| 1. |
- Häfner, Sophia J., et al.
(author)
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Ribosomal RNA 2′-O-methylation dynamics impact cell fate decisions
- 2023
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In: Developmental Cell. - 1534-5807. ; 58:17, s. 9-1609
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Journal article (peer-reviewed)abstract
- Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms. 2′-O-methylation (2′-O-me) of rRNA represents an important source of heterogeneity, where site-specific alteration of methylation levels can modulate translation. Here, we examine changes in rRNA 2′-O-me during mouse brain development and tri-lineage differentiation of human embryonic stem cells (hESCs). We find distinct alterations between brain regions, as well as clear dynamics during cortex development and germ layer differentiation. We identify a methylation site impacting neuronal differentiation. Modulation of its methylation levels affects ribosome association of the fragile X mental retardation protein (FMRP) and is accompanied by an altered translation of WNT pathway-related mRNAs. Together, these data identify ribosome heterogeneity through rRNA 2′-O-me during early development and differentiation and suggest a direct role for ribosomes in regulating translation during cell fate acquisition.
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| 2. |
- Jansson, Martin, et al.
(author)
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Reduced dose direct oral anticoagulants compared with warfarin with high time in therapeutic range in nonvalvular atrial fibrillation
- 2023
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In: Journal of Thrombosis and Thrombolysis. - : Springer Nature. - 0929-5305 .- 1573-742X. ; 55:3, s. 415-425
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Journal article (peer-reviewed)abstract
- Direct oral anticoagulants (DOACs) used in nonvalvular atrial fibrillation (NVAF) are dose-reduced in elderly and patients with impaired renal function. Only reduced dose dabigatran is concluded as having similar stroke risk reduction and lower risk of major bleeding than warfarin in the pivotal studies. In clinical practice, reduced dose is prescribed more often than expected making this an important issue. The objective of this study was to compare effectiveness and safety between reduced dose DOACs and high TTR warfarin treatment (TTR ≥ 70%) in NVAF. A Swedish anticoagulation registry was used in identifying eligible patients from July 2011 to December 2017. The study cohort consisted of 40,564 patients with newly initiated DOAC (apixaban, dabigatran, or rivaroxaban) (11,083 patients) or warfarin treatment (29,481 patients) after exclusion of 374,135 patients due to not being warfarin or DOAC naïve, not being prescribed reduced dose, having previous mechanical heart valve (MHV), or being under 18 years old. The median durations of follow up were 365, 419, 432 and 473 days for apixaban, dabigatran, rivaroxaban and warfarin, respectively. Warfarin TTR identified from Auricula was 70.0%. Endpoints (stroke and major bleeding) and baseline characteristics were collected from hospital administrative registers using ICD-10 codes. Cohorts were compared using weighted adjusted Cox regression after full optimal matching based on propensity scores. DOACs are associated with lower risk of major bleeding (HR with 95% CI) 0.85 (0.78–0.93), intracranial bleeding HR 0.64 (0.51–0.80), hemorrhagic stroke HR 0.68 (0.50–0.92), gastrointestinal bleeding HR 0.81 (0.69–0.96) and all-cause stroke HR 0.87 (0.76–0.99), than warfarin. Apixaban and dabigatran are associated with lower risk of major bleeding, HR 0.70 (0.63–0.78) and HR 0.80 (0.69–0.94), and rivaroxaban is associated with lower risk of ischemic stroke, HR 0.73 (0.59–0.96), with higher major bleeding risk, HR 1.31 (1.15–1.48), compared to warfarin. Apixaban is associated with higher all-cause mortality compared to warfarin, HR 1.12 (1.03–1.21). DOACs are associated with lower risk of major bleeding and all-cause stroke, than high quality warfarin treatment, with exception of rivaroxaban that carried higher risk of major bleeding and lower risk of stroke or systemic embolism. In this large observational registry-based NVAF cohort, DOACs are preferred treatment in patients with indication for DOAC dose reduction, even in a high TTR setting.
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| 3. |
- Jansson, Martin, 1988-
(author)
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Samtidens gränser : Om språkreformer och historisk tid runt sekelskiftet 1900
- 2023
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Doctoral thesis (other academic/artistic)abstract
- This dissertation examines two extensive language reforms that caused controversy and discord in late 19th century Sweden: a comprehensive spelling reform and a formally authorised Bible translation. Among the numerous disagreements and entanglements that afflicted the projects, one issue persisted more than any other: the question of historical time. The correlation between past, present and future was fiercely contested and became a topic of intense negotiation.The purpose of this thesis is to analyse situated constructions of historical time around the turn of the 20th century. By invoking the language reforms as examples of temporal synchronisations, the study contributes to recent debates about modern temporalities and historical time. While earlier research predominantly considers intellectual discourses and abstract notions of temporality, this study emphasises historical time as a consequence of practical measures and applied procedures.The study concludes that historical time was established in order to manage a plethora of conflicting temporalities and asynchronous rhythms. The spelling reform and the Bible translation were affected by a wide range of conflicting times that preceded the notions of progress and acceleration often associated with the modern regime of historicity. The thesis demonstrates how the language reforms established a modern historical order that is often reduced to a passive articulation of an underlying regime.
