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Medizin - Open Access LMU - Teil 16/22 Ludwig-Maximilians-Universität München

    • Onderwijs

Die Universitätsbibliothek (UB) verfügt über ein umfangreiches Archiv an elektronischen Medien, das von Volltextsammlungen über Zeitungsarchive, Wörterbücher und Enzyklopädien bis hin zu ausführlichen Bibliographien und mehr als 1000 Datenbanken reicht. Auf iTunes U stellt die UB unter anderem eine Auswahl an elektronischen Publikationen der Wissenschaftlerinnen und Wissenschaftler an der LMU bereit. (Dies ist der 16. von 22 Teilen der Sammlung 'Medizin - Open Access LMU'.)

    How will their airways be? Respiratory health 15 years after the start of apprenticeship

    How will their airways be? Respiratory health 15 years after the start of apprenticeship

    Declining 1-year case-fatality of stroke and increasing coverage of vascular risk management: population-based cohort study

    Declining 1-year case-fatality of stroke and increasing coverage of vascular risk management: population-based cohort study

    Background The authors estimated trends in 1-year case-fatality of stroke in relation to changes in vascular risk management from 1997 to 2005.Methods A cohort study was implemented using data for 407 family practices in the UK General Practice Research Database, including subjects with first acute strokes between 1997 and 2005. One-year case-fatality was estimated by year and sex. Rate ratios were estimated using Poisson regression.Results There were 19 143 women and 16 552 men who had first acute strokes between 1997 and 2005. In women, the 1-year case-fatality declined from 41.2% in 1997 to 29.2% in 2005. In men, the decline was from 29.2% in 1997 to 22.2% in 2005. The proportion of general practices that prescribed antihypertensive drugs to two-thirds or more of new patients with stroke increased from 6% in 1997 to 48% in 2005, for statins from 1% to 39% and for antiplatelet drugs from 11% to 39%. The rate ratio for 1-year mortality in 2005, compared with 1997--1998, adjusted for age group, sex, prevalent coronary heart disease, prevalent hypertension and deprivation quintile was 0.79 (0.74 to 0.86, p0.001). After adjustment for antihypertensive, statin and antiplatelet prescribing, the rate ratio was 1.29 (1.17 to 1.42).Conclusions Reducing 1-year case-fatality after acute stroke may be partly explained by increased prescribing of antihypertensive, statin and antiplatelet drugs to patients with recent strokes. However, these analyses did not include measures of possible changes over time in stroke severity or acute stroke management.

    ASAS/WHO ICF Core Sets for ankylosing spondylitis (AS): how to classify the impact of AS on functioning and health

    ASAS/WHO ICF Core Sets for ankylosing spondylitis (AS): how to classify the impact of AS on functioning and health

    Objective: To report on the results of a standardised consensus process agreeing on concepts typical and/or relevant when classifying functioning and health in patients with ankylosing spondylitis (AS) based on the International Classification of Functioning and Health (ICF).Methods: Experts in AS from different professional and geographical backgrounds attended a consensus conference and were divided into three working groups. Rheumatologists were selected from members of the Assessment of SpondyloArthritis international Society (ASAS). Other health professionals were recommended by ASAS members. The aim was to compose three working groups with five to seven participants to allow everybody's contribution in the discussions. Experts selected ICF categories that were considered typical and/or relevant for AS during a standardised consensus process by integrating evidence from preceding studies in alternating working group and plenary discussions. A Comprehensive ICF Core Set was selected for the comprehensive classification of functioning and a Brief ICF Core Set for application in trials.Results: The conference was attended by 19 experts from 12 countries. Eighty categories were included in the Comprehensive Core Set, which included 23 Body functions, 19 Body structures, 24 Activities and participation and 14 Environmental factors. Nineteen categories were selected for the Brief Core Set, which included 6 Body functions, 4 Body structures, 7 Activities and participation and 2 Environmental factors.Conclusion: The Comprehensive and Brief ICF Core Sets for AS are now available and aim to represent the external reference to define consequences of AS on functioning.

