2024-03-29T14:00:58Zhttp://oai-repositori.upf.edu/oai/requestoai:repositori.upf.edu:10230/231762020-06-17T08:19:58Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132col_10230_8581
Genome-wide CNV analysis replicates the association between GSTM1 deletion and bladder cancer: a support for using continuous measurement from SNP-array data
Marenne, Gaëlle
Real, Francisco X.
Rothman, Nathaniel
Rodríguez Santiago, Benjamín
Pérez Jurado, Luis Alberto
Kogevinas, Manolis
García Closas, Montserrat
Silverman, Debra T.
Chanock, Stephen J.
Génin, Emmanuelle
Malats i Riera, Núria
BACKGROUND: Structural variations such as copy number variants (CNV) influence the expression of different phenotypic traits. Algorithms to identify CNVs through SNP-array platforms are available. The ability to evaluate well-characterized CNVs such as GSTM1 (1p13.3) deletion provides an important opportunity to assess their performance. RESULTS: 773 cases and 759 controls from the SBC/EPICURO Study were genotyped in the GSTM1 region using TaqMan, Multiplex Ligation-dependent Probe Amplification (MLPA), and Illumina Infinium 1 M SNP-array platforms. CNV callings provided by TaqMan and MLPA were highly concordant and replicated the association between GSTM1 and bladder cancer. This was not the case when CNVs were called using Illumina 1 M data through available algorithms since no deletion was detected across the study samples. In contrast, when the Log R Ratio (LRR) was used as a continuous measure for the 5 probes contained in this locus, we were able to detect their association with bladder cancer using simple regression models or more sophisticated methods such as the ones implemented in the CNVtools package. CONCLUSIONS: This study highlights an important limitation in the CNV calling from SNP-array data in regions of common aberrations and suggests that there may be added advantage for using LRR as a continuous measure in association tests rather than relying on calling algorithms.
2012
info:eu-repo/semantics/article
Marenne G, Real FX, Rothman N, Rodríguez-Santiago B, Pérez-Jurado L, Kogevinas M et al. Genome-wide CNV analysis replicates the association between GSTM1 deletion and bladder cancer: a support for using continuous measurement from SNP-array data. BMC Genomics. 2012;13:326. DOI: 10.1186/1471-2164-13-326
1471-2164
http://hdl.handle.net/10230/23176
http://dx.doi.org/10.1186/1471-2164-13-326
eng
BMC Genomics. 2012;13:326
info:eu-repo/grantAgreement/EC/FP7/201663
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2012 Marenne et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/231862020-11-19T12:17:43Zcom_10230_6237com_10230_5542com_10230_23115com_10230_20719col_10230_6238col_10230_23132col_10230_22498col_10230_8581
Environmental exposure assessment in European birth cohorts: results from the ENRIECO project
Gehring, Ulrike
Casas Sanahuja, Maribel
Brunekreef, Bert
Bergström, Anna
Bonde, Jens Peter
Botton, Jérémie
Chévrier, Cecile
Cordier, Sylvaine
Heinrich, Joachim
Hohmann, Cynthia
Keil, Thomas
Sunyer Deu, Jordi
Tischer, Christina
Toft, Gunnar
Wickman, Magnus
Vrijheid, Martine
Nieuwenhuijsen, Mark J.
Environmental exposures during pregnancy and early life may have adverse health effects. Single birth cohort studies often lack statistical power to tease out such effects reliably. To improve the use of existing data and to facilitate collaboration among these studies, an inventory of the environmental exposure and health data in these studies was made as part of the ENRIECO (Environmental Health Risks in European Birth Cohorts) project. The focus with regard to exposure was on outdoor air pollution, water contamination, allergens and biological organisms, metals, pesticides, smoking and second hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite exposure assessment. Collaborative analyses with data from several birth cohorts have already been performed successfully for outdoor air pollution, water contamination, allergens, biological contaminants, molds, POPs and SHS. Key success factors for collaborative analyses are common definitions of main exposure and health variables. Our review emphasizes that such common definitions need ideally be arrived at in the study design phase. However, careful comparison of methods used in existing studies also offers excellent opportunities for collaborative analyses. Investigators can use this review to evaluate the potential for future collaborative analyses with respect to data availability and methods used in the different cohorts and to identify potential partners for a specific research question.
2013
info:eu-repo/semantics/article
Gehring U, Casas M, Brunekreef B, Bergström A, Bonde JP, Botton J et al. Environmental exposure assessment in European birth cohorts: results from the ENRIECO project. Environmental Health. 2013; 12: 8. DOI 10.1186/1476-069X-12-8
1476-069X
http://hdl.handle.net/10230/23186
http://dx.doi.org/10.1186/1476-069X-12-8
eng
Environmental Health. 2013; 12: 8
info:eu-repo/grantAgreement/EC/FP7/226285
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2013 Gehring et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/231872020-03-05T13:11:08Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
CMV and Immunosenescence: from basics to clinics
Solana, Rafael
Tarazona, Raquel
Aiello, Allison E.
Akbar, Arne N.
Appay, Victor
Beswick, Mark
Bosch, Jos A.
Campos, Carmen
Cantisán, Sara
Cicin Sain, Luca
Derhovanessian, Evelyna
Ferrando Martínez, Sara
Frasca, Daniela
Fulöp, Tamas
Govind, Sheila
Grubeck Loebenstein, Beatrix
Hill, Ann
Hurme, Mikko
Kern, Florian
Larbi, Anis
López-Botet, Miguel
Maier, Andrea B.
McElhaney, Janet E.
Moss, Paul
Naumova, Elissaveta
Nikolich Zugich, Janko
Pera, Alejandra
Rector, Jerrarld L.
Riddell, Natalie
Sanchez Correa, Beatriz
Sansoni, Paolo
Sauce, Delphine
Lier, Rene van
Wang, George C.
Wills, Mark R.
Zielinski, Maciej
Pawelec, Graham
Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates “immunosenescence”. This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.
2012
info:eu-repo/semantics/article
Solana R, Tarazona R, Aiello AE, Akbar AN, Appay V, Beswick M et al. CMV and Immunosenescence: from basics to clinics. Immunity & Ageing. 2012; 9: 23. DOI 10.1186/1742-4933-9-23
1742-4933
http://hdl.handle.net/10230/23187
http://dx.doi.org/10.1186/1742-4933-9-23
eng
Immunity & Ageing. 2012; 9: 23
info:eu-repo/grantAgreement/ES/3PN/SAF2011-16169
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2012 Solana et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/231952018-01-24T08:06:50Zcom_10230_20545com_10230_5542com_10230_20719com_10230_23115col_10230_22227col_10230_22498col_10230_23132col_10230_8581
Worldwide population distribution of the common LCE3C-LCE3B deletion associated with psoriasis and other autoimmune disorders
Bassaganyas Bars, Laia, 1985-
Riveira Muñoz, Eva
García Aragonés, Manel
González Ruiz, Juan Ramón
Cáceres Aguilar, Mario
Armengol i Dulcet, Lluís
Estivill, Xavier, 1955-
Background: There is increasing evidence of the importance of copy number variants (CNV) in genetic diversity among individuals and populations, as well as in some common genetic diseases. We previously characterized a common 32-kb insertion/deletion variant of the PSORS4 locus at chromosome 1q21 that harbours the LCE3C and LCE3B genes. This variant allele (LCE3C_LCE3B-del) is common in patients with psoriasis and other autoimmune disorders from certain ethnic groups./nResults: Using array-CGH (Agilent 244 K) in samples from the HapMap and Human Genome Diversity Panel (HGDP) collections, we identified 54 regions showing population differences in comparison to Africans. We provided here a comprehensive population-genetic analysis of one of these regions, which involves the 32-kb deletion of the PSORS4 locus. By a PCR-based genotyping assay we characterised the profiles of the LCE3C_LCE3B-del and the linkage disequilibrium (LD) pattern between the variant allele and the tag SNP rs4112788. Our results show that most populations tend to have a higher frequency of the deleted allele than Sub-Saharan Africans. Furthermore, we found strong LD between rs4112788G and LCE3C_LCE3B-del in most non-African populations (r2 >0.8), in contrast to the low concordance between loci (r2 <0.3) in the African populations. Conclusions: These results are another example of population variability in terms of biomedical interesting CNV. The frequency distribution of the LCE3C_LCE3B-del allele and the LD pattern across populations suggest that the differences between ethnic groups might not be due to natural selection, but the consequence of genetic drift caused by the strong bottleneck that occurred during “out of Africa” expansion.
2013
info:eu-repo/semantics/article
Bassaganyas L, Riveira-Muñoz E, García-Aragonés M, González JR, Cáceres M, Armengol L et al. Worldwide population distribution of the common LCE3C-LCE3B deletion associated with psoriasis and other autoimmune disorders. BMC Genomics. 2013; 14: 261. DOI 10.1186/1471-2164-14-261
1471-2164
http://hdl.handle.net/10230/23195
http://dx.doi.org/10.1186/1471-2164-14-261
eng
BMC Genomics. 2013; 14: 261
info:eu-repo/grantAgreement/EC/FP7/201413
info:eu-repo/grantAgreement/EC/FP7/037627
info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2013 Bassaganyas et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/231972018-01-24T08:31:13Zcom_10230_20545com_10230_5542com_10230_23115col_10230_22227col_10230_23132col_10230_8581
A common 56-kilobase deletion in a primate-specific segmental duplication creates a novel butyrophilin-like protein
Aigner, Johanna, 1981-
Villatoro, Sergi
Rabionet, Raquel
Roquer, Jaume
Jiménez Conde, Jordi
Martí, Eulàlia
Estivill, Xavier, 1955-
Background: The Butyrophilin-like (BTNL) proteins are likely to play an important role in inflammation and immune response. Like the B7 protein family, many human and murine BTNL members have been shown to control T lymphocytes response, and polymorphisms in human BTNL2 have been linked to several inflammatory diseases, such as pulmonary sarcoidosis, inflammatory bowel disease and neonatal lupus. Results: In this study we provide a comprehensive population, genomic and transcriptomic analysis of a 56-kb deletion copy number variant (CNV), located within two segmental duplications of two genes belonging to the BTNL family, namely BTNL8 and BTNL3. We confirm the presence of a novel BTNL8*3 fusion-protein product, and show an influence of the deletion variant on the expression level of several genes involved in immune function, including BTNL9, another member of the same family. Moreover, by genotyping HapMap and human diversity panel (HGDP) samples, we demonstrate a clear difference in the stratification of the BTNL8_BTNL3-del allele frequency between major continental human populations. Conclusion: Despite tremendous progress in the field of structural variation, rather few CNVs have been functionally characterized so far. Here, we show clear functional consequences of a new deletion CNV (BTNL8_BTNL3-del) with potentially important implication in the human immune system and in inflammatory and proliferative disorders. In addition, the marked population differences found of BTNL8_BTNL3-del frequencies suggest that this deletion CNV might have evolved under positive selection due to environmental conditions in some populations, with potential phenotypic consequences.
2013
info:eu-repo/semantics/article
Aigner J, Villatoro S, Rabionet R, Roquer J, Jiménez-Conde J, Martí E, Estivill X. A common 56-kilobase deletion in a primate-specific segmental duplication creates a novel butyrophilin-like protein. BMC Genetics. 2013; 14: 61. DOI 10.1186/1471-2156-14-61
1471-2156
http://hdl.handle.net/10230/23197
http://dx.doi.org/10.1186/1471-2156-14-61
eng
BMC Genetics. 2013; 14: 61
info:eu-repo/grantAgreement/EC/FP7/201413
info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2013 Aigner et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/232132020-06-17T08:43:30Zcom_10230_6237com_10230_5542com_10230_20545com_10230_20719com_10230_23115col_10230_6238col_10230_22227col_10230_22498col_10230_23132col_10230_8581
A flexible count data model to fit the wide diversity of expression profiles arising from extensively replicated RNA-seq experiments
Esnaola, Mikel
Puig, Pedro
González, David
Castelo Valdueza, Robert
González Ruiz, Juan Ramón
Background: High-throughput RNA sequencing (RNA-seq) offers unprecedented power to capture the real dynamics of gene expression. Experimental designs with extensive biological replication present a unique opportunity to exploit this feature and distinguish expression profiles with higher resolution. RNA-seq data analysis methods so far have been mostly applied to data sets with few replicates and their default settings try to provide the best performance under this constraint. These methods are based on two well-known count data distributions: the Poisson and the negative binomial. The way to properly calibrate them with large RNA-seq data sets is not trivial for the non-expert bioinformatics user. Results: Here we show that expression profiles produced by extensively-replicated RNA-seq experiments lead to a rich diversity of count data distributions beyond the Poisson and the negative binomial, such as Poisson-Inverse Gaussian or Pólya-Aeppli, which can be captured by a more general family of count data distributions called the Poisson-Tweedie. The flexibility of the Poisson-Tweedie family enables a direct fitting of emerging features of large expression profiles, such as heavy-tails or zero-inflation, without the need to alter a single configuration parameter. We provide a software package for R called tweeDEseq implementing a new test for differential expression based on the Poisson-Tweedie family. Using simulations on synthetic and real RNA-seq data we show that tweeDEseq yields P-values that are equally or more accurate than competing methods under different configuration parameters. By surveying the tiny fraction of sex-specific gene expression changes in human lymphoblastoid cell lines, we also show that tweeDEseq accurately detects differentially expressed genes in a real large RNA-seq data set with improved performance and reproducibility over the previously compared methodologies. Finally, we compared the results with those obtained from microarrays in order to check for reproducibility. Conclusions: RNA-seq data with many replicates leads to a handful of count data distributions which can be accurately estimated with the statistical model illustrated in this paper. This method provides a better fit to the underlying biological variability; this may be critical when comparing groups of RNA-seq samples with markedly different count data distributions. The tweeDEseq package forms part of the Bioconductor project and it is available for download at http://www.bioconductor.org webcite.
2013
info:eu-repo/semantics/article
Esnaola M, Puig P, Gonzalez D, Castelo R, Gonzalez JR. A flexible count data model to fit the wide diversity of expression profiles arising from extensively replicated RNA-seq experiments. BMC Bioinformatics. 2013;14:254. DOI 10.1186/1471-2105-14-254
1471-2105
http://hdl.handle.net/10230/23213
http://dx.doi.org/10.1186/1471-2105-14-254
eng
BMC Bioinformatics. 2013;14:254
info:eu-repo/grantAgreement/EC/FP7/268479
info:eu-repo/grantAgreement/ES/3PN/MTM2011-26515
info:eu-repo/grantAgreement/ES/3PN/MTM2010-09526
info:eu-repo/grantAgreement/ES/3PN/MTM2009-10893
info:eu-repo/grantAgreement/ES/3PN/TIN2011-22826
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2013 Esnaola et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/232272024-01-29T12:44:14Zcom_10230_20545com_10230_5542com_10230_23115col_10230_22227col_10230_23132col_10230_8581
Evidence for the biogenesis of more than 1,000 novel human microRNAs
Friedländer, Marc R.
Lizano González, Esther, 1974-
Houben, Anna J.
Bezdan, Daniela
Bañez Coronel, Mónica
Kudla, Grzegorz
Mateu Huertas, Elisabet, 1983-
Kagerbauer, Birgit
González Morilla, Justo
Chen, Kevin C
LeProust, Emily M
Martí Puig, Eulàlia
Estivill, Xavier, 1955-
Background: MicroRNAs (miRNAs) are established regulators of development, cell identity and disease. Although nearly two thousand human miRNA genes are known and new ones are continuously discovered, no attempt has been made to gauge the total miRNA content of the human genome. Results: Employing an innovative computational method on massively pooled small RNA sequencing data, we report 2,469 novel human miRNA candidates of which 1,098 are validated by in-house and published experiments. Almost 300 candidates are robustly expressed in a neuronal cell system and are regulated during differentiation or when biogenesis factors Dicer, Drosha, DGCR8 or Ago2 are silenced. To improve expression profiling, we devised a quantitative miRNA capture system. In a kidney cell system, 400 candidates interact with DGCR8 at transcript positions that suggest miRNA hairpin recognition, and 1,000 of the new miRNA candidates interact with Ago1 or Ago2, indicating that they are directly bound by miRNA effector proteins. From kidney cell CLASH experiments, in which miRNA-target pairs are ligated and sequenced, we observe hundreds of interactions between novel miRNAs and mRNA targets. The novel miRNA candidates are specifically but lowly expressed, raising the possibility that not all may be functional. Interestingly, the majority are evolutionarily young and overrepresented in the human brain. Conclusions: In summary, we present evidence that the complement of human miRNA genes is substantially larger than anticipated, and that more are likely to be discovered in the future as more tissues and experimental conditions are sequenced to greater depth.
2014
info:eu-repo/semantics/article
Friedländer MR, Lizano E, Houben AJ, Bezdan D, Báñez-Coronel M, Kudla G, Mateu-Huertas E, Kagerbauer B, González J, Chen KC, LeProust EM, Martí E, Estivill X. Evidence for the biogenesis of more than 1,000 novel human microRNAs. Genome Biology. 2014; 15: R57. DOI 10.1186/gb-2014-15-4-r57
1465-6906
http://hdl.handle.net/10230/23227
http://dx.doi.org/10.1186/gb-2014-15-4-r57
eng
Genome Biology. 2014; 15: R57
info:eu-repo/grantAgreement/EC/FP7/282510
info:eu-repo/grantAgreement/EC/FP7/262055
info:eu-repo/grantAgreement/EC/FP7/261123
info:eu-repo/grantAgreement/EC/FP7/330133
info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2014 Friedländer et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
BioMed Central
oai:repositori.upf.edu:10230/232382018-01-24T08:07:35Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study
Pozo Mendoza, Óscar J., 1975-
Marcos del Águila, Josep, 1971-
Fabregat Rossell, Andreu, 1986-
Ventura Alemany, Rosa
Casals, Gregori
Aguilera, Paula
Segura Noguera, Jordi
To Figueras, Jordi
Background: Acute Intermittent Porphyria (AIP) is a rare disease that results from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme biosynthetic pathway. AIP carriers are at risk of presenting acute life-threatening neurovisceral attacks. The disease induces overproduction of heme precursors in the liver and long-lasting deregulation of metabolic networks. The clinical history of AIP suggests a strong endocrine influence, being neurovisceral attacks more common in women than in men and very rare before puberty. To asses the hypothesis that steroidogenesis may be modified in AIP patients with biochemically active disease, we undertook a comprehensive analysis of the urinary steroid metabolome. Methods: A case–control study was performed by collecting spot morning urine from 24 AIP patients and 24 healthy controls. Steroids in urine were quantified by liquid chromatography-tandem mass spectrometry. Parent steroids (17-hydroxyprogesterone; deoxycorticosterone; corticoesterone; 11-dehydrocorticosterone; cortisol and cortisone) and a large number of metabolites (N = 55) were investigated. Correlations between the different steroids analyzed and biomarkers of porphyria biochemical status (urinary heme precursors) were also evaluated. The Mann–Whitney U test and Spearman’s correlation with a two tailed test were used for statistical analyses. Results: Forty-one steroids were found to be decreased in the urine of AIP patients (P < 0.05), the decrease being more significant for steroids with a high degree of hydroxylation. Remarkably, 13 cortisol metabolites presented lower concentrations among AIP patients (P < 0.01) whereas no significant differences were found in the main metabolites of cortisol precursors. Nine cortisol metabolites showed a significant negative correlation with heme precursors (p < 0.05). Ratios between the main metabolites of 17-hydroxyprogesterone and cortisol showed positive correlations with heme-precursors (correlation coefficient > 0.51, P < 0.01). Conclusions: Comprehensive study of the urinary steroid metabolome showed that AIP patients present an imbalance in adrenal steroidogenesis, affecting the biosynthesis of cortisol and resulting in decreased out-put of cortisol and metabolites. This may result from alterations of central origin and/or may originate in specific decreased enzymatic activity in the adrenal gland. An imbalance in steroidogenesis may be related to the maintenance of an active disease state among AIP patients.
2014
info:eu-repo/semantics/article
Pozo OJ, Marcos J, Fabregat A, Ventura R, Casals G, Aguilera P, Segura J, To-Figueras J. Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study. Orphanet Journal of Rare Diseases. 2014; 9: 54. DOI 10.1186/1750-1172-9-54
1750-1172
http://hdl.handle.net/10230/23238
http://dx.doi.org/10.1186/1750-1172-9-54
eng
Orphanet Journal of Rare Diseases. 2014; 9: 54
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2014 Pozo et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
BioMed Central
oai:repositori.upf.edu:10230/232622020-06-17T09:35:00Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Uncovering adaptive evolution in the human lineage
Gayà Vidal, Magdalena
Albà Soler, Mar
Background: The recent increase in human polymorphism data, together with the availability of genome sequences from several primate species, provides an unprecedented opportunity to investigate how natural selection has shaped human evolution. Results: We compared human branch-specific substitutions with variation data in the current human population to measure the impact of adaptive evolution on human protein coding genes. The use of single nucleotide polymorphisms (SNPs) with high derived allele frequencies (DAFs) minimized the influence of segregating slightly deleterious mutations and improved the estimation of the number of adaptive sites. Using DAF ≥ 60% we showed that the proportion of adaptive substitutions is 0.2% in the complete gene set. However, the percentage rose to 40% when we focused on genes that are specifically accelerated in the human branch with respect to the chimpanzee branch, or on genes that show signatures of adaptive selection at the codon level by the maximum likelihood based branch-site test. In general, neural genes are enriched in positive selection signatures. Genes with multiple lines of evidence of positive selection include taxilin beta, which is involved in motor nerve regeneration and syntabulin, and is required for the formation of new presynaptic boutons. Conclusions: We combined several methods to detect adaptive evolution in human coding sequences at a genome-wide level. The use of variation data, in addition to sequence divergence information, uncovered previously undetected positive selection signatures in neural genes.
2014
info:eu-repo/semantics/article
Gayà-Vidal M, Albà MM. Uncovering adaptive evolution in the human lineage. BMC Genomics. 2014; 15: 559. DOI 10.1186/1471-2164-15-599
1471-2164
http://hdl.handle.net/10230/23262
http://dx.doi.org/10.1186/1471-2164-15-599
eng
BMC Genomics. 2014;15:559
info:eu-repo/grantAgreement/ES/3PN/BFU2012-36820
http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
© 2014 Gayà-Vidal and Albà; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
BioMed Central
oai:repositori.upf.edu:10230/232692020-06-17T09:37:07Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Network medicine analysis of COPD multimorbidities
Grosdidier, Solène
Ferrer, Antoni-Lluc, 1942-
Faner, Rosa
Piñero González, Janet, 1977-
Roca, Josep
García Cosio, Borja
Agustí, Alvar
Gea Guiral, Joaquim
Sanz, Ferran
Furlong, Laura I., 1971-
Background: Patients with chronic obstructive pulmonary disease (COPD) often suffer concomitant disorders that worsen significantly their health status and vital prognosis. The pathogenic mechanisms underlying COPD multimorbidities are not completely understood, thus the exploration of potential molecular and biological linkages between COPD and their associated diseases is of great interest. Methods: We developed a novel, unbiased, integrative network medicine approach for the analysis of the diseasome, interactome, the biological pathways and tobacco smoke exposome, which has been applied to the study of 16 prevalent COPD multimorbidities identified by clinical experts. Results: Our analyses indicate that all COPD multimorbidities studied here are related at the molecular and biological level, sharing genes, proteins and biological pathways. By inspecting the connections of COPD with their associated diseases in more detail, we identified known biological pathways involved in COPD, such as inflammation, endothelial dysfunction or apoptosis, serving as a proof of concept of the methodology. More interestingly, we found previously overlooked biological pathways that might contribute to explain COPD multimorbidities, such as hemostasis in COPD multimorbidities other than cardiovascular disorders, and cell cycle pathway in the association of COPD with depression. Moreover, we also observed similarities between COPD multimorbidities at the pathway level, suggesting common biological mechanisms for different COPD multimorbidities. Finally, chemicals contained in the tobacco smoke target an average of 69% of the identified proteins participating in COPD multimorbidities. Conclusions: The network medicine approach presented here allowed the identification of plausible molecular links between COPD and comorbid diseases, and showed that many of them are targets of the tobacco exposome, proposing new areas of research for understanding the molecular underpinning of COPD multimorbidities.
2014
info:eu-repo/semantics/article
Grosdidier S, Ferrer A, Faner R, Piñero J, Roca J, Cosío B et al. Network medicine analysis of COPD multimorbidities. Respiratory Research. 2014;15:111. DOI: 10.1186/s12931-014-0111-4
1465-9921
http://hdl.handle.net/10230/23269
http://dx.doi.org/10.1186/s12931-014-0111-4
eng
Respiratory Research. 2014;15:111
info:eu-repo/grantAgreement/ES/3PN/SAF2011-26908
http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
© 2014 Grosdidier et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
BioMed Central
oai:repositori.upf.edu:10230/232712023-09-26T09:32:35Zcom_10230_6237com_10230_5542com_10230_23115com_10230_20719col_10230_6238col_10230_23132col_10230_22498col_10230_8581
Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management
Roca, Josep
Vargas, Claudia
Cano, Isaac
Selivanov, Vitaly
Barreiro Portela, Esther
Maier, Dieter
Falciani, Francesco
Wagner, Peter
Cascante Serratosa, Marta
García Aymerich, Judith
Kalko, Susana G.
Marin de Mas, Igor
Tegnér, Jesper
Escarrabill, Joan
Agustí, Alvar
Gomez Cabrero, David
Synergy-COPD consortium
Background and hypothesis: Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics. Objective and method: To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena. Results: (1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering. Conclusions: The results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD.
2014
info:eu-repo/semantics/article
Roca J, Vargas C, Cano I, Selivanov V, Barreiro E, Maier D et al. Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management. Journal of Translational Medicine. 2014; 12(S2): S3. DOI 10.1186/1479-5876-12-S2-S3
1479-5876
http://hdl.handle.net/10230/23271
http://dx.doi.org/10.1186/1479-5876-12-S2-S3
eng
Journal of Translational Medicine. 2014; 12(S2): S3
info:eu-repo/grantAgreement/EC/FP7/270086
http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
© 2014 Roca et al.; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
BioMed Central
oai:repositori.upf.edu:10230/232752021-07-21T07:36:40Zcom_10230_23115com_10230_5542col_10230_23132
Observación, farmacoterapia y derivación al alta de los pacientes con trastorno de ansiedad en urgencias de psiquiatría
Pailhez, Guillem
Majó, Albert
Córcoles, David
Ginés Miranda, José María
Arcega, José M.
Castaño, Juan R.
Merino Torres, Ana
Bulbena Vilarrasa, Antonio
Pérez Solá, Victor
INTRODUCTION: To analyze factors associated with clinical observation, pharmacotherapy and referral on discharge of patients with anxiety disorder (AD) seeking care at a psychiatric emergency unit. METHOD: A total of 5003 consecutive visits were reviewed over a three-year period at a psychiatric emergency service in a tertiary university hospital. Data collected included sociodemographic and clinical information as well as the Global Assessment of Functioning (GAF) and the Severity Psychiatric Illness (SPI) scale scores. RESULTS: Of all the visits, 992 (19.8%) were diagnosed of AD. Of these, 19.6% required clinical observation and 72.2% were referred to a psychiatrist at discharge. Regression analysis showed that referral to psychiatry was associated with being male, native, psychiatric background, greater severity, lower global functioning, and behavioral disorders. Clinical observation (in a box) was associated with being female, greater severity, and psychotic or behavioral symptoms. Prescription of benzodiazepines was associated with anxiety, no history of addiction, and lower global functioning. Antidepressants were associated with being a native, anxiety with no history of addiction, and lower functioning. Antipsychotics were associated with being native, psychiatric background (not addiction), anxiety, and lower functioning. CONCLUSION: Behavior, psychiatric background and illness severity were determinants of referral to a specialist. Besides these, psychotic symptoms and non-specific clinical symptoms were determinants of observation. Drug prescription in AD is less frequent if the main complaint is not anxiety and depends more on the level of functioning than on that of severity.
