12 research outputs found

    Environmental factors in early childhood are associated with multiple sclerosis: a case-control study

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    <p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with increasing incidence mainly in high-income countries. One explanation of this phenomenon may be a higher prevalence of allergic and autoimmune diseases in industrialized countries as a consequence of otherwise beneficial advances in sanitation (hygiene hypothesis). We investigated environmental factors in early childhood associated with MS.</p> <p>Methods</p> <p>A case-control study was performed of 245 MS patients and 296 population-based controls in Berlin. The study participants completed a standardized questionnaire on environmental factors in childhood and youth, including aspects of personal and community hygiene. Multivariable logistic regression analysis was performed to investigate factors in childhood and youth associated with the occurrence of MS.</p> <p>Results</p> <p>Mean age was 46 years (range, 20-80) in the MS group and 42 years (range 18-80) in the control group, of which 73.9% in the MS and 61.5% in the control group were female. The multivariable analysis showed that having at least two older siblings (OR 0.54; p = 0.05, for individuals with two older siblings compared to individuals without older siblings), attending a day-care center (OR 0.5; p = 0.004) and growing up in an urban center with more than 100, 000 inhabitants (OR 0.43; p = 0.009) were factors independently associated with a lower chance for MS.</p> <p>Conclusions</p> <p>The hygiene hypothesis may play a role in the occurrence of MS and could explain disease distribution and increasing incidence.</p

    Association between the ACCN1 Gene and Multiple Sclerosis in Central East Sardinia

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    Multiple genome screens have been performed to identify regions in linkage or association with Multiple Sclerosis (MS, OMIM 126200), but little overlap has been found among them. This may be, in part, due to a low statistical power to detect small genetic effects and to genetic heterogeneity within and among the studied populations. Motivated by these considerations, we studied a very special population, namely that of Nuoro, Sardinia, Italy. This is an isolated, old, and genetically homogeneous population with high prevalence of MS. Our study sample includes both nuclear families and unrelated cases and controls. A multi-stage study design was adopted. In the first stage, microsatellites were typed in the 17q11.2 region, previously independently found to be in linkage with MS. One significant association was found at microsatellite D17S798. Next, a bioinformatic screening of the region surrounding this marker highlighted an interesting candidate MS susceptibility gene: the Amiloride-sensitive Cation Channel Neuronal 1 (ACCN1) gene. In the second stage of the study, we resequenced the exons and the 3â€Č untranslated (UTR) region of ACCN1, and investigated the MS association of Single Nucleotide Polymorphisms (SNPs) identified in that region. For this purpose, we developed a method of analysis where complete, phase-solved, posterior-weighted haplotype assignments are imputed for each study individual from incomplete, multi-locus, genotyping data. The imputed assignments provide an input to a number of proposed procedures for testing association at a microsatellite level or of a sequence of SNPs. These include a Mantel-Haenszel type test based on expected frequencies of pseudocase/pseudocontrol haplotypes, as well as permutation based tests, including a combination of permutation and weighted logistic regression analysis. Application of these methods allowed us to find a significant association between MS and the SNP rs28936 located in the 3â€Č UTR segment of ACCN1 with p = 0.0004 (p = 0.002, after adjusting for multiple testing). This result is in tune with several recent experimental findings which suggest that ACCN1 may play an important role in the pathogenesis of MS

    What interests do intermediaries prioritize during wind- and solar project development?

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    A transition towards a low-carbon energy system requires the large-scale diffusion of renewable electricity (RE) technologies. Intermediary actors, such as installers, project developers or consultants, can facilitate this process by supporting RE adopters. Recent studies have also pointed out that there are potential drawbacks associated with intermediary support. Acting as filters and gatekeepers, intermediaries have the complex mission to prioritize between various stakeholder interests, including their own profit maximization. The aim of this research is to understand what stakeholder interests intermediaries prioritize when developing RE projects. Results of a choice experiment with third-party developers in Sweden highlight differences between technologies: wind developers prioritize electricity output, while solar developers prioritize client satisfaction. Despite being for-profit organizations, intermediaries did not prioritize their own interests over the interests of their clients. Solar PV developers prioritize client satisfaction over maximization of electricity output, which may have negative implications for the efficiency of the projects

    5th Europe Colloquium of Constance - Final Report

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    Vom 6. bis 8. Juni 2008 diskutierten Studierende aus ganz Europa mit europĂ€ischen Vertretern aus Politik, Wissenschaft und Wirtschaft ĂŒber die Struktur und die Zukunft der europĂ€ischen Energiewirtschaft. Das Thema des 5. Europakolloquiums lautete: Energiewirtschaft in Europa: Im Spannungsfeld zwischen Klimapolitik, Wettbewerb und Versorgungssicherheit.Dieser Abschlußbericht soll die Vorbereitung, die drei Veranstaltungstage und den allgemeinen Ablauf dieser Veranstaltung Revue passieren lassen und dabei auch die angeregten Diskussionen, WidersprĂŒche und weiterfĂŒhrenden Fragen und LösungsvorschlĂ€ge darstellen, die durch die Diskussionen entstanden. Des weiteren soll dieser Bericht Informationen zu der GrĂ¶ĂŸe der Veranstaltung, der Zusammensetzung der Redner und Teilnehmer, sowie zu dem großen Medienecho aufzeigen. Dieser Überblick dient dabei als Dokumentation der vergangenen Veranstaltung, aber auch als Anregung fĂŒr zukĂŒnftige Veranstaltungen Ă€hnlicher Art

