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New approaches in isotope geochemistry require the development of novel methods for the isotopic analysis of crude oil, a typically complex and very hard to digest organic geological matrix. In this work, methods were developed for the determination of isotope ratios of Mg, Sr and Pb in crude oil by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS). Two sample preparation methods, (i) microwave-assisted wet digestion within an ultra-high pressure digestion cavity (MAWD-PDC) and (ii) solubilization of inorganic solids as obtained after the ASTM D4807 test method, were evaluated. Using MAWD-PDC, up to 0.5 g of crude oil was efficiently digested using only 6 mL of 14.4 mol L−1 HNO3 (75 min, temperature up to 250 °C). MAWD-PDC was shown to be a suitable sample preparation method for subsequent determination of Mg, Sr and Pb isotope ratios. On the other hand, the ASTM method does not require sophisticated equipment. With this approach up to 10 g of oil can be dissolved in toluene and filtered through a nylon membrane and elements present as inorganic solids, such as Mg and Sr, are retained on the membrane and can be easily recovered in water. However, Pb was not recovered. Column chromatographic protocols for target element isolation were fine-tuned for each analyte to ensure quantitative yields. No statistical difference was observed between the results for Mg and Sr isotope ratios obtained using both sample preparation methods. A proof-of-concept study showed that the Mg–Sr–Pb isotopic composition of the Brazilian crude oils was within the range observed for seawater and the deposit bedrock, suggesting that the methods developed can be considered as promising tools to decipher the formation history of oil reservoirs.

Sodium polystyrene sulfonate (SPS) is used to reduce intestinal potassium absorption in hyperkalemia during conservative management of chronic renal failure in infants. Milk can be pretreated by SPS to reduce the risk of enteropathy associated with oral or rectal administration. We report the case of an infant for whom this pre-treatment has been implemented. The objective of this work was to define the hospital procedure for the pre-treatment of milk by the SPS. This pre-treatment involves both a drug and infant milk. Each product has its own regulation and their processes do not normally cross each other. The roles of each contributor were therefore defined: prescription of pre-treated milk (dose of SPS and volume of milk) by the physician, dispensing of SPS by the pharmacist, delivery of milk by the milk kitchen staff, pre-treatment by a nurse and administration by a nursing auxiliary. The preparation of the bottles is as follows: placing approximately 1g of SPS per 100mL of milk in contact, stirring, resting in the refrigerator for one hour, taking the supernatant to be administered. In the reported case, serum potassium levels were reduced from 5.57mmol/L before treatment to 4.53mmol/L after treatment, in line with the 20% decrease found in the literature. This method of administration is beneficial in terms of tolerance and acceptability. The preparation is simple and allows going back home under treatment.

The daily use of cosmetics may expose consumers to localized skin problems and systemic effects caused by absorption of chemical elements. The requirements for suitable quality control and maximum limits for toxic and potentially toxic elements in cosmetics have attracted the attention of the scientific community and of the official institutions around the world. Maximum limits for chemical elements in some cosmetics have been set, but there are disagreements between them. In the same context, many analytical methods have been proposed in the literature, but several challenges during the sample preparation and determination steps related to the high complexity of cosmetics' matrices composition still remain. It is extremely difficulty to establish suitable methods, free of interference, even using modern technology. In this review, methods for determining toxic and potentially toxic elements in cosmetics used for make-up on the lips and on the eye area, covering the period since 2000, are presented. Techniques enabling direct analysis and those requiring a sample preparation step prior to the analysis are also discussed. This review focused on cosmetics for make-up on the lips and on the eye area because the risks of percutaneous absorption and oral ingestion of toxic and potentially toxic elements is higher than in other body regions.

In this work, a new portable device based on a monomode microwave applicator was developed and applied for microwave-assisted solid sampling analysis coupled to flame furnace atomic absorption spectrometry (MW-SS-FF-AAS). As an example of application, Hg was determined in polymer samples in order to demonstrate the feasibility of the proposed system. Polymeric samples were weighed directly on a quartz boat, containing a microcrystalline cellulose pellet wetted with 6 mol L−1 NH4NO3 solution, which was introduced into the microwave system for the combustion step. Oxygen flowed continuously through the quartz tube for sample combustion, as well as to carry the combustion products to the flame furnace (FF) atomizer. Microwave irradiation was kept on up to sample ignition (generally

In this work, an analytical method for bromine and iodine determination in human saliva was proposed. A simple protocol based on centrifugation and direct analysis of supernatant by inductively coupled plasma mass spectrometry (ICP-MS) was investigated. Although this method was feasible for bromine determination, iodine was partially present in the supernatant and an agreement about 54% with reference value was obtained. In addition, microwave-induced combustion (MIC) and microwave-assisted dissolution were also evaluated. Using MIC, 0.2 mL of saliva added on 300 mg of microcrystalline cellulose were efficiently digested. A diluted solution (50 mmol L−1 NH4OH) was used for analytes absorption, and a reflux step of 5 min was applied to ensure quantitative recoveries of Br and I. Accuracy was evaluated by analyte recovery experiments, and recoveries between 94% and 98% were obtained. Microwave-assisted dissolution was evaluated for 2.0 mL of saliva using also a diluted alkaline solution (25 mmol L−1 NH4OH) and a microwave irradiation program of 35 min (including the cooling step). Results for this method agreed with those obtained using MIC. Although MIC has also been appropriated for further determination of Br and I in saliva, microwave-assisted dissolution can be considered a simpler sample preparation method and it was effective for high amount of sample (up to 2.0 mL). Moreover, final solutions were compatible with ICP-MS analysis, allowing the quantification of Br and I in human saliva at ultra-trace concentrations (limits of quantification were 0.052 μg mL−1 for Br and 0.022 μg mL−1 for I).

