Diet Quality Scores and Prediction of All-Cause, Cardiovascular and Cancer Mortality in a Pan-European Cohort Study.

Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors.The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/ A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford) (United Kingdom).This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pone.015902

Response of Leucocyte Populations in the Ileal Peyer's Patch of Fetal Lambs Treated with Ferritin Per Os

A combination of immunohistochemical techniques, a panel of monoclonal antibodies, and computer-assisted morphometric analysis was used to examine the response of the ileal Peyerr's patch of fetal lambs 7 days after treatment with ferritin per os. Consistent with previous studies in fetal lambs that have reported the ileal Peyer's patch to be indifferent to antigen, the present study did not find any significant changes in the size of the predominantly B-cell dome/follicle compartment or the predominantly T-cell interfollicular area, nor were differences identified in the distribution of IgM-positive (+), CD4 +, and CD8+ cells in these two compartments. However, both compartments showed a significant increase (P < 0.05) in the percentage of area occupied by MHC II + cells and a significant decrease (P < 0.05) in the percentage of area occupied by CD44+ and B5+ cells. These changes show that the ileal Peyer’s patch of fetal lambs is not indifferent to antigen and may represent the transition of a purely primary lymphoid organ to an organ that has both primary and secondary lymphoid functions

Whole genome sequencing and characterization of a virulent Newcastle disease virus isolated from an outbreak in Sweden

In this study, the complete genome sequence of a Newcastle disease virus (NDV) isolate collected from an outbreak in 1995 in chickens was fully characterized and compared with other NDV sequences. The genome was found to be 15,192 nucleotides long and to consist of six genes in the order 3′-NP-P-M-F-HN-L-5′, similar to other avian paramyxoviruses type-I. However, a six-nucleotide insertion was observed in the 5′ non-coding regions of the nucleoprotein (NP) gene, a feature that is unique to some NDV isolates. The isolate shows the amino acid sequence 112RRQKRF 117 at the cleavage site of the F protein, which is identical to a known motif for virulent pathotypes of NDV. The phylogenetic analysis of the coding region of the F gene indicated that this isolate belongs to genotype VI, more specifically to genotype VId, along with isolates from the other European countries (Denmark, Switzerland and Austria). The same genotype caused outbreaks in the Middle East and Greece in the late 1960s, and in Hungary, in the early 1980s, suggesting a common source for these outbreaks

Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes

A plethora of candidate genes have been identified for complex polygenic disorders, but the underlying disease mechanisms remain largely unknown. We explored the pathophysiology of type 2 diabetes (T2D) by analyzing global gene expression in human pancreatic islets. A group of coexpressed genes (module), enriched for interleukin-1-related genes, was associated with T2D and reduced insulin secretion. One of the module genes that was highly overexpressed in islets from T2D patients is SFRP4, which encodes secreted frizzled-related protein 4. SFRP4 expression correlated with inflammatory markers, and its release from islets was stimulated by interleukin-1β. Elevated systemic SFRP4 caused reduced glucose tolerance through decreased islet expression of Ca(2+) channels and suppressed insulin exocytosis. SFRP4 thus provides a link between islet inflammation and impaired insulin secretion. Moreover, the protein was increased in serum from T2D patients several years before the diagnosis, suggesting that SFRP4 could be a potential biomarker for islet dysfunction in T2D

Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism

Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5'-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion. In addition, we provide a genome-wide catalog of allelic expression imbalance, which is also enriched in known T2D-associated loci. Notably, allelic imbalance in paternally expressed gene 3 (PEG3) was associated with its promoter methylation and T2D status. Finally, RNA editing events were less common in islets than previously suggested in other tissues. Taken together, this study provides new insights into the complexity of gene regulation in human pancreatic islets and better understanding of how genetic variation can influence glucose metabolism

Description of the scoring system of the 10 dietary (and lifestyle) scores.

<p>Description of the scoring system of the 10 dietary (and lifestyle) scores.</p

Characteristics of the study population included, n = 451,256 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC).

<p>Characteristics of the study population included, n = 451,256 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC).</p