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- Cederstrom, S., et al.
(författare)
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New candidate genes for ST-elevation myocardial infarction
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:1, s. 66-77
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Tidskriftsartikel (refereegranskat)abstract
- Background Despite extensive research in atherosclerosis, the mechanisms of coronary atherothrombosis in ST-elevation myocardial infarction (STEMI) patients are undetermined. Objectives Our aim was to find candidate genes involved in STEMI by analysing leucocyte gene expression in STEMI patients, without the influence of secondary inflammation from innate immunity, which was assumed to be a consequence rather than the cause of coronary atherothrombosis. Methods Fifty-one patients were included at coronary angiography because of STEMI. Arterial blood was sampled in the acute phase (P1), at 24-48 h (P2) and at 3 months (P3). Leucocyte RNA was isolated and gene expression analysis was performed by Affymetrix Human Transcriptome Array 2.0. By omission of up- or downregulated genes at P2, secondary changes from innate immunity were excluded. Genes differentially expressed in P1 when compared to the convalescent sample in P3 were determined as genes involved in STEMI. Results Three genes were upregulated at P1 compared to P3; ABCG1 (P = 5.81 x 10(-5)), RAB20 (P = 3.69 x 10(-5)) and TMEM2 (P = 7.75 x 10(-6)) whilst four were downregulated; ACVR1 (P = 9.01 x 10(-5)), NFATC2IP (P = 8.86 x 10(-5)), SUN1 (P = 3.87 x 10(-5)) and TTC9C (P = 7.18 x 10(-6)). These genes were also highly expressed in carotid atherosclerotic plaques. Conclusions We found seven genes involved in STEMI. The study is unique regarding the blood sampling in the acute phase and omission of secondary expressed genes from innate immunity. However, the results need to be replicated by future studies.
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- Edfors, R., et al.
(författare)
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Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 288:5, s. 581-592
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. Methods A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. Results A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min(-1)/1.73 m(2)were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. Conclusion In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.
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- Djupsjo, C, et al.
(författare)
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Preoperative disturbances of glucose metabolism and mortality after coronary artery bypass grafting
- 2020
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Ingår i: Open heart. - : BMJ. - 2053-3624. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Disturbances of glucose metabolism are important risk factors for coronary artery disease and are associated with an increased mortality risk. The aim was to investigate the association between preoperative disturbances of glucose metabolism and long-term all-cause mortality after coronary artery bypass grafting (CABG).MethodsPatients undergoing a first isolated CABG in 2005–2013 were included. All patients without previously known diabetes underwent an oral glucose tolerance test (OGTT) before surgery. They were categorised as having normal glucose tolerance (NGT), pre-diabetes (impaired glucose tolerance and/or impaired fasting glucose) or newly discovered diabetes. Data were collected from nationwide healthcare registers. Cox regression was used to calculate adjusted HR with 95% CI for death in patients with pre-diabetes and diabetes, using NGT as reference.ResultsIn total, 497 patients aged 40–86 years were included. According to OGTT, 170 (34%) patients had NGT, 219 (44%) patients with pre-diabetes and 108 (22%) patients had newly discovered diabetes. Baseline characteristics were similar between the groups except for slightly higher age among patients with newly discovered diabetes. There were 133 (27%) deaths during a mean follow-up time of 10 years. The cumulative 10-year survival was 77% (69%–83%), 83% (77%–87%) and 71% (61%–79%) in patients with NGT, pre-diabetes and newly discovered diabetes, respectively. There was no significant difference in all-cause mortality between the groups after multivariable adjustment.ConclusionIn this study, patients with pre-diabetes or newly discovered diabetes prior to CABG had similar long-term survival compared with patients with NGT.
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- Nativi, Lorenzo, et al.
(författare)
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Are interactions with neutron star merger winds shaping the jets?