International audience; Sodium polystyrene sulfonate (SPS) is used to reduce intestinal potassium absorption in hyperkalemia during conservative management of chronic renal failure in infants. Milk can be pretreated by SPS to reduce the risk of enteropathy associated with oral or rectal administration. We report the case of an infant for whom this pre-treatment has been implemented. The objective of this work was to define the hospital procedure for the pre-treatment of milk by the SPS. This pre-treatment involves both a drug and infant milk. Each product has its own regulation and their processes do not normally cross each other. The roles of each contributor were therefore defined: prescription of pre-treated milk (dose of SPS and volume of milk) by the physician, dispensing of SPS by the pharmacist, delivery of milk by the milk kitchen staff, pre-treatment by a nurse and administration by a nursing auxiliary. The preparation of the bottles is as follows: placing approximately 1 g of SPS per 100 mL of milk in contact, stirring, resting in the refrigerator for one hour, taking the supernatant to be administered. In the reported case, serum potassium levels were reduced from 5.57 mmol/L before treatment to 4.53 mmol/L after treatment, in line with the 20% decrease found in the literature. This method of administration is beneficial in terms of tolerance and acceptability. The preparation is simple and allows going back home under treatment.; Chez le nourrisson, lors de la prise en charge conservatrice de l’insuffisance rénale chronique, le polystyrène sulfonate de sodium (PSS) est utilisé pour diminuer l’absorption intestinale du potassium en cas d’hyperkaliémie. Afin de réduire le risque d’entéropathie lié à l’administration orale ou rectale, il est possible de prétraiter le lait par PSS. Nous rapportons le cas d’un nourrisson pour lequel ce prétraitement a été mis en place. L’objectif de ce travail est de définir le circuit hospitalier permettant la réalisation du prétraitement du lait par le PSS. Ce prétraitement fait intervenir à la fois un médicament et des laits infantiles ayant chacun une réglementation propre et dont les circuits ne se croisent normalement pas. Les rôles de chaque intervenant ont donc été définis : prescription du lait prétraité (dose de PSS et volume de lait) par le médecin, dispensation du PSS par la pharmacie, délivrance du lait par la biberonnerie, réalisation du prétraitement par une infirmière puis administration par une aide-soignante. La préparation des biberons se déroule comme suit : mise en contact d’environ 1 g de PSS par 100 mL de lait, agitation, repos au réfrigérateur pendant 1 h, prélèvement du surnageant à administrer. Dans le cas rapporté, la kaliémie a été réduite de 5,57 mmol/L avant traitement à 4,53 mmol/L après traitement, en accord avec la diminution de 20 % retrouvée dans la littérature. Ce mode d’administration est bénéfique en termes de tolérance et d’acceptabilité. La réalisation de la préparation est simple et permet un retour à domicile sous traitement.

The trend toward using plant-based ingredients in aquafeeds has raised important concerns for aquaculture owing to the negative impacts of mycotoxins on fish health; with emphasis for contamination by fumonisin B

Resume Introduction La realisation de preparations pharmaceutiques est soumise a un cadre legislatif strict et doit se faire en conformite avec les bonnes pratiques de preparation (BPP). Celles-ci definissent de facon precise les differents types de preparation et le systeme d’assurance qualite qui doit etre mis en œuvre pour leur realisation. L’un des elements cles de ce systeme d’assurance qualite est l’etude de faisabilite, qui doit etre faite prealablement a toute realisation de preparation nouvelle. Or, si certaines grandes lignes de cette etude sont decrites dans les BPP, chaque pharmacien responsable de preparatoire conduit cette etude librement, sans « modele » standardise. Materiel et methode A l’occasion d’une reunion de partage d’experiences des pharmaciens du Grand Est de la France, cette question a ete soulevee, et il a ete propose la mise en commun des pratiques des differents centres, dans le but d’harmoniser les pratiques au niveau de la region. Pour ce faire, les formulaires de faisabilite des differents centres ont ete recueillis et une liste exhaustive des criteres analyses etablie. A partir de cette liste, il a ete demande aux pharmaciens participant de coter chaque item, selon qu’il le juge « indispensable », « utile » ou « optionnel ». Resultats Les reponses obtenues ont conduit a l’elaboration d’un modele de fiche reprenant les items a etudier, adaptable aux pratiques des differentes pharmacies.

Standard mode and collision/reaction cell mass spectroscopy methods have been utilised in order to overcome spectral interferences and provide ultra-low quantification of selenium (Se) and tellurium (Te) in British coals for the first time. The accurate detection of Se and Te in coals is becoming increasingly important, as coals and pyrite have been identified as potentially significant trace element sources. The mean Se concentration of British coals bear comparison to that of world coals, with anomalous Se content (concentrations above 4 mg/kg) across westerly exposures, often coinciding with high sulphur (S) content and visible pyrite. New Te data for British coals gives a mean concentration of 0.02 mg/kg, with anomalous Te in Ayrshire. There is a positive correlation in the Te/Se ratio across the sample set. The close relationship between Se and Te, as well as Se-Te with both early syngenetic and later cleat filling pyrite, confirms an important role for sulphides in Se and Te sequestration in British coals. The high Se-Bowland Shale and/or Ordovician volcanics may have provided the trace element source British coals of similar or younger age. Regional intrusive activity (shallow Se and Te concentrations of British coals LB draft manuscript tabular intrusions or more extensive plutons) and episodes of intense deformation can alter the thermal maturity of coals, and may have driven the movement of trace element-rich fluids through strata, locally enriching coals in Se and Te.