Introducción: Analizar los determinantes asociados a indicar observación, prescribir psicofármacos y derivar al especialista en los pacientes con trastorno de ansiedad (TA) visitados en urgencias de psiquiatría. Método: Se analizaron 5003 visitas consecutivas realizadas en un hospital general universitario durante tres años. Se incluyó información sociodemográfica, clínica y puntuación en las escalas de Evaluación de la Actividad Global (EEAG) y de Gravedad de la Enfermedad Psiquiátrica (GEP). Resultados: Del total de visitas, 992 (19,8%) fueron diagnosticadas de TA. De estas visitas, 19,6% utilizaron box y 72,2% fueron derivadas al especialista. El análisis de regresión mostró que la deriva ción a psiquiatría se asociaba con ser hombre, autóctono, tener antecedentes, mayor gravedad, menor actividad global y alteraciones conductuales. La observación (uso del box) se relacionó con ser mujer, mayor gravedad y síntomas psicóticos o de conducta. La prescripción de benzodiacepinas se asoció a ansiedad sin problemas de toxicomanías y a una menor actividad global. Los antidepresivos se relacionaron con ser autóctono, ansiedad sin toxicomanías y con menor actividad. Los antipsicóticos con ser autóctono , tener antecedentes sin toxicomanías, ansiedad y menor actividad. Conclusión: La conducta, los antecedentes y la gravedad resultaron determinantes de derivación al especialista. Además de estos, los síntomas psicóticos y la inespecificidad clínica lo fueron para indicar observación. La prescripción farmacológica en los TA es menos frecuente si el motivo de consulta no es por ansiedad y depende más del nivel de actividad que de la gravedad.
2015
info:eu-repo/semantics/article
Pailhez G, Majó A, Córcoles D, Ginés JM, Arcega JM, Castaño J, Merino A, Bulbena A, Pérez V. Clinical observation, pharmacotherapy and referral on discharge of patients with anxiety disorder in a psychiatric emergency service. Actas Esp Psiquiatr 2015;43(1):8-15.
1139-9287
http://hdl.handle.net/10230/23275
spa
Actas Españolas de Psiquiatría. 2015;43(1):8-15
info:eu-repo/semantics/openAccess
(c) Elsevier http://www.actaspsiquiatria.es/repositorio//17/93/ENG/17-93-ENG-8-15-334304.pdf
Elsevier Masson
oai:repositori.upf.edu:10230/232792020-02-18T10:25:03Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
High throughput molecular dynamics for drug discovery
Stanley, Nathaniel H., 1983-
De Fabritiis, Gianni
Molecular dynamics simulations hold the promise to be an important tool for biological research and drug discovery. Historically, however, there were several obstacles for it to become a practical research tool. Limitations in computer hardware had previously made it difficult to simulate for long enough to see interesting biological processes. Recent improvements in hardware and algorithms have largely removed this issue, leaving data analysis as the main obstacle. Advances in Markov state modeling appear to be on the way to remove this obstacle. We outline these advances here and discuss numerous recent studies that demonstrate that molecular dynamics simulations will start to be an important tool for pharmaceutical research.
2015
info:eu-repo/semantics/article
Stanley N, De Fabritiis G. High throughput molecular dynamics for drug discovery. In Silico Pharmacology. 2015; 3: 3. DOI 10.1186/s40203-015-0007-0
2193-9616
http://hdl.handle.net/10230/23279
http://dx.doi.org/10.1186/s40203-015-0007-0
eng
In Silico Pharmacology. 2015; 3: 3.
http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
© 2015 Stanley and De Fabritiis; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
SpringerOpen
oai:repositori.upf.edu:10230/232862020-06-17T09:43:23Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Genetic adaptation of the antibacterial human innate immunity network
Casals López, Ferran
Sikora, Martin, 1976-
Laayouni, Hafid, 1968-
Montanucci, Ludovica, 1978-
Muntasell i Castellví, Aura, 1972-
Lazarus, Ross
Calafell i Majó, Francesc
Awadalla, Philip
Netea, Mihai G
Bertranpetit, Jaume, 1952-
Background: Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Results: Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. Conclusions: We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.
2011
info:eu-repo/semantics/article
Casals F, Sikora M, Laayouni H, Montanucci L, Muntasell A, Lazarus R et al. Genetic adaptation of the antibacterial human innate immunity network. BMC Evolutionary Biology. 2011;11:202. DOI: 10.1186/1471-2148-11-202
1471-2148
http://hdl.handle.net/10230/23286
http://dx.doi.org/10.1186/1471-2148-11-202
eng
BMC Evolutionary Biology. 2011;11:202
info:eu-repo/grantAgreement/ES/2PN/SAF2007-63171
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2011 Casals et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/232882020-06-17T09:45:47Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Validity of instruments to measure physical activity may be questionable due to a lack of conceptual frameworks: a systematic review
Gimeno Santos, Elena, 1980-
Frei, Anja
Dobbels, Fabienne
Rüdell, Katja
Puhan, Milo A.
García Aymerich, Judith
PROactive consortium
Background: Guidance documents for the development and validation of patient-reported outcomes (PROs) advise the use of conceptual frameworks, which outline the structure of the concept that a PRO aims to measure. It is unknown whether currently available PROs are based on conceptual frameworks. This study, which was limited to a specific case, had the following aims: (i) to identify conceptual frameworks of physical activity in chronic respiratory patients or similar populations (chronic heart disease patients or the elderly) and (ii) to assess whether the development and validation of PROs to measure physical activity in these populations were based on a conceptual framework of physical activity. Methods: Two systematic reviews were conducted through searches of the Medline, Embase, PsycINFO, and Cinahl databases prior to January 2010. Results: In the first review, only 2 out of 581 references pertaining to physical activity in the defined populations provided a conceptual framework of physical activity in COPD patients. In the second review, out of 103 studies developing PROs to measure physical activity or related constructs, none were based on a conceptual framework of physical activity. Conclusions: These findings raise concerns about how the large body of evidence from studies that use physical activity PRO instruments should be evaluated by health care providers, guideline developers, and regulatory agencies.
2011
info:eu-repo/semantics/article
Gimeno-Santos E, Frei A, Dobbels F, Rüdell K, Puhan MA, Garcia-Aymerich J. Validity of instruments to measure physical activity may be questionable due to a lack of conceptual frameworks: a systematic review. Health and Quality of Life Outcomes. 2011;9:86. DOI: 10.1186/1477-7525-9-86
1477-7525
http://hdl.handle.net/10230/23288
http://dx.doi.org/10.1186/1477-7525-9-86
eng
Health and Quality of Life Outcomes. 2011;9:86
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2011 Gimeno-Santos et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/232892020-06-17T09:46:44Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Assessment of NER solutions against the first and second CALBC Silver Standard Corpus
Rebholz-Schuhmann, Dietrich
Furlong, Laura I., 1971-
Rautschka, Michael
Hahn, Udo
Background: Competitions in text mining have been used to measure the performance of automatic text processing solutions against a manually annotated gold standard corpus (GSC). The preparation of the GSC is time-consuming and costly and the final corpus consists at the most of a few thousand documents annotated with a limited set of semantic groups. To overcome these shortcomings, the CALBC project partners (PPs) have produced a large-scale annotated biomedical corpus with four different semantic groups through the harmonisation of annotations from automatic text mining solutions, the first version of the Silver Standard Corpus (SSC-I). The four semantic groups are chemical entities and drugs (CHED), genes and proteins (PRGE), diseases and disorders (DISO) and species (SPE). This corpus has been used for the First CALBC Challenge asking the participants to annotate the corpus with their text processing solutions. Results: All four PPs from the CALBC project and in addition, 12 challenge participants (CPs) contributed annotated data sets for an evaluation against the SSC-I. CPs could ignore the training data and deliver the annotations from their genuine annotation system, or could train a machine-learning approach on the provided pre-annotated data. In general, the performances of the annotation solutions were lower for entities from the categories CHED and PRGE in comparison to the identification of entities categorized as DISO and SPE. The best performance over all semantic groups were achieved from two annotation solutions that have been trained on the SSC-I. The data sets from participants were used to generate the harmonised Silver Standard Corpus II (SSC-II), if the participant did not make use of the annotated data set from the SSC-I for training purposes. The performances of the participants’ solutions were again measured against the SSC-II. The performances of the annotation solutions showed again better results for DISO and SPE in comparison to CHED and PRGE. Conclusions: The SSC-I delivers a large set of annotations (1,121,705) for a large number of documents (100,000 Medline abstracts). The annotations cover four different semantic groups and are sufficiently homogeneous to be reproduced with a trained classifier leading to an average F-measure of 85%. Benchmarking the annotation solutions against the SSC-II leads to better performance for the CPs’ annotation solutions in comparison to the SSC-I.
2011
info:eu-repo/semantics/article
Rebholz-Schuhmann D, Yepes A, Li C, Kafkas S, Lewin I, Kang N et al. Assessment of NER solutions against the first and second CALBC silver standard corpus. Journal of Biomedical Semantics. 2011;2(S5):S11. DOI: 10.1186/2041-1480-2-S5-S11
2041-1480
http://hdl.handle.net/10230/23289
http://dx.doi.org/10.1186/2041-1480-2-S5-S11
eng
Journal of Biomedical Semantics. 2011;2(S5):S11
info:eu-repo/grantAgreement/EC/FP7/231727
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2011 Rebholz-Schuhmann et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/232922020-06-17T09:50:09Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Transient receptor potential genes, smoking, occupational exposures and cough in adults
Smit, Lidwien AM
Kogevinas, Manolis
Antó i Boqué, Josep Maria
Bouzigon, Emmanuelle
González Ruiz, Juan Ramón
Moual, Nicole Le
Kromhout, Hans
Carsin, Anne-Elie
Pin, Isabelle
Jarvis, Deborah
Vermeulen, Roel
Janson, Christer
Heinrich, Joachim
Gut, Ivo Glynne
Lathrop, Mark
Valverde, M. A. (Miguel Ángel), 1963-
Demenais, Florence
Kauffmann, Francine
Background: Transient receptor potential (TRP) vanilloid and ankyrin cation channels are activated by various noxious chemicals and may play an important role in the pathogenesis of cough. The aim was to study the influence of single nucleotide polymorphisms (SNPs) in TRP genes and irritant exposures on cough. Methods: Nocturnal, usual, and chronic cough, smoking, and job history were obtained by questionnaire in 844 asthmatic and 2046 non-asthmatic adults from the Epidemiological study on the Genetics and Environment of Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Occupational exposures to vapors, gases, dusts, and/or fumes were assessed by a job-exposure matrix. Fifty-eight tagging SNPs in TRPV1, TRPV4, and TRPA1 were tested under an additive model. Results: Statistically significant associations of 6 TRPV1 SNPs with cough symptoms were found in non-asthmatics after correction for multiple comparisons. Results were consistent across the eight countries examined. Haplotype-based association analysis confirmed the single SNP analyses for nocturnal cough (7-SNP haplotype: p-global = 4.8 × 10-6) and usual cough (9-SNP haplotype: p-global = 4.5 × 10-6). Cough symptoms were associated with exposure to irritants such as cigarette smoke and occupational exposures (p < 0.05). Four polymorphisms in TRPV1 further increased the risk of cough symptoms from irritant exposures in asthmatics and non-asthmatics (interaction p < 0.05). Conclusions: TRPV1 SNPs were associated with cough among subjects without asthma from two independent studies in eight European countries. TRPV1 SNPs may enhance susceptibility to cough in current smokers and in subjects with a history of workplace exposures.
2012
info:eu-repo/semantics/article
Smit LAM, Kogevinas M, Antó JM, Bouzigon E, González J, Le Moual N et al. Transient receptor potential genes, smoking, occupational exposures and cough in adults. Respiratory Research. 2012; 13: 26. DOI 10.1186/1465-9921-13-26
1465-9921
http://hdl.handle.net/10230/23292
http://dx.doi.org/10.1186/1465-9921-13-26
eng
Respiratory Research. 2012;13:26
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© 2012 Smit et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BioMed Central
oai:repositori.upf.edu:10230/232932020-06-04T09:50:50Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Plasma Concentrations of BDNF and IGF-1 in Abstinent Cocaine Users with High Prevalence of Substance Use Disorders: Relationship to Psychiatric Comorbidity
Pedraz, María
Martín Velasco, Ana Isabel
García Marchena, Nuria
Araos, Pedro
Serrano, Antonia
Romero Sanchiz, Pablo
Suárez, Juan
Castilla Ortega, Estela
Barrios, Vicente
Campos Cloute, Rafael
Ruiz, Juan Jesús
Torrens, Marta
Chowen, Julie A.
Argente, Jesús
Torre Fornell, Rafael de la
Santín, Luis Javier
Villanúa, María Ángeles
Rodríguez de Fonseca, Fernando
Pavón, Francisco Javier
Recent studies have identified biomarkers related to the severity and pathogenesis of cocaine addiction and common comorbid psychiatric disorders. Monitoring these plasma mediators may improve the stratification of cocaine users seeking treatment. Because the neurotrophic factors are involved in neural plasticity, neurogenesis and neuronal survival, we have determined plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1) and IGF-1 binding protein 3 (IGFBP-3) in a cross-sectional study with abstinent cocaine users who sought outpatient treatment for cocaine (n = 100) and age/body mass matched controls (n = 85). Participants were assessed with the diagnostic interview 'Psychiatric Research Interview for Substance and Mental Disorders'. Plasma concentrations of these peptides were not different in cocaine users and controls. They were not associated with length of abstinence, duration of cocaine use or cocaine symptom severity. The pathological use of cocaine did not influence the association of IGF-1 with age observed in healthy subjects, but the correlation between IGF-1 and IGFBP-3 was not significantly detected. Correlation analyses were performed between these peptides and other molecules sensitive to addiction: BDNF concentrations were not associated with inflammatory mediators, lipid derivatives or IGF-1 in cocaine users, but correlated with chemokines (fractalkine/CX3CL1 and SDF-1/CXCL12) and N-acyl-ethanolamines (N-palmitoyl-, N-oleoyl-, N-arachidonoyl-, N-linoleoyl- and N-dihomo-γ-linolenoyl-ethanolamine) in controls; IGF-1 concentrations only showed association with IGFBP-3 concentrations in controls; and IGFBP-3 was only correlated with N-stearoyl-ethanolamine concentrations in cocaine users. Multiple substance use disorders and life-time comorbid psychopathologies were common in abstinent cocaine users. Interestingly, plasma BDNF concentrations were exclusively found to be decreased in users diagnosed with both primary and cocaine-induced disorders for mood and anxiety disorders. In summary, BDNF, IGF-1 and IGFBP-3 were not affected by a history of pathological use of cocaine supported by the absence of associations with other molecules sensitive to cocaine addiction. However, BDNF was affected by comorbid mood disorders. Further research is necessary to elucidate the role of BDNF and IGF-1 in the transition to cocaine addiction and associated psychiatric comorbidity.
2015
info:eu-repo/semantics/article
Pedraz M, Martín-Velasco AI, García-Marchena N, Araos P, Serrano A, Romero-Sanchiz P,et al. Plasma Concentrations of BDNF and/nIGF-1 in Abstinent Cocaine Users with High Prevalence of Substance Use Disorders: Relationship to Psychiatric Comorbidity. PLoS ONE. 2015;10(3):e0118610. DOI: 10.1371/journal.pone.0118610
1932-6203
http://hdl.handle.net/10230/23293
http://dx.doi.org/10.1371/journal.pone.0118610
eng
PLoS ONE. 2015;10(3):e0118610
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
© 2015 Pedraz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Public Library of Science
oai:repositori.upf.edu:10230/233032021-07-21T07:48:20Zcom_10230_23115com_10230_5542col_10230_23132
Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease
Musameh, Muntaser D.
Wang, William Y. S.
Nelson, Christopher P.
Lluís Ganella, Carla, 1984-
Debiec, Radoslaw
Subirana Cachinero, Isaac
Elosua Llanos, Roberto
Balmforth, Anthony J.
Ball, Stephen G.
Hall, Alistair S.
Kathiresan, Sekar
Thompson, John R.
Lucas, Gavin, 1977-
Samani, Nilesh J.
Tomaszewski, Maciej
OBJECTIVE: Only a small fraction of coronary artery disease (CAD) heritability has been explained by common variants identified to date. Interactions between genes of importance to cardiovascular regulation may account for some of the missing heritability of CAD. This study aimed to investigate the role of gene-gene interactions in common variants in candidate cardiovascular genes in CAD. APPROACH AND RESULTS: 2,101 patients with CAD from the British Heart Foundation Family Heart Study and 2,426 CAD-free controls were included in the discovery cohort. All subjects were genotyped with the Illumina HumanCVD BeadChip enriched for genes and pathways relevant to the cardiovascular system and disease. The primary analysis in the discovery cohort examined pairwise interactions among 913 common (minor allele frequency >0.1) independent single nucleotide polymorphisms (SNPs) with at least nominal association with CAD in single locus analysis. A secondary exploratory interaction analysis was performed among all 11,332 independent common SNPs surviving quality control criteria. Replication analyses were conducted in 2,967 patients and 3,075 controls from the Myocardial Infarction Genetics Consortium. None of the interactions amongst 913 SNPs analysed in the primary analysis was statistically significant after correction for multiple testing (required P<1.2x10-7). Similarly, none of the pairwise gene-gene interactions in the secondary analysis reached statistical significance after correction for multiple testing (required P = 7.8x10-10). None of 36 suggestive interactions from the primary analysis or 31 interactions from the secondary analysis was significant in the replication cohort. Our study had 80% power to detect odds ratios > 1.7 for common variants in the primary analysis. CONCLUSIONS: Moderately large additive interactions between common SNPs in genes relevant to cardiovascular disease do not appear to play a major role in genetic predisposition to CAD. The role of genetic interactions amongst less common SNPs and with medium and small magnitude effects remain to be investigated
2015
info:eu-repo/semantics/article
Musameh MD, Wang WYS, Nelson CP, Lluís-Ganella C, Debiec R, Subirana I, et al. Analysis of Gene-Gene Interactions among Common Variants in Candidate Cardiovascular Genes in Coronary Artery Disease. PLoS ONE. 2015; 10(2): e0117684. DOI 10.1371/journal.pone.0117684
1932-6203
http://hdl.handle.net/10230/23303
http://dx.doi.org/10.1371/journal.pone.0117684
eng
PLoS ONE. 2015;10(2):e0117684
info:eu-repo/grantAgreement/ES/3PN/JCI2009-04684
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
© 2015 Musameh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Public Library of Science
oai:repositori.upf.edu:10230/233292019-01-29T12:08:00Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
FISH and immunohistochemical status of the hepatocyte growth factor receptor (c-Met) in 184 invasive breast tumors.
Carracedo, Alma
Egervari, Kristof
Salido, Marta
Rojo, Federico
Arumí, Montserrat
Corominas Torres, Josep Maria
Corzo, Cristina
Tusquets Trias de Bes, Ignacio
Espinet Solà, Blanca
Rovira Guerín, Ana
Albanell Mestres, Joan
Szollosi, Zoltan
Serrano Figueras, Sergi
Solé Ristol, Francesc
2009
info:eu-repo/semantics/article
Carracedo A, Egervari K, Salido M, Rojo F, Corominas JM, Arumi M, Corzo C, Tusquets I, Espinet B, Rovira A, Albanell J, Szollosi Z, Serrano S, Solé F. FISH and immunohistochemical status of the hepatocyte growth factor receptor (c-Met) in 184 invasive breast tumors. Breast Cancer Research. 2009; 11: 402. DOI 10.1186/bcr2239
1465-5411
http://hdl.handle.net/10230/23329
http://dx.doi.org/10.1186/bcr2239
eng
Breast Cancer Research. 2009; 11: 402
info:eu-repo/semantics/openAccess
© 2009 BioMed Central Ltd
BioMed Central
oai:repositori.upf.edu:10230/233482020-06-16T08:49:22Zcom_10230_20719com_10230_5542com_10230_6237com_10230_23115col_10230_22498col_10230_6238col_10230_23132col_10230_8581
Association between traffic-related air pollution in schools and cognitive development in primary school children: a prospective cohort study
Sunyer Deu, Jordi
Esnaola, Mikel
Álvarez Pedrerol, Mar
Forns i Guzman, Joan, 1981-
Rivas, Ioar
López Vicente, Mònica, 1988-
Suades González, Elisabet
Foraster Pulido, Maria, 1984-
García Esteban, Raquel
Basagaña Flores, Xavier
Viana, Maria Carmen
Cirach, Marta
Moreno, Teresa
Alastuey, Andrés
Sebastián Gallés, Núria
Nieuwenhuijsen, Mark J.
Querol, Xavier
Air pollution is a suspected developmental neurotoxicant. Many schools are located in close proximity to busy roads, and traffic air pollution peaks when children are at school. We aimed to assess whether exposure of children in primary school to traffic-related air pollutants is associated with impaired cognitive development. Methods and Findings: We conducted a prospective study of children (n = 2,715, aged 7 to 10 y) from 39 schools in Barcelona (Catalonia, Spain) exposed to high and low traffic-related air pollution, paired by school socioeconomic index; children were tested four times (i.e., to assess the 12-mo developmental trajectories) via computerized tests (n = 10,112). Chronic traffic air pollution (elemental carbon [EC], nitrogen dioxide [NO2], and ultrafine particle number [UFP; 10–700 nm]) was measured twice during 1-wk campaigns both in the courtyard (outdoor) and inside the classroom (indoor) simultaneously in each school pair. Cognitive development was assessed with the n-back and the attentional network tests, in particular, working memory (two-back detectability), superior working memory (three-back detectability), and inattentiveness (hit reaction time standard error). Linear mixed effects models were adjusted for age, sex, maternal education, socioeconomic status, and air pollution exposure at home. Children from highly polluted schools had a smaller growth in cognitive development than children from the paired lowly polluted schools, both in crude and adjusted models (e.g., 7.4% [95% CI 5.6%–8.8%] versus 11.5% [95% CI 8.9%–12.5%] improvement in working memory, p = 0.0024). Cogently, children attending schools with higher levels of EC, NO2, and UFP both indoors and outdoors experienced substantially smaller growth in all the cognitive measurements; for example, a change from the first to the fourth quartile in indoor EC reduced the gain in working memory by 13.0% (95% CI 4.2%–23.1%). Residual confounding for social class could not be discarded completely; however, the associations remained in stratified analyses (e.g., for type of school or high-/low-polluted area) and after additional adjustments (e.g., for commuting, educational quality, or smoking at home), contradicting a potential residual confounding explanation. Conclusions: Children attending schools with higher traffic-related air pollution had a smaller improvement in cognitive development.
2015
info:eu-repo/semantics/article
Sunyer J, Esnaola M, Alvarez-Pedrerol M, Forns J, Rivas I, López-Vicente M. Association between traffic-related air pollution in schools and cognitive development in primary school children: a prospective cohort study. PLoS Med. 2015 Mar 3;12(3):e1001792. DOI: 10.1371/journal.pmed.1001792.
1549-1277
http://hdl.handle.net/10230/23348
http://dx.doi.org/10.1371/journal.pmed.1001792
eng
PLOS Medicine. 2015 Mar 3;12(3):e1001792
info:eu-repo/grantAgreement/EC/FP7/268479
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
© 2015 Sunyer et al. This is an open access article distributed under the terms of the: http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Public Library of Science
oai:repositori.upf.edu:10230/233452020-06-17T10:42:24Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
CAPS-DB: A structural classification of helix-capping motifs
Segura, Joan
Oliva Miguel, Baldomero
Fernández Fuentes, Narcís
The regions of the polypeptide chain immediately preceding or following an α-helix are known as Nt- and Ct cappings, respectively. Cappings play a central role stabilizing α-helices due to lack of intrahelical hydrogen bonds in the first and last turn. Sequence patterns of amino acid type preferences have been derived for cappings but the structural motifs associated to them are still unclassified. CAPS-DB is a database of clusters of structural patterns of different capping types. The clustering algorithm is based in the geometry and the (ϕ–ψ)-space conformation of these regions. CAPS-DB is a relational database that allows the user to search, browse, inspect and retrieve structural data associated to cappings. The contents of CAPS-DB might be of interest to a wide range of scientist covering different areas such as protein design and engineering, structural biology and bioinformatics. The database is accessible at: http://www.bioinsilico.org/CAPSDB.
2012
info:eu-repo/semantics/article
Segura J, Oliva B, Fernandez-Fuentes N. CAPS-DB: A structural classification of helix-capping motifs. Nucleic Acids Research. 2012;40(D1):D479-D485. DO:I 10.1093/nar/gkr879
0305-1048
http://hdl.handle.net/10230/23345
http://dx.doi.org/10.1093/nar/gkr879
eng
Nucleic Acids Research. 2012;40(D1):D479-D485
info:eu-repo/grantAgreement/ES/3PN/BIO2011-22568
http://creativecommons.org/licenses/by-nc/3.0
info:eu-repo/semantics/openAccess
© Segura J, Oliva B, Fernandez-Fuentes N [2012]. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution License
Oxford University Press
oai:repositori.upf.edu:10230/233462023-01-31T14:06:09Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and stability
Viñas Castells, Rosa, 1985-
Frías Hernández, Àlex, 1985-
Robles Lanuza, Estefanía
Zhang, Kun
Longmore, Gregory D
García de Herreros, Antonio
Díaz, Víctor M.
The zinc finger transcription factor Snail1 regulates epithelial to mesenchymal transition, repressing epithelial markers and activating mesenchymal genes. Snail1 is an extremely labile protein degraded by the cytoplasmic ubiquitin-ligases β-TrCP1/FBXW1 and Ppa/FBXL14. Using a short hairpin RNA screening, we have identified FBXL5 as a novel Snail1 ubiquitin ligase. FBXL5 is located in the nucleus where it interacts with Snail1 promoting its polyubiquitination and affecting Snail1 protein stability and function by impairing DNA binding. Snail1 downregulation by FBXL5 is prevented by Lats2, a protein kinase that phosphorylates Snail1 precluding its nuclear export but not its polyubiquitination. Actually, although polyubiquitination by FBXL5 takes place in the nucleus, Snail1 is degraded in the cytosol. Finally, FBXL5 is highly sensitive to stress conditions and is downregulated by iron depletion and γ-irradiation, explaining Snail1 stabilization in these conditions. These results characterize a novel nuclear ubiquitin ligase controlling Snail1 protein stability and provide the molecular basis for understanding how radiotherapy upregulates the epithelial to mesenchymal transition-inducer Snail1.