    A sorrow shared is a sorrow halved? Patient and parental anxiety associated with venipuncture in children before and after liver transplantation

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    Taking blood via venipuncture is part of the necessary surveillance before and after liver transplantation. The spectrum of response from children and their parents is variable, ranging from a short and limited aversion to paralyzing phobia. The aim of this retrospective, cross-sectional study was to determine the level of anxiety amongst children during venipuncture, to compare the anxiety reported by children and parents, and to identify the factors affecting the children’s and parents’ anxiety in order to develop therapeutic strategies. In total, 147 children (aged 0–17 years, 78 female) and their parents completed questionnaires. Statistical analysis was performed using qualitative and quantitative methods. Results showed that the majority of children reported anxiety and pain during venipuncture. Younger children had more anxiety (self-reported or assessed by parents). Children and parental reports of anxiety were highly correlated. However, the child’s anxiety was often reported as higher by parents than by the children themselves. The child’s general anxiety as well as the parents’ perceived stress from surgical interventions (but not the number of surgical interventions) prompted parental report of child anxiety. For children, the main stressors that correlated with anxiety and pain were factors during the blood collection itself (e.g., feeling the puncture, seeing the syringe). Parental anxiety was mainly related to circumstances before the blood collection (e.g., approaching the clinic, sitting in the waiting room). The main stressors mentioned by parents were the child’s discomfort and their inability to calm the child. Results indicate that the children’s fear of factors during the blood collection, along with the parents’ perceived stress and helplessness as well as their anticipatory anxiety are important starting points for facilitating the drawing of blood from children before and after liver transplantation, thereby supporting a better disease course in the future

    Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

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    Background Vitamin D insufficiency has been implicated in autoimmunity. ChIP-seq experiments using immune cell lines have shown that vitamin D receptor (VDR) binding sites are enriched near regions of the genome associated with autoimmune diseases. We aimed to investigate VDR binding in primary CD4+ cells from healthy volunteers. Methods We extracted CD4+ cells from nine healthy volunteers. Each sample underwent VDR ChIP-seq. Our results were analyzed in relation to published ChIP-seq and RNA-seq data in the Genomic HyperBrowser. We used MEMEChIP for de novo motif discovery. 25-Hydroxyvitamin D levels were measured using liquid chromatography–tandem mass spectrometry and samples were divided into vitamin D sufficient (25(OH)D ≄75 nmol/L) and insufficient/deficient (25(OH)D <75 nmol/L) groups. Results We found that the amount of VDR binding is correlated with the serum level of 25-hydroxyvitamin D (r = 0.92, P= 0.0005). In vivo VDR binding sites are enriched for autoimmune disease associated loci, especially when 25-hydroxyvitamin D levels (25(OH)D) were sufficient (25(OH)D ≄75: 3.13-fold, P<0.0001; 25(OH)D <75: 2.76-fold, P<0.0001; 25(OH)D ≄75 enrichment versus 25(OH)D <75 enrichment: P= 0.0002). VDR binding was also enriched near genes associated specifically with T-regulatory and T-helper cells in the 25(OH)D ≄75 group. MEME ChIP did not identify any VDR-like motifs underlying our VDR ChIP-seq peaks. Conclusion Our results show a direct correlation between in vivo 25-hydroxyvitamin D levels and the number of VDR binding sites, although our sample size is relatively small. Our study further implicates VDR binding as important in gene-environment interactions underlying the development of autoimmunity and provides a biological rationale for 25-hydroxyvitamin D sufficiency being based at 75 nmol/L. Our results also suggest that VDR binding in response to physiological levels of vitamin D occurs predominantly in a VDR motif-independent manner

    Inhibitory Effect of Polyunsaturated Fatty Acids on MMP-9 Release from Microglial Cells – Implications for Complementary Multiple Sclerosis Treatment

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    We investigated whether polyunsaturated fatty acids (PUFA), which might be a useful complementary therapy among patients with multiple sclerosis (MS), are able to modulate matrix metalloproteinase (MMP) production in microglial cultures. MMPs are myelinotoxic factors. Primary cultures of rat microglia were treated with different doses of omega-3 (x-3) PUFA or puriïŹed ïŹsh oil, containing a mixture of x-3 and x-6 PUFA, and simultaneously activated by exposure to lipopolysaccharide (LPS). Culture supernatants were subjected to zymography and Western blot analysis for the assessment of MMP-2 and MMP-9 levels. Increased amounts of MMP-9, but not of the constitutively expressed MMP-2, were observed in supernatants from LPS-treated microglia in comparison with non-treated control cells. The treatment with both x-3 PUFA and ïŹsh oil dose-dependently inhibited the LPSinduced production of MMP-9. Our results suggest that a low fat diet supplemented with x-3 PUFA may become recommended for the well being of MS patients under therap
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