A method is proposed for the determination of selenium at low concentration in coal by collision/reaction cell technology inductively coupled plasma mass spectrometry (CRC-ICP-MS). Samples were decomposed by high pressure microwave-assisted wet digestion (MAWD) using 250 mg of coal, a mixture of 5 mL of 14.4 mol L−1 HNO3 and 1 mL of 40% HF and 70 min of heating program (200 °C and 40 bar). Hydrogen gas used in the collision/reaction cell was investigated to minimize the argon-based interferences at m/z 77, 78 and 80. The rejection parameter (RPq) and the H2 gas flow rate were set to 0.45 and 4.8 mL min−1, respectively. The use of H2 in the cell resulted in other polyatomic interferences, such as 76Ge1H+, 79Br1H+ and 81Br1H+, which impaired Se determination using 77Se, 80Se and 82Se isotopes, thus Se determination was carried out by monitoring only 78Se isotope. Selenium was determined in certified reference materials of coal (NIST 1635 and SARM 20) and an agreement better than 95% was observed between the results obtained by CRC-ICP-MS and the certified values. Under optimized conditions, the instrumental limit of detection was 0.01 μg L−1 and the method limit of detection was 0.01 μg g−1, which was suitable for Se determination at very low concentration in coal.

A comprehensive study was developed showing the feasibility of determination of rare earth elements (REE) in low concentration in crude oil by using direct sampling electrothermal vaporization system coupled to inductively coupled plasma mass spectrometry (ETV-ICP-MS). The effect of organic modifier on the REE signal was evaluated and the use of 6 mg of citric acid allowed calibration using aqueous reference solutions (selected pyrolysis and vaporization temperatures were 700 and 2200 °C, respectively). Because of the facility of REE in forming refractory compounds inside the graphite furnace during the heating step, the use of a modifier gas (Freon R-12, 3.0 mL min–1) was necessary to allow quantitative vaporization of these elements. A flow rate of 0.40 L min–1 was selected for both bypass and carrier gases. Under optimized conditions, the influence of sample mass was evaluated, and even using a relatively high mass of crude oil (up to 18 mg), accurate results were obtained. The accuracy was evaluated b...

In this work, a method for the determination of As, Sb, Se and Te in mineral coal was developed using solid sampling electrothermal vaporization inductively coupled plasma mass spectrometry (SS-ETV-ICP-MS). The following operational parameters of the ETV-ICP-MS system were evaluated: the furnace temperature program, the mass of Ir used as the modifier, the oxygen flow rate (used in the pyrolysis step) and carrier and bypass gas flow rates. The possibility of using calibration with aqueous standard solutions was also investigated. Calibration using aqueous standard solutions was feasible for As, Sb and Te determination, and calibration using certified reference materials (CRMs) of coal was required for Se determination. For comparison of the results, coal samples were decomposed by microwave-assisted wet digestion to obtain reference values for As and Sb by ICP-MS and Se by collision/reaction cell technology inductively coupled plasma mass spectrometry (CRC-ICP-MS). In addition, samples were digested by microwave-induced combustion to obtain reference values for Te by ICP-MS. No statistical difference was observed between the results by SS-ETV-ICP-MS and those obtained by ICP-MS (As, Sb and Te) or CRC-ICP-MS (Se) after sample digestion. Additionally, CRMs of coal (NIST 1632b, NIST 1632c and NIST 1635) were analysed by SS-ETV-ICP-MS, and the results were in agreement with the certified values. The limit of quantification was 0.03, 0.01, 0.03 and 0.006 μg g−1 for As, Sb, Se and Te, respectively. These values were lower than those obtained by other methods and allowed the determination of analytes at trace and ultra-trace levels. The SS-ETV-ICP-MS method for coal presented other advantages, such as minimization of the sample preparation step, minimization of the use of large amounts of reagents and suitability of accurate determination of those analytes commonly susceptible to limitations using conventional methods.

In this work, a method for the determination of bromine and iodine in medicinal plants by inductively coupled plasma mass spectrometry (ICP-MS) after digestion by microwave-induced combustion (MIC) was developed. Medicinal plants were pressed as pellets and combusted at 20 bar of oxygen. The suitability of absorbing solution (water, 50 mmol L− 1 (NH4)2CO3, 10 mmol L− 1, 25 mmol L− 1, 50 mmol L− 1 or 100 mmol L− 1 NH4OH) was evaluated and a reflux step of 5 min was applied after combustion. The accuracy of the proposed method was evaluated by using certified reference materials (CRMs) of apple leaves and peach leaves and also by spiked samples. Using 50 mmol L− 1 NH4OH as absorbing solution, recoveries close to 100% for bromine and iodine were obtained as well as a low relative standard deviation (5%). No statistical difference (t-test, 95% of confidence level) was observed between the values obtained by ICP-MS after MIC digestion and the certified values. One of the important advantages of the proposed method is that it allowed the use of a relatively high sample mass (1000 mg) of medicinal plant resulting in low limits of quantification (0.033 μg g− 1 and 0.003 μg g− 1 for Br and I, respectively). Blanks were always negligible and only diluted solutions were used, in agreement with current recommendations for analytical methods. A high digestion efficiency was achieved (> 99%) assuring quantitative results. The concentration of analytes in medicinal plants was in the range of 0.17 μg g− 1 to 53.1 μg g− 1 for Br and

