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- Andersson, Linda, 1973, et al.
(författare)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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| 4. |
- Sandström, Anna, et al.
(författare)
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Routinely collected antenatal data for longitudinal prediction of preeclampsia in nulliparous women: a population-based study
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 17973-
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to evaluate the sequentially updated predictive capacity for preeclampsia during pregnancy, using multivariable longitudinal models including data from antenatal care. This population-based cohort study in the Stockholm-Gotland Counties, Sweden, included 58,899 pregnancies of nulliparous women 2008–2013. Prospectively collected data from each antenatal care visit was used, including maternal characteristics, reproductive and medical history, and repeated measurements of blood pressure, weight, symphysis-fundal height, proteinuria, hemoglobin and blood glucose levels. We used a shared-effects joint longitudinal model including all available information up until a given gestational length (week 24, 28, 32, 34 and 36), to update preeclampsia prediction sequentially. Outcome measures were prediction of preeclampsia, preeclampsia with delivery < 37, and preeclampsia with delivery ≥ 37 weeks’ gestation. The area under the curve (AUC) increased with gestational length. AUC for preeclampsia with delivery < 37 weeks’ gestation was 0.73 (95% CI 0.68–0.79) at week 24, and increased to 0.87 (95% CI 0.84–0.90) in week 34. For preeclampsia with delivery ≥ 37 weeks’ gestation, the AUC in week 24 was 0.65 (95% CI 0.63–0.68), but increased to 0.79 (95% CI 0.78–0.80) in week 36. The addition of routinely collected clinical measurements throughout pregnancy improve preeclampsia prediction and may be useful to individualize antenatal care.
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| 5. |
- Trischler, Jakob, et al.
(författare)
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Citizens as an innovation source in sustainability transitions - linking the directionality of innovations with the locus of the problem in transformative innovation policy
- 2023
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Ingår i: Public Management Review. - : Taylor & Francis. - 1471-9037 .- 1471-9045. ; 25:11, s. 2093-2115
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Tidskriftsartikel (refereegranskat)abstract
- This article argues that citizens play a key role in sustainability transitions: Citizens have unique knowledge on why social problems occur and experiment with possible solutions to these problems. Yet transformative innovation policy - a policy frame that promotes socio-technical systems change - is guided by a producer-centric innovation paradigm, which focuses on technological breakthroughs rather than social changes driven by citizens. By drawing on multiple research fields, and by using the example of household food waste, this article challenges this paradigm and asserts that addressing sustainability challenges requires a policy frame that defines citizens as an innovation source.
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| 6. |
- Valgeirsdóttir, Inga Rós, 1984-, et al.
(författare)
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Metformin as treatment of GDM
- 2023
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Whether metformin should be used as treatment for gestational diabetes mellitus (GDM) is a matter of controversy. Concerns about the effects on neonatal birth weight (mainly small for gestational age, SGA) have been raised in one randomized controlled trial in type 2 diabetes in pregnancy. [1] The aim of this study was to evaluate pregnancy outcomes based on different GDM treatment modalities with focus on metformin.Methods: A cohort study, based on data from the stepped wedge cluster randomized trial; CDC4G (Changing diagnostic criteria for GDM in Sweden - www.cdc4g.se). Screening for GDM involved repeated random plasma glucose measurements and/or clinical risk factors. [2] Data were collected from electronic case record forms, and national health and quality registers. Singleton pregnancies during 2018 (last birth in August 2019) from eight clusters were included. Women with pregestational diabetes and/or previous gastric bypass surgery were excluded. Pregnancy outcomes for different treatment regimens were analyzed for women with GDM compared to the background population without GDM. Logistic regression analyzes with adjustments for confounders (body mass index, age, smoking, country of birth, chronic hypertensive disease and cluster) was performed (adjusted odds ratio (aOR) with 95% confidence interval (CI)) for all outcomes. Results: Of the 54 678 pregnancies included, 2 169 (4.0%) were diagnosed with GDM; of whom 1 076 (49.6%) were treated with diet only (dGDM), 668 (30.8%) with metformin only (mGDM), 116 (5.3%) with insulin only (iGDM), and 309 (14.2%) with both metformin and insulin (miGDM). Pregnancy outcomes were as follows: SGA (10th percentile) was significantly decreased in the mGDM group [aOR 0.57 (95% CI 0.41-0.79)] compared to the background population and no significant difference was found in the miGDM group [aOR 0.78 (95% CI 0.51-1.18)] compared to the background population. No significant difference in SGA (10th percentile) was found in the dGDM group [aOR 1.02 (CI 0.83-1.25)] compared to the background population. There was significant difference in neonates born large for gestational age (LGA, 90th percentile) in both mGDM and miGDM groups compared to the background population [aOR 2.29 (95% CI 1.88-2.78) and aOR 2.32 (95% CI 1.76-3.07), respectively]. There was not significant difference in LGA (90th percentile) in dGDM compared to the background population [aOR 0.90 (95% CI 0.73-1.12].Conclusions: These preliminary unpublished results show no increase in SGA for metformin treated GDM compared to the background population. Outcomes in the diet treated GDM group were similar to the background population. Further analyzes are needed to compare outcomes between pharmacologic treatment groups and assess whether specific treatment regimens lead to similar outcomes in different subgroups (eg ethnicity, obesity and glucose values on diagnostic oral glucose tolerance test).References:1.Feig DS, Donovan LE, Zinman B, Sanchez JJ, Asztalos E, Ryan EA, et al. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. The lancet Diabetes & endocrinology. 2020;8(10):834-44.2.Fadl H, Saeedi M, Montgomery S, Magnuson A, Schwarcz E, Berntorp K, et al. Changing diagnostic criteria for gestational diabetes in Sweden - a stepped wedge national cluster randomised controlled trial - the CDC4G study protocol. BMC pregnancy and childbirth. 2019;19(1):398.
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| 7. |
- Wennerholm, U. B., et al.
(författare)
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Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks (SWEdish Post-term Induction Study, SWEPIS) : multicentre, open label, randomised, superiority trial
- 2020
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Ingår i: Geburtshilfe und Frauenheilkunde. - : Georg Thieme Verlag KG. - 0016-5751 .- 1438-8804. ; 80:10, s. E76-E76
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To evaluate if induction of labour at 41 weeks improves perinatal and maternal outcomes in women with low risk pregnancies compared with expectant management and induction at 42 weeks.Methods: A multicenter, randomised controlled superiority trial.Women with low risk singleton pregnanies (n = 2760) were randomised to either induction or expectant management group. The primary outcome was a composite perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar score < 7 at five minutes, pH < 7.00 or metabolic acidosis (pH < 7.05 and base deficit >12 mmol/L) in the umbilical artery, hypoxic ischaemic encephalopathy, intracranial haemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, obstetric brachial plexus injury. Primary analysis was by intention to treat.Results: The study was stopped early owing to a significantly higher rate of perinatal mortality in the expectant management group (no deaths compared to six deaths, p = 0.03). The primary outcome did not differ: 2.4 % (33/1381) in the induction group and 2.2 % (31/1379) in the expectant management group (RR 1.06, 95 %CI 0.65 to 1.73; p = 0.90). The proportion of caesarean delivery, instrumental vaginal delivery, or any major maternal morbidity did not differ between the groups.Conclusions: There was no significant difference in the primary composite outcome when comparing induction at 41 weeks with expectant management and induction at 42. However, a reduction of the secondary outcome perinatal mortality was observed without increasing adverse maternal outcomes. To offer induction at 41 weeks could be one of few interventions that reduces the rate of stillbirths.
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