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- Bak, Geske S., et al.
(författare)
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Prospective population-based cohort study of maternal obesity as a source of error in gestational age estimation at 11–14 weeks
- 2016
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 95:11, s. 1281-1287
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: An impact of maternal obesity on ultrasound dating of pregnancy at 11–14 gestational weeks is possible and was investigated. Material and methods: A prospective cohort study based on the Danish national population during a 4-year period in which we entered all mothers with singleton pregnancies who had a known last menstrual period (LMP), a recorded booking of body mass index (BMI), and a late first trimester ultrasound dating scan using crown-rump-length measurement (gestational age 11+0–13+6 weeks). Almost all scans were performed transabdominally. Transvaginal ultrasound was only performed in the case of limited visibility by transabdominal scanning. Differences between LMP and ultrasound estimated date of delivery (EDD) were stratified by BMI classes. Odds ratios (ORs) were calculated and adjusted for maternal age, parity and smoking. Results: In total, 187 486 women were analyzed: 21.8% were overweight and 12.3% obese. Ultrasound EDD was ≥7 days later than by LMP in 5.8% of normal-weight women, 7.3% of obese women, and 10.0% of women with morbid obesity. Compared with normal BMI (18.5–24.9), the OR for postponing EDD increased with increasing BMI; BMI 25–29.9 [OR 0.97, 95% confidence interval (CI) 0.93–1.02], BMI 30–34.9 (OR 1.14, 95% CI 1.07–1.23), BMI 35–39.9 (OR 1.28, 95% CI 1.15–1.42), and BMI 40+ (OR 1.73, 95% CI 1.50–1.98). Lean pregnant women (BMI <18.5) also had a higher chance of having EDD postponed 7 days or more (OR 1.11, 95% CI 1.01–1.22). Conclusion: Rising maternal BMI appears to be associated with postponement of ultrasound EDD.
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- Bak, Nina Friis, et al.
(författare)
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High-dose vitamin D3 supplementation decreases the number of colonic CD103+ dendritic cells in healthy subjects.
- 2018
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Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 57:7, s. 2607-2619
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D may induce tolerance in the intestinal immune system and has been shown to regulate the phenotype of tolerogenic intestinal dendritic cells (DCs) in vitro. It is unknown whether vitamin D supplementation affects human intestinal DCs in vivo, and we aimed to investigate the tolerability and effect on intestinal CD103+DCs of high-dose vitamin D3 treatment in healthy subjects.Ten healthy subjects received a total of 480,000IU oral vitamin D3 over 15days and colonic biopsies were obtained before and after intervention by endoscopy. Lamina propria mononuclear cells (LPMCs) were isolated from the biopsies, stained with DC surface markers and analysed with flow cytometry. Snap-frozen biopsies were analysed with qPCR for DC and regulatory T cell-related genes.No hypercalcemia or other adverse events occurred in the test subjects. Vitamin D decreased the number of CD103+ DCs among LPMCs (p=0.006). Furthermore, vitamin D induced mRNA expression of TGF-β (p=0.048), TNF-α (p=0.006) and PD-L1 (p=0.02) and tended to induce IL-10 expression (p=0.06). Multivariate factor analysis discriminated between pre- and post-vitamin D supplementation with a combined increased qPCR expression of PD1, PD-L1, TGF-β, IL-10, CD80, CD86, FOXP3, NFATc2 and cathelicidin.High-dose vitamin D supplementation is well tolerated by healthy subjects and has a direct effect on the CD103+ DCs, local cytokine and surface marker mRNA expression in the colonic mucosa, suggestive of a shift towards a more tolerogenic milieu.
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- Bogetofte, Helle, et al.
(författare)
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PARK2 mutation causes metabolic disturbances and impaired survival of human iPSC-derived neurons
- 2019
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The protein parkin, encoded by the PARK2 gene, is vital for mitochondrial homeostasis, and although it has been implicated in Parkinson’s disease (PD), the disease mechanisms remain unclear. We have applied mass spectrometry-based proteomics to investigate the effects of parkin dysfunction on the mitochondrial proteome in human isogenic induced pluripotent stem cell-derived neurons with and without PARK2 knockout (KO). The proteomic analysis quantified nearly 60% of all mitochondrial proteins, 119 of which were dysregulated in neurons with PARK2 KO. The protein changes indicated disturbances in oxidative stress defense, mitochondrial respiration and morphology, cell cycle control, and cell viability. Structural and functional analyses revealed an increase in mitochondrial area and the presence of elongated mitochondria as well as impaired glycolysis and lactate-supported respiration, leading to an impaired cell survival in PARK2 KO neurons. This adds valuable insight into the effect of parkin dysfunction in human neurons and provides knowledge of disease-related pathways that can potentially be targeted for therapeutic intervention.
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- de Bruijn, Winnie, et al.
(författare)
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Introduction and Utilization of High Priced HCV Medicines across Europe : Implications for the Future
- 2016
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (Hs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIEN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIOs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new Pls vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes monitored in the future to provide additional guidance.
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- Pedersen, Helle Krogh, et al.
(författare)
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Human gut microbes impact host serum metabolome and insulin sensitivity
- 2016
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 535:7612, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
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