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| 4. |
- Jansson, Martin, et al.
(author)
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Direct comparisons of effectiveness and safety of treatment with Apixaban, Dabigatran and rivaroxaban in atrial fibrillation
- 2020
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In: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 185, s. 135-141
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Journal article (peer-reviewed)abstract
- Introduction: Direct oral anticoagulants (DOACs) have been proven non-inferior or superior to warfarin in preventing stroke and systemic embolism, with a lower risk of major hemorrhage, in patients with non-valvular atrial fibrillation (NVAF). We sought to investigate whether effectiveness and safety differs among apixaban, rivaroxaban and dabigatran. Materials and methods: Patients with newly initiated DOAC treatment were identified from the Swedish anticoagulation quality registry, ranging from January 1, 2013 to December 31, 2015. Patients were assigned to apixaban, dabigatran or rivaroxaban cohorts based on initiated DOAC and dose (standard or reduced). Baseline characteristics and endpoints were retrieved from validated Swedish quality registers and the National Patient Registry. Cohorts were matched using full optimal matching and directly compared. Results: A total of 25,843 NVAF patients were included. Patients treated with standard dose apixaban or dabigatran had lower risk of major bleeding than patients treated with rivaroxaban, HR 0.69 (95% CI 0.54–0.88) and HR 0.64 (95% CI 0.48–0.87). Regarding reduced dose, patients treated with apixaban had lower risk of major bleeding than those treated with dabigatran or rivaroxaban, HR 0.62 (95% CI 0.44–0.88) and HR 0.45 (95% CI 0.33–0.61). In reduced dose, patients treated with dabigatran had the lowest all-cause mortality. No differences in effectiveness were found. Conclusions: In this large real-world NVAF cohort, direct comparisons show a favorable bleeding risk profile for dabigatran and apixaban in standard dose, and for apixaban in reduced dose. No differences in effectiveness were found. This study confirms previous indirect DOAC comparisons. Further studies are needed.
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| 5. |
- Henrohn, Dan, et al.
(author)
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Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.
- 2018
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In: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 24:10, s. 640-653
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Journal article (peer-reviewed)abstract
- BACKGROUND: The nitrate-nitrite-nitric oxide (NO) pathway may represent a potential therapeutic target in patients with pulmonary arterial hypertension (PAH). We explored the effects of dietary nitrate supplementation, with the use of nitrate-rich beetroot juice (BRJ), in patients with PAH.METHODS AND RESULTS: We prospectively studied 15 patients with PAH in an exploratory randomized, double-blind, placebo-controlled, crossover trial. The patients received nitrate-rich beetroot juice (∼16 mmol nitrate per day) and placebo in 2 treatment periods of 7 days each. The assessments included; exhaled NO and NO flow-independent parameters (alveolar NO and bronchial NO flux), plasma and salivary nitrate and nitrite, biomarkers and metabolites of the NO-system, N-terminal pro-B-type natriuretic peptide, echocardiography, ergospirometry, diffusing capacity of the lung for carbon monoxide, and the 6-minute walk test. Compared with placebo ingestion of BRJ resulted in increases in; fractional exhaled NO at all flow-rates, alveolar NO concentrations and bronchial NO flux, and plasma and salivary levels of nitrate and nitrite. Plasma ornithine levels decreased and indices of relative arginine availability increased after BRJ compared to placebo. A decrease in breathing frequency was observed during ergospirometry after BRJ. A tendency for an improvement in right ventricular function was observed after ingestion of BRJ. In addition a tendency for an increase in the peak power output to peak oxygen consumption ratio (W peak/VO2 peak) was observed, which became significant in patients reaching an increase of plasma nitrite >30% (responders).CONCLUSIONS: BRJ administered for 1 week increases pulmonary NO production and the relative arginine bioavailability in patients with PAH, compared with placebo. An increase in the W peak/VO2 peak ratio was observed after BRJ ingestion in plasma nitrite responders. These findings indicate that supplementation with inorganic nitrate increase NO synthase-independent NO production from the nitrate-nitrite-NO pathway.
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| 6. |
- Strigård, Karin, et al.
(author)
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[Laparoscopic colorectal surgery. Five-year experience at Huddinge University Hospital].
- 2002
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 99:35, s. 3396-3399
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Journal article (peer-reviewed)abstract
- By education of one to two surgeons at the time we limit the learning curve and reduce the complications. 250 patients have been operated for both benign and malignant colorectal diseases. The operation time is still longer than with the open technique. Conversion rate is 18 per cent, no mortality and few serious complications are seen. The blood loss is in mean 150 ml. With shorter time at the operation theatre through optimal education of the hole operation team, the costs for laparoscopic colorectal surgery will diminish. In the future with better laparoscopic technique, we believe there will be increased numbers of total colectomies and operations in the small pelvic.
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| 7. |
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