| 1. |
- Hageman, S., et al.
(författare)
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SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
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| 2. |
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| 3. |
- Jain, Ruchi, et al.
(författare)
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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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| 4. |
- He, W., et al.
(författare)
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CYP2D6 genotype predicts tamoxifen discontinuation and drug response : a secondary analysis of the KARISMA trial
- 2021
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 32:10, s. 1286-1293
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Tidskriftsartikel (refereegranskat)abstract
- Background: Guidelines regarding whether tamoxifen should be prescribed based on women's cytochrome P450 2D6 (CYP2D6) genotypes are conflicting and have caused confusion. This study aims to investigate if CYP2D6 metabolizer status isa associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change. Patients and methods: We used data from 1440 healthy women who participated the KARISMA dose determination trial. Endocrine symptoms were measured using a modified Functional Assessment of Cancer Therapy – Endocrine Symptoms (FACT-ES) questionnaire. Change in mammographic density was measured and used as a proxy for tamoxifen response. Participants were genotyped and categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. Results: The median endoxifen level per mg oral tamoxifen among poor, intermediate, normal and ultrarapid CYP2D6 metabolizers were 0.18 ng/ml, 0.38 ng/ml, 0.56 ng/ml and 0.67 ng/ml, respectively. Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Among those who continued and finished the 6-month tamoxifen intervention, the mean change in dense area among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were −0.8 cm2, −4.5 cm2, −4.1 cm2, and −8.0 cm2 respectively. Conclusions: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. In contrast, ultrarapid CYP2D6 metabolizers are at risk for exaggerated response with pronounced adverse effects that may lead to treatment discontinuation.
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| 5. |
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| 6. |
- Eliasson, H., et al.
(författare)
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Modeling of high power impulse magnetron sputtering discharges with graphite target
- 2021
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Ingår i: Plasma sources science & technology. - : IOP Publishing Ltd. - 0963-0252 .- 1361-6595. ; 30:11
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Tidskriftsartikel (refereegranskat)abstract
- The ionization region model (IRM) is applied to model a high power impulse magnetron sputtering discharge in argon with a graphite target. Using the IRM, the temporal variation of the various species and the average electron energy, as well as internal parameters such as the ionization probability, back-attraction probability, and the ionized flux fraction of the sputtered species, is determined. It is found that thedischarge develops into working gas recycling and most of the discharge current at the cathode target surface is composed of Ar+ ions, which constitute over 90% of the discharge current, while the contribution of the C+ ions is always small (<5%), even for peak current densities close to 3 A cm(-2). For the target species, the time-averaged ionization probability is low, or 13-27%, the ion back-attraction probability during the pulse is high (>92%), and the ionized flux fraction is about 2%. It is concluded that in the operation range studied here it is a challenge to ionize carbon atoms, that are sputtered off of a graphite target in a magnetron sputtering discharge, when depositing amorphous carbon films.
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| 7. |
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| 8. |
- Alonso, Lorena, et al.
(författare)
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TIGER : The gene expression regulatory variation landscape of human pancreatic islets
- 2021
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 37:2
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.
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| 9. |
- Balintescu, A., et al.
(författare)
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Glycaemic control and sepsis risk in adults with type 1 diabetes
- 2023
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 25:7, s. 1942-1949
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To study the association between glycated haemoglobin (HbA1c) and sepsis in adults with type 1 diabetes, and to explore the relationship between HbA1c and mortality among individuals who developed sepsis.Materials and Methods: We included 33 549 adult individuals with type 1 diabetes recorded in the Swedish National Diabetes Register between January 2005 and December 2015. We used multivariable Cox regression and restricted cubic spline analyses to study the relationship between HbA1c values and sepsis occurrence and association between HbA1c and mortality among those with sepsis.Results: In total, 713 (2.1%) individuals developed sepsis during the study period. Com-pared with the HbA1c reference interval of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was: 2.50 [95% confidence interval (CI) 1.18-5.29] for HbA1c <43 mmol/mol; 1.88 (95% CI 0.96-3.67) for HbA1c 43-47 mmol/mol; 1.78 (95% CI 1.09-2.89) for HbA1c 53-62 mmol/mol; 1.86 (95% CI 1.14-3.03) for HbA1c 63-72 mmol/mol; 3.15 (95% CI 1.91-5.19) for HbA1c 73-82 mmol/mol; and 4.26 (95% CI 2.53-7.16) for HbA1c >82 mmol/mol. On multivariable restricted cubic spline analy-sis, we found a J-shaped association between HbA1c and sepsis risk, with the lowest risk observed at HbA1c of approximately 53 mmol/mol. We found no association between HbA1c and mortality among those individuals who developed sepsis.Conclusions: In our nationwide observational study of adult individuals with type 1 diabetes we found a J-shaped relationship between HbA1c and risk of sepsis, with the lowest risk at HbA1c levels about 53 mmol/mol (7.0%). HbA1c was not associ-ated with mortality in individuals affected by sepsis.
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| 10. |
- Balintescu, A., et al.
