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- Eriksson, Bengt I., 1946, et al.
(författare)
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Efficacy of delayed thromboprophylaxis with dabigatran: Pooled analysis.
- 2012
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Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 130:6, s. 871-876
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Oral thromboprophylaxis with dabigatran etexilate should be initiated as a half dose 1 to 4h after major orthopaedic surgery. However, a delay in dosing could occur for clinical or logistical reasons. A post hoc analysis was carried out to determine if patients with delayed dosing received adequate anticoagulation. PATIENTS AND METHODS: The RE-MODEL™ and RE-NOVATE® trials compared 220mg and 150mg dabigatran etexilate with 40mg enoxaparin. Pooled data for major venous thromboembolism (VTE) and VTE-related mortality (efficacy outcome) and major bleeding events (MBE), MBE/clinically relevant bleeding events, and all bleeding events (safety outcomes) were analysed. Results in patients with dosing delayed more than 4h postsurgery were compared with those of patients without a delay. RESULTS: Onset of treatment was delayed in 724 (13.3%) of 5425 patients. Efficacy of 220mg dabigatran etexilate was similar in patients without delayed dosing, patients with a delay and patients with a delay until the day after surgery. Rates of efficacy outcome were higher in patients on 150mg dabigatran etexilate, but more than 80% of these patients were undertreated based on age or renal clearance status. Some differences in bleeding events were seen among patient groups by treatment arm. CONCLUSION: Dabigatran etexilate thromboprophylaxis should be initiated 1 to 4h postsurgery. Results from our post-hoc analysis indicate that no loss of efficacy appears to occur if initiation of dabigatran etexilate 220mg needs to be delayed.
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- Kirchhof, Paulus, et al.
(författare)
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Comprehensive risk reduction in patients with atrial fibrillation : emerging diagnostic and therapeutic options - a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference
- 2012
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 14:1, s. 8-27
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Forskningsöversikt (refereegranskat)abstract
- While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.
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| 5. |
- Schafmayer, Clemens, et al.
(författare)
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Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms
- 2019
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 68:5, s. 854-865
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Tidskriftsartikel (refereegranskat)abstract
- Objective Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. Design Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. Results We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p< 0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3x10-10 and 0.002 (OR allelic = 1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). Conclusion I n silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.
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| 6. |
- Schosserer, Markus, et al.
(författare)
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Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA. Loss of Rcm1 alters the structural conformation of the ribosome in close proximity to C2278, as well as translational fidelity, and favours recruitment of a distinct subset of oxidative stress-responsive mRNAs into polysomes. Thus, rather than merely being a static molecular machine executing translation, the ribosome exhibits functional diversity by modification of just a single rRNA nucleotide, resulting in an alteration of organismal physiological behaviour, and linking rRNA-mediated translational regulation to modulation of lifespan, and differential stress response.
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| 7. |
- Stief, Peter, et al.
(författare)
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Intracellular nitrate storage by diatoms can be an important nitrogen pool in freshwater and marine ecosystems
- 2022
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Ingår i: Communications Earth and Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Identifying and quantifying nitrogen pools is essential for understanding the nitrogen cycle in aquatic ecosystems. The ubiquitous diatoms represent an overlooked nitrate pool as they can accumulate nitrate intracellularly and utilize it for nitrogen assimilation, dissipation of excess photosynthetic energy, and Dissimilatory Nitrate Reduction to Ammonium (DNRA). Here, we document the global co-occurrence of diatoms and intracellular nitrate in phototrophic microbial communities in freshwater (n = 69), coastal (n = 44), and open marine (n = 4) habitats. Diatom abundance and total intracellular nitrate contents in water columns, sediments, microbial mats, and epilithic biofilms were highly significantly correlated. In contrast, diatom community composition had only a marginal influence on total intracellular nitrate contents. Nitrate concentrations inside diatom cells exceeded ambient nitrate concentrations ∼100–4000-fold. The collective intracellular nitrate pool of the diatom community accounted for <1% of total nitrate in pelagic habitats and 65–95% in benthic habitats. Accordingly, nitrate-storing diatoms are emerging as significant contributors to benthic nitrogen cycling, in particular through Dissimilatory Nitrate Reduction to Ammonium activity under anoxic conditions.
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| 8. |
- Yin, Wenguang, et al.
(författare)
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An essential function for autocrine hedgehog signaling in epithelial proliferation and differentiation in the trachea
- 2022
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Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 149:3
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Tidskriftsartikel (refereegranskat)abstract
- The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (HH) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a previously unreported autocrine function of HH signaling in airway epithelial cells. Epithelial cell depletion of the ligand sonic hedgehog (SHH) or its effector smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, HH signaling inhibition also hampers cell proliferation and differentiation. Epithelial HH function is mediated, at least in part, through transcriptional activation, as HH signaling inhibition leads to downregulation of cell type-specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.
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