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL

Mercury (Hg) induces neurobehavioral disorders through reactive oxygen species (ROS) elevation and impairment of brain key enzyme activities. Nevertheless, the therapeutic and toxic selenium concentrations for fish are very close; diphenyl diselenide (Ph2Se2), an organoselenium compound with neuroprotective effects, may be an alternative to elemental Se. Therefore, the aim of this study was to determine whether dietary supplementation with Ph2Se2 prevented or reduced the neurobehavioral alterations and oxidative damage elicited by CH3HgCl in grass carp Ctenopharyngodon idella. Fish exposed to CH3HgCl exhibited significantly reduced distance travelled and swimming speed compared to the control group, as well as augmented cortisol and ROS levels and xanthine oxidase (XO) activities. CH3HgCl exposure significantly increased lipid peroxidation (LOOH) and protein carbonylation (PC) levels compared to those of the control group, while acetylcholinesterase (AChE) and sodium-potassium pump (Na+, K+-ATPase) activities were inhibited. Dietary supplementation with 3 mg/kg Ph2Se2 ameliorated locomotor activity impairment and prevented the augmented brain cortisol and ROS levels as well as XO activity. The supplement reduced lipid and protein damage elicited by CH3HgCl and exerted protective effects on brain AChE and Na+, K+-ATPase activities. Exposure to an environmental concentration of CH3HgCl elicited neurobehavioral alterations linked to reduced locomotor activity, a finding that can be explained by oxidative damage and reduced activity of AChE and Na+, K+-ATPase in telencephalon and mesencephalon structures. Dietary supplementation with Ph2Se2 prevented CH3HgCl-induced locomotor impairment. This effect appeared to be mediated by antioxidant action. Ph2Se2 may be a viable approach to prevention or reduction CH3HgCl-mediated neurotoxic effects.

Proton Pump Inhibitors (PPIs) are a pharmacological class designed to reduce the acidity of gastric secretions. They are prescribed for 11 % of the children in our institution.To assess the relevance of PPI prescriptions in pediatrics.A clinical audit according to the methodology proposed by the High Authority of Health was carried out between August 27 and August 31, 2018 in the pediatric departments of our institution. The main judgement criteria were the indication of the PPI. The main guidelines are the recommendations of the European society of pediatric gastroenterology, hepatology and nutrition.Thirty patients were included. The average age was 8.6 years. The indication was compliant in 19 patients. The non-compliant indications were: two ulcer risk preventions related to the prescription of non-steroidal anti-inflammatory drugs (NSAIDs), one endoscopic biopsy, four ulcer risk preventions related to corticosteroid therapy, one hematopoietic stem cell transplantation and three mucositis.The sample of patients included in the study was representative of the pediatric population with PPIs in our institution. The non-conformities identified could be justified in some cases. Only one study reported a compliance rate for PPI indications in pediatrics in the literature. This rate, in the order of 34 %, was much lower than that found in our institution (P0.01).The respect of the latest recommendations for the prescription of PPIs is quite good. A usage sheet will be diffused to improve the practices.

RATIONALE Bromine and iodine have important physiological functions; however, in inadequate concentration, they can also cause several physiological problems. Their mobility assessment in human organisms through biological sampling may help clarify some doubts related to metabolic routes, which are still not well elucidated. In this context, a suitable analytical method for this purpose should be developed. METHODS An analytical method for determining ultratrace levels of bromine and iodine in human nail samples was developed. Inductively coupled plasma mass spectrometry (ICP-MS) using a conventional nebulization system was immediately chosen as the determination tool because of its powerful sensitivity and selectivity. Sample preparation methods including microwave-induced combustion (MIC), microwave-assisted extraction, and microwave-assisted digestion were evaluated. The compatibility of the final solutions with ICP-MS analysis was considered while the method was developed. RESULTS MIC was chosen as the most suitable method for the sample preparation for determining the levels of bromine and iodine in human nail samples using ICP-MS. Unlike other sample preparation methods, this one fully eliminated interferences related to the carbon content and memory effects. Sample masses up to 100 mg were efficiently digested, and the analytes were quantitatively absorbed using only 50 mmol L-1 NH4 OH solution. Recoveries ranged from 93% to 102%, and the relative standard deviation was < 8%. CONCLUSIONS The proposed analytical method presents important characteristics for routine analysis. It allows ultratrace determination even when low sample masses are used because of the low blank values, reduced volume of reagents, and powerful detectability using ICP-MS.