(författare)
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Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:1, s. 127-133
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes, and to assess the association between sepsis and all-cause mortality in such patients. RESEARCH DESIGN AND METHODS We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between 1 January 2005 and 31 December 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. RESULTS Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48–52 mmol/mol (6.5–6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07–1.24) for HbA1c <43 mmol/mol (6.1%), 0.93 (0.87–0.99) for HbA1c 53–62 mmol/mol (7.0–7.8%), 1.05 (0.97–1.13) for HbA1c 63–72 mmol/mol (7.9–8.7%), 1.14 (1.04–1.25) for HbA1c 73–82 mmol/mol (8.8–9.7%), and 1.52 (1.37–1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73–0.82) per SD; it increased thereafter (P for nonlinearity <0.001). As compared with patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03–4.30). CONCLUSIONS In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a fourfold increased risk of death among those developing sepsis. © 2021 by the American Diabetes Association.
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| 11. |
- Dakhel, Ardwan, et al.
(författare)
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Worse cardiovascular prognosis after endovascular surgery for intermittent claudication caused by infrainguinal atherosclerotic disease in patients with diabetes
- 2020
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Ingår i: Therapeutic Advances in Endocrinology and Metabolism. - : SAGE Publications. - 2042-0188 .- 2042-0196. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes mellitus (DM) is an established risk factor for intermittent claudication (IC) and other manifestations of atherosclerotic peripheral arterial disease. Indications for surgery in infrainguinal IC are debated, and there are conflicting reports regarding its outcomes in patients with DM. Aims of this study were to compare both short- and long-term effects on total- and cardiovascular (CV) mortality, major adverse cardiovascular events (MACEs), acute myocardial infarction (AMI), stroke, and major amputation following infrainguinal endovascular surgery for IC in patients with and without DM. We also evaluated potential relationships between diabetic control and outcomes in patients with DM. Methods: Nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Registry. Propensity score adjusted comparison of total and CV mortality, MACE, AMI, stroke, and major amputation after elective infrainguinal endovascular surgery for IC in 626 patients with and 1112 without DM at 30 postoperative days and after median 5.2 [interquartile range (IQR) 4.2-6.3] years of follow-up for patients with DM, and 5.4 (IQR 4.3-6.5) years for those without. Results: In propensity score adjusted Cox regression after 30 postoperative days, there were no differences between groups in morbidity or mortality. At last follow-up, patients with DM showed higher rates of MACE [hazard ratio (HR) 1.26, confidence interval (CI) 1.07-1.48;p < 0.01], AMI (HR 1.48, CI 1.09-2.00;p = 0.01), and major amputation (HR 2.31, CI 1.24-4.32;p < 0.01). Among patients with DM, higher HbA1c was associated with higher total mortality during follow-up (HR 1.01, CI 1.00-1.03;p = 0.045). Conclusion: Patients with DM have higher rates of MACE, AMI, and major amputation in propensity score adjusted analysis during 5 years of follow-up after infrainguinal endovascular surgery for IC. Furthermore, HbA1c is associated with total mortality in patients with DM. Prevention and treatment of DM is important to improve cardiovascular and limb outcomes.
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| 12. |
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| 13. |
- Eliasson, Björn, 1959, et al.
(författare)
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Persistence with IDegLira in Patients in Clinical Practice: A Nationwide Observational Study in Sweden
- 2020
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Ingår i: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; 11, s. 1807-1820
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Tidskriftsartikel (refereegranskat)abstract
- Aims To explore persistence with insulin degludec/liraglutide (IDegLira) treatment, clinical characteristics and concomitant medications in a large population of patients in clinical practice. Methods This was an observational study in patients with type 2 diabetes (n = 2432) who initiated IDegLira between 26 May 2015 and 31 December 2017. Data were obtained from Swedish nationwide registers and linked on an individual level using unique Swedish personal identifiers. Dose calculations were made for patients with >= 180 days between the first and last collections of IDegLira prescription. Changes in clinical parameters were evaluated as change from the last observation during 12 months prior to the initiation date until +/- 90 days from the last collection of IDegLira. Results Pre-index regimens (index date being the date of filling the first prescription of IDegLira) included: multiple daily insulin injections (45.1%); insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA) (19.7%); long-acting insulins (11.8%); non-injectable therapy only (11.4%); GLP-1 RA only (9.8%); and no collection of diabetes medication during the 6-month pre-index period (2.3%). The majority of patients (94 and 84%) were persistent with IDegLira at 6 and 12 months, respectively. The most commonly used concomitant medication was metformin (69.4%). Mean daily dose was 33 dose steps. Overall, there was a mean decrease in HbA1c (approx. 10 mmol/mol [1%]) and body weight (- 1.1 kg). Improvements in HbA1c were observed regardless of pre-index treatment. Conclusion After 12 months, 84% of patients were persistent on IDegLira, with improved glycaemic control and reductions in body weight.
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| 14. |
- Höskuldsdottir, G., et al.