    The NOD2 single nucleotide polymorphisms rs2066843 and rs2076756 are novel and common Crohn's disease susceptibility gene variants

    The NOD2 single nucleotide polymorphisms rs2066843 and rs2076756 are novel and common Crohn's disease susceptibility gene variants

    Background: The aims were to analyze two novel NOD2 variants (rs2066843 and rs2076756) in a large cohort of patients with inflammatory bowel disease and to elucidate phenotypic consequences. Methodology/Principal Findings:
    Genomic DNA from 2700 Caucasians including 812 patients with Crohn's disease (CD), 442 patients with ulcerative colitis (UC), and 1446 healthy controls was analyzed for the NOD2 SNPs rs2066843 and rs2076756 and the three main CD-associated NOD2 variants p.Arg702Trp (rs2066844), p.Gly908Arg (rs2066847), and p.Leu1007fsX1008 (rs2066847). Haplotype and genotype-phenotype analyses were performed. The SNPs rs2066843 (p = 3.01×10−5, OR 1.48, [95% CI 1.23-1.78]) and rs2076756 (p = 4.01×10−6; OR 1.54, [95% CI 1.28-1.86]) were significantly associated with CD but not with UC susceptibility. Haplotype analysis revealed a number of significant associations with CD susceptibility with omnibus p values 0.9). However, in CD, SNPs rs2066843 and rs2076756 were more frequently observed than the other three common NOD2 mutations (minor allele frequencies for rs2066843 and rs2076756: 0.390 and 0.380, respectively). In CD patients homozygous for these novel NOD2 variants, genotype-phenotype analysis revealed higher rates of a penetrating phenotype (rs2076756: p = 0.015) and fistulas (rs2076756: p = 0.015) and significant associations with CD-related surgery (rs2076756: p = 0.003; rs2066843: p = 0.015). However, in multivariate analysis only disease localization (p2×10−16) and behaviour (p = 0.02) were significantly associated with the need for surgery.
    Conclusion/Significance:
    The NOD2 variants rs2066843 and rs2076756 are novel and common CD susceptibility gene variants.

    Approaching the secrets of N-glycosylation in Aspergillus fumigatus

    Approaching the secrets of N-glycosylation in Aspergillus fumigatus

    The mannosyltransferase Och1 is the key enzyme for synthesis of elaborated protein N-glycans in yeast. In filamentous fungi genes implicated in outer chain formation are present, but their function is unclear. In this study we have analyzed the Och1 protein of Aspergillus fumigatus. We provide first evidence that poly-mannosylated N-glycans exist in A. fumigatus and that their synthesis requires AfOch1 activity. This implies that AfOch1 plays a similar role as S. cerevisiae ScOch1 in the initiation of an N-glycan outer chain. A Δafoch1 mutant showed normal growth under standard and various stress conditions including elevated temperature, cell wall and oxidative stress. However, sporulation of this mutant was dramatically reduced in the presence of high calcium concentrations, suggesting that certain proteins engaged in sporulation require N-glycan outer chains to be fully functional. A characteristic feature of AfOch1 and Och1 homologues from other filamentous fungi is a signal peptide that clearly distinguishes them from their yeast counterparts. However, this difference does not appear to have consequences for its localization in the Golgi. Replacing the signal peptide of AfOch1 by a membrane anchor had no impact on its ability to complement the sporulation defect of the Δafoch1 strain. The mutant triggered a normal cytokine response in infected murine macrophages, arguing against a role of outer chains as relevant Aspergillus pathogen associated molecular patterns. Infection experiments provided no evidence for attenuation in virulence; in fact, according to our data the Δafoch1 mutant may even be slightly more virulent than the control strains.

    Multiple events lead to dendritic spine loss in triple transgenic Alzheimer's disease mice

    Multiple events lead to dendritic spine loss in triple transgenic Alzheimer's disease mice

    The pathology of Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) peptide, hyperphosphorylated tau protein, neuronal death, and synaptic loss. By means of long-term two-photon in vivo imaging and confocal imaging, we characterized the spatio-temporal pattern of dendritic spine loss for the first time in 3xTg-AD mice. These mice exhibit an early loss of layer III neurons at 4 months of age, at a time when only soluble Aβ is abundant. Later on, dendritic spines are lost around amyloid plaques once they appear at 13 months of age. At the same age, we observed spine loss also in areas apart from amyloid plaques. This plaque independent spine loss manifests exclusively at dystrophic dendrites that accumulate both soluble Aβ and hyperphosphorylated tau intracellularly. Collectively, our data shows that three spatio-temporally independent events contribute to a net loss of dendritic spines. These events coincided either with the occurrence of intracellular soluble or extracellular fibrillar Aβ alone, or the combination of intracellular soluble Aβ and hyperphosphorylated tau.

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