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Sökning: WFRF:(Carlberg L) > (2015-2019)

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  • Carlberg, Konstantin, et al. (författare)
  • Exploring inflammatory signatures in arthritic joint biopsies with Spatial Transcriptomics
  • 2019
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322 .- 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Lately it has become possible to analyze transcriptomic profiles in tissue sections with retained cellular context. We aimed to explore synovial biopsies from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients, using Spatial Transcriptomics (ST) as a proof of principle approach for unbiased mRNA studies at the site of inflammation in these chronic inflammatory diseases. Synovial tissue biopsies from affected joints were studied with ST. The transcriptome data was subjected to differential gene expression analysis (DEA), pathway analysis, immune cell type identification using Xcell analysis and validation with immunohistochemistry (IHC). The ST technology allows selective analyses on areas of interest, thus we analyzed morphologically distinct areas of mononuclear cell infiltrates. The top differentially expressed genes revealed an adaptive immune response profile and T-B cell interactions in RA, while in SpA, the profiles implicate functions associated with tissue repair. With spatially resolved gene expression data, overlaid on high-resolution histological images, we digitally portrayed pre-selected cell types in silico. The RA displayed an overrepresentation of central memory T cells, while in SpA effector memory T cells were most prominent. Consequently, ST allows for deeper understanding of cellular mechanisms and diversity in tissues from chronic inflammatory diseases.
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  • Modin Asper, Michaela, et al. (författare)
  • Screening fathers for postpartum depression can be cost-effective : an example from Sweden
  • 2018
  • Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 241, s. 154-163
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Postpartum depression negatively affects the whole family and its prevalence in Sweden ranges between 6-10% for fathers and 13-16% for mothers. However, only mothers in Sweden are currently routinely screened.Aim: The aim of this study was to determine if a postpartum depression screening for fathers in Stockholm County could be cost-effective.Methods: National Swedish databases were used to find registry data and a literature review was undertaken to identify the model data inputs associated with postpartum depression in Sweden. The generated evidence was used to build a Markov model in TreeAge. One-way and probabilistic sensitivity analyses were performed to account for parameter uncertainties. Alternative scenario analyses were further undertaken to test the assumptions in the base case analysis.Results: A postpartum screening for depression in fathers is cost-effective in base case and alternative scenarios. The results indicate that the screening program is associated with lower costs and higher health effects. The results were sensitive to variables of quality adjusted life years for the depressed fathers, probabilities of remission in treatment and no treatment groups and start age and productivity losses. The probabilistic sensitivity analysis resulted in a 70% probability of the postnatal depression screening intervention being cost-effective.Limitations: The current study only uses secondary data; therefore future research should assess the cost-effectiveness of screening fathers for depression.Conclusion: The postpartum screening intervention for fathers could be cost-effective compared to no screening. Future research should replicate the potential cost-effectiveness for screening fathers for postpartum depression.
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  • Wallace, Stephanie E., et al. (författare)
  • MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants
  • 2019
  • Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 21:1, s. 144-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLKmissense variants are pathogenic and information to guide aortic disease management are limited.Methods: Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed.Results: Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm repair or dissection); the majority of these events (87%) were aortic dissections. Aortic diameters were minimally enlarged at the time of dissection in many cases. Time-to-aortic-event curves showed that missense pathogenic variant (PV) carriers have earlier-onset aortic events than null PV carriers. An MYLK missense variant segregated with aortic disease over five generations but decreases MYLK kinase acitivity marginally. Functional Assays fail to identify all pathogenic variants in MYLK.Conclusion: These data further define the aortic phenotype associated with MYLKpathogenic variants. Given minimal aortic enlargement before dissection, an alternative approach to guide the timing of aortic repair is proposed based on the probability of a dissection at a given age.
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