(författare)
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Effects of bariatric surgery on the incidence of heart failure and atrial fibrillation in patients with type 2 diabetes and obesity
- 2020
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:Suppl. 1, s. S262-S262
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: To study the effects of obesity treatment with gastric bypass surgery on hospitalization for heart failure (HF) and atrial fibrillation (AF) in patients with type 2 diabetes (T2D) and obesity. We also studied the effects of gastric bypass surgery on mortality in a subgroup of individuals with preexisting heart failure.Materials and methods: In this register-based nationwide cohort study we compared individuals with T2D and obesity that underwent Roux-en-Y gastric bypass surgery (RYGB) with matched individuals with T2D and obesity that did not undergo surgery. Data was gathered by linking the Swedish National Diabetes Register and Scandinavian Obesity Surgery Registry. Matching of individuals for age, gender, BMI and calendar time was done using a time updated propensity score. The main outcome measures were hospitalization for HF and/or AF, and mortality in patients with preexisting HF. The risk for heart failure, AF and death were assessed using a Cox-proportional hazards regression model that addressed measured confounding.Results: We identified 5321 individuals with T2D and obesity that had undergone RYGB between January 2007 and December 2013 and 5321 matched controls. The individuals includedwere between 18 and 65 years old and had a BMI > 27.5 kg/m2. The follow-up time for hospitalization was until the end of 2015 (mean 4.5 years) and the end of 2016 for death. Our results show a 73% lower risk for HF (HR 0.27 (0.19, 0.38) p<0.001), 41% for AF (HF 0.59 (0.44, 0.78) p < 0.001), and 77% for concomitant AF and HF (HR0.23 (0.12, 0.46) p < 0.001) in the surgically treated group. In patients with preexisting HF we observed significantly lower mortality in the group that underwent surgery (HR0.23 (0.12, 0.43) p < 0.001).Conclusion: Bariatric surgery may reduce risk for HF and AF in patients with T2D and obesity, speculatively via positive cardiovascular and renal effects. Obesity treatment with surgery may also be a valuable alternative in selected patients with T2D and HF.
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| 15. |
- Keindl, Magdalena, et al.
(författare)
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Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With IL2RA and PTPN2 Gene Polymorphisms
- 2020
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic beta cells. Further, patients with T1D have 3-4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naive to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care.
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| 16. |
- Lilja, E., et al.
(författare)
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Diabetes mellitus was not associated with lower amputation-free survival after open revascularization for chronic limb-threatening ischemia - A nationwide propensity score adjusted analysis
- 2021
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Ingår i: Vascular Medicine. - : SAGE Publications. - 1358-863X .- 1477-0377. ; 26:5, s. 507-514
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Tidskriftsartikel (refereegranskat)abstract
- The risk of major amputation is higher after urgently planned endovascular therapy for chronic limb-threatening ischemia (CLTI) in patients with diabetes mellitus (DM). The aim of this nationwide cohort study was to compare outcomes between patients with and without DM following urgently planned open revascularization for CLTI from 2010 to 2014. Out of 1537 individuals registered in the Swedish Vascular Registry, 569 were registered in the National Diabetes Register. A propensity score adjusted Cox regression analysis was conducted to compare outcome between the groups with and without DM. Median follow-up was 4.3 years and 4.5 years for patients with and without DM, respectively. Patients with DM more often had foot ulcers (p = 0.034) and had undergone more previous amputations (p = 0.001) at baseline. No differences in mortality, cardiovascular death, major adverse cardiovascular events (MACE), or major amputation were observed between groups. The incidence rate of stroke was 70% higher (95% CI: 1.11-2.59; p = 0.0137) and the incidence rate of acute myocardial infarction (AMI) 39% higher (95% CI: 1.00-1.92; p = 0.0472) among patients with DM in comparison to those without. Open vascular surgery remains a first-line option for a substantial number of patients with CLTI, especially for limb salvage in patients with DM. The higher incidence rates of stroke and AMI among patients with DM following open vascular surgery for infrainguinal CLTI require specific consideration preoperatively with the aim of optimizing medical treatment to improve cardiovascular outcome postoperatively.
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| 17. |
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| 18. |
- Odak, I., et al.
(författare)
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Teachers’ Social and Emotional Competencies : A Lever for Social and Emotional Learning in Schools
- 2023
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Ingår i: Sociologija i Prostor. - : Institute for Social Research Zagreb. - 1846-5226. ; 61:1, s. 105-122
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Tidskriftsartikel (refereegranskat)abstract
- The present paper focuses on social and emotional learning, and highlights empirical findings on its importance for teachers, students and schools. The importance of social and emotional learning in school settings has been a central focus of research for the last 30 years. The development of teachers’ social and emotional competencies has been an essential factor for improving social and emotional learning of students. Only when teachers are able to create a school climate in which students feel included and welcome, students can develop and enhance their social and emotional competencies. In this paper, we outline the main conceptual frameworks on social and emotional learning, emphasizing the CASEL framework, relevant for both young people and adults. We proceed by focusing on teachers’ social and emotional competencies, as teachers are one of the key figures for fostering and developing social and emotional competencies in school settings. Afterwards, we address the issue of development of teachers’ social and emotional competencies in various settings. The last part of the paper links teachers’ and students’ social and emotional competencies. We stress the importance of teachers’ social and emotional competencies for healthy teacher-student relationships, and students’ well-being and academic achievement. As teachers also need support for the development of these competencies, we advocate for comprehensive school-wide approach, in order to ensure the successful implementation of social and emotional learning in classrooms.
