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MOCHA defines school health services as those that exist due to a formal arrangement between educational institutions and primary health care. School health services are unique in that they are designed exclusively to address the needs of children and adolescents in this age group and setting. We investigated school health services have been provided to schools, and how they contribute to primary health care services for school children. We did this by mapping the national school health systems against the standards of the World Health Organization, and against a framework measuring the strength of primary care, adapting this from an existing, adult-focused framework. We found that all but two countries in the EU and EEA have school health services. There, however, remains a need for much greater investment in the professional workforce to run the services, including training to ensure appropriateness and acceptability to young people. Greater collaboration between school health services and primary care services would lead to better coordination, and the potential for better health (and educational) outcomes. Involving young people and families in the design of school health services and as participants in its outputs would also improve school health.

Fifteen experimental literature data sets on the acute toxicity of substituted nitrobenzenes to algae (Scenedesmus obliquus, Chlorella pyrenoidosa, C. vulgaris), daphnids (Daphnia magna, D. carinata), fish (Cyprinus carpio, Poecilia reticulata), protozoa (Tetrahymena pyriformis), bacteria (Phosphobacterium phosphoreum), and yeast (Saccharomyces cerevisiae) were used to establish quantum chemistry based quantitative structure-activity relationships (QSARs). The logarithm of the octanol/water partition coefficient, log Kow, and the energy of the lowest unoccupied molecular orbital, Elumo were used as descriptors. Suitable QSAR models (0.65 < r2 < 0.98) to predict acute toxicity of substituted mononitrobenzenes to protozoa, fish, daphnids, yeast, and algae have been derived. The log Kow was a sufficient descriptor for all cases, with the additional Elumo descriptor being required only for algae. The QSARs were found to be valid for neutral substituted mononitrobenzenes with no -OH, -COOH, or -CN substituents attached directly to the ring. From the 100,196 European Inventory of Existing Commercial Substances (EINECS), 497 chemicals were identified that fit the selection criteria for the established QSARs. Based on these results, an advisory tool has been developed that directs users to the appropriate QSAR model to apply for various types of organisms within specified log Kow ranges. Using this tool, it is possible to obtain a good indication of the toxicity of a large set of EINECS chemicals and newly developed substituted mononitrobenzenes to five different organisms without the need for additional experimental testing. © 2006 SETAC.

Gingival re-epithelialization represents an essential phase of oral wound healing in which epithelial integrity is re-establish. We developed an automated high-throughput re-epithelialization kinetic model, using the gingival epithelial cell line Ca9-22. The model was employed to screen 39 lactic acid bacteria, predominantly including oral isolates, for their capacity to accelerate gingival re-epithelialization. This screen identified several strains of Streptococcus salivarius that stimulated re-epithelialization. Further analysis revealed that S. salivarius strain MS-oral-D6 significantly promoted re-epithelialization through a secreted proteinaceous compound and subsequent experiments identified a secreted serine protease as the most likely candidate to be involved in re-epithelialization stimulation. The identification of bacteria or their products that stimulate gingival wound repair may inspire novel strategies for the maintenance of oral health. © 2017 The Author(s).

Background and objectives Adolescent sexual and reproductive health and rights (SRHR) are of particular relevance given their potential short-term or long-term health consequences. This study evaluates recommendations and policies regarding access to care in this area in 31 European countries (European Union (EU) plus Iceland, Norway and Switzerland). Methods As part of the EU funded Models of Child Health Appraised project, data were gathered using a 43-item questionnaire sent to experts responsible for collecting information in each country. Results Ten countries have not developed any formal policy or recommendation that guarantee the respect of confidentiality and the possibility of consulting a physician without parents knowing. Nearly half of the countries do not have centres specialised in adolescent healthcare, tackling comprehensive health issues or focusing specifically on SRH. Access to emergency contraception and information regarding pregnancy, including testing, is easy in most countries. However, oral contraception is delivered free of charge in only 10 countries. Twenty-three countries do not meet current standards in terms of providing policy-based pregnancy care, and only 13 have set up special programmes for pregnant adolescents. In only seven countries can adolescents definitely have their pregnancy terminated without their parents knowing (and in another seven countries in selected situations). Conclusion The provision and availability of adolescent-friendly SRHR care are far from optimal in around half of the surveyed countries. These results call for the review and implementation of policies, specialised healthcare centres and training initiatives for primary care providers.

Objective: Aim is to predict successful weight loss by metabolic signatures at baseline and to identify which differences in metabolic status may underlie variations in weight loss success. Methods: In DiOGenes, a randomized, controlled trial, weight loss was induced using a low calorie diet (800 kcal) for 8-weeks. Men (N5236) and women (N5431) as well as groups with overweight/obesity and morbid obesity were studied separately. The relation between the metabolic status before weight loss and weight loss was assessed by stepwise regression on multiple datasets, including anthropometric parameters, NMR-based plasma metabolites, and LC-MS-based plasma lipid species. Results: Maximally, 57% of the variation in weight loss success can be predicted by baseline parameters. The most powerful predictive models were obtained in subjects with morbid obesity. In these models, the metabolites most predictive for weight loss were acetoacetate, triacylglycerols, phosphatidylcholines, specific amino acids, and creatine and creatinine. This metabolic profile suggests that high energy metabolism activity results in higher amounts of weight loss. Conclusions: Possible predictive (pre-diet) markers were found for amount of weight loss for specific subgroups.