2014
info:eu-repo/semantics/article
Vinas-Castells R, Frias A, Robles-Lanuza E, Zhang K, Longmore GD, Garcia De Herreros A, Diaz VM. Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and stability. Nucleic Acids Research. 2014;42(2):1079-94. DOI: 10.1093/nar/gkt935
0305-1048
http://hdl.handle.net/10230/23346
http://dx.doi.org/10.1093/nar/gkt935
eng
Nucleic Acids Research. 2014;42(2):1079-94
info:eu-repo/grantAgreement/ES/3PN/SAF2010-16089
http://creativecommons.org/licenses/by/3.0/
info:eu-repo/semantics/openAccess
© Vinas-Castells R, Frias A, Robles-Lanuza E, Zhang K, Longmore GD, Garcia De Herreros A, Diaz VM [2014]. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution License
Oxford University Press
oai:repositori.upf.edu:10230/233492021-04-13T11:00:09Zcom_10230_20719com_10230_5542com_10230_23115col_10230_22498col_10230_23132col_10230_8581
Following the footprints of polymorphic inversions on SNP data: from detection to association tests
Cáceres, Alejandro
González Ruiz, Juan Ramón
Inversion polymorphisms have important phenotypic and evolutionary consequences in humans. Two different methodologies have been used to infer inversions from SNP dense data, enabling the use of large cohorts for their study. One approach relies on the differences in linkage disequilibrium across breakpoints; the other one captures the internal haplotype groups that tag the inversion status of chromosomes. In this article, we assessed the convergence of the two methods in the detection of 20 human inversions that have been reported in the literature. The methods converged in four inversions including inv-8p23, for which we studied its association with low-BMI in American children. Using a novel haplotype tagging method with control on inversion ancestry, we computed the frequency of inv-8p23 in two American cohorts and observed inversion haplotype admixture. Accounting for haplotype ancestry, we found that the European inverted allele in children carries a recessive risk of underweight, validated in an independent Spanish cohort (combined: OR= 2.00, P = 0.001). While the footprints of inversions on SNP data are complex, we show that systematic analyses, such as convergence of different methods and controlling for ancestry, can reveal the contribution of inversions to the ancestral composition of populations and to the heritability of human disease
2015
info:eu-repo/semantics/article
Cáceres A, González JR. Following the footprints of polymorphic inversions on SNP data: from detection to association tests. Nucl. Acids Res. 2015;43(8):e53. doi: 10.1093/nar/gkv073
0305-1048
http://hdl.handle.net/10230/23349
http://dx.doi.org/10.1093/nar/gkv073
eng
Nucleic Acids Research. 2015;43(8):e53
info:eu-repo/grantAgreement/EC/FP7/201413
info:eu-repo/grantAgreement/ES/3PN/MTM2011-26515
info:eu-repo/grantAgreement/ES/3PN/MTM2010-09526
info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357
info:eu-repo/semantics/openAccess
© Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Nucleic Acids Research following peer review. The definitive publisher-authenticated version Cáceres A, González JR. Following the footprints of polymorphic inversions on SNP data: from detection to association tests. Nucl. Acids Res. (2015, February 11 is available online at: [http://dx.doi.org/10.1093/nar/gkv073
Oxford University Press
oai:repositori.upf.edu:10230/233622021-07-21T07:49:38Zcom_10230_23115com_10230_5542col_10230_23132
Stromal gene expression defines poor-prognosis subtypes in colorectal cancer
Calon, Alexandre
Lonardo, Enza
Berenguer-Llergo, Antonio
Espinet, Elisa
Hernando-Momblona, Xavier
Iglesias Coma, Mar
Sevillano, Marta
Palomo-Ponce, Sergio
Tauriello, Daniele V.F.
Byrom, Daniel
Cortina Duran, Carme
Morral, Clara
Barceló, Carles
Tosi, Sebastien
Riera, Antoni
Attolini, Camille Stephan-Otto
Rossell, David
Sancho, Elena
Batlle Gómez, Eduard
Recent molecular classifications of colorectal cancer (CRC) based on global gene expression profiles have defined subtypes displaying resistance to therapy and poor prognosis. Upon evaluation of these classification systems, we discovered that their predictive power arises from genes expressed by stromal cells rather than epithelial tumor cells. Bioinformatic and immunohistochemical analyses identify stromal markers that associate robustly with disease relapse across the various classifications. Functional studies indicate that cancer-associated fibroblasts (CAFs) increase the frequency of tumor-initiating cells, an effect that is dramatically enhanced by transforming growth factor (TGF)-β signaling. Likewise, we find that all poor-prognosis CRC subtypes share a gene program induced by TGF-β in tumor stromal cells. Using patient-derived tumor organoids and xenografts, we show that the use of TGF-β signaling inhibitors to block the cross-talk between cancer cells and the microenvironment halts disease progression
2015
info:eu-repo/semantics/article
Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M. et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015 Apr;47(4):320-9. doi: 10.1038/ng.3225.
1061-4036
http://hdl.handle.net/10230/23362
http://dx.doi.org/10.1038/ng.3225
eng
Nature Genetics. 2015 Apr;47(4):320-9
info:eu-repo/semantics/openAccess
© Nature Publishing Group http://dx.doi.org/10.1038/ng.3225
Nature Publishing Group
oai:repositori.upf.edu:10230/233502021-04-07T08:15:17Zcom_10230_6237com_10230_5542com_10230_20545com_10230_23115col_10230_6238col_10230_22227col_10230_23132col_10230_8581
Overexpression of α3/α5/β4 nicotinic receptor subunits modifies impulsive-like behavior
Viñals Álvarez, Xavier, 1985-
Molas Casacuberta, Susanna, 1985-
Gallego, Xavier
Fernández Montes, Rubén D.
Robledo, Patricia, 1958-
Dierssen, Mara
Maldonado, Rafael, 1961-
Recent studies have revealed that sequence variants in genes encoding the α3/α5/β4 nicotinic acetylcholine receptor subunits are associated with nicotine dependence. In this study, we evaluated two specific aspects of executive functioning related to drug addiction (impulsivity and working memory) in transgenic mice over expressing α3/α5/β4 nicotinic receptor subunits. Impulsivity and working memory were evaluated in an operant delayed alternation task, where mice must inhibit responding between 2 and 8s in order to receive food reinforcement. Working memory was also evaluated in a spontaneous alternation task in an open field. Transgenic mice showed less impulsive-like behavior than wild-type controls, and this behavioral phenotype was related to the number of copies of the transgene. Thus, transgenic Line 22 (16-28 copies) showed a more pronounced phenotype than Line 30 (4-5 copies). Overexpression of these subunits in Line 22 reduced spontaneous alternation behavior suggesting deficits in working memory processing in this particular paradigm. These results reveal the involvement of α3/α5/β4 nicotinic receptor subunits in working memory and impulsivity, two behavioral traits directly related to the vulnerability to develop nicotine dependence.
2012
info:eu-repo/semantics/article
Viñals X, Molas S, Gallego X, Fernández-Montes RD, Robledo P, Dierssen M et al. Overexpression of α3/α5/β4 nicotinic receptor subunits modifies impulsive-like behavior. Drug Alcohol Depend. 2012 May 1;122(3):247-52. DOI: 10.1016/j.drugalcdep.2011.09.027
0376-8716
http://hdl.handle.net/10230/23350
http://dx.doi.org/10.1016/j.drugalcdep.2011.09.027
eng
Drug and Alcohol Dependence. 2012 May 1;122(3):247-52
info:eu-repo/grantAgreement/EC/FP7/037669
info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
info:eu-repo/grantAgreement/ES/2PN/SAF2007-60827
info:eu-repo/grantAgreement/ES/2PN/SAF2007-31093
info:eu-repo/grantAgreement/ES/3PN/SAF2010-16427
info:eu-repo/semantics/openAccess
© Elsevier http://dx.doi.org/10.1016/j.drugalcdep.2011.09.027
Elsevier
oai:repositori.upf.edu:10230/233522020-06-17T10:48:46Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Polymorphisms in GSTT1, GSTZ1, AND CYP2E1, disinfection by-products, and risk of bladder cancer in Spain
Cantor, Kenneth P
Villanueva Belmonte, Cristina
Silverman, Debra T.
Figueroa, Jonine D.
Real, Francisco X.
García Closas, Montserrat
Malats i Riera, Núria
Chanock, Stephen J.
Yeager, Meredith
Tardón, Adonina
García Closas, Reina
Serra, Consol
Carrato, Alfredo
Castaño Vinyals, Gemma
Samanic, Claudine
Rothman, Nathaniel
Kogevinas, Manolis
Background: Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water.Objectives: In this study we investigated the combined influence of DBP exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based case–control study in Spain. Methods: Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms. Results: THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8–1.8), 1.8 (1.1–2.9), and 1.8 (0.9–3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/– versus GSTT1 null (pinteraction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (pinteraction = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (pinteraction = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7–3.5), 3.4 (1.4–8.2), and 5.9 (1.8–19.0), respectively. Conclusions: Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated.
2010
info:eu-repo/semantics/article
Cantor KP, Villanueva CM, Silverman DT, Figueroa JD, Real FX, Garcia-Closas M et al. Polymorphisms in GSTT1, GSTZ1, AND CYP2E1, disinfection by-products, and risk of bladder cancer in Spain. Environmental Health Perspectives. 2010;118(11):1545-50. DOI: 10.1289/ehp.1002206
0091-6765
http://hdl.handle.net/10230/23352
http://dx.doi.org/10.1289/ehp.1002206
eng
Environmental Health Perspectives. 2010;118(11):1545-50
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233542020-06-17T10:53:11Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Prenatal organochlorine compound exposure, rapid weight gain, and overweight in infancy
Mendez, Michelle A.
García Esteban, Raquel
Guxens Junyent, Mònica
Vrijheid, Martine
Kogevinas, Manolis
Goñi, Fernando
Fochs, Silvia
Sunyer Deu, Jordi
Background: Although it has been hypothesized that fetal exposure to endocrine-disrupting chemicals may increase obesity risk, empirical data are limited, and it is uncertain how early in life any effects may begin. Objectives: We explored whether prenatal exposure to several organochlorine compounds (OCs) is associated with rapid growth in the first 6 months of life and body mass index (BMI) later in infancy. Methods: Data come from the INMA (Infancia y Medio-Ambiente) Child and Environment birth cohort in Spain, which recruited 657 women in early pregnancy. Rapid growth during the first 6 months was defined as a change in weight-for-age z-scores > 0.67, and elevated BMI at 14 months, as a z-score ≥ the 85th percentile. Generalized linear models were used to estimate the risk of rapid growth or elevated BMI associated with 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), hexachlorobenzene, β-hexachlorohexane, and polychlorinated biphenyls in first-trimester maternal serum. Results: After multivariable adjustment including other OCs, DDE exposure above the first quartile was associated with doubling of the risk of rapid growth among children of normal-weight (BMI < 25 kg/m2), but not overweight, mothers. DDE was also associated with elevated BMI at 14 months (relative risk per unit increase in log DDE = 1.50; 95% confidence interval, 1.11–2.03). Other OCs were not associated with rapid growth or elevated BMI after adjustment. Conclusions: In this study we found prenatal DDE exposure to be associated with rapid weight gain in the first 6 months and elevated BMI later in infancy, among infants of normal-weight mothers. More research exploring the potential role of chemical exposures in early-onset obesity is needed.
2011
info:eu-repo/semantics/article
Mendez MA, Garcia-Esteban R, Guxens M, Vrijheid M, Kogevinas M, Goni F, Fochs S et al. Prenatal organochlorine compound exposure, rapid weight gain, and overweight in infancy. Environmental Health Perspectives. 2011;119(2):272-8. DOI: 10.1289/ehp.1002169
0091-6765
http://hdl.handle.net/10230/23354
http://dx.doi.org/10.1289/ehp.1002169
eng
Environmental Health Perspectives. 2011;119(2): 272-8
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233552020-06-17T10:55:32Zcom_10230_6237com_10230_5542com_10230_23115com_10230_20719col_10230_6238col_10230_23132col_10230_22498
Residential exposure to outdoor air pollution during pregnancy and anthropometric measures at birth in a multicenter cohort in Spain
Estarlich, Marisa
Ballester Díez, Ferran
Fernández Somoano, Ana
Aguilera Jiménez, Inmaculada, 1977-
Lertxundi, Aitana
Llop, Sabrina
Freire, Carmen
Tardón, Adonina
Basterrechea, Mikel
Sunyer Deu, Jordi
Iñiguez, Carmen
Background: A growing body of research suggests that prenatal exposure to air pollution may be harmful to fetal development. We assessed the association between exposure to air pollution during pregnancy and anthropometric measures at birth in four areas within the Spanish Children’s Health and Environment (INMA) mother and child cohort study. Methods: Exposure to ambient nitrogen dioxide (NO2) and benzene was estimated for the residence of each woman (n = 2,337) for each trimester and for the entire pregnancy. Outcomes included birth weight, length, and head circumference. The association between residential outdoor air pollution exposure and birth outcomes was assessed with linear regression models controlled for potential confounders. We also performed sensitivity analyses for the subset of women who spent more time at home during pregnancy. Finally, we performed a combined analysis with meta-analysis techniques. Results: In the combined analysis, an increase of 10 µg/m3 in NO2 exposure during pregnancy was associated with a decrease in birth length of –0.9 mm [95% confidence interval (CI), –1.8 to –0.1 mm]. For the subset of women who spent ≥ 15 hr/day at home, the association was stronger (–0.16 mm; 95% CI, –0.27 to –0.04). For this same subset of women, a reduction of 22 g in birth weight was associated with each 10-µg/m3 increase in NO2 exposure in the second trimester (95% CI, –45.3 to 1.9). We observed no significant relationship between benzene levels and birth outcomes. Conclusions: NO2 exposure was associated with reductions in both length and weight at birth. This association was clearer for the subset of women who spent more time at home.
2011
info:eu-repo/semantics/article
Estarlich M, Ballester F, Aguilera I, Fernandez-Somoano A, Lertxundi A, Llop S et al. Residential exposure to outdoor air pollution during pregnancy and anthropometric measures at birth in a multicenter cohort in Spain. Environmental Health Perspectives. 2011;119(9):1333-8. DOI: 10.1289/ehp.1002918
0091-6765
http://hdl.handle.net/10230/23355
http://dx.doi.org/10.1289/ehp.1002918
eng
Environmental Health Perspectives. 2011;119(9):1333-8
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233562020-06-17T10:58:04Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Climate extremes and the length of gestation
Dadvand, Payam
Basagaña Flores, Xavier
Sartini, Claudio
Figueras, Francesc
Vrijheid, Martine
De Nazelle, Audrey
Sunyer Deu, Jordi
Nieuwenhuijsen, Mark J.
Background: Although future climate is predicted to have more extreme heat conditions, the available evidence on the impact of these conditions on pregnancy length is very scarce and inconclusive. Objectives: We investigated the impact of maternal short-term exposure to extreme ambient heat on the length of pregnancy. Methods: This study was based on a cohort of births that occurred in a major university hospital in Barcelona during 2001–2005. Three indicators of extreme heat conditions based on 1-day exposure to an unusually high heat–humidity index were applied. Each mother was assigned the measures made by the meteorological station closest to maternal residential postcodes. A two-stage analysis was developed to quantify the change in pregnancy length after maternal exposure to extreme heat conditions adjusted for a range of covariates. The second step was repeated for lags 0 (delivery date) to 6 days. Results: We included data from 7,585 pregnant women in our analysis. We estimated a 5-day reduction in average gestational age at delivery after an unusually high heat–humidity index on the day before delivery. Conclusion: Extreme heat was associated with a reduction in the average gestational age of children delivered the next day, suggesting an immediate effect of this exposure on pregnant women. Further studies are required to confirm our findings in different settings.
2011
info:eu-repo/semantics/article
Dadvand P, Basagana X, Sartini C, Figueras F, Vrijheid M, de Nazelle A et al. Climate extremes and the length of gestation. Environmental Health Perspectives. 2011;119(10):1449-53. DOI: 10.1289/ehp.1003241
0091-6765
http://hdl.handle.net/10230/23356
http://dx.doi.org/10.1289/ehp.1003241
eng
Environmental Health Perspectives. 2011;119(10):1449-53
info:eu-repo/grantAgreement/ES/3PN/JCI2011-09937
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233582020-06-18T07:16:20Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Exposure to trihalomethanes through different water uses and birth weight, small for gestational age, and preterm delivery in Spain
Villanueva Belmonte, Cristina
Gracia Lavedan, Esther
Ibarluzea, Jesús
Marina, Loreto Santa
Ballester Díez, Ferran
Llop, Sabrina
Tardón, Adonina
Fernandez, Mariana F.
Freire, Carmen
Goñi, Fernando
Basagaña Flores, Xavier
Kogevinas, Manolis
Grimalt Obrador, Joan
Sunyer Deu, Jordi
Background: Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive. Objective: We assessed exposure to trihalomethanes (THMs) during pregnancy through different water uses and evaluated the association with birth weight, small for gestational age (SGA), low birth weight (LBW), and preterm delivery. Methods: Mother–child cohorts set up in five Spanish areas during the years 2000–2008 contributed data on water ingestion, showering, bathing, and swimming in pools. We ascertained residential THM levels during pregnancy periods through ad hoc sampling campaigns (828 measurements) and regulatory data (264 measurements), which were modeled and combined with personal water use and uptake factors to estimate personal uptake. We defined outcomes following standard definitions and included 2,158 newborns in the analysis. Results: Median residential THM ranged from 5.9 μg/L (Valencia) to 114.7 μg/L (Sabadell), and speciation differed across areas. We estimated that 89% of residential chloroform and 96% of brominated THM uptakes were from showering/bathing. The estimated change of birth weight for a 10% increase in residential uptake was –0.45 g (95% confidence interval: –1.36, 0.45 g) for chloroform and 0.16 g (–1.38, 1.70 g) for brominated THMs. Overall, THMs were not associated with SGA, LBW, or preterm delivery. Conclusions: Despite the high THM levels in some areas and the extensive exposure assessment, results suggest that residential THM exposure during pregnancy driven by inhalation and dermal contact routes is not associated with birth weight, SGA, LBW, or preterm delivery in Spain.
2011
info:eu-repo/semantics/article
Villanueva CM, Gracia-Lavedan E, Ibarluzea J, Marina LS, Ballester F, Llop S et al. Exposure to trihalomethanes through different water uses and birth weight, small for gestational age, and preterm delivery in Spain. Environ Health Perspect. 2011;119(12):1824-30. DOI: 10.1289/ehp.1002425
0091-6765
http://hdl.handle.net/10230/23358
http://dx.doi.org/10.1289/ehp.1002425
eng
Environmental Health Perspectives. 2011;119(12):1824-30
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233592020-06-18T07:18:32Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Prenatal exposure to residential air pollution and infant mental development: modulation by antioxidants and detoxification factors
Guxens Junyent, Mònica
Aguilera Jiménez, Inmaculada, 1977-
Ballester Díez, Ferran
Estarlich, Marisa
Fernández Somoano, Ana
Lertxundi, Aitana
Lertxundi, Nerea
Mendez, Michelle A.
Tardón, Adonina
Vrijheid, Martine
Sunyer Deu, Jordi
INMA (Infancia y Medio Ambiente) Project
Background: Air pollution effects on children’s neurodevelopment have recently been suggested to occur most likely through the oxidative stress pathway. Objective: We aimed to assess whether prenatal exposure to residential air pollution is associated with impaired infant mental development, and whether antioxidant/detoxification factors modulate this association. Methods: In the Spanish INfancia y Medio Ambiente (INMA; Environment and Childhood) Project, 2,644 pregnant women were recruited during their first trimester. Nitrogen dioxide (NO2) and benzene were measured with passive samplers covering the study areas. Land use regression models were developed for each pollutant to predict average outdoor air pollution levels for the entire pregnancy at each residential address. Maternal diet was obtained at first trimester through a validated food frequency questionnaire. Around 14 months, infant mental development was assessed using Bayley Scales of Infant Development. Results: Among the 1,889 children included in the analysis, mean exposure during pregnancy was 29.0 μg/m3 for NO2 and 1.5 μg/m3 for benzene. Exposure to NO2 and benzene showed an inverse association with mental development, although not statistically significant, after adjusting for potential confounders [β (95% confidence interval) = –0.95 (–3.90, 1.89) and –1.57 (–3.69, 0.56), respectively, for a doubling of each compound]. Stronger inverse associations were estimated for both pollutants among infants whose mothers reported low intakes of fruits/vegetables during pregnancy [–4.13 (–7.06, –1.21) and –4.37 (–6.89, –1.86) for NO2 and benzene, respectively], with little evidence of associations in the high-intake group (interaction p-values of 0.073 and 0.047). Inverse associations were also stronger in non-breast-fed infants and infants with low maternal vitamin D, but effect estimates and interactions were not significant. Conclusions: Our findings suggest that prenatal exposure to residential air pollutants may adversely affect infant mental development, but potential effects may be limited to infants whose mothers report low antioxidant intakes.
2012
info:eu-repo/semantics/article
Guxens M, Aguilera I, Ballester F, Estarlich M, Fernandez-Somoano A, Lertxundi A et al. Prenatal exposure to residential air pollution and infant mental development: modulation by antioxidants and detoxification factors. Environ Health Perspect. 2012;120(1):144-9. DOI: 10.1289/ehp.1103469
0091-6765
http://hdl.handle.net/10230/23359
http://dx.doi.org/10.1289/ehp.1103469
eng
Environmental Health Perspectives. 2012;120(1):144-9
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233612021-07-21T07:48:58Zcom_10230_23115com_10230_5542col_10230_23132
Discrepancies in Composition and Biological Effects of Different Formulations of Chondroitin Sulfate
Martel-Pelletier, Johanne
Farran Díaz Cano, Aina
Montell, Eulàlia
Vergés, Josep
Pelletier, Jean-Pierre
Osteoarthritis is a common, progressive joint disease, and treatments generally aim for symptomatic improvement. However, SYmptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOAs) not only reduce joint pain, but slow structural disease progression. One such agent is chondroitin sulfate-a complex, heterogeneous polysaccharide. It is extracted from various animal cartilages, thus has a wide range of molecular weights and different amounts and patterns of sulfation. Chondroitin sulfate has an excellent safety profile, and although various meta-analyses have concluded that it has a beneficial effect on symptoms and structure, others have concluded little or no benefit. This may be due, at least partly, to variations in the quality of the chondroitin sulfate used for a particular study. Chondroitin sulfate is available as pharmaceutical- and nutraceutical-grade products, and the latter have great variations in preparation, composition, purity and effects. Moreover, some products contain a negligible amount of chondroitin sulfate and among samples with reasonable amounts, in vitro testing showed widely varying effects. Of importance, although some showed anti-inflammatory effects, others demonstrated weak effects, and some instances were even pro-inflammatory. This could be related to contaminants, which depend on the origin, production and purification process. It is therefore vitally important that only pharmaceutical-grade chondroitin sulfate be used for treating osteoarthritis patients
2015
info:eu-repo/semantics/article
Martel-Pelletier J, Farran A, Montell E, Vergés J, Pelletier J-P. Discrepancies in Composition and Biological Effects of Different Formulations of Chondroitin Sulfate. Molecules. 2015; 20(3):4277-89. doi: 10.3390/molecules20034277.
1420-3049
http://hdl.handle.net/10230/23361
http://dx.doi.org/10.3390/molecules20034277
eng
Molecules. 2015;20(3):4277-89
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
MDPI
oai:repositori.upf.edu:10230/233632020-06-04T09:47:00Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Metabolic abnormalities in Williams-Beuren syndrome
Palacios Verdú, María Gabriela, 1983-
Segura Puimedon, Maria, 1985-
Borralleras Fumaña, Cristina, 1988-
Flores, Raquel
Campo Casanelles, Miguel del, 1966-
Campuzano Uceda, María Victoria
Pérez Jurado, Luis Alberto
BACKGROUND: Williams-Beuren syndrome (WBS, OMIM-194050) is a neurodevelopmental disorder with multisystemic manifestations caused by a 1.55-1.83 Mb deletion at 7q11.23 including 26-28 genes. Reported endocrine and metabolic abnormalities include transient hypercalcaemia of infancy, subclinical hypothyroidism in ∼30% of children and impaired glucose tolerance in ∼75% of adult individuals. The purpose of this study was to further study metabolic alterations in patients with WBS, as well as in several mouse models, to establish potential candidate genes. METHODS: We analysed several metabolic parameters in a cohort of 154 individuals with WBS (data available from 69 to 151 cases per arameter), as well as in several mouse models with complete and partial deletions of the orthologous WBS locus, and searched for causative genes and potential modifiers. RESULTS: Triglyceride plasma levels were significantly decreased in individuals with WBS while cholesterol levels were slightly decreased compared with controls. Hyperbilirubinemia, mostly unconjugated, was found in 18.3% of WBS cases and correlated with subclinical hypothyroidism and hypotriglyceridemia, suggesting common pathogenic mechanisms. Haploinsufficiency at MLXIPL and increased penetrance for hypomorphic alleles at the UGT1A1 gene promoter might underlie the lipid and bilirubin alterations. Other disturbances included increased protein and iron levels, as well as the known subclinical hypothyroidism and glucose intolerance. CONCLUSIONS: Our results show that several unreported biochemical alterations, related to haploinsufficiency for specific genes at 7q11.23, are relatively common in WBS. The early diagnosis, follow-up and management of these metabolic disturbances could prevent long-term complications in this disorder.
2015
info:eu-repo/semantics/article
Palacios-Verdu MG, Segura-Puimedon M, Borralleras C, Flores R, Del Campo M, Campuzano V. et al. Metabolic abnormalities in Williams–Beuren syndrome. J Med Genet. 2015;52:248-55. DOI: 10.1136/jmedgenet-2014-102713
0022-2593
http://hdl.handle.net/10230/23363
http://dx.doi.org/10.1136/jmedgenet-2014-102713
eng
Journal of Medical Genetics. 2015;52:248-55
info:eu-repo/grantAgreement/ES/3PN/SAF2012-40036
info:eu-repo/semantics/openAccess
© BMJ Publishing Group http://dx.doi.org/[doi: 10.1136/jmedgenet-2014-102713
BMJ
oai:repositori.upf.edu:10230/233672020-06-18T07:23:19Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Prenatal concentrations of polychlorinated biphenyls, DDE, and DDT and overweight in children: a prospective birth cohort study
Valvi, Damaskini, 1983-
Mendez, Michelle A.
Martínez Muriano, David
Grimalt Obrador, Joan
Torrent Quetglas, Maties
Sunyer Deu, Jordi
Vrijheid, Martine
Background: Recent experimental evidence suggests that prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase postnatal obesity risk and that these effects may be sex or diet dependent. Objectives: We explored whether prenatal organochlorine compound (OC) concentrations [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT)] were associated with overweight at 6.5 years of age and whether child sex or fat intakes modified these associations. Methods: We studied 344 children from a Spanish birth cohort established in 1997–1998. Overweight at 6.5 years was defined as a body mass index (BMI) z-score ≥ 85th percentile of the World Health Organization reference. Cord blood OC concentrations were measured and treated as categorical variables (tertiles). Children’s diet was assessed by food frequency questionnaire. Relative risks (RRs) were estimated using generalized linear models. Results: After multivariable adjustment, we found an increased RR of overweight in the third tertile of PCB exposure [RR = 1.70; 95% confidence interval (CI): 1.09, 2.64] and the second tertile of DDE exposure (RR = 1.67; 95% CI: 1.10, 2.55), but no association with DDT exposure in the population overall. Associations between overweight and PCB and DDE concentrations were strongest in girls (p-interaction between 0.01 and 0.28); DDT was associated with overweight only in boys. For DDT we observed stronger associations in children with fat intakes at or above compared with below the median, but this interaction was not significant (p-interaction > 0.05). Conclusions: This study suggests that prenatal OC exposures may be associated with overweight in children and that sex and high-fat intake may influence susceptibility.
2012
info:eu-repo/semantics/article
Valvi D, Mendez MA, Martinez D, Grimalt JO, Torrent M, Sunyer J, Vrijheid M. Prenatal concentrations of polychlorinated biphenyls, DDE, and DDT and overweight in children: a prospective birth cohort study. Environ Health Perspect. 2012;120(3):451-7. DOI: 10.1289/ehp.1103862
0091-6765
http://hdl.handle.net/10230/23367
http://dx.doi.org/10.1289/ehp.1103862
eng
Environmental Health Perspectives. 2012;120(3):451-7
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233682020-06-18T07:25:14Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132col_10230_8581
Surrounding greenness and pregnancy outcomes in four Spanish birth cohorts
Dadvand, Payam
Sunyer Deu, Jordi
Basagaña Flores, Xavier
Ballester Díez, Ferran
Lertxundi, Aitana
Fernández Somoano, Ana
Estarlich, Marisa
García Esteban, Raquel
Mendez, Michelle A.
Nieuwenhuijsen, Mark J.
Background: Green spaces have been associated with improved physical and mental health; however, the available evidence on the impact of green spaces on pregnancy is scarce. Objectives: We investigated the association between surrounding greenness and birth weight, head circumference, and gestational age at delivery. Methods: This study was based on 2, 393 singleton live births from four Spanish birth cohorts (Asturias, Gipuzkoa, Sabadell, and Valencia) located in two regions of the Iberian Peninsula with distinct climates and vegetation patterns (2003–2008). We defined surrounding greenness as average of satellite-based Normalized Difference Vegetation Index (NDVI) (Landsat 4–5 TM data at 30 m × 30 m resolution) during 2007 in buffers of 100 m, 250 m, and 500 m around each maternal place of residence. Separate linear mixed models with adjustment for potential confounders and a random cohort effect were used to estimate the change in birth weight, head circumference, and gestational age for 1-interquartile range increase in surrounding greenness. Results: Higher surrounding greenness was associated with increases in birth weight and head circumference [adjusted regression coefficients (95% confidence interval) of 44.2 g (20.2 g, 68.2 g) and 1.7 mm (0.5 mm, 2.9 mm) for an interquartile range increase in average NDVI within a 500-m buffer] but not gestational age. These findings were robust against the choice of the buffer size and the season of data acquisition for surrounding greenness, and when the analysis was limited to term births. Stratified analyses indicated stronger associations among children of mothers with lower education, suggesting greater benefits from surrounding greenness. Conclusions: Our findings suggest a beneficial impact of surrounding greenness on measures of fetal growth but not pregnancy length.