A method for ultra-trace determination of Se and Te in coal by inductively coupled plasma mass spectrometry (ICP-MS) was developed. Samples (up to 500 mg) were prepared by microwave-induced combustion (MIC) in a closed system pressurized with 20 bar of oxygen. Inorganic acids or their mixtures were evaluated as absorbing solution. Using HNO3 + HCl (1 + 1), results obtained for Se and Te after sample preparation by MIC agreed with those obtained by reference methods, microwave-assisted wet digestion (MAWD) using concentrated HNO3 and HF, and solid sampling electrothermal vaporization inductively coupled plasma mass spectrometry (SS-ETV-ICP-MS), and also with a certified reference material of coal (NIST 1632c) for Se. Very low limits of quantification (LOQ) were obtained: 0.002 and 0.007 mg kg1 for Se and Te, respectively. Major elements were determined in final solutions obtained by MAWD and MIC, and their concentration in solutions of MIC was negligible (

Background Some drug forms are not adapted to young children or the elderly. Lists of crushable tablets are already published but do not t consider palatability, which is an additional challenge for drug compliance. Purpose To determine the palatability of diluted oral solid medications and oral liquid forms. Material and methods The powder extracted from crushed tablets or opened capsules was diluted in water and flavoured suspending excipient. The minimum solvent needed for dissolution was determined by increments of 1 mL. The solution was then smelled and tasted by three pharmacists to determine the taste and the palatability score (PS) using the 5-point numeric rating scale (1=really bad; 5=really good) of the European Medicines Agency. PS were reported on a visual analogue scale for each drug. The quantity tested by each pharmacist was two drops. The time between two medications was at least 5 min. The possibility of administration of a fraction of the dose was also determined. Modified release formulations and cytotoxic drugs were excluded. Liquid forms were tested with the same method. Results One-hundred and fifty drugs were tested including 43 liquid forms and 107 solid forms. The average PS was smaller for diluted solid forms than for liquid forms (2.3 vs 2.9, p Conclusion This database provides part of the answer regarding the acceptability of a treatment. PS is an important factor in compliance, particularly in the paediatric population. This method requires to be validated because taste varies with age, ethnic … This study must be completed by other elements such as pH of the solution, stability of the active substance or solubility parameters. References and/or acknowledgements https://www.ema.europa.eu/documents/presentation/presentation-acceptability-palatability-methods-available-assessment_en.pdf No conflict of interest.

This study aimed to evaluate whether dietary supplementation with diphenyl diselenide (Ph2Se2) would prevent the impaired immune and inflammatory responses elicited by methylmercury chloride (CH3HgCl) via protective effects on purinergic signaling in fish immune organs. Tissue and lymphocytic nucleoside triphosphate diphosphohydrolase (NTPDase) activity for adenosine triphosphate (ATP) and adenosine diphosphate (ADP) was downregulated in the head kidney and spleen of grass carp (Ctenopharyngodon idella) exposed to CH3HgCl. Concomitantly, adenosine deaminase (ADA) activity was upregulated. Further, nucleotide-binding oligomerization domain-like receptor (NLRP3) inflammasome gene expression was upregulated in the spleen and head kidney of CH3HgCl-exposed grass carp. Dietary supplementation with Ph2Se2 ameliorated these CH3HgCl-mediated alterations on purinergic enzymes, and their activities returned to baseline levels (except NTPDase activity for ADP). Based on these results, purinergic signaling in immune organs and lymphocytes can be considered a pathway linked to pro-inflammatory effects during exposure to environmental CH3HgCl concentrations, which may contribute to mortality of the affected fish. Since dietary supplementation with 3 mg Ph2Se2/kg in the feed prevented the CH3HgCl-induced alterations, it can be considered a potential suitable treatment to prevent impaired immune and inflammatory responses caused by Hg.

Recent updates to U.S. regulatory guidelines for modeling impacts of single sources to secondary pollutants, such as ozone (O3) and fine particulate matter (PM2.5), require the use of established photochemical models with a complete treatment of gas-phase and aerosol chemistry as the preferred method for a Tier 2 demonstration approach. Such models include photochemical grid models (PGMs), as well as Lagrangian puff models with the requisite treatment of processes governing the formation of secondary pollutants from their precursors. SCICHEM is an open source reactive puff model that includes treatments for gas, aerosol, and aqueous-phase chemistry that are comparable to those in PGMs. The dispersion component of SCICHEM is based on the state-of-the-science puff model, SCIPUFF (Second-order Closure Integrated Puff). The model is a valuable tool that requires fewer resources and setup cost to run than PGMs to calculate the impacts of a single source or a small number of sources on downwind ozone and PM2.5. This paper describes a model inter-comparison study of secondary pollutant impacts due to emissions from a hypothetical coal-fired power plant stack. The models compared in this study include SCICHEM and the two most commonly used PGMs, CMAQ and CAMx. Stacks are located in 4 separate regions of the U.S. with distinct differences in chemical environments and geographical features. The key inputs (hypothetical stack parameters and emission rates, meteorology) to the three models are based on a common dataset for consistency. The source impacts calculated by the PGMs are based on zero-out simulations (i.e., with and without the source of interest) as well as the source apportionment tools available in CAMx, while SCICHEM directly predicts source impacts in a single simulation. Annual simulations are conducted to determine the frequency distribution of source impacts over the 4 regions. The comparison of model results shows both similarities and differences in the frequencies and magnitudes of peak impacts predicted by the three models. There is good agreement among all models in their predictions of 98th and 99th percentile impacts.

