Publications

958 Publications visible to you, out of a total of 958

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PURPOSE: The aim of this study was to test psychometric properties of the Satisfaction with Life Scale (SWLS), to provide normative values, and to analyze associations between life satisfaction and sociodemographic and behavioral data. METHODS: A German community sample (n = 9711) with an age range of 18-80 years was surveyed using the SWLS and several other questionnaires. Confirmatory factor analysis (CFA) was used to test the dimensionality of the SWLS. Invariance across gender and age groups was tested with multiple-group CFA. Associations between SWLS, sociodemographic variables, and behavioral variables were tested with ANOVAs. RESULTS: Confirmatory factorial analysis results confirmed that the SWLS is a one-dimensional scale. Measurement invariance across gender was completely confirmed, while concerning age strict measurement invariance was confirmed. The effects of gender and age on satisfaction with life were weak. Satisfaction with life was associated with fatigue (r = - .49), the mental component of quality of life (r = .45), anxiety (r = - .42), dispositional optimism (r = .41), pessimism (r = - .34), sleep quality (r = - .32), and sociodemographic factors such as marital status, income, and occupational status. Non-smokers reported higher life satisfaction than smokers. CONCLUSIONS: Because of the good psychometric properties, the SWLS can be recommended for use in epidemiological research. Normative values based on a large community sample are provided.

Authors: A. Hinz, I. Conrad, M. L. Schroeter, H. Glaesmer, E. Brahler, M. Zenger, R. D. Kocalevent, P. Y. Herzberg

Date Published: 29th Mar 2018

Publication Type: Not specified

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In the development of cell-based medicinal products, it is crucial to guarantee that the application of such an advanced therapy medicinal product (ATMP) is safe for the patients. The consensus of the European regulatory authorities is: \textquotedblIn conclusion, on the basis of the state of art, conventional karyotyping can be considered a valuable and useful technique to analyse chromosomal stability during preclinical studies\textquotedbl. 408 chondrocyte samples (84 monolayers and 324 spheroids) from six patients were analysed using trypsin-Giemsa staining, spectral karyotyping and fluorescence in situ hybridisation, to evaluate the genetic stability of chondrocyte samples from non-clinical studies. Single nucleotide polymorphism (SNP) array analysis was performed on chondrocyte spheroids from five of the six donors. Applying this combination of techniques, the genetic analyses performed revealed no significant genetic instability until passage 3 in monolayer cells and interphase cells from spheroid cultures at different time points. Clonal occurrence of polyploid metaphases and endoreduplications were identified associated with prolonged cultivation time. Also, gonosomal losses were observed in chondrocyte spheroids, with increasing passage and duration of the differentiation phase. Interestingly, in one of the donors, chromosomal aberrations that are also described in extraskeletal myxoid chondrosarcoma were identified. The SNP array analysis exhibited chromosomal aberrations in two donors and copy neutral losses of heterozygosity regions in four donors. This study showed the necessity of combined genetic analyses at defined cultivation time points in quality studies within the field of cell therapy.

Authors: M. Wallenborn, O. Petters, D. Rudolf, H. Hantmann, M. Richter, P. Ahnert, L. Rohani, J. J. Smink, G. C. Bulwin, W. Krupp, R. M. Schulz, H. Holland

Date Published: 23rd Mar 2018

Publication Type: Journal article

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An increasing number of genetic variants involved in dyslexia development were discovered during the last years, yet little is known about the molecular functional mechanisms of these SNPs. In this study we investigated whether dyslexia candidate SNPs have a direct, disease-specific effect on local expression levels of the assumed target gene by using a differential allelic expression assay. In total, 12 SNPs previously associated with dyslexia and related phenotypes were suitable for analysis. Transcripts corresponding to four SNPs were sufficiently expressed in 28 cell lines originating from controls and a family affected by dyslexia. We observed a significant effect of rs600753 on expression levels of DYX1C1 in forward and reverse sequencing approaches. The expression level of the rs600753 risk allele was increased in the respective seven cell lines from members of the dyslexia family which might be due to a disturbed transcription factor binding sites. When considering our results in the context of neuroanatomical dyslexia-specific findings, we speculate that this mechanism may be part of the pathomechanisms underlying the dyslexia-specific brain phenotype. Our results suggest that allele-specific DYX1C1 expression levels depend on genetic variants of rs600753 and contribute to dyslexia. However, these results are preliminary and need replication.