2012
info:eu-repo/semantics/article
Dadvand P, Sunyer J, Basagana X, Ballester F, Lertxundi A, Fernandez-Somoano A et al. Surrounding greenness and pregnancy outcomes in four Spanish birth cohorts. Environ Health Perspect. 2012;120(10):1481-7. DOI: 10.1289/ehp.1205244
0091-6765
http://hdl.handle.net/10230/23368
http://dx.doi.org/10.1289/ehp.1205244
eng
Environmental Health Perspectives. 2012;120(10):1481-7
info:eu-repo/grantAgreement/EC/FP7/282996
info:eu-repo/grantAgreement/ES/3PN/JCI2011-09937
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233692020-06-18T07:27:50Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132col_10230_8581
Birth weight, head circumference, and prenatal exposure to acrylamide from maternal diet: The European prospective mother-child study (NewGeneris)
Sunyer Deu, Jordi
Pedersen, Marie
Stedingk, Hans von
Botsivali, Maria
Agramunt, Silvia
Alexander, Jan
Brunborg, Gunnar
Chatzi, Leda
Fleming, Sarah
Fthenou, Eleni
Granum, Berit
Gutzkow, Kristine B.
Hardie, Laura J.
Knudsen, Lisbeth E.
Kyrtopoulos, Sosterios A.
Mendez, Michelle A.
Merlo, Domenico Franco
Nielsen, Jeanette K.
Rydberg, Per
Segerbäck, Dan
Wright, John
Törnqvist, Margareta
Kleinjans, Jos C.
Kogevinas, Manolis
NewGeneris Consortium
Background: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. Objectives: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother–child study. Methods: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006–2010. Maternal diet was estimated through food-frequency questionnaires. Results: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was –132 g (95% CI: –207, –56); the corresponding difference for head circumference was –0.33 cm (95% CI: –0.61, –0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. Conclusions: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. If confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.
2012
info:eu-repo/semantics/article
Pedersen M, von Stedingk H, Botsivali M, Agramunt S, Alexander J, Brunborg G et al. Birth weight, head circumference, and prenatal exposure to acrylamide from maternal diet: The European prospective mother-child study (NewGeneris). Environ Health Perspect. 2012;120(12):1739-45. DOI: 10.1289/ehp.1205327
0091-6765
http://hdl.handle.net/10230/23369
http://dx.doi.org/10.1289/ehp.1205327
eng
Environmental Health Perspectives. 2012; 120(12): 1739-1745
info:eu-repo/grantAgreement/EC/FP6/016320
info:eu-repo/grantAgreement/EC/FP6/036224
info:eu-repo/grantAgreement/ES/3PN/JCI2011-09479
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233702020-06-18T07:30:20Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Polybrominated diphenyl ethers (PBDEs) in breast milk and neuropsychological development in infants
Gascon Merlos, Mireia, 1984-
Fort, Marta
Martínez, David
Carsin, Anne-Elie
Forns i Guzman, Joan, 1981-
Grimalt Obrador, Joan
Santa Marina, Loreto
Lertxundi, Nerea
Sunyer Deu, Jordi
Vrijheid, Martine
Background: There is increasing interest in the potential effects of polybrominated diphenyl ethers (PBDEs) on children’s neuropsychological development, but only a few small studies have evaluated such effects. Objectives: Our goal was to examine the association between PBDE concentrations in colostrum and infant neuropsychological development and to assess the influence of other persistent organic pollutants (POPs) on such association. Methods: We measured concentrations of PBDEs and other POPs in colostrum samples of 290 women recruited in a Spanish birth cohort. We tested children for mental and psychomotor development with the Bayley Scales of Infant Development at 12–18 months of age. We analyzed the sum of the seven most common PBDE congeners (BDEs 47, 99, 100, 153, 154, 183, 209) and each congener separately. Results: Increasing Σ7PBDEs concentrations showed an association of borderline statistical significance with decreasing mental development scores (β per log ng/g lipid = –2.25; 95% CI: –4.75, 0.26). BDE-209, the congener present in highest concentrations, appeared to be the main congener responsible for this association (β = –2.40, 95% CI: –4.79, –0.01). There was little evidence for an association with psychomotor development. After adjustment for other POPs, the BDE-209 association with mental development score became slightly weaker (β = –2.10, 95% CI: –4.66, 0.46). Conclusions: Our findings suggest an association between increasing PBDE concentrations in colostrum and a worse infant mental development, particularly for BDE-209, but require confirmation in larger studies. The association, if causal, may be due to unmeasured BDE-209 metabolites, including OH-PBDEs (hydroxylated PBDEs), which are more toxic, more stable, and more likely to cross the placenta and to easily reach the brain than BDE-209.
2012
info:eu-repo/semantics/article
Gascon M, Fort M, Martinez D, Carsin AE, Forns J, Grimalt JO et al. Polybrominated diphenyl ethers (PBDEs) in breast milk and neuropsychological development in infants. Environ Health Perspect. 2012;120(12):1760-5. DOI: 10.1289/ehp.1205266
0091-6765
http://hdl.handle.net/10230/23370
http://dx.doi.org/10.1289/ehp.1205266
eng
Environmental Health Perspectives. 2012;120(12):1760-5
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233712020-06-18T07:31:35Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Early-life exposure to outdoor air pollution and respiratory health, ear infections, and eczema in infants from the INMA study
Aguilera Jiménez, Inmaculada, 1977-
Pedersen, Marie
García Esteban, Raquel
Ballester Díez, Ferran
Basterrechea, Mikel
Esplugues, Ana
Fernández Somoano, Ana
Lertxundi, Aitana
Tardón, Adonina
Sunyer Deu, Jordi
Background: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health. Objectives: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12–18 months of age in a Spanish birth cohort of 2,199 infants. Methods: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO2) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations. Results: A 10-µg/m3 increase in average NO2 during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO2 were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO2, the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period. Conclusions: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.
2013
info:eu-repo/semantics/article
Aguilera I, Pedersen M, Garcia-Esteban R, Ballester F, Basterrechea M, Esplugues A et al. Early-life exposure to outdoor air pollution and respiratory health, ear infections, and eczema in infants from the INMA study. Environ Health Perspect. 2013;121(3):387-92. DOI: 10.1289/ehp.1205281
0091-6765
http://hdl.handle.net/10230/23371
http://dx.doi.org/10.1289/ehp.1205281
eng
Environmental Health Perspectives. 2013;121(3):387-92
info:eu-repo/grantAgreement/ES/3PN/JCI2011-09479
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233732020-06-18T07:34:52Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132col_10230_8581
Bulky dna adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother-child study (NewGeneris)
Pedersen, Marie
Sunyer Deu, Jordi
Mendez, Michelle A.
Espinosa, Aina
Agramunt, Silvia
Kogevinas, Manolis
Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy. Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006–2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires. Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of –129 g (95% CI: –233, –25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (–248 g; 95% CI: –405, –92 g) compared with those with high intake (–58 g; 95% CI: –206, 90 g). Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.
2013
info:eu-repo/semantics/article
Pedersen M, Schoket B, Godschalk RW, Wright J, von Stedingk H, Tornqvist M et al. Bulky dna adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother-child study (NewGeneris). Environ Health Perspect. 2013;121(10):1200-6. DOI: 10.1289/ehp.1206333
0091-6765
http://hdl.handle.net/10230/23373
http://dx.doi.org/10.1289/ehp.1206333
eng
Environmental Health Perspectives. 2013;121(10):1200-6
info:eu-repo/grantAgreement/EC/FP6/016320
info:eu-repo/grantAgreement/EC/FP6/036224
info:eu-repo/grantAgreement/ES/3PN/JCI2011-09479
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233742021-07-21T07:51:17Zcom_10230_23115com_10230_5542col_10230_23132
Emotion processing in joint hypermobility: A potential link to the neural bases of anxiety and related somatic symptoms in collagen anomalies
Mallorquí Bagué, Joaquim
Bulbena Vilarrasa, Antonio
Roé -Vellvé, Núria
Hoekzema, Elseline
Carmona, Susanna
Barba-Müller, Erika
Fauquet, Jordi
Pailhez, Guillem
Vilarroya, Óscar
BACKGROUND: Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disorders, fibromyalgia, irritable bowel syndrome and temporomandibular joint disorder. However, the neural underpinnings of these associations still remain unclear. This study explored brain responses to facial visual stimuli with emotional cues using fMRI techniques in general population with different ranges of hypermobility. METHODS: Fifty-one non-clinical volunteers (33 women) completed state and trait anxiety questionnaire measures, were assessed with a clinical examination for hypermobility (Beighton system) and performed an emotional face processing paradigm during functional neuroimaging. RESULTS: Trait anxiety scores did significantly correlate with both state anxiety and hypermobility scores. BOLD signals of the hippocampus did positively correlate with hypermobility scores for the crying faces versus neutral faces contrast in ROI analyses. No results were found for any of the other studied ROIs. Additionally, hypermobility scores were also associated with other key affective processing areas (i.e. the middle and anterior cingulate gyrus, fusiform gyrus, parahippocampal region, orbitofrontal cortex and cerebellum) in the whole brain analysis. CONCLUSIONS: Hypermobility scores are associated with trait anxiety and higher brain responses to emotional faces in emotion processing brain areas (including hippocampus) described to be linked to anxiety and somatic symptoms. These findings increase our understanding of emotion processing in people bearing this heritable variant of collagen and the mechanisms through which vulnerability to anxiety and somatic symptoms arises in this population.
2015
info:eu-repo/semantics/article
Mallorquí-Bagué N, Bulbena A, Roé-Vellvé N, Hoekzema E, Carmona S, Barba-Müller E. et al. Emotion processing in joint hypermobility: A potential link to the neural bases of anxiety and related somatic symptoms in collagen anomalies. Eur Psychiatry. 2015 Feb 12;30(4):454-8. doi: 10.1016/.
0924-9338
http://hdl.handle.net/10230/23374
http://dx.doi.org/10.1016/j.eurpsy.2015.01.004
eng
European Psychiatry. 2015 Feb 12;30(4):454-8
info:eu-repo/semantics/openAccess
© Elsevier http://dx.doi.org/10.1016/j.eurpsy.2015.01.004I
Elsevier Masson
oai:repositori.upf.edu:10230/234462021-07-13T09:09:28Zcom_10230_23115com_10230_5542col_10230_23132
Temperature Thresholds in Assessment of the Clinical Course of Acquired Cold Contact Urticaria: A Prospective Observational One-year Study
Martínez Escala, M. Estela
Curto Barredo, Laia
Carnero Sánchez, Luïsa
Pujol Vallverdú, Ramon Maria
Giménez Arnau, Anna Maria
Cold contact urticaria is the second most common subtype of physical urticaria. Cold stimulation standardized tests are mandatory to confirm the diagnosis. The aim of this study is to define the utility of determining thresholds (critical time and temperature) in assessment of the clinical course of typical acquired cold contact urticaria. Nineteen adult patients (10 women and 9 men; mean age 45 years) were included in the study and the diagnosis was confirmed with the ice-cube test and TempTest 3.0. Patients were treated continuously for 1 year with 20 mg/day rupatadine (anti-H1). Thresholds measurements were made before and after treatment. Improvements in temperature and critical time thresholds were found in the study sample, demonstrating the efficacy of continuous treatment with rupatadine. In most cases association with a clinical improvement was found. We propose an algorithm for the management of acquired cold contact urticaria based on these results
2015
info:eu-repo/semantics/article
Martinez-Escala ME, Curto-Barredo L, Carnero L, Pujol RM, Giménez-Arnau AM. Temperature Thresholds in Assessment of the Clinical Course of Acquired Cold Contact Urticaria: A Prospective Observational One-year Study. Acta Derm Venereol. 2015 Mar 9;95(2):278-82. doi: 10.2340/00015555-1918.
0001-5555
http://hdl.handle.net/10230/23446
http://dx.doi.org/10.2340/00015555-1918
eng
Acta Dermato-Venereologica. 2015 Mar 9;95(2):278-82
info:eu-repo/semantics/openAccess
© 2015 The Authors. doi: 10.2340/00015555-1918 © 2015 Acta Dermato-Venereologica. ISSN 0001-5555
Society for Publication of Acta Dermato-Venereologica
oai:repositori.upf.edu:10230/233752021-07-21T07:52:40Zcom_10230_23115com_10230_5542col_10230_23132
Prevalence of anti-rubella, anti-measles and anti-mumps IgG antibodies in neonates and pregnant women in Catalonia (Spain) in 2013: susceptibility to measles increased from 2003 to 2013.
Plans, Pedro
Ory, Fernando de
Campins, Magda
Álvarez, Elena
Payà, Toni
Guisasola, Eulalia
Compte, Carme
Vellbé, Kilian
Sánchez, Consol
Lozano, María José
Aran, Iris
Bonmatí, Alexandra
Carreras Collado, Ramón
Jané, Mireia
Cabero, Lluís
Non-immune neonates and non-immune pregnant women are at risk of developing rubella, measles and mumps infections, including congenital rubella syndrome. We describe the seroepidemiology of measles, mumps and rubella (MMR) in neonates and pregnant women in Catalonia (Spain). Anti-rubella, anti-measles and anti-mumps serum IgG titres were assessed using enzyme-linked immunosorbent assay (ELISA) tests in 353 cord blood samples from neonates of a representative sample of pregnant women obtained in 2013. The prevalence of protective antibody titres in neonates was 96 % for rubella IgG (≥8 IU/ml), 90 % for measles IgG (>300 IU/ml) and 84 % for mumps IgG (>460 EU/ml). Slightly lower prevalences of protective IgG titres, as estimated from the cord blood titres, were found in pregnant women: 95 % for rubella IgG, 89 % for measles IgG and 81 % for mumps IgG. The anti-measles and anti-mumps IgG titres and the prevalences of protective IgG titres against measles and mumps increased significantly (p < 0.001) with maternal age. The prevalence of protective anti-measles IgG titres decreased by 7 % [odds ratio (OR) = 0.15, p < 0.001), the prevalence of protective anti-rubella IgG titres increased by 3 % (OR = 1.80, p < 0.05) and the MMR vaccination coverage (during childhood) in pregnant women increased by 54 % (OR = 2.09, p < 0.001) from 2003 to 2013. We recommend to develop an MMR prevention programme in women of childbearing age based on mass MMR vaccination or MMR screening and vaccination of susceptible women to increase immunity levels against MMR. PMID: 25666082 [PubMed - as supplied by publisher]
2015
info:eu-repo/semantics/article
Plans P, de Ory F, Campins M, Álvarez E, Payà T, Guisasola E. et al. Prevalence of anti-rubella, anti-measles and anti-mumps IgG antibodies in neonates and pregnant women in Catalonia (Spain) in 2013: susceptibility to measles increased from 2003 to 2013. Eur J Clin Microbiol Infect Dis. 2015 Jun;34(6):1161-71.
0934-9723
http://hdl.handle.net/10230/23375
http://dx.doi.org/10.1007/s10096-015-2339-4
eng
European Journal of Clinical Microbiology & Infectious Diseases. 2015 Jun;34(6):1161-71
info:eu-repo/semantics/openAccess
© Springer (The original publication is available at www.springerlink.com)
Springer Verlag
oai:repositori.upf.edu:10230/233832023-07-06T08:39:16Zcom_10230_23115com_10230_5542col_10230_23132
HER2 as a target in invasive urothelial carcinoma
Bellmunt Molins, Joaquim, 1959-
Werner, Lillian
Bamias, Aristotle
Fay, André P.
Park, Rachel S.
Riester, Markus
Selvarajah, Shamini
Barletta, Justine A.
Berman, David M.
Muga, Silvia de
Salido, Marta
Gallardo, Enrique
Rojo, Federico
Guancial, Elizabeth A.
Bambury, Richard
Mullane, Stephanie A.
Choueiri, Toni K.
Loda, Massimo
Stack, Edward
Rosenberg, Jonathan E.
We evaluated primary tumors from two cohorts, Spain (N = 111) and Greece (N = 102), for patients who were treated with platinum-based chemotherapy. Patients were tested for HER2 status (IHC score of 3+ or FISH ratio of ≥2.2) by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), DNA copy number, mRNA expression, and mutation status in patients with metastatic urothelial carcinoma (UC), and its impact on survival. ERBB2 mutation was determined by hotspot sequencing. mRNA expression was assessed using NanoString counting. Association of overall survival (OS) and HER2 status was assessed by a Cox regression model. NIH-3T3 cells containing HER2 V777L were assessed for growth, invasion, and HER2 kinase activation. In all, 22% of Spanish and 4% of Greek cohorts had 3+ HER2 staining by IHC. FISH amplification was identified in 20% of Spanish and 4% of Greek cohorts. Kappa coefficient between FISH and IHC was 0.47. HER2 status was not associated with OS in univariate (Spanish P = 0.34; Greek P = 0.11) or multivariate (Spanish P = 0.49; Greek P = 0.12) analysis. HER2-positive tumors expressed higher levels of HER2 mRNA than HER2-negative tumors (P < 0.001). HER2 mutations (V777L and L755S) were identified in two (2%) patients. In vitro analysis of V777L results in transformation of NIH-3T3 cells, leading to increased growth, invasion on soft agar, and HER2 kinase constitutive activation. In summary, HER2 overexpression or amplification in the primary tumor did not predict OS in patients with metastatic UC. HER2 positivity rates can differ between different populations. Further trials in genomically screened patients are needed to assess HER2-targeted therapies in UC
2015
info:eu-repo/semantics/article
Bellmunt J, Werner L, Bamias A, Fay AP, Park RS, Riester M, et al. HER2 as a target in invasive urothelial carcinoma. Cancer Med. 2015 Feb 26;4(6):844-52. doi: 10.1002/cam4.432.
2045-7634
http://hdl.handle.net/10230/23383
http://dx.doi.org/10.1002/cam4.432
eng
Cancer Medicine. 2015 Feb 26;4(6):844-52
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
Wiley
oai:repositori.upf.edu:10230/233912020-06-18T07:40:30Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132col_10230_8581
Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE Project
MacIntyre, Elaina A
Gascon Merlos, Mireia, 1984-
Sunyer Deu, Jordi
Cirach, Marta
Nieuwenhuijsen, Mark J.
Heinrich, Joachim
Background: Few studies have investigated traffic-related air pollution as a risk factor for respiratory infections during early childhood. Objectives: We aimed to investigate the association between air pollution and pneumonia, croup, and otitis media in 10 European birth cohorts—BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), MAAS (United Kingdom), PIAMA (the Netherlands), and four INMA cohorts (Spain)—and to derive combined effect estimates using meta-analysis. Methods: Parent report of physician-diagnosed pneumonia, otitis media, and croup during early childhood were assessed in relation to annual average pollutant levels [nitrogen dioxide (NO2), nitrogen oxide (NOx), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, PM10, PM2.5–10 (coarse PM)], which were estimated using land use regression models and assigned to children based on their residential address at birth. Identical protocols were used to develop regression models for each study area as part of the ESCAPE project. Logistic regression was used to calculate adjusted effect estimates for each study, and random-effects meta-analysis was used to calculate combined estimates. Results: For pneumonia, combined adjusted odds ratios (ORs) were elevated and statistically significant for all pollutants except PM2.5 (e.g., OR = 1.30; 95% CI: 1.02, 1.65 per 10-μg/m3 increase in NO2 and OR = 1.76; 95% CI: 1.00, 3.09 per 10-μg/m3 PM10). For otitis media and croup, results were generally null across all analyses except for NO2 and otitis media (OR = 1.09; 95% CI: 1.02, 1.16 per 10-μg/m3). Conclusion: Our meta-analysis of 10 European birth cohorts within the ESCAPE project found consistent evidence for an association between air pollution and pneumonia in early childhood, and some evidence for an association with otitis media.
2014
info:eu-repo/semantics/article
MacIntyre EA, Gehring U, Molter A, Fuertes E, Klumper C, Kramer U et al. Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE Project. Environ Health Perspect. 2014;122(1):107-13. DOI: 10.1289/ehp.1306755
0091-6765
http://hdl.handle.net/10230/23391
http://dx.doi.org/10.1289/ehp.1306755
eng
Environmental Health Perspectives. 2014;122(1):107-13
info:eu-repo/grantAgreement/EC/FP7/211250
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233922020-06-18T07:41:59Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132col_10230_8581
Micronuclei in cord blood lymphocytes and associations with biomarkers of exposure to carcinogens and hormonally active factors, gene polymorphisms, and gene expression: the NewGeneris cohort
Merlo, Domenico Franco
Agramunt, Silvia
Kogevinas, Manolis
Pedersen, Marie
Delft, Joost H.M. van
NewGeneris Consortium
Background: Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure–outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG–DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.
2014
info:eu-repo/semantics/article
Merlo DF, Agramunt S, Anna L, Besselink H, Botsivali M, Brady NJ et al. Micronuclei in cord blood lymphocytes and associations with biomarkers of exposure to carcinogens and hormonally active factors, gene polymorphisms, and gene expression: the NewGeneris cohort. Environ Health Perspect. 2014;122(2):193-200. DOI: 10.1289/ehp.1206324
0091-6765
http://hdl.handle.net/10230/23392
http://dx.doi.org/10.1289/ehp.1206324
eng
Environmental Health Perspectives. 2014;122(2):193-200
info:eu-repo/grantAgreement/EC/FP6/016320
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233932020-06-18T07:42:54Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Association of long-term exposure to traffic-related air pollution with blood pressure and hypertension in an adult population-based cohort in Spain (the REGICOR study)
Foraster Pulido, Maria, 1984-
Basagaña Flores, Xavier
Aguilera Jiménez, Inmaculada, 1977-
Rivera, Marcela, 1982-
Agis, David
Bouso, Laura
Deltell, Alexandre
Marrugat de la Iglesia, Jaume
Ramos, Rafel
Sunyer Deu, Jordi
Vila, Joan
Elosua Llanos, Roberto
Künzli, Nino
Background: Long-term exposure to traffic-related air pollution may increase blood pressure (BP) and induce hypertension. However, evidence supporting these associations is limited, and they may be confounded by exposure to traffic noise and biased due to inappropriate control for use of BP-lowering medications. Objectives: We evaluated the associations of long-term traffic-related air pollution with BP and prevalent hypertension, adjusting for transportation noise and assessing different methodologies to control for BP-lowering medications. Methods: We measured systolic (SBP) and diastolic BP (DBP) at baseline (years 2003–2005) in 3,700 participants, 35–83 years of age, from a population-based cohort in Spain. We estimated home outdoor annual average concentrations of nitrogen dioxide (NO2) with a land-use regression model. We used multivariate linear and logistic regression. Results: A 10-μg/m3 increase in NO2 levels was associated with 1.34 mmHg (95% CI: 0.14, 2.55) higher SBP in nonmedicated individuals, after adjusting for transportation noise. Results were similar in the entire population after adjusting for medication, as commonly done, but weaker when other methods were used to account for medication use. For example, when 10 mmHg were added to the measured SBP levels of medicated participants, the association was β = 0.78 (95% CI: –0.43, 2.00). NO2 was not associated with hypertension. Associations of NO2 with SBP and DBP were stronger in participants with cardiovascular disease, and the association with SBP was stronger in those exposed to high traffic density and traffic noise levels ≥ 55 dB(A). Conclusions: We observed a positive association between long-term exposure to NO2 and SBP, after adjustment for transportation noise, which was sensitive to the methodology used to account for medication.
2014
info:eu-repo/semantics/article
Foraster M, Basagana X, Aguilera I, Rivera M, Agis D, Bouso L et al. Association of long-term exposure to traffic-related air pollution with blood pressure and hypertension in an adult population-based cohort in Spain (the REGICOR study). Environ Health Perspect. 2014;122(4):404-11. DOI: 10.1289/ehp.1306497
0091-6765
http://hdl.handle.net/10230/23393
http://dx.doi.org/10.1289/ehp.1306497
eng
Environmental Health Perspectives. 2014;122(4):404-11
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233942020-11-19T12:18:03Zcom_10230_6237com_10230_5542com_10230_20719com_10230_20545com_10230_23115col_10230_6238col_10230_22498col_10230_22227col_10230_23132col_10230_8581
The Human Early-Life Exposome (HELIX): project rationale and design
Vrijheid, Martine
Robinson, Oliver
Basagaña Flores, Xavier
Bustamante Pineda, Mariona
Casas Sanahuja, Maribel
Estivill, Xavier, 1955-
van Gent, Diana
González Ruiz, Juan Ramón
Júlvez Calvo, Jordi
Kogevinas, Manolis
Sabidó Aguadé, Eduard, 1981-
Sunyer Deu, Jordi
Nieuwenhuijsen, Mark J.
Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome. Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project. Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.
2014
info:eu-repo/semantics/article
Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P et al. The human early-life exposome (HELIX): project rationale and design. Environ Health Perspect. 2014;122(6):535-44. DOI: 10.1289/ehp.1307204
0091-6765
http://hdl.handle.net/10230/23394
http://dx.doi.org/10.1289/ehp.1307204
eng
Environmental Health Perspectives. 2014;122(6):535-44
info:eu-repo/grantAgreement/EC/FP7/308333
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences (NIEHS)
oai:repositori.upf.edu:10230/233952020-06-18T07:45:56Zcom_10230_6237com_10230_5542com_10230_20545com_10230_23115col_10230_6238col_10230_22227col_10230_23132
Genome-wide analysis of wild-type epstein-barr virus genomes derived from healthy individuals of the 1000 genomes project
Santpere Baró, Gabriel, 1981-
Darre, Fleur
Blanco, Soledad
Alcami, Antonio
Villoslada, Pablo
Albà Soler, Mar
Navarro i Cuartiellas, Arcadi, 1969-
Most people in the world (∼90%) are infected by the Epstein–Barr virus (EBV), which establishes itself permanently in B cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis, and different types of cancer. So far, only seven complete EBV strains have been described, all of them coming from donors presenting EBV-related diseases. To perform a detailed comparative genomic analysis of EBV including, for the first time, EBV strains derived from healthy individuals, we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project. As strain B95-8 was used to transform B cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains. After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV. By mapping the natural EBV reads into the EBV reference genome (NC007605), we constructed nearly complete wild-type viral genomes from three individuals. Adding them to the five disease-derived EBV genomic sequences available in the literature, we performed an in-depth comparative genomic analysis. We found that latency genes harbor more nucleotide diversity than lytic genes and that six out of nine latency-related genes, as well as other genes involved in viral attachment and entry into host cells, packaging, and the capsid, present the molecular signature of accelerated protein evolution rates, suggesting rapid host–parasite coevolution.
2014
info:eu-repo/semantics/article
Santpere G, Darre F, Blanco S, Alcami A, Villoslada P, Alba MM, Navarro A. Genome-wide analysis of wild-type epstein-barr virus genomes derived from healthy individuals of the 1000 genomes project. Genome Biol Evol. 2014;6(4):846-60. DOI: 10.1093/gbe/evu054
1759-6653
http://hdl.handle.net/10230/23395
http://dx.doi.org/10.1093/gbe/evu054
eng
Genome Biology and Evolution. 2014;6(4):846-60
info:eu-repo/grantAgreement/ES/3PN/BFU2009-13409
info:eu-repo/grantAgreement/ES/3PN/BFU2012-38236
http://creativecommons.org/licenses/by-nc/3.0/
info:eu-repo/semantics/openAccess
© Santpere G, Darre F, Blanco S, Alcami A, Villoslada P, Alba MM, Navarro A [2014]. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution License
Oxford University Press
oai:repositori.upf.edu:10230/233962020-06-18T07:47:04Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
A fast and accurate method to detect allelic genomic imbalances underlying mosaic rearrangements using SNP array data
González Ruiz, Juan Ramón
Rodríguez Santiago, Benjamín
Cáceres, Alejandro
Pique Regi, Roger
Rothman, Nathaniel
Chanock, Stephen J.