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| 19. |
- Oskarsdotter, Kristin, 1995, et al.
(författare)
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Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting
- 2023
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Ingår i: Gels. - 2310-2861. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Autologous fat grafting is hampered by unpredictable outcomes due to high tissue resorption. Hydrogels based on enzymatically pretreated tunicate nanocellulose (ETC) and alginate (ALG) are biocompatible, safe, and present physiochemical properties capable of promoting cell survival. Here, we compared in situ and ex situ crosslinking of ETC/ALG hydrogels combined with lipoaspirate human adipose tissue (LAT) to generate an injectable formulation capable of retaining dimensional stability in vivo. We performed in situ crosslinking using two different approaches; inducing Ca2+ release from CaCO3 microparticles (CMPs) and physiologically available Ca2+ in vivo. Additionally, we generated ex situ-crosslinked, 3D-bioprinted hydrogel-fat grafts. We found that in vitro optimization generated a CMP-crosslinking system with comparable stiffness to ex situ-crosslinked gels. Comparison of outcomes following in vivo injection of each respective crosslinked hydrogel revealed that after 30 days, in situ crosslinking generated fat grafts with less shape retention than 3D-bioprinted constructs that had undergone ex situ crosslinking. However, CMP addition improved fat-cell distribution and cell survival relative to grafts dependent on physiological Ca2+ alone. These findings suggested that in situ crosslinking using CMP might promote the dimensional stability of injectable fat-hydrogel grafts, although 3D bioprinting with ex situ crosslinking more effectively ensured proper shape stability in vivo.
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| 20. |
- Ozgumus, T., et al.
(författare)
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Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes: the PROLONG study
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes.
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| 21. |
- Taimour, Soumia, et al.
(författare)
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Nationwide comparison of long-term survival and cardiovascular morbidity after acute aortic aneurysm repair in patients with and without type 2 diabetes
- 2020
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214. ; 71:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Epidemiologic data indicate decreased risk for development, growth, and rupture of abdominal aortic aneurysm (AAA) among patients with type 2 diabetes mellitus (DM). We therefore evaluated mortality and cardiovascular morbidity after acute repair of AAA in diabetic and nondiabetic patients. Methods: In this nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Register, we compared mortality and morbidity after acute open (n = 1357 [61%]) or endovascular (n = 860 [39%]) repair of ruptured (n = 1469 [66%]) or otherwise symptomatic (n = 748 [34%]) AAAs in 363 patients with and 1854 patients without DM with propensity score-adjusted analysis. Results: Follow-up was 3.91 years for patients with DM and 3.18 years for those without. In propensity-adjusted analysis, diabetic patients showed lower total mortality (relative risk [RR], 0.75; 95% confidence interval [CI], 0.59-0.95; P = .016) and cardiovascular mortality (RR, 0.17; 95% CI, 0.06-0.50; P = .01) than those without DM, whereas there were no differences in rates of major adverse cardiovascular events (RR, 1.10; 95% CI, 0.87-1.42; P = .42), acute myocardial infarction (RR, 1.36; 95% CI, 0.70-2.63; P = .37), or stroke (RR, 1.31; 95% CI, 0.84-2.03; P = .23). Conclusions: Patients with type 2 DM had lower rates of both total and cardiovascular mortality after acute AAA repair than those without DM, whereas rates of cardiovascular events, acute myocardial infarction, and stroke did not differ between groups. This might be explained by putative protective effects of DM on the aortic wall.
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| 22. |
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| 23. |
- Zabala, A., et al.
(författare)
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Risk of first stroke in people with type 2 diabetes and its relation to glycaemic control: A nationwide observational study
- 2020
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 22:2, s. 182-190
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Tidskriftsartikel (refereegranskat)abstract
- Aims To compare stroke incidence in people with type 2 diabetes (T2D) with that in a matched control group, and to investigate whether glucose exposure in people with T2D can predict a first-time stroke event and mortality. Material and methods In a nationwide observational cohort study, individuals with T2D were linked in the Swedish National Diabetes Register and matched with five individual population-based control subjects. We calculated crude incidence rates and 95% confidence intervals (CIs), and used Cox regression and multivariable hazard ratios (HRs), to estimate the risk of stroke and mortality in relation to glycated haemoglobin (HbA1c) levels. Results A total of 406 271 people with T2D (age 64.1 +/- 12.4 years, 45.7% women) and 2086 440 control subjects (age 64.0 +/- 12.4 years, 45.7% women) were included. During a median follow-up of 7.3 years, 26 380 people with T2D (6.5%) versus 92 375 control subjects (4.4%) were diagnosed with a stroke. The incidence rate was 10.12 events per 1000 person-years versus 7.26 events per 1000 person-years (HR 1.54, 95% CI 1.52-1.56). In the T2D group after multivariable adjustments, the HRs for stroke stratified by HbA1c level were: 54-64 mmol/mol: 1.27 (95% CI 1.22-1.32); 65-75 mmol/mol: 1.68 (95% CI 1.60-1.76); 76-86 mmol/mol: 1.89 (95% CI, 1.75-2.05); and > 87 mmol/mol: 2.14 (95% CI 1.90-2.42), respectively, compared with the reference category of HbA1c <= 53 mmol/mol. There was a stepwise increased risk of death after stroke, for every 10-mmol/mol categorical increment of HbA1c (HR 1.71; 95% CI 1.47-2.00) for the highest HbA1c category. Conclusions An increased risk of stroke and death was associated with poor glycaemic control in people with T2D.