Using 1H NMR two diastereoisomers of the ethacrynic acid glutathione conjugate (EASG) as well as ethacrynic acid (EA) could be distinguished and quantified individually. Chemically prepared EASG consists of equal amounts of both diastereoisomers. GSTP1-1 stereospecifically catalyzes formation of one of the diastereoisomers (A). The GSTP1-1 mutant C47S and GSTA1-1 preferentially form the same diastereoisomer of EASG as GSTP1-1. Glutathione conjugation of EA by GSTA1-2 and GSTA2-2 is not stereoselective. When human melanoma cells, expressing GSTP1-1, were exposed to ethacrynic acid, diastereoisomer A was the principal conjugate formed, indicating that even at physiological pH the enzyme catalyzed reaction dominates over the chemical conjugation. Copyright (C) 1998 Federation of European Biochemical Societies.

Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and their formation in incubations with human intestinal and liver cytosol and purified human glutathione S-transferases and also in human Caco-2 cells was characterized. The results obtained demonstrate the site for glutathione conjugation to be the C1 atom, leading to two diastereoisomeric monoglutathionyl curcumin conjugates (CURSG-1 and CURSG-2). The formation of both glutathionyl conjugates appeared to be reversible. The monoglutathionyl curcumin conjugates decompose with a t1/2 of about 4 h to curcumin and other unidentified degradation products. Both human intestinal and liver cytosol catalyzed curcumin glutathione conjugation. At saturating substrate concentrations, human GSTM1a-1a and GSTA1-1 are shown to be especially active in the formation of CURSG-1, whereas GSTP1-1 and GSTA2-2 have no preference for the formation of CURSG-1 or CURSG-2. GSTT1-1 hardly catalyzes the glutathione conjugation of curcumin. In the Caco-2 human intestinal monolayer transwell model, CURSG-1 and CURSG-2 were formed at a ratio of about 2:1 followed by their excretion, which appeared to be three times higher to the apical (lumen) side than to the basolateral (blood) side. Given that GSTM1a-1a and GSTP1-1 are present in the intestinal epithelial cells, it can be concluded that efficient glutathione conjugation of curcumin may already occur in the enterocytes, followed by an efficient excretion of these glutathione conjugates to the lumen, thereby reducing the bioavailability of (unconjugated) curcumin. In conclusion, the present study identifies the nature of the diastereoisomeric monoglutathionyl curcumin conjugates, CURSG-1 and CURSG-2 formed in biological systems, and reveals that conjugate formation is catalyzed by GSTM1a-1a, GSTA1-1, and/or GSTP1-1 with different stereoselective preference. The formation of glutathione conjugates can already occur during intestinal transport, after which the monoglutathionyl conjugates are efficiently excreted to the intestinal lumen, thereby influencing the bioavailability of curcumin and, as a result, its beneficial biological effects. © 2007 American Chemical Society.

Quantitative structure-activity relationship (QSAR) models are expected to play a crucial role in reducing the number of animals to be used for toxicity testing resulting from the adoption of the new European Union chemical control system called Registration, Evaluation, and Authorization of Chemicals (REACH). The objective of the present study was to generate in vitro acute toxicity data that could be used to develop a QSAR model to describe acute in vivo toxicity of chlorinated alkanes. Cytotoxicity of a series of chlorinated alkanes to Chinese hamster ovary (CHO) cells was observed at concentrations similar to those that have been shown previously to be toxic to fish. Strong correlations exist between the acute in vitro toxicity of the chlorinated alkanes and (i) hydrophobicity [modeled by the calculated log Kow (octanol-water partition coefficient); r2 = 0.883 and rint2 = 0.854] and (ii) in vivo acute toxicity to fish (r2 = 0.758). A QSAR model has been developed to predict in vivo acute toxicity to fish, based on the in vitro data and even on in silico log Kow data only. The developed QSAR model is applicable to chlorinated alkanes with up to 10 carbon atoms, up to eight chlorine atoms, and log Kow values lying within the range from 1.71 to 5.70. Out of the 100204 compounds on the European Inventory of Existing Chemicals (EINECS), our QSAR model covers 77 (0.1%) of them. Our findings demonstrate that in vitro experiments and even in silico calculations can replace animal experiments in the prediction of the acute toxicity of chlorinated alkanes. © 2008 American Chemical Society.

