18 research outputs found

    Associations of Serum Vitamin D Concentrations with Dietary Patterns in US Children

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    Background: Contribution of dietary sources to vitamin D status is not clearly known. Some studies have shown that dietary intake of certain vitamin D rich foods had a significant positive influence on serum 25-hydroxyvitamin D [25(OH)D] concentrations, whereas other studies have shown no effect. Although sunlight exposure is a major source of circulating serum 25(OH)D, children and adolescents have been advised on the dangers of sun exposure. Diet may therefore be an important contributor of circulating serum 25(OH)D in absence of or reduced sunlight exposure. Objective: The aim of this study was to determine whether serum 25(OH)D concentrations were associated with any specific dietary patterns in US children and adolescents using assay-adjusted serum 25(OH)D data from National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2005-2006. Methods: Data from 2 cycles of the NHANES 2003-2004 and 2005-2006 for individuals aged 2 to ≤19 y, were used to study the association between dietary patterns and serum 25(OH)D. Dietary patterns were established using factor analysis based on food-frequency questionnaire data. Eigenvalues and Scree plot were used to derive 2 major principal factors. They were labeled as High Fat Low Vegetable (HFLV) and Prudent dietary patterns. Results: Serum 25(OH)D was significantly lower in HFLV dietary pattern group compared to Prudent dietary pattern group (25.1 vs 27.0 ng/mL; P=0.001). The highest serum 25(OH)D concentrations for all subjects were in the low-intake HFLV group or medium and high-intake Prudent groups (P=0.003 and P=0.012, respectively). In multivariate adjusted analysis, children with higher Prudent dietary contribution scores to overall diet showed a significant positive relation with serum 25(OH)D (β=62.01, P=0.016). When data were stratified by sex, a significant positive relation was observed in girls who consumed the Prudent diet (β=86.34, P=0.014) and a significant negative relation was observed in girls who consumed the HFLV diet (β=-84.32, P=0.022). Conclusion: Overall, serum 25(OH)D concentrations were associated with Prudent dietary pattern but not with HFLV dietary pattern in US children and adolescents. When stratified by sex, the relation between dietary patterns and serum 25(OH)D was confined to only girls. Children consuming HFLV pattern diet may benefit from vitamin D supplementation and sunlight exposure (outdoor activities), and should be encouraged to consume more vitamin D fortified foods

    Association of serum vitamin D concentrations with dietary patterns in children and adolescents.

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    Because children have been advised on the dangers of sun exposure, diet is an important contributor of serum 25 hydroxyvitamin D [25(OH)D] concentrations. Aim of this study was to determine whether serum 25(OH)D concentrations were associated with any specific dietary patterns in US children. Data from 2 cycles of National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2005-2006 for individuals aged 2 to ≤19 y, were used to study relation between dietary patterns and serum 25(OH)D. We derived 2 major dietary patterns based on the food frequency questionnaire data. These were labeled as High-Fat-Low-Vegetable Dietary (HFLVD) pattern and Prudent Dietary (PD) pattern. In multivariate adjusted analysis, there was no significant relationship between serum 25(OH)D concentrations and tertiles of HFLVD and PD dietary pattern scores in all subjects, boys, and girls. When dietary patterns scores were used as a continuous variable in adjusted analysis, children (all) with higher PD contribution scores to overall diet showed a significant positive relation with serum 25(OH)D (β = 59.1, P = 0.017). When data were stratified by sex, a significant positive relation was observed in girls between serum 25(OH)D concentration and PD pattern scores (β = 82.1, P = 0.015). A significant negative relation was observed in girls between serum 25(OH)D and HFLVD pattern scores (β = - 88.5, P = 0.016). Overall, serum 25(OH)D were associated with PD pattern but not with HFLVD pattern in US children. In public health perspective, it is important to encourage children, especially girls who are consuming HFLVD pattern to shift to healthier diet

    Pharmacological targeting of the protein synthesis mTOR/4E-BP1 pathway in cancer-associated fibroblasts abrogates pancreatic tumourchemoresistance