Armengol i Dulcet, Lluís
Pérez Jurado, Luis Alberto
Background: Mosaicism for copy number and copy neutral chromosomal rearrangements has been recently identified as a relatively common source of genetic variation in the normal population. However its prevalence is poorly defined since it has been only studied systematically in one large-scale study and by using non optimal ad-hoc SNP array data analysis tools, uncovering rather large alterations (> 1 Mb) and affecting a high proportion of cells. Here we propose a novel methodology, Mosaic Alteration Detection-MAD, by providing a software tool that is effective for capturing previously described alterations as wells as new variants that are smaller in size and/or affecting a low percentage of cells. Results: The developed method identified all previously known mosaic abnormalities reported in SNP array data obtained from controls, bladder cancer and HapMap individuals. In addition MAD tool was able to detect new mosaic variants not reported before that were smaller in size and with lower percentage of cells affected. The performance of the tool was analysed by studying simulated data for different scenarios. Our method showed high sensitivity and specificity for all assessed scenarios. Conclusions: The tool presented here has the ability to identify mosaic abnormalities with high sensitivity and specificity. Our results confirm the lack of sensitivity of former methods by identifying new mosaic variants not reported in previously utilised datasets. Our work suggests that the prevalence of mosaic alterations could be higher than initially thought. The use of appropriate SNP array data analysis methods would help in defining the human genome mosaic map.
2011
info:eu-repo/semantics/article
Gonzalez JR, Rodriguez-Santiago B, Caceres A, Pique-Regi R, Rothman N, Chanock SJ et al. A fast and accurate method to detect allelic genomic imbalances underlying mosaic rearrangements using SNP array data. BMC Bioinformatics. 2011;12:166. DOI: 10.1186/1471-2105-12-166
1471-2105
http://hdl.handle.net/10230/23396
http://dx.doi.org/10.1186/1471-2105-12-166
eng
BMC Bioinformatics. 2011;12:166
info:eu-repo/grantAgreement/ES/3PN/MTM2008-02457
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© Gonzalez JR, Rodriguez-Santiago B, Caceres A, Pique-Regi R, Rothman N, Chanock SJ, Armengol L, Perez-Jurado LA. Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0/
BioMed Central
oai:repositori.upf.edu:10230/234002021-04-14T10:50:43Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132col_10230_8581
Cross-national epidemiology of DSM-IV major depressive episode
Alonso Caballero, Jordi
Bromet, Evelyn J.
Kessler, Ronald C.
Background: Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low- to middle-income countries in the World Mental Health Survey Initiative. Methods: Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults. Results: The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2:1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low- to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed. Conclusions: MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.
2011
info:eu-repo/semantics/article
Bromet E, Andrade LH, Hwang I, Sampson NA, Alonso J, de Girolamo G et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Medicine. 2011;9:90. DOI: 10.1186/1741-7015-9-90
1741-7015
http://hdl.handle.net/10230/23400
http://dx.doi.org/10.1186/1741-7015-9-90
eng
BMC Medicine. 2011;9:90
info:eu-repo/grantAgreement/EC/FP7/2004123
info:eu-repo/grantAgreement/ES/1PN/SAF2000-158-CE
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© Bromet E, Andrade LH, Hwang I, Sampson NA, Alonso J, de Girolamo G et al. Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0/
BioMed Central
oai:repositori.upf.edu:10230/234142020-06-18T08:08:18Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
The effect of perceived discrimination on the health of immigrant workers in Spain
Agudelo Suárez, Andrés A
Ronda-Pérez, Elena
Gil González, Diana
Vives Cases, Carmen
García, Ana María
Ruiz Frutos, Carlos
Felt, Emily
Benavides, Fernando G. (Fernando García)
Background: Discrimination is an important determinant of health inequalities, and immigrants may be more vulnerable to certain types of discrimination than the native-born. This study analyses the relationship between immigrants' perceived discrimination and various self-reported health indicators. Methods: A cross-sectional survey was conducted (2008) amongst a non-random sample of 2434 immigrants from Ecuador, Morocco, Romania and Colombia in four Spanish cities: Barcelona, Huelva, Madrid and Valencia. A factorial analysis of variables revealed three dimensions of perceived discrimination (due to immigrant status, due to physical appearance, and workplace-related). The association of these dimensions with self-rated health, mental health (GHQ-12), change in self-rated health between origin and host country, and other self-reported health outcomes was analysed. Logistic regression was used adjusting for potential confounders (aOR-95%CI). Subjects with worsening self-reported health status potentially attributable to perceived discrimination was estimated (population attributable proportion, PAP %). Results: 73.3% of men and 69.3% of women immigrants reported discrimination due to immigrant status. Moroccans showed the highest prevalence of perceived discrimination. Immigrants reporting discrimination were at significantly higher risk of reporting health problems than those not reporting discrimination. Workplace-related discrimination was associated with poor mental health (aOR 2.97 95%CI 2.45-3.60), and the worsening of self-rated health (aOR 2.20 95%CI 1.73- 2.80). 40% (95% CI 24-53) PAP of those reporting worse self-rated health could be attributable to discrimination due to immigrant status. Conclusions: Discrimination may constitute a risk factor for health in immigrant workers in Spain and could explain some health inequalities among immigrant populations in Spanish society.
2011
info:eu-repo/semantics/article
Agudelo-Suarez AA, Ronda-Perez E, Gil-Gonzalez D, Vives-Cases C, Garcia AM, Ruiz-Frutos C et al. The effect of perceived discrimination on the health of immigrant workers in Spain. BMC Public Health. 2011;11:652. DOI: 10.1186/1471-2458-11-652
1471-2458
http://hdl.handle.net/10230/23414
http://dx.doi.org/10.1186/1471-2458-11-652
eng
BMC Public Health. 2011;11:652
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© Agudelo-Suarez AA, Ronda-Perez E, Gil-Gonzalez D, Vives-Cases C, Garcia AM, Ruiz-Frutos C, Felt E, Benavides FG. Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0/
BioMed Central
oai:repositori.upf.edu:10230/234152020-02-25T11:23:58Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Social factors related to the clinical severity of influenza cases in Spain during the A (H1N1) 2009 virus pandemic
Mayoral, José María
Alonso Caballero, Jordi
Garin Boronat, Olatz, 1979-
Herrador, Zaida
Astray, Jenaro
Baricot, Maretva
Castilla, Jesús
Cantón, Rafael
Castro, Ady
Delgado Rodríguez, Miguel
Ferri, Alicia
Godoy i García, Pere
González Candela, Fernando
Martín, Vicente
Pumarola, Tomás
Quintana, José María
Soldevila, Núria
Tramames, Sonia
Domínguez García, Àngela
CIBERESP Cases and Controls in Pandemic Influenza Working Group
Background: During the 2009 influenza pandemic, a change in the type of patients most often affected by influenza was observed. The objective of this study was to assess the role of individual and social determinants in hospitalizations due to influenza A (H1N1) 2009 infection. Methods: We studied hospitalized patients (cases) and outpatients (controls) with confirmed influenza A (H1N1) 2009 infection. A standardized questionnaire was used to collect data. Variables that might be related to the hospitalization of influenza cases were compared by estimation of the odds ratio (OR) and 95% confidence intervals (CI) and the variables entered into binomial logistic regression models. Results: Hospitalization due to pandemic A (H1N1) 2009 influenza virus infections was associated with non-Caucasian ethnicity (OR: 2.18, 95% CI 1.17 − 4.08), overcrowding (OR: 2.84, 95% CI 1.20 − 6.72), comorbidity and the lack of previous preventive information (OR: 2.69, 95% CI: 1.50 − 4.83). Secondary or higher education was associated with a lower risk of hospitalization (OR 0.56, 95% CI: 0.36 − 0.87). Conclusions: In addition to individual factors such as comorbidity, other factors such as educational level, ethnicity or overcrowding were associated with hospitalization due to A (H1N1) 2009 influenza virus infections.
2013
info:eu-repo/semantics/article
Mayoral JM, Alonso J, Garin O, Herrador Z, Astray J, Baricot M et al. Social factors related to the clinical severity of influenza cases in Spain during the A (H1N1) 2009 virus pandemic. BMC Public Health. 2013; 13: 118. DOI 10.1186/1471-2458-13-118
1471-2458
http://hdl.handle.net/10230/23415
http://dx.doi.org/10.1186/1471-2458-13-118
eng
BMC Public Health. 2013; 13: 118
http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
© Mayoral JM, Alonso J, Garin O, Herrador Z, Astray J, Baricot M et al. Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0/
BioMed Central
oai:repositori.upf.edu:10230/234162018-01-24T08:08:24Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132
Large-scale international validation of the ADO index in subjects with COPD: an individual subject data analysis of 10 cohorts
Puhan, Milo A.
Hansel, Nadia N
Sobradillo, Patricia
Enright, Paul
Lange, Peter
Hickson, DeMarc
Menezes, Ana M
Riet, Gerben ter
Held, Ulrike
Domingo i Salvany, Antònia
Mosenifar, Zab
Antó i Boqué, Josep Maria
Moons, Karel G M
Kessels, Alphons
García Aymerich, Judith
International COPD Cohorts Collaboration Working Group
Background: Little evidence on the validity of simple and widely applicable tools to predict mortality in patients with chronic obstructive pulmonary disease (COPD) exists. Objective: To conduct a large international study to validate the ADO index that uses age, dyspnoea and FEV1 to predict 3-year mortality and to update it in order to make prediction of mortality in COPD patients as generalisable as possible. Design: Individual subject data analysis of 10 European and American cohorts (n=13 914). Setting: Population-based, primary, secondary and tertiary care. Patients: COPD GOLD stages I–IV. Measurements: We validated the original ADO index. We then obtained an updated ADO index in half of our cohorts to improve its predictive accuracy, which in turn was validated comprehensively in the remaining cohorts using discrimination, calibration and decision curve analysis and a number of sensitivity analyses. Results: 1350 (9.7%) of all subjects with COPD (60% male, mean age 61 years, mean FEV1 66% predicted) had died at 3 years. The original ADO index showed high discrimination but poor calibration (p<0.001 for difference between predicted and observed risk). The updated ADO index (scores from 0 to 14) preserved excellent discrimination (area under curve 0.81, 95% CI 0.80 to 0.82) but showed much improved calibration with predicted 3-year risks from 0.7% (95% CI 0.6% to 0.9%, score of 0) to 64.5% (61.2% to 67.7%, score of 14). The ADO index showed higher net benefit in subjects at low-to-moderate risk of 3-year mortality than FEV1 alone. Interpretation: The updated 15-point ADO index accurately predicts 3-year mortality across the COPD severity spectrum and can be used to inform patients about their prognosis, clinical trial study design or benefit harm assessment of medical interventions.
2012
info:eu-repo/semantics/article
Puhan MA, Hansel NN, Sobradillo P, Enright P, Lange P, Hickson D et al. Large-scale international validation of the ADO index in subjects with COPD: an individual subject data analysis of 10 cohorts. BMJ Open. 2012; 2: e002152. DOI 10.1136/bmjopen-2012-002152
2044-6055
http://hdl.handle.net/10230/23416
http://dx.doi.org/10.1136/bmjopen-2012-002152
eng
BMJ Open. 2012; 2: e002152
http://creativecommons.org/licenses/by-nc/2.0/
info:eu-repo/semantics/openAccess
© Puhan MA, Hansel NN, Sobradillo P, Enright P, Lange P, Hickson D et al. "This article was published in BMJ Open following peer review and can also be viewed on the journal’s website at http://bmjopen.bmj.com"/nCreative Commons Attribution Non-Commercial License
BMJ Publishing Group
oai:repositori.upf.edu:10230/234172019-01-22T11:55:52Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Epidemiology and genetics of common mental disorders in the general population: the PEGASUS-Murcia project
Navarro Mateu, Fernando
Tormo, M.J.
Vilagut Saiz, Gemma, 1975-
Alonso Caballero, Jordi
Ruíz Merino, G.
Escamez, T.
Salmerón, Diego
Judez, J.
Martínez, S.
Navarro, Carmen
Background: Multidisciplinary collaboration between clinicians, epidemiologists, neurogeneticists and statisticians on research projects has been encouraged to improve our knowledge of the complex mechanisms underlying the aetiology and burden of mental disorders. The PEGASUS-Murcia (Psychiatric Enquiry to General Population in Southeast Spain-Murcia) project was designed to assess the prevalence of common mental disorders and to identify the risk and protective factors, and it also included the collection of biological samples to study the gene–environmental interactions in the context of the World Mental Health Survey Initiative. Methods and analysis: The PEGASUS-Murcia project is a new cross-sectional face-to-face interview survey based on a representative sample of non-institutionalised adults in the Region of Murcia (Mediterranean Southeast, Spain). Trained lay interviewers used the latest version of the computer-assisted personal interview of the Composite International Diagnostic Interview (CIDI 3.0) for use in Spain, specifically adapted for the project. Two biological samples of buccal mucosal epithelium will be collected from each interviewed participant, one for DNA extraction for genomic and epigenomic analyses and the other to obtain mRNA for gene expression quantification. Several quality control procedures will be implemented to assure the highest reliability and validity of the data. This article describes the rationale, sampling methods and questionnaire content as well as the laboratory methodology. Ethics and dissemination: Informed consent will be obtained from all participants and a Regional Ethics Research Committee has approved the protocol. Results will be disseminated in peer-reviewed publications and presented at the national and the international conferences. Discussion: Cross-sectional studies, which combine detailed personal information with biological data, offer new and exciting opportunities to study the gene–environmental interactions in the aetiology of common mental disorders in representative samples of the general population. A collaborative multidisciplinary research approach offers the potential to advance our knowledge of the underlying complex interactions and this opens the field for further innovative study designs in psychiatric epidemiology
2013
info:eu-repo/semantics/article
Navarro-Mateu F, Tormo MJ, Vilagut G, Alonso J, Ruiz-Merino G, Escamez T et al. Epidemiology and genetics of common mental disorders in the general population: the PEGASUS-Murcia project. BMJ Open. 2013; 3: e004035. DOI 10.1136/bmjopen-2013-004035
2044-6055
http://hdl.handle.net/10230/23417
http://dx.doi.org/10.1136/bmjopen-2013-004035
eng
BMJ Open. 2013; 3: e004035
http://creativecommons.org/licenses/by-nc/3.0/
info:eu-repo/semantics/openAccess
© Navarro-Mateu F, Tormo MJ, Vilagut G, Alonso J, Ruiz-Merino G, Escamez T et al. "This article was published in BMJ Open following peer review and can also be viewed on the journal's website at http://bmjopen.bmj.com". Creative Commons Attribution Non-Commercial License
BMJ Publishing Group
oai:repositori.upf.edu:10230/234182023-07-06T11:21:33Zcom_10230_6237com_10230_5542com_10230_20719com_10230_23115col_10230_6238col_10230_22498col_10230_23132col_10230_8581
Positive health effects of the natural outdoor environment in typical populations in different regions in Europe (PHENOTYPE): a study programme protocol
Nieuwenhuijsen, Mark J.
Antó i Boqué, Josep Maria
Basagaña Flores, Xavier
Cirach, Marta
Dadvand, Payam
Donaire González, David
García Aymerich, Judith
Júlvez Calvo, Jordi
Triguero Mas, Margarita, 1985-
Gražulevičienė, Regina
Introduction: Growing evidence suggests that close contact with nature brings benefits to human health and well-being, but the proposed mechanisms are still not well understood and the associations with health remain uncertain. The Positive Health Effects of the Natural Outdoor environment in Typical Populations in different regions in Europe (PHENOTYPE) project investigates the interconnections between natural outdoor environments and better human health and well-being. Aims and methods: The PHENOTYPE project explores the proposed underlying mechanisms at work (stress reduction/restorative function, physical activity, social interaction, exposure to environmental hazards) and examines the associations with health outcomes for different population groups. It implements conventional and new innovative high-tech methods to characterise the natural environment in terms of quality and quantity. Preventive as well as therapeutic effects of contact with the natural environment are being covered. PHENOTYPE further addresses implications for land-use planning and green space management. The main innovative part of the study is the evaluation of possible short-term and long-term associations of green space and health and the possible underlying mechanisms in four different countries (each with quite a different type of green space and a different use), using the same methodology, in one research programme. This type of holistic approach has not been undertaken before. Furthermore there are technological innovations such as the use of remote sensing and smartphones in the assessment of green space. Conclusions: The project will produce a more robust evidence base on links between exposure to natural outdoor environment and human health and well-being, in addition to a better integration of human health needs into land-use planning and green space management in rural as well as urban areas.
2014
info:eu-repo/semantics/article
Nieuwenhuijsen MJ, Kruize H, Gidlow C, Andrusaityte S, Antó JM, Basagana X et al. Positive health effects of the natural outdoor environment in typical populations in different regions in Europe (PHENOTYPE): a study programme protocol. BMJ Open. 2014; 4: e004951. DOI 10.1136/bmjopen-2014-004951
2044-6055
http://hdl.handle.net/10230/23418
http://dx.doi.org/10.1136/bmjopen-2014-004951
eng
BMJ Open. 2014; 4: e004951
info:eu-repo/grantAgreement/EC/FP7/282996
http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
© Nieuwenhuijsen MJ, Kruize H, Gidlow C, Andrusaityte S, Antó JM, Basagana X et al. "This article was published in BMJ Open following peer review and can also be viewed on the journal’s website at http://bmjopen.bmj.com". Creative Commons Attribution Non-Commercial License
BMJ Publishing Group
oai:repositori.upf.edu:10230/237162024-02-27T12:17:30Zcom_10230_23115com_10230_5542col_10230_23132
HIV-infection impact on clinical-biological features and outcome of diffuse large B-cell lymphoma treated with R-CHOP in the combination antiretroviral therapy era
Baptista, Maria Joao
García, Olga
Morgades, Mireia
González, Eva
Miralles, Eva
López Guillermo, Armando
Abella Monreal, Eugenia
Moreno, Miriam
Sancho, Juan Manuel
Feliu, Evarist
Ribera, Josep Maria
Navarro, José Tomás
OBJECTIVE: Since the introduction of combination antiretroviral therapy (cART) patients with HIV-related diffuse large B-cell lymphoma (DLBCL) show better control of immunosuppression, which may have an impact on the characteristics and prognosis of the disease. We aimed to compare the clinical presentation and prognosis of patients with HIV-related and HIV-unrelated DLBCL treated with R-CHOP in the cART era. METHODS AND DESIGN:: Eighty-one HIV-infected patients included in a Spanish multicentre trial were compared with 84 HIV-uninfected patients diagnosed in a Spanish institution in the same period all treated with R-CHOP. RESULTS: HIV-infected patients had a worse performance status, more frequent B-symptoms, and higher Ann-Arbor stages than HIV-uninfected patients, with similar frequency of extranodal involvement. The complete response (CR) rate of patients with high tumor burden was not different in HIV-infected and HIV-uninfected patients. Patients with HIV-related DLBCL showed a worse overall survival (OS) (5-year OS: 56 vs. 74%) but a similar disease-free survival (DFS) (5-year DFS: 84 vs. 73%). In the subgroup of patients with high tumor, the results regarding survival were similar to the whole series. Previous AIDS-defining illness was the strongest negative prognostic factor for OS in HIV-infected patients. CONCLUSION: In the cART era, HIV-related DLBCL still presents more aggressive features than HIV-unrelated DLBCL, and has a worse OS despite having a similar DFS. Prevention of HIV-related complications is essential to achieve outcomes comparable with HIV-uninfected patients with DLBCL.
2015
info:eu-repo/semantics/article
Baptista MJ, Garcia O, Morgades M, Gonzalez-Barca E, Miralles P, Lopez-Guillermo A. HIV-infection impact on clinical-biological features and outcome of diffuse large B-cell lymphoma treated with R-CHOP in the combination antiretroviral therapy era. AIDS. 2015; 29(7): 811-8. doi: 10.1097/QAD.0000000000000624
0269-9370
http://hdl.handle.net/10230/23716
http://dx.doi.org/10.1097/QAD.0000000000000624
eng
AIDS. 2015;29(7):811-8
info:eu-repo/semantics/openAccess
(c) Lippincott, Williams & Wilkins. Baptista MJ, Garcia O, Morgades M, Gonzalez-Barca E, Miralles P, Lopez-Guillermo A. HIV-infection impact on clinical-biological features and outcome of diffuse large B-cell lymphoma treated with R-CHOP in the combination antiretroviral therapy era. AIDS. 2015; 29(7): 811-8. doi: 10.1097/QAD.0000000000000624
Lippincott, Williams & Wilkins
oai:repositori.upf.edu:10230/234302020-06-04T08:18:38Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Induced effects of sodium ions on dopaminergic G-protein coupled receptors
Selent, Jana
Sanz, Ferran
Pastor Maeso, Manuel
De Fabritiis, Gianni
G-protein coupled receptors, the largest family of proteins in the human genome, are involved in many complex signal transduction pathways, typically activated by orthosteric ligand binding and subject to allosteric modulation. Dopaminergic receptors, belonging to the class A family of G-protein coupled receptors, are known to be modulated by sodium ions from an allosteric binding site, although the details of sodium effects on the receptor have not yet been described. In an effort to understand these effects, we performed microsecond scale all-atom molecular dynamics simulations on the dopaminergic D2 receptor, finding that sodium ions enter the receptor from the extracellular side and bind at a deep allosteric site (Asp2.50). Remarkably, the presence of a sodium ion at this allosteric site induces a conformational change of the rotamer toggle switch Trp6.48 which locks in a conformation identical to the one found in the partially inactive state of the crystallized human β2 adrenergic receptor. This study provides detailed quantitative information about binding of sodium ions in the D2 receptor and reports a possibly important sodium-induced conformational change for modulation of D2 receptor function.
2010
info:eu-repo/semantics/article
Selent J, Sanz F, Pastor M, de Fabritiis G. Induced effects of sodium ions on dopaminergic G-protein coupled receptors. PLoS Computational Biology. 2010;6(8):e1000884. DOI: 10.1371/journal.pcbi.1000884
1553-734X
http://hdl.handle.net/10230/23430
http://dx.doi.org/10.1371/journal.pcbi.1000884
eng
PLoS Computational Biology. 2010;6(8):e1000884
info:eu-repo/grantAgreement/ES/3PN/SAF2009-13609
info:eu-repo/grantAgreement/ES/3PN/FIS2008-01040
info:eu-repo/semantics/openAccess
© 2010 Selent et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/234512021-04-14T11:12:02Zcom_10230_23115com_10230_5542col_10230_23132col_10230_8581
Role of group 3 innate lymphoid cells in antibody production
Magri, Giuliana, 1978-
Cerutti, Andrea, 1965-
Innate lymphoid cells (ILCs) constitute a heterogeneous family of effector lymphocytes of the innate immune system that mediate lymphoid organogenesis, tissue repair, immunity and inflammation. The initial view that ILCs exert their protective functions solely during the innate phase of an immune response has been recently challenged by evidence indicating that ILCs shape adaptive immunity by establishing both contact-dependent and contact-independent interactions with multiple hematopoietic and non-hematopoietic cells, including B cells. Some of these interactions enhance antibody responses both systemically and at mucosal sites of entry
2015
info:eu-repo/semantics/article
Magri G, Cerutti A. Role of group 3 innate lymphoid cells in antibody production. Curr Opin Immunol. 2015 Apr;33:36-42. doi: 10.1016/j.coi.2015.01.008.
0952-7915
http://hdl.handle.net/10230/23451
http://dx.doi.org/10.1016/j.coi.2015.01.008
eng
Current Opinion in Immunology. 2015 Apr;33:36-42
info:eu-repo/grantAgreement/EC/FP7/294561
info:eu-repo/grantAgreement/ES/3PN/SAF2011-25241
info:eu-repo/semantics/openAccess
© Elsevier http://dx.doi.org/doi: 10.1016/j.coi.2015.01.008
Elsevier
oai:repositori.upf.edu:10230/234742020-06-04T09:29:56Zcom_10230_23115com_10230_5542com_10230_6237com_10230_20719col_10230_23132col_10230_6238col_10230_22498
IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans
Pearce, Neil E.
Zahm, Sheila Hoar
Andersen, Aage
Antó i Boqué, Josep Maria
Cardis, Elisabeth
Grimsrud, Tom K.
Kjaerheim, Kristina
Kogevinas, Manolis
Porta Serra, Miquel
Background: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups’ failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. Objectives: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed. Discussion: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health.
2015
info:eu-repo/semantics/article
Pearce NE, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, et al. ARC Monographs: 40 years of evaluating carcinogenic hazards to humans. Environ Health Perspect. 2015 Feb 24;123(6):[37 p.]. DOI: 10.1289/ehp.1409149
0091-6765
http://hdl.handle.net/10230/23474
http://dx.doi.org/10.1289/ehp.1409149
eng
Environ Health Perspect. 2015 Feb 24;123(6):[37 p.]
info:eu-repo/semantics/openAccess
Reproduced with permission from Environmental Health Perspectives
National Institute of Environmental Health Sciences
oai:repositori.upf.edu:10230/234582021-07-13T09:20:40Zcom_10230_23115com_10230_5542col_10230_23132
A European benchmarking system to evaluate in-hospital mortality rates in acute coronary syndrome: The EURHOBOP project.
Dégano, Irene R.
Subirana Cachinero, Isaac
Torre, Marina
Grau Magaña, Maria
Vila, Joan
Fusco, Danilo
Kirchberger, Inge
Ferrières, Jean
Malmivaara, Antti
Azevedo, Ana
Meisinger, Christa
Bongard, Vanina
Farmakis, Dimitrios
Davoli, Marina
Häkkinen, Unto
Araújo, Carla
Lekakis, John
Elosua Llanos, Roberto
Marrugat de la Iglesia, Jaume
BACKGROUND: Hospital performance models in acute myocardial infarction (AMI) are useful to assess patient management. While models are available for individual countries, mainly US, cross-European performance models are lacking. Thus, we aimed to develop a system to benchmark European hospitals in AMI and percutaneous coronary intervention (PCI), based on predicted in-hospital mortality. METHODS AND RESULTS: We used the EURopean HOspital Benchmarking by Outcomes in ACS Processes (EURHOBOP) cohort to develop the models, which included 11,631 AMI patients and 8276 acute coronary syndrome (ACS) patients who underwent PCI. Models were validated with a cohort of 55,955 European ACS patients. Multilevel logistic regression was used to predict in-hospital mortality in European hospitals for AMI and PCI. Administrative and clinical models were constructed with patient- and hospital-level covariates, as well as hospital- and country-based random effects. Internal cross-validation and external validation showed good discrimination at the patient level and good calibration at the hospital level, based on the C-index (0.736-0.819) and the concordance correlation coefficient (55.4%-80.3%). Mortality ratios (MRs) showed excellent concordance between administrative and clinical models (97.5% for AMI and 91.6% for PCI). Exclusion of transfers and hospital stays ≤1day did not affect in-hospital mortality prediction in sensitivity analyses, as shown by MR concordance (80.9%-85.4%). Models were used to develop a benchmarking system to compare in-hospital mortality rates of European hospitals with similar characteristics. CONCLUSIONS: The developed system, based on the EURHOBOP models, is a simple and reliable tool to compare in-hospital mortality rates between European hospitals in AMI and PCI.