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| 24. |
- Amer, Ahmed, 1984-, et al.
(författare)
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Cross-cultural adaptation and reliability of the Arabic version of Children's Hand-use Experience Questionnaire (CHEQ)
- 2022
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Ingår i: Hong Kong Journal of Occupational Therapy. - : Elsevier. - 1569-1861 .- 1876-4398. ; 35:1, s. 84-95
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Tidskriftsartikel (refereegranskat)abstract
- Background: Validated outcome measures are essential for assessment and treatment of children with disabilities. The Children's Hand-use Experience Questionnaire (CHEQ) was developed and validated for use in Western countries for children with unilateral hand dysfunction. This study aimed to perform a cross-cultural adaptation and investigate reliability for the Arabic CHEQ.Methods: Translation and cross-cultural adaptation were performed in four phases: (i) forward-translation and reconciliation with feedback from parents and typically developing children from Jordan (n = 14); (ii) backward-translation and review; (iii) cognitive debriefing with parents and/or their children with unilateral hand dysfunction (n = 17); and (iv) review and proofreading. In the psychometric analyses, 161 children from Jordan (mean age [SD] 10y 8 m [5y 8 m]; 88 males) participated. Internal consistency was evaluated with Cronbach's alpha. Test-retest reliability was evaluated in 39 children with intraclass correlation coefficient (ICC) and weighted kappa (kappa).Results: Synonyms of four words were added to accommodate for different Arabic dialects. On average, 93% of children with unilateral hand dysfunction and their parents understood the CHEQ items. One response alternative, 'Get help', to the opening question was unclear for 70% of the respondents and need further explanation. Two items about using a knife and fork were difficult to comprehend and culturally irrelevant. High internal consistency was demonstrated (Cronbach's alphas 0.94- 0.97) and moderate to excellent ICC (0.77-0.93). For 18 individual items, kappa indicated poor to good agreement (kappa between 0.28 and 0.66).Conclusions: After the suggested minor adjustments, the Arabic CHEQ will be comprehensible, culturally relevant and reliable for assessing children with unilateral hand dysfunction in Jordan.
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| 25. |
- Atla, Goutham, et al.
(författare)
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Genetic regulation of RNA splicing in human pancreatic islets
- 2022
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-760X. ; 23, s. 1-28
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNon-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown.ResultsWe examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform in ERO1B, a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such as DCLRE1B, a senescence regulator, and lncRNA MEG3.ConclusionsThese data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.
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| 26. |
- Barghouth, Mohammad, et al.
(författare)
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The structure of insulin granule core determines secretory capacity being reduced in type-2 diabetes
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Exocytosis in excitable cells is essential for their physiological functions. Although the exocytotic machinery controlling cellular secretion has been well investigated, the function of the vesicular cargo, i.e. secretory granular content remains obscure. Here we combine dSTORM imaging and single-domain insulin antibody, to dissect the in situ structure of insulin granule cores (IGCs) at nano level. We demonstrate that the size and shape of the IGCs can be regulated by the juxta-granular molecules Nucleobindin-2 and Enolase-1, that further contribute to the stimulated insulin secretion. IGCs located at the plasma membrane are larger than those in the cytosol. The IGCs size is decreased by ∼20% after glucose stimulation due to the release of the peripheral part of IGCs through incomplete granule fusion. Importantly, the reduction of the IGCs size is also observed in non-stimulatory pancreatic β-cells from diabetic db/db mice, Akita (Ins2+/-) mice and human Type-2 diabetic donors, in accordance with impaired secretion. These findings overall highlight the structure of exocytotic insulin cores as a novel modality amenable to targeting in the stimulated exocytosis in β-cells with impaired insulin secretion.Competing Interest StatementThe authors have declared no competing interest.
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| 27. |
- Battisti, M., et al.
(författare)
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Overview of the Mini-EUSO μs trigger logic performance
- 2022
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Ingår i: 37th International Cosmic Ray Conference, ICRC 2021. - : Sissa Medialab Srl.
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Konferensbidrag (refereegranskat)abstract
- Mini-EUSO is the first detector of the JEM-EUSO program deployed on the ISS. It is a wide field of view telescope currently operating from a nadir-facing UV-transparent window on the ISS. It is based on an array of MAPMTs working in photon counting mode with a 2.5 μs time resolution. Among the different scientific objectives it searches for light signals with time duration compatible to those expected from Extensive Air Showers (EAS) generated by EECRs interacting in the atmosphere. Although the energy threshold for cosmic ray showers is above E > 1021eV, due the constraints given by the size of the UV-transparent window, the dedicated trigger logic has been capable of the detection of other interesting classes of events, like elves and ground flashers. An overview of the general performance of the trigger system is provided, with a particular focus on the identification of classes of events responsible for the triggers.
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| 28. |
- Berntsson, K., et al.