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    International audiencePancreatic ductal adenocarcinoma (PDAC) is extremely stroma-rich. Cancer-associated fibroblasts (CAFs) secrete proteins that activate survival and promote chemoresistance of cancer cells. Our results demonstrate that CAF secretome-triggered chemoresistance is abolished upon inhibition of the protein synthesis mTOR/4E-BP1 regulatory pathway which we found highly activated in primary cultures of -SMA-positive CAFs, isolated from human PDAC resections. CAFs selectively express the sst1 somatostatin receptor. The SOM230 analogue (Pasireotide) activates the sst1 receptor and inhibits the mTOR/4E-BP1 pathway and the resultant synthesis of secreted proteins including IL-6. Consequently, tumour growth and chemoresistance in nude mice xenografted with pancreatic cancer cells and CAFs, or with pieces of resected human PDACs, are reduced when chemotherapy (gemcitabine) is combined with SOM230 treatment. While gemcitabine alone has marginal effects, SOM230 is permissive to gemcitabine-induced cancer cell apoptosis and acts as an antifibrotic agent. We propose that selective inhibition of CAF protein synthesis with sst1-directed pharmacological compounds represents an anti-stromal-targeted therapy with promising chemosensitization potential

    Key contribution of eIF4H-mediated translational control in tumor promotion.

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    Dysregulated expression of translation initiation factors has been associated with carcinogenesis, but underlying mechanisms remains to be fully understood. Here we show that eIF4H (eukaryotic translation initiation factor 4H), an activator of the RNA helicase eIF4A, is overexpressed in lung carcinomas and predictive of response to chemotherapy. In lung cancer cells, depletion of eIF4H enhances sensitization to chemotherapy, decreases cell migration and inhibits tumor growth in vivo, in association with reduced translation of mRNA encoding cell-proliferation (c-Myc, cyclin D1) angiogenic (FGF-2) and anti-apoptotic factors (CIAP-1, BCL-xL). Conversely, each isoform of eIF4H acts as an oncogene in NIH3T3 cells by stimulating transformation, invasion, tumor growth and resistance to drug-induced apoptosis together with increased translation of IRES-containing or structured 5'UTR mRNAs. These results demonstrate that eIF4H plays a crucial role in translational control and can promote cellular transformation by preferentially regulating the translation of potent growth and survival factor mRNAs, indicating that eIF4H is a promising new molecular target for cancer therapy

    Evaluation of a local government "shelter and van" intervention to improve safety and reduce alcohol-related harm.

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    Background: The entertainment precincts of cities, while contributing to local economies, need to be carefully managed to mitigate harms. Individual behaviours and government regulation have typically been the foci of interventions aimed at reducing alcohol-related harm. Little is known about how changes to the built environment might influence alcohol-related harms in these settings. The aim of this study was to explore how a public shelter and a volunteer-funded and staffed mobile van in a regional city influenced perceptions of safety and reduction in alcohol-related harm. Methods: An intrinsic case-study approach was used. Document reviews, qualitative interviews with 16 key informants (volunteers, licensees, police, local business owners, patrons, community members and security guards), observation, and secondary data analysis were conducted in 2016. A conceptual framework of the causative pathways linking the drivers of alcohol consumption with social and health outcomes was used to inform the analysis. Results: The shelter and van were frequently utilised but there was no significant association with a reduction in the proportion of alcohol-related hospital emergency department presentations or police incident reports. Occupational health and safety risks were identified for the volunteers which had no management plan. Conclusions: The findings highlight the challenge faced by local governments/authorities wanting to provide community-based interventions to complement other evidence-based approaches to reduce alcohol-related harm. Local governments/authorities with restricted regulatory oversight need to collaborate with key agencies for targeted upstream and evidence-based alcohol prevention and management interventions before investing resources. Such approaches are critical for improving community safety as well as health and social outcomes in communities at greatest risk of alcohol-related harm

    Two data pre‑processing workflows to facilitate the discovery of biomarkers by 2D NMR metabolomics

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    Abstract Introduction The pre-processing of analytical data in metabolomics must be considered as a whole to allow the construction of a global and unique object for any further simultaneous data analysis or multivariate statistical modelling. For 1D 1H-NMR metabolomics experiments, best practices for data pre-processing are well defined, but not yet for 2D experiments (for instance COSY in this paper). Objective By considering the added value of a second dimension, the objective is to propose two workflows dedicated to 2D NMR data handling and preparation (the Global Peak List and Vectorization approaches) and to compare them (with respect to each other and with 1D standards). This will allow to detect which methodology is the best in terms of amount of metabolomic content and to explore the advantages of the selected workflow in distinguishing among treatment groups and identifying relevant biomarkers. Therefore, this paper explores both the necessity of novel 2D pre-processing workflows, the evaluation of their quality and the evaluation of their performance in the subsequent determination of accurate (2D) biomarkers. Methods To select the more informative data source, MIC (Metabolomic Informative Content) indexes are used, based on clustering and inertia measures of quality. Then, to highlight biomarkers or critical spectral zones, the PLS-DA model is used, along with more advanced sparse algorithms (sPLS and L-sOPLS). Results Results are discussed according to two different experimental designs (one which is unsupervised and based on human urine samples, and the other which is controlled and based on spiked serum media). MIC indexes are shown, leading to the choice of the more relevant workflow to use thereafter. Finally, biomarkers are provided for each case and the predictive power of each candidate model is assessed with cross-validated measures of RMSEP. Conclusion In conclusion, it is shown that no solution can be universally the best in every case, but that 2D experiments allow to clearly find relevant cross peak biomarkers even with a poor initial separability between groups. The MIC measures linked with the candidate workflows (2D GPL, 2D vectorization, 1D, and with specific parameters) lead to visualize which data set must be used as a priority to more easily find biomarkers. The diversity of data sources, mainly 1D versus 2D, may often lead to complementary or confirmatory results