2015
info:eu-repo/semantics/article
Dégano IR, Subirana I, Torre M, Grau M, Vila J, Fusco D. A European benchmarking system to evaluate in-hospital mortality rates in acute coronary syndrome: The EURHOBOP project. Int J Cardiol. 2015 Mar 1;182:509-16. doi: 10.1016/j.ijcard.2015.01.019
0167-5273
http://hdl.handle.net/10230/23458
http://dx.doi.org/10.1016/j.ijcard.2015.01.019
eng
International Journal of Cardiology 2015 Mar 1;182:509-16
info:eu-repo/semantics/openAccess
© Elsevier http://dx.doi.org/10.1016/j.ijcard.2015.01.019
Elsevier
oai:repositori.upf.edu:10230/234652021-07-13T09:28:00Zcom_10230_23115com_10230_5542col_10230_23132
Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial
Checa Vizcaíno, Miguel Angel
Brassesco, Mario
Sastre, Margalida
Gómez, Manuel
Herrero, Julio
Marque, Laura
Brassesco, Arturo
Espinós, Juan José
The aim of this study is to evaluate the feasibility and safety of random-start controlled ovarian hyperstimulation (COH) for emergency fertility preservation, regardless of the phase of the menstrual cycle. A self-controlled pilot clinical trial (NCT01385332) was performed in an acute-care teaching hospital and in two private reproductive centers in Barcelona, Spain. Eleven egg donors participated in the study. Two random-start gonadotropin-releasing hormone (GnRH) antagonist protocols were assessed in which ganirelix was initiated on either day 10 (protocol B) or on day 20 (protocol C) of the menstrual cycle and was continued until estradiol levels were below 60 pg/dL. These protocols were compared with a standard protocol (protocol A). The main outcome of interest was the number of metaphase 2 oocytes retrieved. Results from this study show that the number of mature oocytes retrieved was comparable across the different protocols (14.3±4.6 in the standard protocol versus 13.0±9.1 and 13.2±5.2 in protocols B and C, respectively; values expressed as mean ± standard deviation). The mean number of days needed for a GnRH antagonist to lower estradiol levels, as well as the ongoing pregnancy rates, were also similar when protocols B (stimulation in follicular phase) and C (stimulation on luteal phase) were compared with protocol A (standard stimulation). GnRH antagonists can be effectively used for random-start controlled ovarian hyperstimulation with an ovarian response similar to that of standard protocols, and the antagonists appear suitable for emergency fertility preservation in cancer patients
2015
info:eu-repo/semantics/article
Checa MA, Brassesco M, Sastre M, Gómez M, Herrero J, Marque L et al. Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial. Int J Womens Health. 2015; Feb 12(7):219-25. doi: 10.2147/IJWH.S66743.
1179-1411
http://hdl.handle.net/10230/23465
http://dx.doi.org/10.2147/IJWH.S66743
eng
International Journal of Women's Health. 2015;(7):219-25
http://creativecommons.org/licenses/by-nc/3.0/
info:eu-repo/semantics/openAccess
2015 Checa et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php
Dove Medical Press
oai:repositori.upf.edu:10230/234782021-07-13T10:04:35Zcom_10230_23115com_10230_5542col_10230_23132
Improved diagnosis of orthopedic implant-associated infection by inoculation of sonication fluid into blood culture bottles
Portillo, María Eugenia
Salvadó, Margarita
Trampuz, Andrej
Siverio, Ana
Alier Fabrego, Albert
Sorli Redó, M. Luisa
Martínez, Santos
Pérez, Daniel
Horcajada Gallego, Juan Pablo
Puig Verdié, Luís
Sonication improved the diagnosis of orthopedic implant-associated infections (OIAI). We investigated the diagnostic performance of sonication fluid inoculated into blood culture bottles in comparison with that of intraoperative tissue and sonication fluid cultures. Consecutive patients with removed orthopedic hardware were prospectively included and classified as having OIAI or aseptic failure (AF) according to standardized criteria. The diagnostic procedure included the collection of five intraoperative tissue cultures and sonication of the removed device, followed by conventional culture of the sonication fluid. Cultures were incubated for 7 days (aerobic) or 14 days (anaerobic). In addition, 10 ml of sonication fluid was inoculated into each aerobic and anaerobic BacT/Alert FAN blood culture bottle and incubated in the automated blood culture system for 5 days. Of 75 included patients, 39 had OIAI and 36 AF. The sensitivity of sonication fluid inoculated into blood culture bottles (100%) was higher than that of conventional sonication fluid (87%; P = 0.05) or intraoperative tissue cultures (59%; P < 0.01). Previous antibiotic therapy reduced the culture sensitivity of conventional sonication fluid to 77% and that of intraoperative tissue to 55%, while it remained 100% for blood culture-inoculated sonication fluid. The time to positivity was shorter in blood culture-inoculated sonication fluid, with detection of 72% of microorganisms after 1 day of incubation, than for intraoperative tissue and conventional sonication fluid cultures, with detection of 18% and 28% of microorganisms, respectively. In conclusion, compared to conventional sonication fluid and intraoperative tissue cultures, sonication fluid inoculated into blood culture bottles improved the diagnosis of OIAI and considerably reduced the time to culture positivity.
2015
info:eu-repo/semantics/article
Portillo ME, Salvadó M, Trampuz A, Siverio A, Alier A, Sorli L et al. Improved diagnosis of orthopedic implant-associated infection by inoculation of sonication fluid into blood culture bottles. J Clin Microbiol. 2015 May;53(5):1622-7. doi: 10.1128/JCM.03683-14. Epub 2015 Mar 4.
0095-1137
http://hdl.handle.net/10230/23478
http://dx.doi.org/10.1128/JCM.03683-14
eng
Journal of Clinical Microbiology. 2015 May;53(5):1622-7
info:eu-repo/semantics/openAccess
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
American Society for Microbiology
oai:repositori.upf.edu:10230/234842023-03-29T13:53:34Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation
Rodríguez, María Isabel
Peralta-Leal, Andreína
O'Valle, Francisco
Rodríguez-Vargas, José Manuel
González-Flores, Ariannys
Majuelos-Melguizo, Jara
López Muñoz, Laura
Serrano, Santiago
García de Herreros, Antonio
Rodríguez-Manzaneque, Juan Carlos
Fernández Montes, Rubén D.
del Moral, Raimundo G.
de Almodovar, José Mariano
Oliver, F. Javier
PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-β-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells.
2013
info:eu-repo/semantics/article
Rodriguez MI, Peralta-Leal A, O'Valle F, Rodriguez-Vargas JM, Gonzalez-Flores A, Majuelos-Melguizo J et al. PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation. PLoS Genetics. 2013;9(6):e1003531. DOI: 10.1371/journal.pgen.1003531
1553-7390
http://hdl.handle.net/10230/23484
http://dx.doi.org/10.1371/journal.pgen.1003531
eng
PLoS Genetics. 2013;9(6):e1003531
info:eu-repo/grantAgreement/ES/1PE/SAF2013-4889
info:eu-repo/grantAgreement/ES/3PN/SAF2009-13281
info:eu-repo/grantAgreement/ES/2PN/SAF2007-64597
info:eu-repo/grantAgreement/ES/2PN/SAF2006-01094
http://creativecommons.org/licenses/by/2.5/
info:eu-repo/semantics/openAccess
© Rodriguez MI, Peralta-Leal A, O'Valle F, Rodriguez-Vargas JM, Gonzalez-Flores A, Majuelos-Melguizo J et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution...(CC BY) (http://creativecommons.org/licenses/by/2.5/).
Public Library of Science (PLoS)
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Novel snail1 target proteins in human colon cancer identified by proteomic analysis
Larriba, María Jesús
Casado Vela, Juan
Pendás Franco, Natalia
Peña, Raúl
García de Herreros, Antonio
Berciano, María Teresa
Lafarga, Miguel
Casal, José Ignacio
Muñoz, Alberto
Background: The transcription factor Snail1 induces epithelial-to-mesenchymal transition (EMT), a process responsible for the acquisition of invasiveness during tumorigenesis. Several transcriptomic studies have reported Snail1-regulated genes in different cell types, many of them involved in cell adhesion. However, only a few studies have used proteomics as a tool for the characterization of proteins mediating EMT. Methodology/Principal Findings: We identified by proteomic analysis using 2D-DIGE electrophoresis combined with MALDI-TOF-TOF and ESI-linear ion trap mass spectrometry a number of proteins with variable functions whose expression is modulated by Snail1 in SW480-ADH human colon cancer cells. Validation was performed by Western blot and immunofluorescence analyses. Snail1 repressed several members of the 14-3-3 family of phosphoserine/phosphothreonine binding proteins and also the expression of the Proliferation-associated protein 2G4 (PA2G4) that was mainly localized at the nuclear Cajal bodies. In contrast, the expression of two proteins involved in RNA processing, the Cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and the Splicing factor proline/glutamine-rich (SFPQ), was higher in Snail1-expressing cells than in controls. The regulation of 14-3-3e, 14-3-3t, 14-3-3f and PA2G4 by Snail1 was reproduced in HT29 colon cancer cells. In addition, we found an inverse correlation between 14-3-3 s and Snail1 expression in human colorectal tumors. Conclusions/Significance: We have identified a set of novel Snail1 target proteins in colon cancer that expand the cellular processes affected by Snail1 and thus its relevance for cell function and phenotype.
2010
info:eu-repo/semantics/article
Larriba MJ, Casado-Vela J, Pendas-Franco N, Pena R, Herreros de AG, Berciano M et al. Novel snail1 target proteins in human colon cancer identified by proteomic analysis. PLoS ONE. 2010;5(4):e10221. DOI: 10.1371/journal.pone.0010221
1932-6203
http://hdl.handle.net/10230/23486
http://dx.doi.org/10.1371/journal.pone.0010221
eng
PLoS ONE. 2010;5(4):e10221
info:eu-repo/grantAgreement/ES/2PN/SAF2007-60341
info:eu-repo/grantAgreement/ES/2PN/BIO2006-07689
info:eu-repo/semantics/openAccess
© 2010 Larriba et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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oai:repositori.upf.edu:10230/234882021-04-14T10:49:50Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238col_10230_8581
Cross-national analysis of the associations between traumatic events and suicidal behavior: findings from the who world mental health surveys
Stein, Dan J.
Alonso Caballero, Jordi
Nock, Matthew K.
Background: Community and clinical data have suggested there is an association between trauma exposure and suicidal behavior (i.e., suicide ideation, plans and attempts). However, few studies have assessed which traumas are uniquely predictive of: the first onset of suicidal behavior, the progression from suicide ideation to plans and attempts, or the persistence of each form of suicidal behavior over time. Moreover, few data are available on such associations in developing countries. The current study addresses each of these issues. Methodology/Principal Findings: Data on trauma exposure and subsequent first onset of suicidal behavior were collected via structured interviews conducted in the households of 102,245 (age 18+) respondents from 21 countries participating in the WHO World Mental Health Surveys. Bivariate and multivariate survival models tested the relationship between the type and number of traumatic events and subsequent suicidal behavior. A range of traumatic events are associated with suicidal behavior, with sexual and interpersonal violence consistently showing the strongest effects. There is a dose-response relationship between the number of traumatic events and suicide ideation/attempt; however, there is decay in the strength of the association with more events. Although a range of traumatic events are associated with the onset of suicide ideation, fewer events predict which people with suicide ideation progress to suicide plan and attempt, or the persistence of suicidal behavior over time. Associations generally are consistent across high-, middle-, and low-income countries. Conclusions/Significance: This study provides more detailed information than previously available on the relationship between traumatic events and suicidal behavior and indicates that this association is fairly consistent across developed and developing countries. These data reinforce the importance of psychological trauma as a major public health problem, and highlight the significance of screening for the presence and accumulation of traumatic exposures as a risk factor for suicide ideation and attempt.
2010
info:eu-repo/semantics/article
Stein DJ, Chiu WT, Hwang I, Kessler RC, Sampson N, Alonso J et al. Cross-national analysis of the associations between traumatic events and suicidal behavior: findings from the who world mental health surveys. PLoS ONE. 2010;5(5):e10574. DOI: 10.1371/journal.pone.0010574
1932-6203
http://hdl.handle.net/10230/23488
http://dx.doi.org/10.1371/journal.pone.0010574
eng
PLoS ONE. 2010;5(5):e10574
info:eu-repo/grantAgreement/EC/FP7/2004123
info:eu-repo/grantAgreement/ES/1PN/SAF2000-158-CE
info:eu-repo/semantics/openAccess
© 2010 Stein et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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oai:repositori.upf.edu:10230/235012020-06-04T09:26:32Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
Fonseca Casals, Francina, 1972-
Torre Fornell, Rafael de la
Díaz, Laura
Pastor, Antonio
Cuyàs, Elisabet
Pizarro Lozano, Mª Nieves
Khymenets, Olha, 1974-
Farré Albaladejo, Magí
Torrens, Marta
Although the efficacy of methadone maintenance treatment (MMT) in opioid dependence disorder has been well established, the influence of methadone pharmacokinetics in dose requirement and clinical outcome remains controversial. The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy. Opioid dependence patients (meeting Diagnostic and Statistical Manual of Mental Disorders, [4th Edition] criteria) from a MMT community program were recruited. Patients were clinically assessed and blood samples were obtained to determine plasma concentrations of (R,S)-, (R) and (S)- methadone and to study allelic variants of genes encoding CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, and P-glycoprotein. Responders and nonresponders were defined by illicit opioid consumption detected in random urinalysis. The final sample consisted in 105 opioid dependent patients of Caucasian origin. Responder patients received higher doses of methadone and have been included into treatment for a longer period. No differences were found in terms of genotype frequencies between groups. Only CYP2D6 metabolizing phenotype differences were found in outcome status, methadone dose requirements, and plasma concentrations, being higher in the ultrarapid metabolizers. No other differences were found between phenotype and responder status, methadone dose requirements, neither in methadone plasma concentrations. Pharmacokinetic factors could explain some but not all differences in MMT outcome and methadone dose requirements.
2011
info:eu-repo/semantics/article
Fonseca F, de la Torre R, Diaz L, Pastor A, Cuyas E, Pizarro N et al. Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response. PLoS ONE. 2011;6(5):e19527. DOI: 10.1371/journal.pone.0019527
1932-6203
http://hdl.handle.net/10230/23501
http://dx.doi.org/10.1371/journal.pone.0019527
eng
PLoS ONE. 2011;6(5):e19527
info:eu-repo/semantics/openAccess
© 2011 Fonseca et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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oai:repositori.upf.edu:10230/235142020-06-04T09:23:54Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
The influence of genetic and environmental factors among MDMA users in cognitive performance
Cuyàs, Elisabet
Verdejo García, Antonio
Fagundo, Ana B.
Khymenets, Olha, 1974-
Rodríguez, Joan
Cuenca Royo, Aida Ma, 1981-
De Sola Llopis, Susana
Langohr, Klaus
Peña-Casanova, J. (Jordi)
Torrens, Marta
Martín Santos, Rocío
Farré Albaladejo, Magí
Torre Fornell, Rafael de la
This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy
2011
info:eu-repo/semantics/article
Cuyas E, Verdejo-Garcia A, Fagundo AB, Khymenets O, Rodriguez J, Cuenca A et al. The influence of genetic and environmental factors among MDMA users in cognitive performance. PLoS ONE. 2011;6(11):e27206. DOI: 10.1371/journal.pone.0027206
1932-6203
http://hdl.handle.net/10230/23514
http://dx.doi.org/10.1371/journal.pone.0027206
eng
PLoS ONE. 2011;6(11):e27206
info:eu-repo/semantics/openAccess
© 2011 Cuyàs et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits/nunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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oai:repositori.upf.edu:10230/235152020-06-04T09:27:22Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
The prosensory function of Sox2 in the chicken inner ear relies on the direct regulation of Atoh1
Neves, Joana
Uchikawa, Masanori
Bigas Salvans, Anna
Giráldez, Fernando
The proneural gene Atoh1 is crucial for the development of inner ear hair cells and it requires the function of the transcription factor Sox2 through yet unknown mechanisms. In the present work, we used the chicken embryo and HEK293T cells to explore the regulation of Atoh1 by Sox2. The results show that hair cells derive from Sox2-positive otic progenitors and that Sox2 directly activates Atoh1 through a transcriptional activator function that requires the integrity of Sox2 DNA binding domain. Atoh1 activation depends on Sox transcription factor binding sites (SoxTFBS) present in the Atoh1 3′ enhancer where Sox2 directly binds, as shown by site directed mutagenesis and chromatin immunoprecipitation (ChIP). In the inner ear, Atoh1 enhancer activity is detected in the neurosensory domain and it depends on Sox2. Dominant negative competition (Sox2HMG-Engrailed) and mutation of the SoxTFBS abolish the reporter activity in vivo. Moreover, ChIP assay in isolated otic vesicles shows that Sox2 is bound to the Atoh1 enhancer in vivo. However, besides activating Atoh1, Sox2 also promotes the expression of Atoh1 negative regulators and the temporal profile of Atoh1 activation by Sox2 is transient suggesting that Sox2 triggers an incoherent feed-forward loop. These results provide a mechanism for the prosensory function of Sox2 in the inner ear. We suggest that sensory competence is established early in otic development through the activation of Atoh1 by Sox2, however, hair cell differentiation is prevented until later stages by the parallel activation of negative regulators of Atoh1 function
2011
info:eu-repo/semantics/article
Neves J, Uchikawa M, Bigas A, Giraldez F. The prosensory function of Sox2 in the chicken inner ear relies on the direct regulation of Aoh1. PLoS ONE. 2011;7(1):e30871. DOI: 10.1371/journal.pone.0030871
1932-6203
http://hdl.handle.net/10230/23515
http://dx.doi.org/10.1371/journal.pone.0030871
eng
PLoS ONE. 2011;7(1):e30871
info:eu-repo/grantAgreement/ES/3PN/BFU2008-00714
info:eu-repo/grantAgreement/ES/3PN/PLE2009-0098
info:eu-repo/semantics/openAccess
© 2012 Neves et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits/nunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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oai:repositori.upf.edu:10230/235162020-06-04T09:44:40Zcom_10230_20719com_10230_5542com_10230_23115com_10230_6237col_10230_22498col_10230_23132col_10230_6238col_10230_8581
Large-scale pathway-based analysis of bladder cancer genome-wide association data from five studies of European background
Menashe, Idan
Real, Francisco X.
Kogevinas, Manolis
Serra, Consol
Lloreta Trull, Josep, 1958-
Rothman, Nathaniel
Pathway analysis of genome-wide association studies (GWAS) offer a unique opportunity to collectively evaluate genetic variants with effects that are too small to be detected individually. We applied a pathway analysis to a bladder cancer GWAS containing data from 3,532 cases and 5,120 controls of European background (n = 5 studies). Thirteen hundred and ninety-nine pathways were drawn from five publicly available resources (Biocarta, Kegg, NCI-PID, HumanCyc, and Reactome), and we constructed 22 additional candidate pathways previously hypothesized to be related to bladder cancer. In total, 1421 pathways, 5647 genes and 90,000 SNPs were included in our study. Logistic regression model adjusting for age, sex, study, DNA source, and smoking status was used to assess the marginal trend effect of SNPs on bladder cancer risk. Two complementary pathway-based methods (gene-set enrichment analysis [GSEA], and adapted rank-truncated product [ARTP]) were used to assess the enrichment of association signals within each pathway. Eighteen pathways were detected by either GSEA or ARTP at P≤0.01. To minimize false positives, we used the I2 statistic to identify SNPs displaying heterogeneous effects across the five studies. After removing these SNPs, seven pathways (‘Aromatic amine metabolism’ [PGSEA = 0.0100, PARTP = 0.0020], ‘NAD biosynthesis’ [PGSEA = 0.0018, PARTP = 0.0086], ‘NAD salvage’ [PARTP = 0.0068], ‘Clathrin derived vesicle budding’ [PARTP = 0.0018], ‘Lysosome vesicle biogenesis’ [PGSEA = 0.0023, PARTP<0.00012], ’Retrograde neurotrophin signaling’ [PGSEA = 0.00840], and ‘Mitotic metaphase/anaphase transition’ [PGSEA = 0.0040]) remained. These pathways seem to belong to three fundamental cellular processes (metabolic detoxification, mitosis, and clathrin-mediated vesicles). Identification of the aromatic amine metabolism pathway provides support for the ability of this approach to identify pathways with established relevance to bladder
2012
info:eu-repo/semantics/article
Menashe I, Figueroa JD, García-Closas M, Chatterjee N, Malats N, Picornell A et al. Large-scale pathway-based analysis of bladder cancer genome-wide association data from five studies of European background. PLoS ONE. 2012;7(1):e29396. DOI: 10.1371/journal.pone.0029396
1932-6203
http://hdl.handle.net/10230/23516
http://dx.doi.org/10.1371/journal.pone.0029396
eng
PLoS ONE. 2012;7(1):e29396
info:eu-repo/grantAgreement/EC/FP7/201663
info:eu-repo/grantAgreement/EC/FP7/089715
info:eu-repo/grantAgreement/EC/FP7/34627
http://creativecommons.org/publicdomain/zero/1.0/
info:eu-repo/semantics/openAccess
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise us/ned by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication
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oai:repositori.upf.edu:10230/235172021-02-18T12:02:43Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Health services utilization, work absenteeism and costs of pandemic influenza A (H1N1) 2009 in Spain: a multicenter-longitudinal study
Galante, Mariana
Garin Boronat, Olatz, 1979-
Sicuri, Elisa
Cots Reguant, Francesc
García-Altés, Anna
Ferrer Forés, Maria Montserrat
Domínguez García, Àngela
Alonso Caballero, Jordi
Background: The aim of this study was to estimate healthcare resource utilization, work absenteeism and cost per patient with pandemic influenza (H1N1)2009, from its beginning to March 2010, in Spain. We also estimated the economic impact on healthcare services. Methods and Findings: Longitudinal, descriptive, multicenter study of in- and outpatients with confirmed diagnosis of influenza A (H1N1) in Spain. Temporal distribution of cases was comparable to that in Spain. Information of healthcare and social resources used from one week before admission (inpatient) or index-medical visit (outpatient) until recovery was gathered. Unit cost was imputed to utilization frequency for the monetary valuation of use. Mean cost per patient was calculated. A sensitivity analysis was conducted, and variables correlated with cost per patient were identified. Economic impact on the healthcare system was estimated using healthcare costs per patient and both, the reported number of confirmed and clinical cases in Spain. 172 inpatients and 224 outpatients were included. Less than 10% were over 65 years old and more than 50% had previous comorbidities. 12.8% of inpatients were admitted to the Intensive Care Unit. Mean length of hospital stay of patients not requiring critical care was 5 days (SD = 4.4). All working-inpatients and 91.7% working-outpatients went on sick leave. On average, work absenteeism was 30.5 days (SD = 20.7) for the first ones and 9 days (SD = 6.3) for the latest. Caregivers of 21.7% of inpatients and 8.5% of outpatients also had work absenteeism during 10.7 and 4.1 days on average respectively. Mean cost was €6,236/inpatient (CI95% = 1,384–14,623) and €940/outpatient (CI95% = 66–3,064). The healthcare economic burden of patients with confirmed influenza was €144,773,577 (IC95% 13,753,043–383,467,535). More than 86% of expenditures were a result of outpatients' utilization. Conclusion: Cost per H1N1-patient did not defer much from seasonal influenza estimates. Hospitalizations and work absenteeism represented the highest cost per patient.
2012
info:eu-repo/semantics/article
Galante M, Garin O, Sicuri E, Cots F, Garcia-Altes A, Ferrer M, et al. Health services utilization, work absenteeism and costs of pandemic influenza A (H1N1) 2009 in Spain: a multicenter-longitudinal study. PLoS ONE. 2012;7(2):e31696. DOI: 10.1371/journal.pone.0031696
1932-6203
http://hdl.handle.net/10230/23517
http://dx.doi.org/10.1371/journal.pone.0031696
eng
PLoS ONE. 2012;7(2):e31696
info:eu-repo/semantics/openAccess
© 2012 Galante et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235382020-06-04T10:24:53Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238col_10230_8581
A chemocentric approach to the identification of cancer targets
Flachner, Beáta
Lorincz, Zsolt
Carotti, Angelo
Nicolotti, Orazio
Kuchipudi, Praveena
Kuchipudi, Praveena
Remez Vinogradov, Nikita, 1985-
Sanz, Ferran
Tóvári, József
Szabo, Miklós J
Bertók, Béla
Cseh, Sándor
Mestres i López, Jordi
Dormán, György
A novel chemocentric approach to identifying cancer-relevant targets is introduced. Starting with a large chemical collection, the strategy uses the list of small molecule hits arising from a differential cytotoxicity screening on tumor HCT116 and normal MRC-5 cell lines to identify proteins associated with cancer emerging from a differential virtual target profiling of the most selective compounds detected in both cell lines. It is shown that this smart combination of differential in vitro and in silico screenings (DIVISS) is capable of detecting a list of proteins that are already well accepted cancer drug targets, while complementing it with additional proteins that, targeted selectively or in combination with others, could lead to synergistic benefits for cancer therapeutics. The complete list of 115 proteins identified as being hit uniquely by compounds showing selective antiproliferative effects for tumor cell lines is provided
2012
info:eu-repo/semantics/article
Flachner B, Lorincz Z, Carotti A, Nicolotti O, Kuchipudi P, Remez N et al. A chemocentric approach to the identification of cancer targets. PLoS ONE. 2012;7(4):e35582. DOI: 10.1371/journal.pone.0035582
1932-6203
http://hdl.handle.net/10230/23538
http://dx.doi.org/10.1371/journal.pone.0035582
eng
PLoS ONE. 2012;7(4):e35582
info:eu-repo/grantAgreement/EC/FP6/37559
info:eu-repo/semantics/openAccess
© 2012 Flachner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits/nunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235402020-06-05T07:41:58Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Inhibition of specific NF-KB activity contributes to the tumor suppressor function of 14-3-3omega in breast cancer
Inglés Esteve, Julia
Morales, Mònica
Dalmases Massegú, Alba, 1982-
Garcia Carbonell, Ricard
Jené i Sanz, Alba, 1984-
López Bigas, Núria
Iglesias Coma, Mar
Ruiz Herguido, Cristina
Rovira Guerín, Ana
Rojo, Federico
Albanell Mestres, Joan
Gomis, Roger R.
Bigas Salvans, Anna
Espinosa Blay, Lluís
14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting.
2012
info:eu-repo/semantics/article
Ingles-Esteve J, Morales M, Dalmases A, Garcia-Carbonell R, Jene-Sanz A, López-Bigas N et al. Inhibition of specific NF-KB activity contributes to the tumor suppressor function of 14-3-3omega in breast cancer. PLoS ONE. 2012;7(5):e38347. DOI: 10.1371/journal.pone.0038347
1932-6203
http://hdl.handle.net/10230/23540
http://dx.doi.org/10.1371/journal.pone.0038347
eng
PLoS ONE. 2012;7(5):e38347
info:eu-repo/grantAgreement/ES/3PN/SAF2009-06954
info:eu-repo/grantAgreement/ES/3PN/BES2008-001850
info:eu-repo/semantics/openAccess
© 2012 Inglés-Esteve et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235452020-06-04T10:25:36Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_8581col_10230_6238
Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 european birth cohorts
Lodrup Carlsen, Karin C.
Sunyer Deu, Jordi
Puig, Carme
Wickman, Magnus
Objective: To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design: Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition: Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition: Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis: Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models.Results: We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions: Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.
2012
info:eu-repo/semantics/article
Lodrup Carlsen KC, Roll S, Carlsen KH, Mowinckel P, Wijga AH, Brunekreef B et al. Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 european birth cohorts. PLoS ONE. 2012;7(8):e43214. DOI: 10.1371/journal.pone.0043214
1932-6203
http://hdl.handle.net/10230/23545
http://dx.doi.org/10.1371/journal.pone.0043214
eng
PLoS ONE. 2012;7(8):e43214
info:eu-repo/grantAgreement/EC/FP6/506378
info:eu-repo/semantics/openAccess
© 2012 Lodrup Carlsen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235462020-06-04T10:53:03Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity
Fagundo, Ana B.
Torre Fornell, Rafael de la
Jiménez Murcia, Susana
Agüera, Zaida
Granero, Roser
Tárrega, Salomé
Botella, Cristina
Baños, Rosa M.
Fernández Real, Jose M.
Rodríguez, Roser
Forcano, Laura
Frühbeck, Gema
Gómez Ambrosi, Javier
Tinahones Madueño, Francisco José
Fernández García, José C.
Casanueva, Felipe F.
