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1.
  • Alsharari, Zayed, et al. (författare)
  • Comparison of a 21-item food questionnaire with a 7-day dietary registration andbiomarkers of fat intake in a Swedish cohort of 60-year-old adults.
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • AbstractPurpose. To evaluate a 21-item food frequency questionnaire (FFQ) in men participating in alarge cohort of Swedish 60-year-old adults (60YO).Methods. A self-reported FFQ (including 21 qualitative and semi-quantitative questions) was completed by >2000 men as part of a detailed baseline examination. A subsample of 301 men was included in a subsequent study in which detailed dietary habits were determined by a 7-day food record. Spearman rank correlations (r) and weighted Kappa (Kw) statistics were used to compare food intake categories in FFQ and 7-day food record. Furthermore, fatty acid (FA) composition in serum cholesteryl esters, assessed concurrent with the FFQ completion, was used to evaluate intakes of specific fat-rich foods from the FFQ.Results. We found good agreement between FFQ and food records for the reported intake ofalcohol (r=0.72, Kw=0.51), margarine (r=0.60, Kw=0.33), and fruit (r=0.49, Kw=0.31), reasonably good agreement for total fish (r=0.25, Kw=0.23), and egg (r=0.35, Kw=0.28), but poor agreement for other food groups such as bread, cheese, vegetables and cookies. In addition, serum proportions of long-chain n-3 polyunsaturated FAs and pentadecanoic acid were significantly higher in men with greater intakes of fish and cheese, respectively.Conclusion. In this evaluation of a short FFQ against 7-d food records and serum biomarkers of fat intake we found that the FFQ reasonably well reflected the intake of certain food groups (e.g. alcohol, fish, and margarine), but performed less accurate for other food groups. Firm and overallconclusions on validity are confined by the time-lag between the test and the reference method.
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2.
  • Klaric, Lucija, et al. (författare)
  • Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
  • 2021
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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