The trend toward using plant-based ingredients in aquafeeds has raised important concerns for aquaculture owing to the negative impacts of mycotoxins on fish health; with emphasis for contamination by fumonisin B1 (FB1). The brain is an important target of FB1; however, study of the pathways linked to brain damage is limited to an analysis of histopathological alterations. Reports have demonstrated the protective effects of dietary supplementation with diphenyl diselenide (Ph2Se2) in the brains of fish subjected to several environmental insults; nevertheless, its neuroprotective effects in fish fed with diets contaminated with FB1 remain unknown. Therefore, the aim of this study was to evaluate whether oxidative damage may be a pathway associated with FB1-induced neurotoxicity, as well as to evaluate whether dietary supplementation with Ph2Se2 prevents or reduces FB1-mediated brain oxidative damage in silver catfish. Brain reactive oxygen species (ROS), lipid peroxidation (LOOH) and protein carbonylation increased on day 30 post-feeding in animals that received FB1-contaminated diets compared to the control group, while brain antioxidant capacity against peroxyl radicals (ACAP) levels and catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were lower. Diphenyl diselenide dietary supplementation avoid increases in brain ROS levels, as well minimizing the augmentation of LOOH levels. Furthermore, Ph2Se2 prevented impairment of brain ACAP levels, as well as GPx and GST activities elicited by FB1-contaminated diets. These data suggest that dietary supplementation with 3 mg/kg Ph2Se2 prevented FB1-induced brain damage in silver catfish, and this protective effect occurred through avoided of excessive ROS production, as well as via prevention of brain lipid damage. Furthermore, Ph2Se2 exerted its neuroprotective effects via ameliorative effects on the enzymatic and non-enzymatic antioxidant defense systems, and may be an approach to prevent FB1-induced brain oxidative stress; however, is not an alternative to prevent the impairment on performance caused by FB1.

The aim of this study was to determine whether purinergic signaling is a pathway associated with fumonisin B1 (FB1)-induced impairment of immune and hemostatic responses. We also determined whether dietary supplementation with diphenyl diselenide (Ph2Se2) prevents or reduces these effects. Splenic nucleoside triphosphate diphosphohydrolase (NTPDase) activity for adenosine triphosphate (ATP) and adenosine diphosphate (ADP) as substrates and total blood thrombocytes counts were significant lower in silver catfish fed with FB1-contaminated diets than in fish fed with a basal diet, while splenic adenosine deaminase (ADA) activity and metabolites of nitric oxide (NOx) levels were significant higher. Also, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significant lower in silver catfish fed with FB1-contaminated diets than in fish fed with a basal diet. Dietary supplementation with 3 mg Ph2Se2/kg of feed effectively modulated splenic NTPDase (ATP as substrate), ADA, GPx and SOD activities, as well as NOx levels, and was partially effective in the modulation of spleen NTPDase activity (ADP as substrate) and total blood thrombocytes count. These data suggest that splenic purinergic signaling of silver catfish fed with FB1-contaminated diets generates a pro-inflammatory profile that contributes to impairment of immune and inflammatory responses, via reduction of splenic ATP hydrolysis followed possible ATP accumulation in the extracellular environment. Reduction of ADP hydrolysis associated with possible accumulation in the extracellular environment can be a pathophysiological response that restricts the hemorrhagic process elicited by FB1 intoxication. Supplementation with Ph2Se2 effectively modulated splenic enzymes associated with control of extracellular nucleotides (except ADP; that was partially modulated) and nucleosides, thereby limiting inflammatory and hemorrhagic processes.

An effective analytical method for bromine and iodine determination in human hair using interference-free inductively coupled plasma mass spectrometry (ICP-MS) was developed. Human hair was digested based on combustion reaction to obtain compatible solutions with ICP-MS analysis. Using microwave-induced combustion (MIC), masses of human hair ranging from 50 to 300 mg were efficiently digested. Only a diluted alkaline solution (100 mmol L−1 NH4OH) was used for the absorption of both analytes, which was fully compatible with ICP-MS analysis. Using these conditions low limits of detection were obtained (LOD of 0.01 μg g−1 for Br and 0.004 μg g−1 for I). Recovery tests at two levels (50% and 100%) using a standard solution or mixtures of the sample with certified reference materials (CRMs) were carried out to evaluate the suitability of proposed method and recoveries between 94% and 102% were always obtained. Accuracy was evaluated by analysis of a human hair CRM, and the Br and I concentrations obtained by the proposed method did not differ significantly from those described in the certificate. Repeatability (RSDs ≤ 4%) and reproducibility (RSDs ≤ 7%) of the results using proposed method were always very suitable. The digests obtained using the MIC method were fully compatible with ICP-MS and the interferences currently found using conventional digestion methods were completely eliminated. Ultra-trace concentrations of Br and I were determined in human hair, demonstrating that the proposed method is a suitable strategy, and it presents several advantages compared to others published in the literature.

The SCICHEM model incorporates complete gas phase, aqueous and aerosol phase chemistry within a state-of-the-science Gaussian puff model SCIPUFF (Second-order Closure Integrated Puff). The model is a valuable tool that can be used to calculate the impacts of a single source or a small number of sources on downwind ozone and PM 2.5 . The model has flexible data requirements: it can be run with routine surface and upper air observations or with prognostic meteorological model outputs and source emissions are specified in a simple text format. This paper describes significant advances to the dispersion and chemistry components of the model in the latest release, SCICHEM 3.0. Some of the major advancements include modeling of skewed turbulence for convective boundary layer and updated chemistry schemes (CB05 gas phase chemical mechanism; AERO5 aerosol and aqueous modules). The results from SCICHEM 3.0 are compared with observations from a tracer study as well as aircraft measurements of reactive species in power plant plumes from two field studies. The results with the tracer experiment (Copenhagen study) show that the incorporation of skewed turbulence improves the calculation of tracer dispersion and transport. The comparisons with the Cumberland and Dolet Hills power plume measurements show good correlation between the observed and predicted concentrations of reactive gaseous species at most downwind distances from the source.