Fernández Aranda, Fernando
Background: Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC). Methods: Thirty five AN patients, fifty two OB and one hundred thirty seven HC were compared using the Wisconsin Card Sorting Test (WCST); Stroop Color and Word Test (SCWT); and Iowa Gambling Task (IGT). All participants were female, aged between 18 and 60 years. Results: There was a significant difference in IGT score (F(1.79); p<.001), with AN and OB groups showing the poorest performance compared to HC. On the WCST, AN and OB made significantly more errors than controls (F(25.73); p<.001), and had significantly fewer correct responses (F(2.71); p<.001). Post hoc analysis revealed that the two clinical groups were not significantly different from each other. Finally, OB showed a significant reduced performance in the inhibition response measured with the Stroop test (F(5.11); p<.001) compared with both AN and HC. Conclusions: These findings suggest that EWC subjects (namely AN and OB) have similar dysfunctional executive profile that may play a role in the development and maintenance of such disorders
2012
info:eu-repo/semantics/article
Fagundo AB, de la Torre R, Jiménez-Murcia S, Aguera Z, Granero R, Tarrega S et al. Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity. PLoS ONE. 2012;7(8):e43382. DOI: 10.1371/journal.pone.0043382
1932-6203
http://hdl.handle.net/10230/23546
http://dx.doi.org/10.1371/journal.pone.0043382
eng
PLoS ONE. 2012;7(8):e43382
info:eu-repo/grantAgreement/ES/3PN/JCI2011-09248
info:eu-repo/semantics/openAccess
© 2012 Fagundo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235552020-06-04T09:55:55Zcom_10230_6237com_10230_5542com_10230_23115com_10230_20719col_10230_6238col_10230_23132col_10230_22498
Hypothesis-based analysis of gene-gene interactions and risk of myocardial infarction
Lucas, Gavin, 1977-
Lluís Ganella, Carla, 1984-
Subirana Cachinero, Isaac
Musameh, Muntaser D.
González Ruiz, Juan Ramón
Nelson, Christopher P.
Sentí Clapés, Mariano
Myocardial Infarction Genetics
Wellcome Trust Case Control Constortium
Schwartz, Stephen M
Siscovick, David
O'Donnell, Christopher J
Melander, Olle
Salomaa, Veikko
Purcell, Shaun
Altshuler, David
Samani, Nilesh J.
Kathiresan, Sekar
Elosua Llanos, Roberto
The genetic loci that have been found by genome-wide association studies to modulate risk of coronary heart disease explain only a fraction of its total variance, and gene-gene interactions have been proposed as a potential source of the remaining heritability. Given the potentially large testing burden, we sought to enrich our search space with real interactions by analyzing variants that may be more likely to interact on the basis of two distinct hypotheses: a biological hypothesis, under which MI risk is modulated by interactions between variants that are known to be relevant for its risk factors; and a statistical hypothesis, under which interacting variants individually show weak marginal association with MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP interaction testing using a logistic regression framework. Despite having reasonable power to detect interaction effects of plausible magnitudes, we observed no statistically significant evidence of interaction under these hypotheses, and no clear consistency between the top results in our discovery sample and those in a large validation sample of 1,766 cases of coronary heart disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our results do not support the existence of strong interaction effects as a common risk factor for MI. Within the scope of the hypotheses we have explored, this study places a modest upper limit on the magnitude that epistatic risk effects are likely to have at the population level (odds ratio for MI risk 1.3–2.0, depending on allele frequency and interaction model).
2012
info:eu-repo/semantics/article
Lucas G, Lluis-Ganella C, Subirana I, Musameh MD, Gonzalez JR, Nelson CP et al. Hypothesis-based analysis of gene-gene interactions and risk of myocardial infarction. PLoS ONE. 2012;7(8):e41730. DOI: 10.1371/journal.pone.0041730
1932-6203
http://hdl.handle.net/10230/23555
http://dx.doi.org/10.1371/journal.pone.0041730
eng
PLoS ONE. 2012;7(8):e41730
info:eu-repo/semantics/openAccess
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235582020-06-05T07:44:43Zcom_10230_6237com_10230_5542com_10230_23115com_10230_20719col_10230_6238col_10230_23132col_10230_22498col_10230_8581
Cyclooxygenase-2 expression in bladder cancer and patient prognosis: results from a large clinical cohort and meta-analysis
Czachorowski, Maciej J
Amaral, André F.S.
Montes-Moreno, Santiago
Lloreta Trull, Josep, 1958-
Carrato, Alfredo
Tardón, Adonina
Morente, Manuel M
Kogevinas, Manolis
Real, Francisco X.
Malats i Riera, Núria
Aberrant overexpression of cyclooxygenase-2 (COX2) is observed in urothelial carcinoma of the bladder (UCB). Studies evaluating COX2 as a prognostic marker in UCB report contradictory results. We determined the prognostic potential of COX2 expression in UCB and quantitatively summarize the results with those of the literature through a meta-analysis. Newly diagnosed UCB patients recruited between 1998–2001 in 18 Spanish hospitals were prospectively included in the study and followed-up (median, 70.7 months). Diagnostic slides were reviewed and uniformly classified by expert pathologists. Clinical data was retrieved from hospital charts. Tissue microarrays containing non-muscle invasive (n = 557) and muscle invasive (n = 216) tumours were analyzed by immunohistochemistry using quantitative image analysis. Expression was evaluated in Cox regression models to assess the risk of recurrence, progression and disease-specific mortality. Meta-hazard ratios were estimated using our results and those from 11 additional evaluable studies. COX2 expression was observed in 38% (211/557) of non-muscle invasive and 63% (137/216) of muscle invasive tumors. Expression was associated with advanced pathological stage and grade (p<0.0001). In the univariable analyses, COX2 expression - as a categorical variable - was not associated with any of the outcomes analyzed. As a continuous variable, a weak association with recurrence in non-muscle invasive tumors was observed (p-value = 0.048). In the multivariable analyses, COX2 expression did not independently predict any of the considered outcomes. The meta-analysis confirmed these results. We did not find evidence that COX2 expression is an independent prognostic marker of recurrence, progression or survival in patients with UCB.
2012
info:eu-repo/semantics/article
Czachorowski MJ, Amaral AFS, Montes-Moreno S, Lloreta J, Carrato A, Tardón A et al. Cyclooxygenase-2 expression in bladder cancer and patient prognosis: results from a large clinical cohort and meta-analysis. PLoS ONE. 2012;7(9):e45025. DOI: 10.1371/journal.pone.0045025
1932-6203
http://hdl.handle.net/10230/23558
http://dx.doi.org/10.1371/journal.pone.0045025
eng
PLoS ONE. 2012;7(9):e45025
info:eu-repo/grantAgreement/EC/FP6/37739
info:eu-repo/grantAgreement/EC/FP7/201663
info:eu-repo/grantAgreement/EC/FP7/201333
info:eu-repo/semantics/openAccess
© 2012 Czachorowski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235592022-06-21T10:07:26Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"): the influence of gender and genetics (CYP2D6, COMT, 5-HTT)
Pardo Lozano, Ricardo
Farré Albaladejo, Magí
Yubero Lahoz, Samanta, 1985-
O'Mathuna, Brian
Torrens, Marta
Mustata, Cristina
Pérez Mañá, Clara
Langohr, Klaus
Cuyàs, Elisabet
Carbó Banús, Marcel·lí
Torre Fornell, Rafael de la
The synthetic psychostimulant MDMA (±3,4-methylenedioxymethamphetamine, ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT) and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT). This clinical study was designed to evaluate the pharmacokinetics and physiological and subjective effects of MDMA considering gender and the genetic polymorphisms of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women) healthy, recreational users of ecstasy were included (all extensive metabolizers for CYP2D6). A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75–100 mg) which was similar to recreational doses. None of the women were taking oral contraceptives and the experimental session was performed during the early follicular phase of their menstrual cycle. Principal findings show that subjects reached similar MDMA plasma concentrations, and experienced similar positive effects, irrespective of gender or CYP2D6 (not taking into consideration poor or ultra-rapid metabolizers) or COMT genotypes. However, HMMA plasma concentrations were linked to CYP2D6 genotype (higher with two functional alleles). Female subjects displayed more intense physiological (heart rate, and oral temperature) and negative effects (dizziness, sedation, depression, and psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/*) determined greater cardiovascular effects, and with low functionality (met/* or s/s) negative subjective effects (dizziness, anxiety, sedation). In conclusion, the contribution of MDMA pharmacokinetics following 1.4 mg/kg MDMA to the gender differences observed in drug effects appears to be negligible or even null. In contrast, 5-HTTLPR and COMT val158met genotypes play a major role.
2012
info:eu-repo/semantics/article
Pardo Lozano R, Farré Albaladejo M, Yubero Lahoz S, O'Mathuna B, Torrens M, Mustata C, Pérez Mañá C, Langohr K, Cuyàs E, Carbó Banús M, de la Torre Fornell R. Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"): the influence of gender and genetics (CYP2D6, COMT, 5-HTT). PLoS ONE. 2012;7(10):e47599. DOI: 10.1371/journal.pone.0047599
1932-6203
http://hdl.handle.net/10230/23559
http://dx.doi.org/10.1371/journal.pone.0047599
eng
PLoS ONE. 2012;7(10):e47599
info:eu-repo/semantics/openAccess
© 2012 Pardo-Lozano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235662020-06-05T07:46:16Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Impact of influenza on health-related quality of life among confirmed (H1N1)2009 patients
Hollmann, Malen
Garin Boronat, Olatz, 1979-
Galante, Mariana
Ferrer Forés, Maria Montserrat
Domínguez García, Àngela
Alonso Caballero, Jordi
Background: We aimed to assess the changes in health-related quality of life (HRQL) in patients with confirmed diagnosis of influenza (H1N1)2009, and to estimate the individual and societal loss of quality-adjusted life years (QALYs) caused by the pandemic. Methods and Results: Longitudinal study of patients recruited at major hospitals and primary care centers in Spain. Patients reported their HRQL (EQ-5D) during their influenza episode and seven days prior to it. A subsample was monitored to evaluate HRQL after recovery. HRQL loss was estimated as the difference between EQ-5D prior to the influenza episode and during it. Individual QALY loss (disutility multiplied by the duration of the influenza episode in days) for confirmed cases was calculated and used to estimate the societal loss in Spain (with the official estimations). A total of 432 inpatients and 563 outpatients were included, of whom 145 and 184, respectively, were followed up. Baseline mean HRQL loss was 0.58 (95% CI, 0.53–0.63) for inpatients and 0.43 (95% CI, 0.40–0.46) for outpatients. The majority of the 145 inpatients and 184 outpatients who were followed up regained initial HRQL levels, presenting a mean difference of 0.01 between the EQ-5D score prior to and after the influenza episode. Individual QALY losses for inpatients (0.031, 95% CI, 0.025–0.037) were higher than for outpatients (0.009, 95% CI, 0.007–0.011), while societal QALY losses were reversed: 94 years for inpatients and 6,778 years for outpatients. For fatal cases (an official number of 318), we estimated a QALY loss of 11,981. Conclusions: The influenza (H1N1)2009 pandemic had a significant but temporary impact on the HRQL of the majority of confirmed in- and outpatients. The societal impact of the influenza pandemic in Spain was estimated to be higher than other acute conditions. These results provide useful data for future cost-utility analyses.
2013
info:eu-repo/semantics/article
Hollmann M, Garin O, Galante M, Ferrer M, Dominguez A, Alonso J. Impact of influenza on health-related quality of life among confirmed (H1N1)2009 patients. PLoS ONE. 2013;8(3):e60477. DOI: 10.1371/journal.pone.0060477
1932-6203
http://hdl.handle.net/10230/23566
http://dx.doi.org/10.1371/journal.pone.0060477
eng
PLoS ONE. 2013;8(3):e60477
info:eu-repo/semantics/openAccess
© 2013 Hollmann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235712020-06-04T09:57:26Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
FGFR4 role in epithelial-mesenchymal transition and its therapeutic value in colorectal cancer
Peláez García, Alberto
Barderas, Rodrigo
Torres, Sofía
Teixidó, Joaquín
Bonilla, Félix
García de Herreros, Antonio
Hernández-Varas, Pablo
Casal, José Ignacio
Fibroblast growth factor receptor 4 (FGFR4) is vital in early development and tissue repair. FGFR4 expression levels are very restricted in adult tissues, except in several solid tumors including colorectal cancer, which showed overexpression of FGFR4. Here, FGFR4 mutation analysis discarded the presence of activating mutations, other than Arg388, in different colorectal cancer cell lines and tumoral samples. Stable shRNA FGFR4-silencing in SW480 and SW48 cell lines resulted in a significant decrease in cell proliferation, adhesion, cell migration and invasion. This decrease in the tumorigenic and invasive capabilities of colorectal cancer cells was accompanied by a decrease of Snail, Twist and TGFβ gene expression levels and an increase of E-cadherin, causing a reversion to a more epithelial phenotype, in three different cell lines. In addition, FGFR4-signaling activated the oncogenic SRC, ERK1/2 and AKT pathways in colon cancer cells and promoted an increase in cell survival. The relevance of FGFR4 in tumor growth was supported by two different strategies. Kinase inhibitors abrogated FGFR4-related cell growth and signaling pathways at the same extent than FGFR4-silenced cells. Specific FGFR4-targeting using antibodies provoked a similar reduction in cell growth. Moreover, FGFR4 knock-down cells displayed a reduced capacity for in vivo tumor formation and angiogenesis in nude mice. Collectively, our data support a crucial role for FGFR4 in tumorigenesis, invasion and survival in colorectal cancer. In addition, FGFR4 targeting demonstrated its applicability for colorectal cancer therapy.
2013
info:eu-repo/semantics/article
Peláez-García A, Barderas R, Torres S, Hernández-Varas P, Teixidó J, Bonilla F et al. FGFR4 role in epithelial-mesenchymal transition and its therapeutic value in colorectal cancer. PLoS ONE. 2013;8(5):e63695. DOI: 10.1371/journal.pone.0063695
1932-6203
http://hdl.handle.net/10230/23571
http://dx.doi.org/10.1371/journal.pone.0063695
eng
PLoS ONE. 2013;8(5):e63695
info:eu-repo/grantAgreement/ES/3PN/BIO2009-08818
info:eu-repo/semantics/openAccess
© 2013 Peláez-García et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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oai:repositori.upf.edu:10230/235732020-06-04T10:54:59Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Meta-analyses of the 5-HTTLPR polymorphisms and post-traumatic stress disorder
Navarro Mateu, Fernando
Escamez, T.
Koenen, Karestan C.
Alonso Caballero, Jordi
Sánchez Meca, Julio
Objective: To conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases. Methods Data Sources: Potential studies were identified through PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK), PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network) up until December 2011. Study Selection: Published observational studies reporting genotype or allele frequencies of this genetic factor in PTSD cases and in non-PTSD controls were all considered eligible for inclusion in this systematic review. Data Extraction: Two reviewers selected studies for possible inclusion and extracted data independently following a standardized protocol. Statistical analysis: A biallelic and a triallelic meta-analysis, including the total S and S' frequencies, the dominant (S+/LL and S'+/L'L') and the recessive model (SS/L+ and S'S'/L'+), was performed with a random-effect model to calculate the pooled OR and its corresponding 95% CI. Forest plots and Cochran's Q-Statistic and I2 index were calculated to check for heterogeneity. Subgroup analyses and meta-regression were carried out to analyze potential moderators. Publication bias and quality of reporting were also analyzed. Results: 13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score) influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias. Conclusions: Current evidence does not support a direct effect of 5-HTTLPR polymorphisms on PTSD. Further analyses of gene-environment interactions, epigenetic modulation and new studies with large samples and/or meta-analyses are required.
2013
info:eu-repo/semantics/article
Navarro Mateu F, Escamez T, Koenen KC, Alonso Caballero J, Sánchez Meca J. Meta-analyses of the 5-HTTLPR polymorphisms and post-traumatic stress disorder. PLoS ONE. 2013;8(6):e66227. DOI: 10.1371/journal.pone.0066227
1932-6203
http://hdl.handle.net/10230/23573
http://dx.doi.org/10.1371/journal.pone.0066227
eng
PLoS ONE. 2013;8(6):e66227
info:eu-repo/semantics/openAccess
© Navarro-Mateu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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oai:repositori.upf.edu:10230/235742020-06-05T07:47:33Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on executive functions in humans
Fagundo, Ana B.
Torre Fornell, Rafael de la
Jiménez Murcia, Susana
Agüera, Zaida
Pastor, Antonio
Casanueva, Felipe F.
Granero, Roser
Baños, Rosa M.
Botella, Cristina
de Pino Gutiárrez, Amparo
Fernández Real, Jose M.
Fernández García, José C.
Frühbeck, Gema
Gómez Ambrosi, Javier
Menchón, José M.
Moragrega, Inés
Rodríguez, Roser
Tárrega, Salomé
Tinahones Madueño, Francisco José
Fernández Aranda, Fernando
Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches.
2013
info:eu-repo/semantics/article
Fagundo AB, de la Torre R, Jiménez-Murcia S, Aguera Z, Pastor A, Casanueva FF et al. Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on executive functions in humans. PLoS ONE. 2013;8(6):e66387. DOI: 10.1371/journal.pone.0066387
1932-6203
http://hdl.handle.net/10230/23574
http://dx.doi.org/10.1371/journal.pone.0066387
eng
PLoS ONE. 2013;8(6):e66387
info:eu-repo/grantAgreement/ES/3PN/JCI2011-09248
info:eu-repo/semantics/openAccess
© 2013 Fagundo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235812020-06-04T10:28:03Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Disability mediates the impact of common conditions on perceived health
Alonso Caballero, Jordi
Vilagut Saiz, Gemma, 1975-
Adroher, Núria D.
Kessler, Ronald C.
Background: We examined the extent to which disability mediates the observed associations of common mental and physical conditions with perceived health.Methods and Findings: WHO World Mental Health (WMH) Surveys carried out in 22 countries worldwide (n = 51,344 respondents, 72.0% response rate). We assessed nine common mental conditions with the WHO Composite International Diagnostic Interview (CIDI), and ten chronic physical with a checklist. A visual analog scale (VAS) score (0, worst to 100, best) measured perceived health in the previous 30 days. Disability was assessed using a modified WHO Disability Assessment Schedule (WHODAS), including: cognition, mobility, self-care, getting along, role functioning (life activities), family burden, stigma, and discrimination. Path analysis was used to estimate total effects of conditions on perceived health VAS and their separate direct and indirect (through the WHODAS dimensions) effects. Twelve-month prevalence was 14.4% for any mental and 51.4% for any physical condition. 31.7% of respondents reported difficulties in role functioning, 11.4% in mobility, 8.3% in stigma, 8.1% in family burden and 6.9% in cognition. Other difficulties were much less common. Mean VAS score was 81.0 (SD = 0.1). Decrements in VAS scores were highest for neurological conditions (9.8), depression (8.2) and bipolar disorder (8.1). Across conditions, 36.8% (IQR: 31.2–51.5%) of the total decrement in perceived health associated with the condition were mediated by WHODAS disabilities (significant for 17 of 19 conditions). Role functioning was the dominant mediator for both mental and physical conditions. Stigma and family burden were also important mediators for mental conditions, and mobility for physical conditions. Conclusions: More than a third of the decrement in perceived health associated with common conditions is mediated by disability. Although the decrement is similar for physical and mental conditions, the pattern of mediation is different. Research is needed on the benefits for perceived health of targeted interventions aimed at particular disability dimensions.
2013
info:eu-repo/semantics/article
Alonso J, Vilagut G, Adroher ND, Chatterji S, He Y, Andrade LH et al. Disability mediates the impact of common conditions on perceived health. PLoS ONE. 2013;8(6):e65858. DOI: 10.1371/journal.pone.0065858
1932-6203
http://hdl.handle.net/10230/23581
http://dx.doi.org/10.1371/journal.pone.0065858
eng
PLoS ONE. 2013;8(6):e65858
info:eu-repo/semantics/openAccess
© 2013 Alonso et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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oai:repositori.upf.edu:10230/235822020-06-04T10:55:31Zcom_10230_5542com_10230_6237com_10230_23115col_10230_8581col_10230_6238col_10230_23132
Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system
Coloma, Preciosa M.
Furlong, Laura I., 1971-
Bauer-Mehren, Anna
Sanz, Ferran
Mestres i López, Jordi
Sturkenboom, Miriam
Background: Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in ‘real-world’ settings. Objective: To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network. Methods: Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996–2010. Primary care physicians’ medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. Results: Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs (‘prime suspects’): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. Limitations: Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. Conclusion: A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical association, but also public health relevance, novelty, and biological plausibility. Although this strategy needs to be further evaluated using other healthcare data sources, the list of ‘prime suspects’ makes a good starting point for further clinical, laboratory, and epidemiologic investigation.
2013
info:eu-repo/semantics/article
Coloma PM, Schuemie MJ, Trifiro G, Furlong L, van Mulligen E, Bauer-Mehren A et al. Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system. PLoS ONE. 2013;8(8):e72148. DOI: 10.1371/journal.pone.0072148
1932-6203
http://hdl.handle.net/10230/23582
http://dx.doi.org/10.1371/journal.pone.0072148
eng
PLoS ONE. 2013;8(8):e72148
info:eu-repo/grantAgreement/EC/FP7/215847
info:eu-repo/semantics/openAccess
© Coloma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/235852020-06-08T09:12:15Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Gene expression of desaturase (FADS1 and FADS2) and elongase (ELOVL5) enzymes in peripheral blood: association with polyunsaturated fatty acid levels and atopic eczema in 4-year-old children
Chisaguano, Aida M.
Montes, Rosa
Pérez Berezo, Teresa
Castellote, Ana Isabel
Guerendiain, Marcela
Bustamante Pineda, Mariona
Morales, Eva
García Esteban, Raquel
Sunyer Deu, Jordi
Franch, Àngels
López Sabater, M. Carmen
Background: It is unknown if changes in the gene expression of the desaturase and elongase enzymes are associated with abnormal n-6 long chain polyunsaturated fatty acid (LC-PUFA) levels in children with atopic eczema (AE). We analyzed whether mRNA-expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. Methods: AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the mRNA-expression of FADS1, FADS2 and ELOVL5. LC-PUFA levels were measured by fast gas chromatography in plasma phospholipids. The relationship of gene expression with LC-PUFA levels and enzyme activities was evaluated by Pearson’s rank correlation coefficient, and logistic regression models were used to study its association with risk of developing AE. Results: Children with AE had lower levels of several n-6 PUFA members, dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids. mRNA-expression levels of FADS1 and 2 strongly correlated with DGLA levels and with D6D activity. FADS2 and ELOVL5 mRNA-expression levels were significantly lower in AE than in non-AE children (-40.30% and -20.36%; respectively), but no differences were found for FADS1. Conclusions and Significance: Changes in the mRNA-expression levels of FADS1 and 2 directly affect blood DGLA levels and D6D activity. This study suggests that lower mRNA-expressions of FADS2 and ELOVL5 are associated with higher risk of atopic eczema in young children.
2013
info:eu-repo/semantics/article
Chisaguano AM, Montes R, Pérez-Berezo T, Castellote AI, Guerendiain M, Bustamante M et al. Gene expression of desaturase (FADS1 and FADS2) and elongase (ELOVL5) enzymes in peripheral blood: association with polyunsaturated fatty acid levels and atopic eczema in 4-year-old children. PLoS ONE. 2013;8(10):e78245. DOI: 10.1371/journal.pone.0078245
1932-6203
http://hdl.handle.net/10230/23585
http://dx.doi.org/10.1371/journal.pone.0078245
eng
PLoS ONE. 2013;8(10):e78245
info:eu-repo/grantAgreement/ES/3PN/AGL2009-09730
info:eu-repo/grantAgreement/ES/3PN/BUF2012-40254
info:eu-repo/semantics/openAccess
© 2013 Chisaguano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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oai:repositori.upf.edu:10230/235872020-06-08T10:08:58Zcom_10230_20719com_10230_5542com_10230_23115com_10230_6237col_10230_22498col_10230_23132col_10230_6238
Chromosomal bands affected by acute oil exposure and DNA repair errors
Monyarch, Gemma
De Castro Reis, Fernanda
Zock, Jan-Paul
Giraldo, Jesús
Pozo Rodríguez, Francisco
Espinosa Díaz, Ana
Rodríguez Trigo, Gema
Gómez, Federico P.
Antó i Boqué, Josep Maria
Coll, Maria
Barberà, Joan Albert
Fuster, Carme
Background: In a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk. Objectives: We analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency. Methods: Cytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin. Results: Three chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016). Conclusion: The present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas) reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure.
2013
info:eu-repo/semantics/article
Monyarch G, De Castro Reis F, Zock JP, Giraldo J, Pozo-Rodriguez F, Espinosa A et al. Chromosomal bands affected by acute oil exposure and DNA repair errors. PLoS ONE. 2013;8(11):e81276. DOI: 10.1371/journal.pone.0081276
1932-6203
http://hdl.handle.net/10230/23587
http://dx.doi.org/10.1371/journal.pone.0081276
eng
PLoS ONE. 2013;8(11):e81276
https://creativecommons.org/licenses/by/3.0/
info:eu-repo/semantics/openAccess
© 2013 Fuster et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236052021-04-14T11:05:33Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238col_10230_8581
Associations between lifetime traumatic events and subsequent chronic physical conditions: a cross-national, cross-sectional study
Scott, Kate M.
Koenen, Karestan C.
Aguilar Gaxiola, Sergio
Alonso Caballero, Jordi
Angermeyer, Matthias C.
Benjet, Corina
Bruffaerts, Ronny
Caldas de Almeida, José Miguel
De Girolamo, Giovanni
Florescu, Silvia
Iwata, Noboru
Levinson, Daphna
Lim, Carmen
Murphy, Sam
Ormel, Johan
Kessler, Ronald C.
Background: Associations between lifetime traumatic event (LTE) exposures and subsequent physical ill-health are well established but it has remained unclear whether these are explained by PTSD or other mental disorders. This study examined this question and investigated whether associations varied by type and number of LTEs, across physical condition outcomes, or across countries. Methods: Cross-sectional, face-to-face household surveys of adults (18+) were conducted in 14 countries (n = 38, 051). The Composite International Diagnostic Interview assessed lifetime LTEs and DSM-IV mental disorders. Chronic physical conditions were ascertained by self-report of physician's diagnosis and year of diagnosis or onset. Survival analyses estimated associations between the number and type of LTEs with the subsequent onset of 11 physical conditions, with and without adjustment for mental disorders. Findings: A dose-response association was found between increasing number of LTEs and odds of any physical condition onset (OR 1.5 [95% CI: 1.4–1.5] for 1 LTE; 2.1 [2.0–2.3] for 5+ LTEs), independent of all mental disorders. Associations did not vary greatly by type of LTE (except for combat and other war experience), nor across countries. A history of 1 LTE was associated with 7/11 of the physical conditions (ORs 1.3 [1.2–1.5] to 1.7 [1.4–2.0]) and a history of 5+ LTEs was associated with 9/11 physical conditions (ORs 1.8 [1.3–2.4] to 3.6 [2.0–6.5]), the exceptions being cancer and stroke. Conclusions: Traumatic events are associated with adverse downstream effects on physical health, independent of PTSD and other mental disorders. Although the associations are modest they have public health implications due to the high prevalence of traumatic events and the range of common physical conditions affected. The effects of traumatic stress are a concern for all medical professionals and researchers, not just mental health specialists.