(författare)
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Patient safety when receiving telephone advice in primary care – a Swedish qualitative interview study
- 2022
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Ingår i: BMC Nursing. - : BioMed Central. - 1472-6955. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A lack of patient safety is a significant global public health challenge and is one of the leading causes of death and disability, entailing significant financial and economic costs. However, patient safety can be improved and patients can avoid being harmed if more knowledge could be gained about what it is that impacts patient safety. Patient safety when receiving telephone advice is an important issue given the increase in digitalization in healthcare services. Aim: The aim of this study was to explore district nurses’ (“telenurses”) experiences and perceptions of patient safety when providing health advice over the phone. Methods: Data collection was performed using semi-structured interviews and analyzed using qualitative content analysis. The participants (n = 12) were telnurses in primary care. Results: The theme “Being able to make the right decision” was formed based on two categories: “Communication” and “Assessment”. Through effective communication with the right conditions to make an assessment, the correct decision can be made when a patient calls, and the district nurse feels that their telephone advice is safe for the patient. Conclusions: Patient safety can be challenged when receiving telephone advice, particularly when they feel stressed due to organizational factors. There is a need to shift from the individual to the organization. Further, while computerized knowledge support generally results in safe decisions, there may also be problems. Hence, it is imperative to develop computerized knowledge support as a part of improved patient safety in telephone advice.
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| 29. |
- Casolino, M., et al.
(författare)
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The Mini-EUSO telescope on board the International Space Station : Launch and first results
- 2022
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Ingår i: 37th International Cosmic Ray Conference, ICRC 2021. - : Sissa Medialab Srl.
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Konferensbidrag (refereegranskat)abstract
- Mini-EUSO is a telescope launched on board the International Space Station in 2019 and currently located in the Russian section of the station. Main scientific objectives of the mission are the search for nuclearites and Strange Quark Matter, the study of atmospheric phenomena such as Transient Luminous Events, meteors and meteoroids, the observation of sea bioluminescence and of artificial satellites and man-made space debris. It is also capable of observing Extensive Air Showers generated by Ultra-High Energy Cosmic Rays with an energy above 1021 eV and detect artificial showers generated with lasers from the ground. Mini-EUSO can map the night-time Earth in the UV range (290 - 430 nm), with a spatial resolution of about 6.3 km and a temporal resolution of 2.5 μs, observing our planet through a nadir-facing UV-transparent window in the Russian Zvezda module. The instrument, launched on 2019/08/22 from the Baikonur cosmodrome, is based on an optical system employing two Fresnel lenses and a focal surface composed of 36 Multi-Anode Photomultiplier tubes, 64 channels each, for a total of 2304 channels with single photon counting sensitivity and an overall field of view of 44◦. Mini-EUSO also contains two ancillary cameras to complement measurements in the near infrared and visible ranges. In this paper we describe the detector and present the various phenomena observed in the first year of operation.
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| 30. |
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| 31. |
- Chriett, S., et al.
(författare)
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SCRT1 is a novel beta cell transcription factor with insulin regulatory properties
- 2021
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 521
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.
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| 32. |
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| 33. |
- Eliasson, Emma T., et al.
(författare)
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Unpacking stigma : Meta-analyses of correlates and moderators of personal stigma in psychosis
- 2021
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Ingår i: Clinical Psychology Review. - : Elsevier. - 0272-7358 .- 1873-7811. ; 89
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Forskningsöversikt (refereegranskat)abstract
- Personal stigma entails perceived, experienced and internalised stigmatisation. Mental Health stigma has been widely researched across a range of countries and a meta-analysis of their associations and moderators in psychosis is timely. Meta-analyses were conducted examining the correlates and moderators of personal stigma in terms of: (1) demographic variables (2) illness related variables (3) symptoms/negative outcomes, and (4) aspects of wellbeing. Associations were obtained from a total of 216 records. Several demographic factors including age, economic status, employment, and rural residence had small associations with aspects of personal stigma (r's = 0.12 to -0.13). Personal stigma aspects were inversely related to medication adherence (r's = -0.20, -0.21), and positively associated with insight and number of hospitalisations (r's = 0.09-0.19). Most symptoms were positively associated with personal stigma (r's = 0.10-0.43), whereas inverse relations with wellbeing variables were identified (r's = -0.13 to -0.54). Moderator effects emerged including that of cultural setting and sex, age and education level, highlighting the role of cultural and demographic factors in shaping personal stigma aspects in psychosis. The present study also highlights the importance of recognizing the negative effect of actual stigma and discrimination experiences; particularly its detrimental impact on self-image and its complex role in shaping the internalisation of societal stigma.
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| 34. |
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| 35. |
- Eliasson, Karin, 1984-, et al.