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 509:1, s. 903-913
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Tidskriftsartikel (refereegranskat)abstract
- Jets can become collimated as they propagate through dense environments and understanding such interactions is crucial for linking physical models of the environments to observations. In this work, we use 3D special-relativistic simulations to study how jets propagate through the environment created around a neutron star merger remnant by neutrino-driven winds. We simulate four jets with two different initial structures, top-hat and Gaussian, and two luminosities. After jet breakout, we study the angular jet structures and the resulting afterglow light curves. We find that the initial angular structures are efficiently washed out during the propagation, despite the small wind mass of only ∼10−3 M. The final structure depends on the jet luminosity as less energetic jets are more strongly collimated, and entrainment of baryons leads to a moderate outflow Lorentz factor (≈40). Although ourjets are not specifically intended to model the outflows of the GW170817 event, we show that they can be used to produce light curves consistent with the afterglow observed in the aftermath of GW170817. Using this procedure, we show how the inferred physical parameters e.g. inclination angle, ambient particle number density, can vary substantially between independent fits of the same dataset, and appear to be sensitive to smaller details of the angular jet shape, indicating that observationally inferred parameters may depend sensitively on the employed jet models.
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- Nativi, Lorenzo, et al.
(författare)
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Can jets make the radioactively powered emission from neutron star mergers bluer?
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 500:2, s. 1772-1783
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Tidskriftsartikel (refereegranskat)abstract
- Neutron star mergers eject neutron-rich matter in which heavy elements are synthesized. The decay of these freshly synthesized elements powers electromagnetic transients ('macronovae' or 'kilonovae') whose luminosity and colour strongly depend on their nuclear composition. If the ejecta are very neutron-rich (electron fraction Ye < 0.25), they contain fair amounts of lanthanides and actinides that have large opacities and therefore efficiently trap the radiation inside the ejecta so that the emission peaks in the red part of the spectrum. Even small amounts of this high-opacity material can obscure emission from lower lying material and therefore act as a 'lanthanide curtain'. Here, we investigate how a relativistic jet that punches through the ejecta can potentially push away a significant fraction of the high opacity material before the macronova begins to shine. We use the results of detailed neutrino-driven wind studies as initial conditions and explore with 3D special relativistic hydrodynamic simulations how jets are propagating through these winds. Subsequently, we perform Monte Carlo radiative transfer calculations to explore the resulting macronova emission. We find that the hole punched by the jet makes the macronova brighter and bluer for on-axis observers during the first few days of emission, and that more powerful jets have larger impacts on the macronova.
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- Tangeraas, T, et al.
(författare)
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Performance of Expanded Newborn Screening in Norway Supported by Post-Analytical Bioinformatics Tools and Rapid Second-Tier DNA Analyses
- 2020
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Ingår i: International journal of neonatal screening. - : MDPI AG. - 2409-515X. ; 6:3, s. 51-
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Tidskriftsartikel (refereegranskat)abstract
- In 2012, the Norwegian newborn screening program (NBS) was expanded (eNBS) from screening for two diseases to that for 23 diseases (20 inborn errors of metabolism, IEMs) and again in 2018, to include a total of 25 conditions (21 IEMs). Between 1 March 2012 and 29 February 2020, 461,369 newborns were screened for 20 IEMs in addition to phenylketonuria (PKU). Excluding PKU, there were 75 true-positive (TP) (1:6151) and 107 (1:4311) false-positive IEM cases. Twenty-one percent of the TP cases were symptomatic at the time of the NBS results, but in two-thirds, the screening result directed the exact diagnosis. Eighty-two percent of the TP cases had good health outcomes, evaluated in 2020. The yearly positive predictive value was increased from 26% to 54% by the use of the Region 4 Stork post-analytical interpretive tool (R4S)/Collaborative Laboratory Integrated Reports 2.0 (CLIR), second-tier biochemical testing and genetic confirmation using DNA extracted from the original dried blood spots. The incidence of IEMs increased by 46% after eNBS was introduced, predominantly due to the finding of attenuated phenotypes. The next step is defining which newborns would truly benefit from screening at the milder end of the disease spectrum. This will require coordinated international collaboration, including proper case definitions and outcome studies.
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