2013
info:eu-repo/semantics/article
Scott KM, Koenen KC, Aguilar-Gaxiola S, Alonso J, Angermeyer MC, Benjet C et al. Associations between lifetime traumatic events and subsequent chronic physical conditions: a cross-national, cross-sectional study. PLoS ONE. 2013;8(11):e80573. DOI: 10.1371/journal.pone.0080573
1932-6203
http://hdl.handle.net/10230/23605
http://dx.doi.org/10.1371/journal.pone.0080573
eng
PLoS ONE. 2013;8(11):e80573
info:eu-repo/grantAgreement/EC/FP7/2004123
info:eu-repo/grantAgreement/ES/1PN/SAF2000-158-CE
info:eu-repo/semantics/openAccess
© 2013 Scott et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236072020-06-04T10:56:01Zcom_10230_20719com_10230_5542com_10230_23115com_10230_6237col_10230_22498col_10230_23132col_10230_6238col_10230_8581
Application of multi-SNP approaches Bayesian LASSO and AUC-RF to detect main effects of inflammatory-gene variants associated with bladder cancer risk
López De Maturana, Evangelina
Ye, Yuanqing
Calle, M. Luz
Rothman, Nathaniel
Urrea, Víctor
Kogevinas, Manolis
Petrus, Sandra
Chanock, Stephen J.
Tardón, Adonina
García Closas, Montserrat
González Neira, Anna
Vellalta, Gemma
Carrato, Alfredo
Navarro i Cuartiellas, Arcadi, 1969-
Lorente-Galdós, Belén, 1981-
Silverman, Debra T.
Real, Francisco X.
Wu, Xifeng
Malats i Riera, Núria
The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL), a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk.
2013
info:eu-repo/semantics/article
De Maturana EL, Ye Y, Calle ML, Rothman N, Urrea V, Kogevinas M et al. Application of multi-SNP approaches Bayesian LASSO and AUC-RF to detect main effects of inflammatory-gene variants associated with bladder cancer risk. PLoS ONE. 2013;8(12):e83745. DOI: 10.1371/journal.pone.0083745
1932-6203
http://hdl.handle.net/10230/23607
http://dx.doi.org/10.1371/journal.pone.0083745
eng
PLoS ONE. 2013;8(12):e83745
info:eu-repo/grantAgreement/ES/3PN/MTM2008-06747
info:eu-repo/grantAgreement/EC/FP7/201663
info:eu-repo/semantics/openAccess
© 2013 de Maturana et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236082020-06-05T07:49:50Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_8581col_10230_6238
Gathering and exploring scientific knowledge in pharmacovigilance
Lopes, Pedro
Nunes, Tiago
Campos, David
Furlong, Laura I., 1971-
Bauer-Mehren, Anna
Sanz, Ferran
Carrascosa Baena, María Carmen, 1972-
Mestres i López, Jordi
Kors, Jan A.
Singh, Barat
van Mulligen, Erik M.
van der Lei, Johan
Diallo, Gayo
Avillach, Paul
Ahlberg Helgee, Ernst
Boyer, Scott
Díaz, Carlos
Oliveira, José Luis
Pharmacovigilance plays a key role in the healthcare domain through the assessment, monitoring and discovery of interactions amongst drugs and their effects in the human organism. However, technological advances in this field have been slowing down over the last decade due to miscellaneous legal, ethical and methodological constraints. Pharmaceutical companies started to realize that collaborative and integrative approaches boost current drug research and development processes. Hence, new strategies are required to connect researchers, datasets, biomedical knowledge and analysis algorithms, allowing them to fully exploit the true value behind state-of-the-art pharmacovigilance efforts. This manuscript introduces a new platform directed towards pharmacovigilance knowledge providers. This system, based on a service-oriented architecture, adopts a plugin-based approach to solve fundamental pharmacovigilance software challenges. With the wealth of collected clinical and pharmaceutical data, it is now possible to connect knowledge providers’ analysis and exploration algorithms with real data. As a result, new strategies allow a faster identification of high-risk interactions between marketed drugs and adverse events, and enable the automated uncovering of scientific evidence behind them. With this architecture, the pharmacovigilance field has a new platform to coordinate large-scale drug evaluation efforts in a unique ecosystem, publicly available at http://bioinformatics.ua.pt/euadr/.
2013
info:eu-repo/semantics/article
Lopes P, Nunes T, Campos D, Furlong LI, Bauer-Mehren A, Sanz F et al. Gathering and exploring scientific knowledge in pharmacovigilance. PLoS ONE. 2013;8(12):e83016. DOI: 10.1371/journal.pone.0083016
1932-6203
http://hdl.handle.net/10230/23608
http://dx.doi.org/10.1371/journal.pone.0083016
eng
PLoS ONE. 2013;8(12):e83016
info:eu-repo/grantAgreement/EC/FP7/215847
info:eu-repo/semantics/openAccess
© 2013 Lopes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits/nunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236102021-07-14T10:18:48Zcom_10230_23115com_10230_5542col_10230_23132
Vitamin D metabolic pathway genes and pancreatic cancer risk
Arem, Hannah
Stolzenberg-Solomon, Rachael Z.
Porta Serra, Miquel
Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186), LRP2 (rs4668123), CYP24A1 (rs2762932), GC (rs2282679), and CUBN (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.
2015
info:eu-repo/semantics/article
Arem H, Yu K, Xiong X, Moy K, Freedman ND, Mayne ST. Vitamin D Metabolic Pathway Genes and Pancreatic Cancer Risk. PLoS ONE. 2015;10(3):e0117574. doi:10.1371/journal.pone.0117574
1932-6203
http://hdl.handle.net/10230/23610
http://dx.doi.org/10.1371/journal.pone.0117574
eng
PLoS ONE. 2015;10(3):e0117574.
https://creativecommons.org/publicdomain/zero/1.0/
info:eu-repo/semantics/openAccess
This is an open access article, free of allcopyright, and may be freely reproduced, distributed,transmitted, modified, built upon, or otherwise usedby anyone for any lawful purpose. The work is madeavailable under the https://creativecommons.org/publicdomain/zero/1.0/ publicdomain dedicatio
Public Library of Science
oai:repositori.upf.edu:10230/236112020-06-04T09:39:38Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
VORFFIP-driven dock: V-D2OCK, a fast and accurate protein docking strategy.
Segura, Joan
Marín López, Manuel Alejandro, 1987-
Jones, Pamela F.
Oliva Miguel, Baldomero
Fernández Fuentes, Narcís
The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK). This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers.
2015
info:eu-repo/semantics/article
Segura J, Marín-López MA, Jones PF,Oliva B, Fernandez-Fuentes N (2015) VORFFIP-Driven Dock: V-D2OCK, a Fast and Accurate ProteinDocking Strategy. PLoS ONE. 2015;10(3):e0118107. DOI: 10.1371/journal.pone.0118107
1932-6203
http://hdl.handle.net/10230/23611
http://dx.doi.org/10.1371/journal.pone.0118107
eng
PLoS ONE. 2015;10(3):e0118107
info:eu-repo/grantAgreement/ES/3PN/BIO2011-22568
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
© 2015 Segura et al. This is an openaccess article distributed under the terms of the http://creativecommons.org/licenses/by/4.0/, which permitsunrestricted use, distribution, and reproduction in anymedium, provided the original author and source arecredited
Public Library of Science
oai:repositori.upf.edu:10230/236122021-05-04T11:02:34Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Effect of insulin on ACE2 activity and kidney function in the non-obese diabetic mouse (PLoS ONE (2014))
Riera Oliva, Marta
Márquez, Eva
Clotet, Sergi
Gimeno Beltran, Javier
Roca-Ho, Heleia
Lloreta Trull, Josep, 1958-
Juanpere, Nuria
Batlle, Daniel
Pascual Santos, Julio
Soler, María José
We studied the non-obese diabetic (NOD) mice model because it develops autoimmune diabetes that resembles human type 1 diabetes. In diabetic mice, urinary albumin excretion (UAE) was ten-fold increased at an “early stage” of diabetes, and twenty-fold increased at a “later stage” (21 and 40 days, respectively after diabetes diagnosis) as compared to non-obese resistant controls. In NOD Diabetic mice, glomerular enlargement, increased glomerular filtration rate (GFR) and increased blood pressure were observed in the early stage. In the late stage, NOD Diabetic mice developed mesangial expansion and reduced podocyte number. Circulating and urine ACE2 activity were markedly increased both, early and late in Diabetic mice. Insulin administration prevented albuminuria, markedly reduced GFR, blood pressure, and glomerular enlargement in the early stage; and prevented mesangial expansion and the reduced podocyte number in the late stage of diabetes. The increase in serum and urine ACE2 activity was normalized by insulin administration at the early and late stages of diabetes in Diabetic mice. We conclude that the Diabetic mice develops features of early kidney disease, including albuminuria and a marked increase in GFR. ACE2 activity is increased starting at an early stage in both serum and urine. Moreover, these alterations can be completely prevented by the chronic administration of insulin.
2014
info:eu-repo/semantics/article
Riera M, Márquez E, Clotet S, Gimeno J, Roca-Ho H, Lloreta J et al. Effect of insulin on ACE2 activity and kidney function in the non-obese diabetic mouse. PLoS ONE. 2014;9(1):e84683. DOI: 10.1371/journal.pone.0084683
1932-6203
http://hdl.handle.net/10230/23612
http://dx.doi.org/10.1371/journal.pone.0084683
eng
PLoS ONE. 2014;9(1):e84683
info:eu-repo/semantics/openAccess
© 2014 Riera et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236142020-06-04T10:29:18Zcom_10230_20719com_10230_5542com_10230_23115com_10230_6237col_10230_22498col_10230_23132col_10230_6238
Lifetime occupational exposure to dusts, gases and fumes is associated with bronchitis symptoms and higher diffusion capacity in COPD patients
Rodríguez, Esther
Zock, Jan-Paul
Serra, Ignasi
Antó i Boqué, Josep Maria
Batlle Garcia, Jordi de, 1981-
Donaire González, David
Benet, Marta
Balcells Vilarnau, Eva, 1967-
Monsó, Eduard
Gayete, Angel
García Aymerich, Judith
PAC-COPD Study Group
Background: Occupational exposure to dusts, gases and fumes has been associated with reduced FEV1 and sputum production in COPD patients. The effect of occupational exposure on other characteristics of COPD, especially those reflecting emphysema, has not been studied in these patients. Methods: We studied 338 patients hospitalized for a first exacerbation of COPD in 9 Spanish hospitals, obtaining full occupational history in a face-to-face interview; job codes were linked to a job exposure matrix for semi-quantitative estimation of exposure to mineral/biological dust, and gases/fumes for each job held. Patients underwent spirometry, diffusing capacity testing and analysis of gases in stable conditions. Quality of life, dyspnea and chronic bronchitis symptoms were determined with a questionnaire interview. A high- resolution CT scan was available in 133 patients. Results: 94% of the patients included were men, with a mean age of 68(8.5) years and a mean FEV1% predicted 52 (16). High exposure to gases or fumes was associated with chronic bronchitis, and exposure to mineral dust and gases/fumes was associated with higher scores for symptom perception in the St. George’s questionnaire. No occupational agent was associated with a lower FEV1. High exposure to all occupational agents was associated with better lung diffusion capacity, in long-term quitters. In the subgroup with CT data, patients with emphysema had 18% lower DLCO compared to those without emphysema. Conclusions: In our cohort of COPD patients, high exposure to gases or fumes was associated with chronic bronchitis, and high exposure to all occupational agents was consistently associated with better diffusion capacity in long-term quitters.
2014
info:eu-repo/semantics/article
Rodríguez E, Ferrer J, Zock JP, Serra I, Antó JM, Batlle J et al. Lifetime occupational exposure to dusts, gases and fumes is associated with bronchitis symptoms and higher diffusion capacity in COPD patients. PLoS ONE. 2014;9(2):e88426. DOI: 10.1371/journal.pone.0088426
1932-6203
http://hdl.handle.net/10230/23614
http://dx.doi.org/10.1371/journal.pone.0088426
eng
PLoS ONE. 2014;9(2):e88426
info:eu-repo/semantics/openAccess
© 2014 Rodríguez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236162020-06-05T07:51:08Zcom_10230_20545com_10230_5542com_10230_23115com_10230_20719com_10230_6237col_10230_22227col_10230_23132col_10230_22498col_10230_8581col_10230_6238
Polymorphisms in ABC transporter genes and concentrations of mercury in newborns - Evidence from two Mediterranean birth cohorts
Llop, Sabrina
Engström, Karin
Ballester Díez, Ferran
Franforte, Elisa
Alhamdow, Ayman
Pisa, Federica
Tratnik, Janja Snoj
Mazej, Datja
Murcia, Mario
Rebagliato, Marisa
Bustamante Pineda, Mariona
Sunyer Deu, Jordi
Sofianou-Katsoulis, Aikaterini
Prasouli, Alexia
Antonopoulou, Eleni
Antoniadou, Ioanna
Nakou, Sheena
Barbone, Fabio
Horvat, Milena
Broberg, Karin
Background: The genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes. Objective: To investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg. Methods: The study population consisted of participants (n = 1651) in two birth cohorts, one in Italy and Greece (PHIME) and the other in Spain (INMA). Women were recruited during pregnancy in Italy and Spain, and during the perinatal period in Greece. Total mercury concentrations were measured in cord blood samples by atomic absorption spectrometry. Maternal fish intake during pregnancy was determined from questionnaires. Polymorphisms (n = 5) in the ABC genes ABCA1, ABCB1, ABCC1 and ABCC2 were analysed in both cohorts. Results: ABCB1 rs2032582, ABCC1 rs11075290, and ABCC2 rs2273697 modified the associations between maternal fish intake and cord blood mercury concentrations. The overall interaction coefficient between rs2032582 and log2-transformed fish intake was negative for carriers of GT (β = −0.29, 95%CI −0.47, −0.12) and TT (β = −0.49, 95%CI −0.71, −0.26) versus GG, meaning that for a doubling in fish intake of the mothers, children with the rs2032582 GG genotype accumulated 35% more mercury than children with TT. For rs11075290, the interaction coefficient was negative for carriers of TC (β = −0.12, 95%CI −0.33, 0.09), and TT (β = −0.28, 95%CI −0.51, −0.06) versus CC. For rs2273697, the interaction coefficient was positive when combining GA+AA (β = 0.16, 95%CI 0.01, 0.32) versus GG. Conclusion: The ABC transporters appear to play a role in accumulation of MeHg during early development.
2014
info:eu-repo/semantics/article
Llop S, Engstrom K, Ballester F, Franforte E, Alhamdow A, Pisa F et al. Polymorphisms in ABC transporter genes and concentrations of mercury in newborns - Evidence from two Mediterranean birth cohorts. PLoS ONE. 2014;9(5):e97172. DOI: 10.1371/journal.pone.0097172
1932-6203
http://hdl.handle.net/10230/23616
http://dx.doi.org/10.1371/journal.pone.0097172
eng
PLoS ONE. 2014;9(5):e97172
info:eu-repo/grantAgreement/EC/FP6/16320
info:eu-repo/grantAgreement/EC/FP7/282957
info:eu-repo/semantics/openAccess
© 2014 Llop et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236182020-06-08T09:14:27Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation
Kuypers, Kim PC
Torre Fornell, Rafael de la
Farré Albaladejo, Magí
Yubero Lahoz, Samanta, 1985-
Dziobek, Isabel
Van Den Bos, Wouter
Ramaekers, Johannes G.
The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg), with or without pindolol (20 mg), oxytocin nasal spray (40 IU+16 IU) or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18–26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg) selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors.
2014
info:eu-repo/semantics/article
Kuypers KPC, De La Torre R, Farre M, Yubero-Lahoz S, Dziobek I, Van Den Bos W, Ramaekers JG. No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation. PLoS ONE. 2014;9(6):e100719. DOI: 10.1371/journal.pone.0100719
1932-6203
http://hdl.handle.net/10230/23618
http://dx.doi.org/10.1371/journal.pone.0100719
eng
PLoS ONE. 2014;9(6):e100719
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
© 2014 Kuypers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236202021-12-20T11:13:43Zcom_10230_23115com_10230_5542col_10230_23132
The neuroanatomical basis of panic disorder and social phobia in schizophrenia: a voxel based morphometric study.
Picado, Marisol
Carmona, Susanna
Hoekzema, Elseline
Pailhez, Guillem
Berge Baquero, Daniel
Mané Santacana, Anna
Fauquet, Jordi
Hilferty, Joseph
Moreno, Ana
Cortizo Vidal, Romina
Vilarroya, Óscar
Bulbena Vilarrasa, Antonio
OBJECTIVE: It is known that there is a high prevalence of certain anxiety disorders among schizophrenic patients, especially panic disorder and social phobia. However, the neural underpinnings of the comorbidity of such anxiety disorders and schizophrenia remain unclear. Our study aims to determine the neuroanatomical basis of the co-occurrence of schizophrenia with panic disorder and social phobia. METHODS: Voxel-based morphometry was used in order to examine brain structure and to measure between-group differences, comparing magnetic resonance images of 20 anxious patients, 20 schizophrenic patients, 20 schizophrenic patients with comorbid anxiety, and 20 healthy control subjects. RESULTS: Compared to the schizophrenic patients, we observed smaller grey-matter volume (GMV) decreases in the dorsolateral prefrontal cortex and precentral gyrus in the schizophrenic-anxiety group. Additionally, the schizophrenic group showed significantly reduced GMV in the dorsolateral prefrontal cortex, precentral gyrus, orbitofrontal cortex, temporal gyrus and angular/inferior parietal gyrus when compared to the control group. CONCLUSIONS: Our findings suggest that the comorbidity of schizophrenia with panic disorder and social phobia might be characterized by specific neuroanatomical and clinical alterations that may be related to maladaptive emotion regulation related to anxiety. Even thought our findings need to be replicated, our study suggests that the identification of neural abnormalities involved in anxiety, schizophrenia and schizophrenia-anxiety may lead to an improved diagnosis and management of these conditions.
2015
info:eu-repo/semantics/article
Picado M, Carmona S, Hoekzema E, Pailhez G, Bergé D, Mané A. The neuroanatomical basis of panic disorder and social phobia in schizophrenia: a voxel based morphometric study. PLoS One. 2015 Mar 16;10(3):e0119847. doi: 10.1371/journal.pone.0119847. eCollection 2015.
1932-6203
http://hdl.handle.net/10230/23620
http://dx.doi.org/10.1371/journal.pone.0119847
eng
PLoS One. 2015 Mar 16;10(3):e0119847
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
© 2015 Picado et al. This is an openaccess article distributed under the terms of the http://creativecommons.org/licenses/by/4.0/, which permitsunrestricted use, distribution, and reproduction in anymedium, provided the original author and source arecredited.
Public Library of Science
oai:repositori.upf.edu:10230/236292020-06-04T10:30:01Zcom_10230_6237com_10230_5542com_10230_23115col_10230_6238col_10230_23132
Transient exposure to ethanol during zebrafish embryogenesis results in defects in neuronal differentiation: An alternative model system to study FASD
Joya, Xavier
García Algar, Oscar
Vall, Oriol
Pujades Corbi, Cristina
Background: The exposure of the human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the impairment of the development of the central nervous system (CNS). In spite of the importance for human health, the molecular basis of prenatal ethanol exposure remains poorly understood, mainly to the difficulty of sample collection. Zebrafish is now emerging as a powerful organism for the modeling and the study of human diseases. In this work, we have assessed the sensitivity of specific subsets of neurons to ethanol exposure during embryogenesis and we have visualized the sensitive embryonic developmental periods for specific neuronal groups by the use of different transgenic zebrafish lines. Methodology/Principal Findings: In order to evaluate the teratogenic effects of acute ethanol exposure, we exposed zebrafish embryos to ethanol in a given time window and analyzed the effects in neurogenesis, neuronal differentiation and brain patterning. Zebrafish larvae exposed to ethanol displayed small eyes and/or a reduction of the body length, phenotypical features similar to the observed in children with prenatal exposure to ethanol. When neuronal populations were analyzed, we observed a clear reduction in the number of differentiated neurons in the spinal cord upon ethanol exposure. There was a decrease in the population of sensory neurons mainly due to a decrease in cell proliferation and subsequent apoptosis during neuronal differentiation, with no effect in motoneuron specification. Conclusion: Our investigation highlights that transient exposure to ethanol during early embryonic development affects neuronal differentiation although does not result in defects in early neurogenesis. These results establish the use of zebrafish embryos as an alternative research model to elucidate the molecular mechanism(s) of ethanol-induced developmental toxicity at very early stages of embryonic development.
2014
info:eu-repo/semantics/article
Joya X, García-Algar O, Vall O, Pujades C. Transient exposure to ethanol during zebrafish embryogenesis results in defects in neuronal differentiation: An alternative model system to study FASD. PLoS ONE. 2014;9(11):e112148. DOI: 10.1371/journal.pone.0112851
1932-6203
http://hdl.handle.net/10230/23629
http://dx.doi.org/10.1371/journal.pone.0112851
eng
PLoS ONE. 2014;9(11):e11214
info:eu-repo/grantAgreement/ES/3PN/BFU2012-31994
info:eu-repo/semantics/openAccess
© 2014 Joya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236312020-06-05T07:54:21Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238
Increased N-glycosylation efficiency by generation of an aromatic sequon on N135 of antithrombin
Águila, Sonia
Martínez-Martínez, Irene
Dichiara, Gilda
Gutiérrez Gallego, Ricardo, 1968-
Navarro-Fernández, José
Vicente, Vicente
Corral, Javier
The inefficient glycosylation of consensus sequence on N135 in antithrombin explains the two glycoforms of this key anticoagulant serpin found in plasma: α and β, with four and three N-glycans, respectively. The lack of this N-glycan increases the heparin affinity of the β-glycoform. Recent studies have demonstrated that an aromatic sequon (Phe-Y-Asn-X-Thr) in reverse β-turns enhances N-glycosylation efficiency and stability of different proteins. We evaluated the effect of the aromatic sequon in this defective glycosylation site of antithrombin, despite of being located in a loop between the helix D and the strand 2A. We analyzed the biochemical and functional features of variants generated in a recombinant cell system (HEK-EBNA). Cells transfected with wild-type plasmid (K133-Y-N135-X-S137) generated 50% of α and β-antithrombin. The S137T, as previously reported, K133F, and the double mutant (K133F/S137T) had improved glycosylation efficiency, leading to the secretion of α-antithrombin, as shown by electrophoretic and mass analysis. The presence of the aromatic sequon did not significantly affect the stability of this conformationally sensitive serpin, as revealed by thermal denaturation assay. Moreover, the aromatic sequon hindered the activation induced by heparin, in which is involved the helix D. Accordingly, K133F and particularly K133F/S137T mutants had a reduced anticoagulant activity. Our data support that aromatic sequons in a different structural context from reverse turns might also improve the efficiency of N-glycosylation.
2014
info:eu-repo/semantics/article
Aguila S, Martínez-Martínez I, Dichiara G, Gutiárrez-Gallego R, Navarro-Fernández J, Vicente V, Corral J. Increased N-glycosylation efficiency by generation of an aromatic sequon on N135 of antithrombin. PLoS ONE. 2014;9(12):e114454. DOI: 10.1371/journal.pone.0114454
1932-6203
http://hdl.handle.net/10230/23631
http://dx.doi.org/10.1371/journal.pone.0114454
eng
PLoS ONE. 2014;9(12):e114454
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
2014 Águila et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Public Library of Science (PLoS)
oai:repositori.upf.edu:10230/236352020-06-08T10:11:59Zcom_10230_23115com_10230_5542com_10230_6237col_10230_23132col_10230_6238col_10230_8581
A knowledge-driven approach to extract disease-related biomarkers from the literature
Bravo Serrano, Àlex, 1984-
Cases, Montserrat
Queralt Rosinach, Núria
Sanz, Ferran
Furlong, Laura I., 1971-
The biomedical literature represents a rich source of biomarker information. However, both the size of literature databases and their lack of standardization hamper the automatic exploitation of the information contained in these resources. Text mining approaches have proven to be useful for the exploitation of information contained in the scientific publications. Here, we show that a knowledge-driven text mining approach can exploit a large literature database to extract a dataset of biomarkers related to diseases covering all therapeutic areas. Our methodology takes advantage of the annotation of MEDLINE publications pertaining to biomarkers with MeSH terms, narrowing the search to specific publications and, therefore, minimizing the false positive ratio. It is based on a dictionary-based named entity recognition system and a relation extraction module. The application of this methodology resulted in the identification of 131,012 disease-biomarker associations between 2,803 genes and 2,751 diseases, and represents a valuable knowledge base for those interested in disease-related biomarkers. Additionally, we present a bibliometric analysis of the journals reporting biomarker related information during the last 40 years.
2014
info:eu-repo/semantics/article
Bravo A, Cases M, Queralt-Rosinach N, Sanz F, Furlong LI. A knowledge-driven approach to extract disease-related biomarkers from the literature. BioMed Research International. 2014;2014:253128. DOI: 10.1155/2014/253128
2314-6133
http://hdl.handle.net/10230/23635
http://dx.doi.org/10.1155/2014/253128
eng
BioMed Research International. 2014;2014:253128
info:eu-repo/grantAgreement/EC/FP7/115191
info:eu-repo/grantAgreement/EC/FP7/115002
https://creativecommons.org/licenses/by/3.0/
info:eu-repo/semantics/openAccess
© 2014 À. Bravo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Hindawi
oai:repositori.upf.edu:10230/236362021-07-13T10:06:20Zcom_10230_23115com_10230_5542col_10230_23132
Prediction of week 4 virological response in hepatitis C for making decision on triple therapy: the Optim study.
Romero Gómez, Manuel
Turnes, Juan
Ampuero, Javier
Oyagüez, Itziar
Cuenca, Beatriz
Gonzalez-Garcia, Juan
Muñoz-Molina, Belén
Aguilar, Rocio
Leal, Sandra
Planas, Ramon
Garcia-Samaniego, Javier
Diago, Moises
Crespo, Javier
Calleja, Jose Luis
Casado, Miguel Angel
Solà Lamoglia, Ricard
BACKGROUND: Virological response to peginterferon + ribavirin (P+R) at week 4 can predict sustained virological response (SVR). While patients with rapid virological response (RVR) do not require triple therapy, patients with a decline <1 log10 IU/ml HCVRNA (D1L) should have treatment discontinued due to low SVR rate. AIM: To develop a tool to predict first 4 weeks' viral response in patients with hepatitis C genotype 1&4 treated with P+R. METHODS: In this prospective and multicenter study, HCV mono-infected (n=538) and HCV/HIV co-infected (n=186) patients were included. To develop and validate a prognostic tool to detect RVR and D1L, we segregated the patients as an estimation cohort (to construct the model) and a validation cohort (to validate the model). RESULTS: D1L was reached in 509 (80.2%) and RVR in 148 (22.5%) patients. Multivariate analyses demonstrated that HIV co-infection, Forns' index, LVL, IL28B-CC and Genotype-1 were independently related to RVR as well as D1L. Diagnostic accuracy (AUROC) for D1L was: 0.81 (95%CI: 0.76 ̶ 0.86) in the estimation cohort and 0.71 (95%CI: 0.62 ̶ 0.79) in the validation cohort; RVR prediction: AUROC 0.83 (95%CI: 0.78 ̶ 0.88) in the estimation cohort and 0.82 (95%CI: 0.76 ̶ 0.88) in the validation cohort. Cost-analysis of standard 48-week treatment indicated a saving of 30.3% if the prognostic tool is implemented. CONCLUSIONS:/nThe combination of genetic (IL28B polymorphism) and viral genotype together with viral load, HIV co-infection and fibrosis stage defined a tool able to predict RVR and D1L at week 4. Using this tool would be a cost-saving strategy compared to universal triple therapy for hepatitis C.
2015
info:eu-repo/semantics/article
Romero-Gómez M, Turnes J, Ampuero J, Oyagüez I, Cuenca B, Gonzalez-Garcia J. et. al. Prediction of Week 4 Virological Response in Hepatitis C for Making Decision on Triple Therapy: The Optim Study. /n PLoS One. 2015 Mar 31;10(3):e0122613. doi: 10.1371/journal.pone.0122613. eCollection 2015.
1932-6203
http://hdl.handle.net/10230/23636
http://dx.doi.org/10.1371/journal.pone.0122613
eng
PLoS One. 2015 Mar 31;10(3):e0122613
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
© 2015 Romero-Gómez et al. This is anopen access article distributed under the terms of the http://creativecommons.org/licenses/by/4.0/, which permitsunrestricted use, distribution, and reproduction in anymedium, provided the original author and source arecredited.
Public Library of Science
qdc///col_10230_23132/100