    Combining rapid 2D NMR experiments with novel pre-processing workflows and MIC quality measures for metabolomics

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    Introduction The use of 2D NMR data sources (COSY in this paper) allows to reach general metabolomics results which are at least as good as the results obtained with 1D NMR data, and this with a less advanced and less complex level of preprocessing. But a major issue still exists and can largely slow down a generalized use of 2D data sources in metabolomics: the experiment duration. Objective The goal of this paper is to overcome the experiment duration issue in our recently published MIC strategy by considering faster 2D COSY acquisition techniques: a conventional COSY with a reduced number of transients and the use of the Non-Uniform Sampling (NUS) method. These faster alternatives are all submitted to novel 2D pre-processing workflows and to Metabolomic Informative Content analyses. Eventually, results are compared to those obtained with conventional COSY spectra. Methods To pre-process the 2D data sources, the Global Peak List (GPL) workflow and the Vectorization workflow are used. To compare this data sources and to detect the more informative one(s), MIC (Metabolomic Informative Content) indexes are used, based on clustering and inertia measures of quality. Results Results are discussed according to a multi-factor experimental design (which is unsupervised and based on human urine samples). Descriptive PCA results and MIC indexes are shown, leading to the direct and objective comparison of the different data sets. Conclusion In conclusion, it is demonstrated that conventional COSY spectra recorded with only one transient per increment and COSY spectra recorded with 50% of non-uniform sampling provide very similar MIC results as the initial COSY recorded with four transients, but in a much shorter time. Consequently, using techniques like the reduction of the number of transients or NUS can really open the door to a potential high-throughput use of 2D COSY spectra in metabolomics

    Two data pre-processing workflows to facilitate the discovery of biomarkers by 2D NMR metabolomics

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    peer reviewedAbstract Introduction The pre-processing of analytical data in metabolomics must be considered as a whole to allow the construction of a global and unique object for any further simultaneous data analysis or multivariate statistical modelling. For 1D 1H-NMR metabolomics experiments, best practices for data pre-processing are well defined, but not yet for 2D experiments (for instance COSY in this paper). Objective By considering the added value of a second dimension, the objective is to propose two workflows dedicated to 2D NMR data handling and preparation (the Global Peak List and Vectorization approaches) and to compare them (with respect to each other and with 1D standards). This will allow to detect which methodology is the best in terms of amount of metabolomic content and to explore the advantages of the selected workflow in distinguishing among treatment groups and identifying relevant biomarkers. Therefore, this paper explores both the necessity of novel 2D pre-processing workflows, the evaluation of their quality and the evaluation of their performance in the subsequent determination of accurate (2D) biomarkers. Methods To select the more informative data source, MIC (Metabolomic Informative Content) indexes are used, based on clustering and inertia measures of quality. Then, to highlight biomarkers or critical spectral zones, the PLS-DA model is used, along with more advanced sparse algorithms (sPLS and L-sOPLS). Results Results are discussed according to two different experimental designs (one which is unsupervised and based on human urine samples, and the other which is controlled and based on spiked serum media). MIC indexes are shown, leading to the choice of the more relevant workflow to use thereafter. Finally, biomarkers are provided for each case and the predictive power of each candidate model is assessed with cross-validated measures of RMSEP. Conclusion In conclusion, it is shown that no solution can be universally the best in every case, but that 2D experiments allow to clearly find relevant cross peak biomarkers even with a poor initial separability between groups. The MIC measures linked with the candidate workflows (2D GPL, 2D vectorization, 1D, and with specific parameters) lead to visualize which data set must be used as a priority to more easily find biomarkers. The diversity of data sources, mainly 1D versus 2D, may often lead to complementary or confirmatory results
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