A versatile, rapid and safe green method for chlorine and sulfur determination using ion chromatography in cereals and legumes was developed. Microwave-induced combustion was evaluated for sample preparation. Ultrapure water and alkaline solutions were assessed for absorption of the analytes. Water was selected because good recoveries (97–109%) were obtained for both analytes. Low consumption of reagents and small quantities of waste are two important advantages of the proposed method. Accuracy was evaluated by analysis of a standard reference material, which agreed with certified values (91–101%). The results for repeatability (RSDs ≤ 4%) and intermediate precision (RSDs ≤ 7%) prove the good precision of the proposed method. Limits of quantification were 16 and 17 mg kg−1 for Cl and S, respectively. Concentrations of Cl and S varied across a wide range (Cl: 35–930 mg kg−1; S: 678–5124 mg kg−1) for 34 samples analyzed, which were, for most of the results, close to the values found in the literature.

Summary Background Once daily regimens are preferred for HIV-1 treatment, to facilitate adherence and improve quality of life. We compared a new once daily formulation of raltegravir to the currently marketed twice daily formulation. Methods In this randomised, double-blind, parallel-group, phase 3, non-inferiority study, we enrolled participants aged 18 years or older with HIV-1 RNA of 1000 or more copies per mL and no previous antiretroviral treatment at 139 sites worldwide. We randomly assigned participants (2:1) via an interactive voice and web response system to raltegravir 1200 mg (two 600 mg tablets) orally once daily or raltegravir 400 mg (one tablet) orally twice daily, each with tenofovir disoproxil fumarate and emtricitabine orally once daily, for up to 96 weeks. A computer-generated allocation schedule stratified randomisation by screening HIV-1 RNA value and co-infection with hepatitis B or C. Participants, sponsor personnel, investigators, and study site personnel involved in the treatment or evaluation of the participants were unaware of the treatment group assignments. The primary endpoint was the proportion of participants with HIV-1 RNA less than 40 copies per mL at week 48 assessed with the US Food and Drug Administration Snapshot algorithm. Non-inferiority was concluded if the lower bound of the two-sided 95% CI was greater than −10%. We assessed efficacy and safety in all participants who received one dose or more of study treatment. This study is registered with ClinicalTrials.gov, number NCT02131233. Findings Between May 26, 2014, and Dec 5, 2014, 802 participants were enrolled and randomly assigned, 533 to once daily treatment and 269 to twice daily; 797 received study therapy, 531 once daily and 266 twice daily. At week 48, 472 (89%) of 531 once daily recipients and 235 (88%) of 266 twice daily recipients achieved HIV-1 RNA less than 40 copies per mL (treatment difference 0·5%, 95% CI −4·2 to 5·2). Drug-related adverse events occurred in 130 (24%) of 531 participants in the once daily group (one of which was serious; none led to treatment discontinuation) and 68 (26%) of 266 participants in the twice daily group (two of which were serious; two led to treatment discontinuation). The most common drug-related adverse events were nausea (39 [7%] vs 18 [7%]), headache (16 [3%] vs 12 [5%]), and dizziness (12 [2%] vs eight [3%]). No treatment-related deaths were reported. Interpretation A once daily raltegravir 1200 mg regimen was non-inferior compared with raltegravir 400 mg twice daily for initial treatment of HIV-1 infection. These results support the use of raltegravir 1200 mg once daily for first-line therapy. Funding Merck & Co, Inc.

Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate.EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1-infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load50 copies per mL for ≥2 months; one viral load of 50-200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web-response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2:1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load ≥50 copies per mL or premature discontinuations, with last viral load ≥50 copies per mL) cumulative through week 48; we tested non-inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917.The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening antiretrovirals, and 169 (15%) had previous virological failure on a non-darunavir regimen. The study regimen was non-inferior to the control for virological rebound cumulative through week 48 (19 [2·5%] of 763 patients in the study group vs eight (2·1%) of 378 patients in the control group; difference 0·4%, 95% CI -1·5 to 2·2; p0·0001). No resistance to any study drug was observed. Numbers of discontinuations related to adverse events (11 [1%] of 763 patients in the study group vs four [1%] of 378 patients in the control group) and grade 3-4 adverse events (52 [7%] patients vs 31 [8%] patients) were similar between the two groups. There was a small non-clinically relevant but statistically significant (0·2 [SD 1·1] vs 0·1 [1·1], p=0.010) difference between the two groups in change from baseline in total cholesterol to HDL-cholesterol ratio. Only one serious adverse event (pancreatitis in the study group) was deemed as possibly related to the study regimen.Our findings show the safety and efficacy of single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide as a potential switch option for the treatment of HIV-1 infection in adults with viral suppression.Janssen.