(författare)
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A spatially explicit approach to assessing commodity-driven fertilizer use and its impact on biodiversity
- 2023
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Ingår i: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 382
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Tidskriftsartikel (refereegranskat)abstract
- Global demand for food, including rising consumption of meat and dairy products, is increasing pressure on the environment and natural resources, often in locations distant from points of consumption. To identify and quantify consumer driven impacts and the components of the supply chain where sustainability interventions will be most effective, spatially explicit consumption-linked indicators that encompass environmental risks are required. Large amounts of phosphorus fertilizers are used in Brazilian soybean cultivation, which potentially cause eutrophication and impact freshwater species. We use a sub-national trade model to develop a spatially explicit approach for assessing commodity-driven phosphorus fertilizer use and its potential impact on biodiversity linked to four key consumers. The use of phosphorus for embedded consumption per capita of Brazilian soybean in China, the EU, the UK, and Sweden are estimated at municipal level and combined with metrics that influence losses of phosphorus to create a normalised relative risk index. The relative risk index is presented in geospatial visualisations to explore geographical patterns of risk to freshwater biodiversity and make the link between consumer and producer countries less obscure. The results indicate high phosphorus-linked species risk in municipalities within Mato Grosso, Rio Grande do Sul, Paraná, and Goiás. Sweden and the UK generate the highest relative risk and the geographical patterns of risk differ between the investigated consuming countries, showing that smaller countries can have relatively large impacts at a spatially explicit scale. In the Amazon biome, risk of nutrient losses and biodiversity are relatively high, creating concerns as soybean production is expanding into the area. The results and methodological approach can contribute to understanding of accountability, agency, and increased transparency for the governance of global supply chains, necessary for enabling transformations towards sustainable food systems.
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| 36. |
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| 37. |
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| 38. |
- Engstrom, A., et al.
(författare)
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Sodium-Glucose Cotransporter 2 Inhibitor Treatment and Risk of Atrial Fibrillation: Scandinavian Cohort Study
- 2023
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:2, s. 351-360
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To assess the association between use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of new-onset atrial fibrillation (AF) in routine clinical practice. RESEARCH DESIGN AND METHODS We used nationwide registers in Denmark, Norway, and Sweden from 2013 to 2018 in order to include patients without a history of AF who were newly prescribed an SGLT2 inhibitor or an active comparator (glucagon-like peptide 1 [GLP-1] receptor agonist). We performed a cohort study to assess new-onset AF in intention-to-treat analyses using Cox regression, adjusted for baseline covariates with propensity score weighting. RESULTS We identified 79,343 new users of SGLT2 inhibitors (59.2% dapagliflozin, 40.0% empagliflozin, 0.8% canagliflozin, <0.1% ertugliflozin) and 57,613 new users of GLP-1 receptor agonists. Mean age of the study cohort was 61 years and 60% were men. The adjusted incidence rate of new-onset AF was 8.6 per 1,000 person-years for new users of SGLT2 inhibitors compared with 10.0 per 1,000 person-years for new users of GLP-1 receptor agonists. The adjusted hazard ratio (aHR) was 0.89 (95% CI 0.81-0.96), and the rate difference was 1.4 fewer events per 1,000 person-years (95% CI 0.6-2.1). Using an as-treated exposure definition, the aHR for new-onset AF was 0.87 (95% CI 0.76-0.99). No statistically significant heterogeneity of the aHRs was observed between subgroups of patients with and without a history of heart failure or major cardiovascular disease. CONCLUSIONS In this cohort study using nationwide data from three countries, use of SGLT2 inhibitors, compared with GLP-1 receptor agonists, was associated with a modestly reduced risk of new-onset AF.
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| 39. |
- Eriksson, J., et al.
(författare)
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Metformin or SGLT2 inhibitor as 1st line treatment of type 2 diabetes? Design and interim results of the SMARTEST trial
- 2023
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 197:Supl. 1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Metformin is generally recommended as 1 st line medication in T2D. However, there is no compelling evidence of its superiority in preventing diabetes complications. SGLT2 inhibitors prevent cardiovascular mortality, heart failure and renal impairment in T2D patients at high cardiovascular risk.Aim: To assess whether an SGLT2 inhibitor is superior to metformin in preventing organ complications and premature death in early-stage T2D.Method: The SMARTEST study (SGLT2 inhibitor or Metformin As standaRd Treatment of Early Stage Type 2 diabetes) is a registry-based trial in primary care. Participants are included via on-site or video visits at 31 centers across Sweden; T2D <4 yr; drugnaïve (currently 31%) or montherapy; no cardiorenal diseases. Randomizaton 1:1, open label metformin (individualized dose) or dapagliflozin 10 mg/day. Diet, exercise and other medications are stipulated according to national guidelines. Patients are followed 2–6 yrs.Endpoints are collected using NDR and the national Patient Registry. The study will close when 844 primary endpoint events have occurred, giving 90% power to detect a HR of 0.8 for dapagliflozin vs metformin. Primary composite endpoint: time to death, myocardial infarction, stroke, heart failure or appearance/progression of microvascular complications (retinopathy, nephropathy, diabetic foot lesions). Other endpoints include: need for insulin therapy; blood pressure, BMI, HbA1c, PROM and health economy.Results: From late 2019 until May 2022 1100 patients are included. 38% are females, mean age is 60 years and HbA1c 46.5 mmol/mol (6.4%). So far, the primary endpoint event rate is 11/100 patient years (PY), whereas 7/100 PY was estimated from previous data. Nephropathy and foot-at-risk had high rates (6 and 3/100 PY) but MACE was rare (1/100 PY). The recruitment target is 2700 participants, expected by end 2023.Conclusion: Final results are expected in 2025 and can challenge or, equally important, reinforce the current metformin paradigm in early T2D. Event rates are higher than previously recognized for nephropathy and diabetic foot problems but lower for MACE.