A systematic approach is described for building validated PLS models that predict cholesterol and triglyceride concentrations in lipoprotein subclasses in fasting serum from a normolipidemic, healthy population. The PLS models were built on diffusion-edited 1H NMR spectra and calibrated on HPLC-derived lipoprotein subclasses. The PLS models were validated using an independent test set. In addition to total VLDL, LDL, and HDL lipoproteins, statistically significant PLS models were obtained for 13 subclasses, including 5 VLDLs (particle size 64-31.3 nm), 4 LDLs (particle size 28.6-20.7 nm) and 4 HDLs (particle size 13.5-9.8 nm). The best models were obtained for triglycerides in VLDL (0.82 < Q2 <0.92) and HDL (0.69 < Q2 <0.79) subclasses and for cholesterol in HDL subclasses (0.68 < Q2 <0.96). Larger variations in the model performance were observed for triglycerides in LDL subclasses and cholesterol in VLDL and LDL subclasses. The potential of the NMR-PLS model was assessed by comparing the LPD of 52 subjects before and after a 4-week treatment with dietary supplements that were hypothesized to change blood lipids. The supplements induced significant (p < 0.001) changes on multiple subclasses, all of which clearly exceeded the prediction errors. © 2013 American Chemical Society.

In the present study, the inhibition of human glutathione S-transferase P1-1 (GSTP1-1) by the flavonoid quercetin has been investigated. The results show a time- and concentration-dependent inhibition of GSTP1-1 by quercetin. GSTP1-1 activity is completely inhibited upon 1 h incubation with 100 μM quercetin or 2 h incubation with 25 μM quercetin, whereas 1 and 10 μM quercetin inhibit GSTP1-1 activity to a significant extent reaching a maximum of 25 and 42% inhibition respectively after 2 h. Co-incubation with tyrosinase greatly enhances the rate of inactivation, whereas co-incubation with ascorbic acid or glutathione prevents this inhibition. Addition of glutathione upon complete inactivation of GSTP1-1 partially restores the activity. Inhibition studies with the GSTP1-1 mutants C47S, C101S and the double mutant C47S/C101S showed that cysteine 47 is the key residue in the interaction between quercetin and GSTP1-1. HPLC and LC-MS analysis of trypsin digested GSTP1-1 inhibited by quercetin did not show formation of a covalent bond between Cys 47 residue of the peptide fragment 45-54 and quercetin. It was demonstrated that the inability to detect the covalent quercetin-peptide adduct using LC-MS is due to the reversible nature of the adduct-formation in combination with rapid and preferential dimerization of the peptide fragment once liberated from the protein. Nevertheless, the results of the present study indicate that quinone-type oxidation products of quercetin likely act as specific active site inhibitors of GSTP1-1 by binding to cysteine 47. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Scope: Consumption of a low-fat spread enriched with plant sterols (PS) and different low doses (<2 g/day) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil reduces serum triglycerides (TGs) and low-density lipoprotein-cholesterol (LDL-Chol) and thus beneficially affects two blood lipid risk factors. Yet, their combined effects on TG and Chol in various lipoprotein subclasses have been investigated to a limited extent. Methods and results: In a randomized, double-blind, placebo-controlled, parallel study, we determined TG and Chol in 13 LP subclasses in fasting serum of 282 hypercholesterolemic subjects, who consumed either a placebo spread or one of the four spreads containing PS (2.5 g/day) and EPA+DHA (0.0, 0.9, 1.3, and 1.8 g/day) for 4 weeks. After PS treatment, total LDL-Chol was reduced, which was not further changed by EPA+DHA. No shift in the LDL-Chol particle distribution was observed. The addition of EPA+DHA to PS dose-dependently reduced VLDL-Chol and VLDL-TG mainly in larger particles. Furthermore, the two highest doses of EPA+DHA increased Chol and TG in the larger HDL particles, while these concentrations were decreased in the smallest HDL particles. Conclusion: The consumption of a low-fat spread enriched with both PS and EPA+DHA induced shifts in the lipoprotein distribution that may provide additional cardiovascular benefits over PS consumption alone. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Obesity is a risk factor for cardiovascular diseases and type 2 diabetes especially when the fat is accumulated to central depots. Novel biomarkers are crucial to develop diagnostics for obesity and related metabolic disorders. We evaluated the associations between metabolite profiles (136 lipid components, 12 lipoprotein subclasses, 17 low-molecular-weight metabolites, 12 clinical markers) and 28 phenotype parameters (including different body fat distribution parameters such as android (A), gynoid (G), abdominal visceral (VAT), subcutaneous (SAT) fat) in 215 plasma/serum samples from healthy overweight men (n=32) and women (n=83) with central obesity. (Partial) correlation analysis and partial least squares (PLS) regression analysis showed that only specific metabolites were associated to A:G ratio, VAT, and SAT, respectively. These association patterns were gender dependent. For example, insulin, cholesterol, VLDL, and certain triacylglycerols (TG 54:1-3) correlated to VAT in women, while in men VAT was associated with TG 50:1-5, TG 55:1, phosphatidylcholine (PC 32:0), and VLDL ((X)L). Moreover, multiple regression analysis revealed that waist circumference and total fat were sufficient to predict VAT and SAT in women. In contrast, only VAT but not SAT could be predicted in men and only when plasma metabolites were included, with PC 32:0 being most strongly associated with VAT. These findings collectively highlight the potential of metabolomics in obesity and that gender differences need to be taken into account for novel biomarker and diagnostic discovery for obesity and metabolic disorders. © Copyright 2012 Mary Ann Liebert, Inc.