Fibromodulin Deficiency Reduces Low-Density Lipoprotein Accumulation in Atherosclerotic Plaques in Apolipoprotein E-Null Mice.

OBJECTIVE: The aim of this study was to analyze how an altered collagen structure affects development of atherosclerotic plaques. METHODS AND RESULTS: Fibromodulin-null mice develop an abnormal collagen fibril structure. In apolipoprotein E (ApoE)-null and ApoE/fibromodulin-null mice, a shear stress-modifying carotid artery cast induced formation of atherosclerotic plaques of different phenotypes; inflammatory in low-shear stress regions and fibrous in oscillatory shear stress regions. Electron microscopy showed that collagen fibrils were thicker and more heterogeneous in oscillatory shear stress lesions from ApoE/fibromodulin-null mice. Low-shear stress lesions were smaller in ApoE/fibromodulin-null mice and contained less lipids. Total plaque burden in aortas stained en face with Oil Red O, as well as lipid accumulation in aortic root lesions, was also decreased in ApoE/fibromodulin-null mice. In addition, lipid accumulation in RAW264.7 macrophages cultured on fibromodulin-deficient extracellular matrix was decreased, whereas levels of interleukin-6 and -10 were increased. Our results show that an abnormal plaque collagen fibril structure can influence atherosclerotic plaque development. CONCLUSIONS: The present findings suggest a more complex role for collagen in plaque stability than previously anticipated, in that it may promote lipid-accumulation and inflammation at the same time as it provides mechanical stability

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Strukturomvandling och politisk socialisation

digitalisering@um

Akademiska folkhälsoutbildningar i Sverige – en översikt

Folkhälsovetenskap är sedan två decennier ett etablerat ämne inom den svenska högskolans alla tre utbildningsnivåer. Under åren har antalet utbildningar varierat och finns 2017 som akademisk utbildning vid 18 lärosäten. På grundnivå finns nio program och på avancerad nivå 18 olika program med vardera nio som magister- respektive masterutbildningar. Forskarutbildning i ämnet bedrivs vid tio lärosäten. Medan de varit en nedgång av antalet utbildningar på grundutbildningsnivå har det varit en kraftig utbyggnad på avancerad- och forskarutbildningsnivå. Utbildningens innehåll återspeglar väl ämnets tvärvetenskapliga karaktär och dess förankring i epidemiologi. Grundutbildningen visar på en bred inriktning och master programmen finns med flera specifika inriktningar, bland annat Global hälsa, Hälsoekonomi och Epidemiologi.Public health science has been an established subject within Swedish universities for two decades, all three levels of higher education. Over the years, the number of courses has varied and the subject is in 2017 available at 18 universities. At the undergraduate level there are nine programmes and at advanced level 18 different programmes, with each nine as master’s (60 credits) respectively and master’s programmes (120 credits). Postgraduate studies in the subject are conducted at ten universities. While there has been a decline in the number of students at undergraduate level, there has been a vigorous expansion in advanced and postgraduate level. The content of the education clearly reflects the interdisciplinary nature of the subject and its anchoring in epidemiology. Undergraduate studies show a broad alignment and the master programmes are available with several specific foci, including Global Health, Health Economics and Epidemiology

Primärvårdens förutsättningar och befolkningens behov i sju vårdverksamheter

Developing a program theory for a project and evaluate the project based on this program theory has both its merits and limitations. These merits and limitations in turn may be depend on the existing attitude towards a particular program theory. This study is about exploring how different phases and parts of the national learning project Care on equal terms (2011-2014) functioned in relation to the program theory developed in the beginning of the project. The result shows that the program theoretical perspective on the project contributed to a better structuring of the various forms of evaluation, given a broader understanding of the project's components and provided better opportunities to improve monitoring of the project by the research team in collaboration with the project management of the Swedish Association of Local Authorities and Regions (SALAR) and the participating health care units.Lärandeprojektet - Vård på lika villko