Authors: Bent Müller, Johannes Boltze, Ivonne Czepezauer, Volker Hesse, Arndt Wilcke, Holger Kirsten

Date Published: 1st Mar 2018

Publication Type: Journal article

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Objective Adipose tissue-derived signals potentially link obesity and adipose tissue dysfunction with metabolic and cardiovascular diseases. Although some adipocytokines have been closely related too metabolic and cardiovascular traits, it remains open which adipocytokine or adipocytokine cluster serve as meaningful marker of metabolic syndrome (MS) components. Therefore, this study investigates the associations of twelve adipocytokines with components of the MS to identify the most relevant cytokines potentially related to specific metabolic profiles. Research Design/Methods Twelve cytokines (adiponectin, adipocyte fatty acid-binding protein [AFABP], angiopoietin-related growth factor, chemerin, fibroblast growth factor [FGF] 19, FGF21, FGF23, insulin-like growth factor-1, interleukin 10, irisin, progranulin, vaspin) were quantified in a cross-sectional cohort of 1046 subjects. Hypothesis-free cluster analysis, multivariate regression analyses with parameters of the MS, and discriminant analysis were performed to assess associations and the relative importance of each cytokine for reflecting MS and its components. Results Among the studied adipocytokines, adiponectin, AFABP, chemerin, and FGF21 showed the strongest associations with MS and several MS components in discriminant analyses and multiple regression models. For certain metabolic components, these adipocytokines were better discriminators than routine metabolic markers. Other cytokines investigated in the present cohort are less potent to discriminate between metabolically healthy and unhealthy subjects. Conclusions Adiponectin, AFABP, chemerin, and FGF21 show strongest associations with MS components in a general population suggesting that adverse adipose tissue function represents a major contributor to these metabolic abnormalities. Future prospective studies need to address the question whether these adipocytokines are able to predict the development of metabolic disease states.

Authors: Thomas Ebert, Claudia Gebhardt, Markus Scholz, Tobias Wohland, Dorit Schleinitz, Mathias Fasshauer, Matthias Blüher, Michael Stumvoll, Peter Kovacs, Anke Tönjes

Date Published: 1st Mar 2018

Publication Type: Journal article

Abstract (Expand)

Progranulin is a secreted protein with important functions in processes including immune and inflammatory response, metabolism and embryonic development. The present study aimed at identification of genetic factors determining progranulin concentrations. We conducted a genome-wide association meta-analysis for serum progranulin in three independent cohorts from Europe: Sorbs (N = 848) and KORA (N = 1628) from Germany and PPP-Botnia (N = 335) from Finland (total N = 2811). Single nucleotide polymorphisms (SNPs) associated with progranulin levels were replicated in two additional German cohorts: LIFE-Heart Study (Leipzig; N = 967) and Metabolic Syndrome Berlin Potsdam (Berlin cohort; N = 833). We measured mRNA expression of genes in peripheral blood mononuclear cells (PBMC) by micro-arrays and performed mRNA expression quantitative trait and expression-progranulin association studies to functionally substantiate identified loci. Finally, we conducted siRNA silencing experiments in vitro to validate potential candidate genes within the associated loci. Heritability of circulating progranulin levels was estimated at 31.8% and 26.1% in the Sorbs and LIFE-Heart cohort, respectively. SNPs at three loci reached study-wide significance (rs660240 in CELSR2-PSRC1-MYBPHL-SORT1, rs4747197 in CDH23-PSAP and rs5848 in GRN) explaining 19.4%/15.0% of the variance and 61%/57% of total heritability in the Sorbs/LIFE-Heart Study. The strongest evidence for association was at rs660240 (P = 5.75 x 10-50), which was also associated with mRNA expression of PSRC1 in PBMC (P = 1.51 x 10-21). Psrc1 knockdown in murine preadipocytes led to a consecutive 30% reduction in progranulin secretion. In conclusion, the present meta-GWAS combined with mRNA expression identified three loci associated with progranulin and supports the role of PSRC1 in the regulation of progranulin secretion.

Authors: A. Tonjes, M. Scholz, J. Kruger, K. Krause, D. Schleinitz, H. Kirsten, C. Gebhardt, C. Marzi, H. Grallert, C. Ladenvall, H. Heyne, E. Laurila, J. Kriebel, C. Meisinger, W. Rathmann, C. Gieger, L. Groop, I. Prokopenko, B. Isomaa, F. Beutner, J. Kratzsch, A. Fischer-Rosinsky, A. Pfeiffer, K. Krohn, J. Spranger, J. Thiery, M. Bluher, M. Stumvoll, P. Kovacs

Date Published: 1st Feb 2018

Publication Type: Journal article

Abstract

Not specified

Authors: Alfred Winter, Katsuhiko Takabayashi, Franziska Jahn, Eizen Kimura, Rolf Engelbrecht, Reinhold Haux, Masayuki Honda, Ursula Hübner, Sozo Inoue, Christian Dominik Kohl, Takehiro Matsumoto, Yasushi Matsumura, Kengo Miyo, Naoki Nakashima, Hans-Ulrich Prokosch, Martin Staemmler

Date Published: 31st Jan 2018

Publication Type: Journal article

Abstract (Expand)

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper \textquotedblRepresentation of People’s Decisions in Health Information Systems: A Complementary Approach for Understanding Health Care Systems and Population Health\textquotedbl written by Fernan Gonzalez Bernaldo de Quiros, Adriana Ruth Dawidowski, and Silvana Figar. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the paper of de Quiros, Dawidowski, and Figar. In subsequent issues the discussion can continue through letters to the editor.

Authors: Najeeb Al-Shorbaji, Elizabeth M. Borycki, Michio Kimura, Christoph U. Lehmann, Nancy M. Lorenzi, Lincoln A. Moura, Alfred Winter

Date Published: 31st Jan 2018

Publication Type: Journal article

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