Resume Objectif Lors du controle de routine de perfusions d’aciclovir, il a ete demontre un defaut qualite de la specialite utilisee pour la fabrication des preparations hospitalieres. Ce travail a pour but de montrer l’interet d’un controle analytique systematique dont les consequences peuvent etre un retrait de lot du marche. Materiel et methodes La premiere etape de fabrication est la realisation, a partir de la specialite commercialisee, d’une solution mere d’aciclovir a 5,0 mg/mL. Celle-ci fait l’objet d’un controle analytique par une methode validee d’analyse en flux continu avec detection UV a 255 nm. La survenue aleatoire de non-conformites a oriente la recherche vers le controle de la specialite generique utilisee. Resultats L’analyse individuelle de 25 flacons du lot de la specialite utilisee pour la preparation des solutions meres a montre cinq non-conformites majeures variant de 55,2 % a 93,2 % de la teneur theorique en aciclovir (specification : 95,0 % a 105,0 %). Discussion L’importance de ces resultats a conduit a faire une declaration de defaut de qualite aupres de l’Agence nationale de securite du medicament et des produits de sante (ANSM). Celle-ci, apres confirmation par un controle dans ses laboratoires, a prononce un retrait de lot du marche dans un delai de 51 jours apres la declaration. Conclusion Ce fait remarquable montre l’interet de l’existence d’un controle de routine des preparations hospitalieres par les PUI. Ce dernier peut contribuer a la surveillance du marche et constituer une activite complementaire a celle de l’ANSM.

Resume Introduction L’informatisation du circuit des preparations permet de securiser leur processus. L’objectif de ce travail etait d’elaborer un cahier des charges pour l’evaluation, en vue de son acquisition, d’un progiciel de gestion des preparations, conforme aux bonnes pratiques de preparation (BPP). Methodes Une analyse retrospective des incidents, menee sur le circuit des preparations de quatre pharmacies a usage interieur a permis de completer les fonctionnalites du cahier des charges. Ce dernier a ete envoye aux fournisseurs du marche francophone afin d’evaluer la conformite des progiciels aux exigences des BPP et leurs reponses a nos besoins. Resultats L’analyse des incidents montre que l’informatisation aurait pu reduire leur survenue de 50 % a 98 %. Deux progiciels sont actuellement commercialises : BP’Prep® (Accoss) et Prep's® (Computer Engineering, non sterile). Deux logiciels internes ont ete evalues : Panoramix et Prepa. Prep's®, BP’Prep®, Panoramix et Prepa repondent respectivement a 91 %, 90 %, 62 % et 21 % des fonctionnalites requises par les BPP et a 93 %, 83 %, 54 % et 15 % des fonctionnalites facultatives. Conclusion L’evaluation des progiciels disponibles sur le marche francophone a montre que les deux progiciels commercialises repondent de facon satisfaisante aux BPP.

Introduction La pholcodine, derive opioide proche de la codeine, a ete proposee comme agent de sensibilisation croisee avec les curares depuis 2005 [1] , [2] . Dans le cadre du deploiement de l’etude ALPHO (anaphylaxie aux curares et exposition a la pholcodine), nous avions montre la stabilite sur 15 jours de la solution aqueuse de pholcodine a 1 mg/mL utilisee pour la realisation d’intradermoreactions. Nous avons poursuivi cette demarche de stabilite et souhaite la tester sur une periode de 12 mois. Methodes La solution de pholcodine monohydrate 1 mg/mL, preparee par notre pharmacie a usage interieur, filtree (0,2 μm) dans des flacons steriles de 5 mL a ete stockee a l’obscurite a 4 °C et a temperature ambiante. Pendant 12 mois, la stabilite a ete evaluee mensuellement par chromatographie liquide, selon la technique de la pharmacopee europeenne (PE), a l’aide d’une colonne ELITE LaChrom® et d’un detecteur a barrette de diode. La sterilite etait controlee selon la methode preconisee par la PE. Resultats Pendant les 12 mois, la teneur en pholcodine a ete stable, comprise entre 95 et 105 % de la teneur initiale, quelle que soit la temperature de conservation. L’analyse du chromatogramme montrait que les impuretes, y compris la codeine, restaient inferieures a 0,2 % (limite autorisee dans la monographie de la PE). Aucune nouvelle impurete n’a pu etre detectee (seuil de detection a 0,1 %). Les tests microbiologiques sont restes negatifs sur cette periode de 12 mois. Conclusion La teneur inchangee en pholcodine et l’absence d’augmentation de la teneur en codeine sont deux elements attestant de la stabilite de la solution. Cette stabilite sur 12 mois nous permet d’envisager la preparation de series de flacons et de faciliter la realisation de tests cutanes avec une solution diluee de pholcodine.

In this work, a method using microwave-induced combustion (MIC) was optimized in order to obtain a fast, simple, efficient and greener sample preparation method for coal digestion and further determination of sulfur by inductively coupled plasma optical emission spectrometry (ICP OES). Accuracy was evaluated by comparison of the results with those obtained using elemental analysis by UV-fluorescence, microwave-assisted acid digestion with determination by ICP OES and by analysis of certified reference materials of coal. Some parameters that influence MIC method, such as the type and concentration of absorbing solution, the necessity of using a reflux step as well as the cooling time were carefully optimized. No statistical difference was observed for combustion without reflux followed by 5 min of cooling, in comparison to the reference values obtained by elemental analysis. Complete digestion was obtained with this fast and simple method (total digestion program required only 6 min) and using a diluted acid solution for quantitative recovery. The feasibility of digests for sulfur determination as sulfate by ion chromatography (IC) with conductivity detection was also demonstrated. The possibility of determining other elements, commonly monitored in coals, is another advantage of this high-efficiency digestion method (MIC) combined with the multielemental capacity of ICP OES or IC instruments.