based on GC-MS was developed, and a second method, based on UPLC-TOF, was also developed for the determination of the non-persistent FR (organophosphates) in urine. The main persistent FRs detected in blood were anti-Dechlorane Plus (0.85 ng/g lipid) > BDE-153 (0.82 ng/g lipid) > BDE-47 (0.49 ng/g lipid) > syn-Dechlorane Plus (0.45 ng/g lipid). The sum of the emerging FRs were found in comparable concentrations to the sum of polybrominated diphenyl ethers, diet being one of the most important sources of FRs in this study group. The two main metabolites detected in urine from children and mothers were diphenyl phosphate (1 ng/mL) and bis(1,3-dichloro-2-propyl) phosphate (0.2-0.3 ng/mL). A strong relationship between the concentrations of these two metabolites in urine and the concentrations of the parent compounds in indoor air and dust for children was found. This finding suggests that the indoor environment contributes more importantly to the body burden of organophosphates in children from the cohort than other sources like diet