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Hero, Christel, et al.
(författare)
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Impact of Socioeconomic Factors and Gender on Refill Adherence and Persistence to Lipid-Lowering Therapy in Type 1 Diabetes
- 2021
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Ingår i: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; 12:9, s. 2371-2386
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Lipid-lowering therapy (LLT) reduces the risk of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D). However, socioeconomic factors and gender may have an impact on the adherence to and non-persistence with LLT. Methods This was a nationwide register-based cohort study that included 6192 individuals with T1D aged >= 18 years who were registered in the Swedish National Diabetes Register and had initiated novel use of LLT. Information on socioeconomic parameters (source: Statistics Sweden) and comorbidity (source: National Patient Register) was collected. The individuals were followed for 36 months, and adherence to LLT was analyzed according to age, socioeconomics and gender. The medication possession ratio (MPR; categorized into <= 80% and > 80%) and non-persistence (discontinuation) with medication was calculated after 18 and 36 months. Results Individuals older than 53 years were more adherent to LLT (MPR > 80%) than those younger than 36 years (odds ratio [(OR] 1.30, p < 0.0001) at 36 months. Women were more adherent and less prone to discontinue LLT at 18 months (OR 1.05, p = 0.0005 and OR 0.95, p = 0.0004, respectively), but not at 36 months. Divorced individuals were less adherent than married ones (OR 0.93, p = 0.0005) and discontinued LLT more often than the latter (OR 1.06, p = 0.003). Education had no impact on adherence, but individuals with higher incomes discontinued LLT less frequently than those with lower incomes. Individuals with a country of origin other than Sweden discontinued LLT more often. Conclusion Lower adherence to LLT in individuals with T1D was associated with male gender, younger age, marital status and country of birth. These factors should be considered when evaluating adherence to LLT in clinical practice, with the aim to help patients achieve full cardioprotective treatment.
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| 44. |
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| 45. |
- Höskuldsdóttir, Gudrun, et al.
(författare)
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Potential Effects of Bariatric Surgery on the Incidence of Heart Failure and Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus and Obesity and on Mortality in Patients With Preexisting Heart Failure: A Nationwide, Matched, Observational Cohort Study
- 2021
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Obesity and diabetes mellitus are strongly associated with heart failure (HF) and atrial fibrillation (AF). The benefits of bariatric surgery on cardiovascular outcomes are known in people with or without diabetes mellitus. Surgical treatment of obesity might also reduce the incidence of HF and AF in individuals with obesity and type 2 diabetes mellitus (T2DM). Methods and Results In this register-based nationwide cohort study we compared individuals with T2DM and obesity who underwent Roux-en-Y gastric bypass surgery with matched individuals not treated with surgery. The main outcome measures were hospitalization for HF and/or AF and mortality in patients with preexisting HF. We identified 5321 individuals with T2DM and obesity who had undergone Roux-en-Y gastric bypass surgery between January 2007 and December 2013 and 5321 matched controls. The individuals included were 18 to 65 years old and had a body mass index >27.5 kg/m(2). The follow-up time for hospitalization was until the end of 2015 (mean 4.5 years) and the end of 2016 for death. Our results show a 73% lower risk for HF (hazard ratio [HR], 0.27; CI, 0.19-0.38), 41% for AF (HR, 0.59; CI, 0.44-0.78), and 77% for concomitant AF and HF (HR, 0.23; CI, 0.12-0.46) in the surgically treated group. In patients with preexisting HF we observed significantly lower mortality in the group who underwent surgery (HR, 0.23; 95% CI, 0.12-0.43). Conclusions Bariatric surgery may reduce risk for HF and AF in patients with T2DM and obesity, speculatively via positive cardiovascular and renal effects. Obesity treatment with surgery may also be a valuable alternative in selected patients with T2DM and HF.
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| 46. |
- Kattner, Nicole, et al.
(författare)
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Development and validation of a quantitative electron microscopy score to assess acute cellular stress in the human exocrine pancreas
- 2021
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Ingår i: Journal of Pathology: Clinical Research. - : Wiley. - 2056-4538. ; 7:2, s. 173-187
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Tidskriftsartikel (refereegranskat)abstract
- The pancreas is particularly sensitive to acute cellular stress, but this has been difficult to evaluate using light microscopy. Pancreatic ischaemia associated with deceased organ donation negatively impacts whole-organ and isolated-islet transplantation outcomes. Post-mortem changes have also hampered accurate interpretation of ante-mortem pancreatic pathology. A rigorous histological scoring system accurately quantifying ischaemia is required to experimentally evaluate innovations in organ preservation and to increase rigour in clinical/research evaluation of underlying pancreatic pathology. We developed and validated an unbiased electron microscopy (EM) score of acute pancreatic exocrine cellular stress in deceased organ donor cohorts (development [n = 28] and validation [n = 16]). Standardised assessment led to clearly described numerical scores (0–3) for nuclear, mitochondrial and endoplasmic reticulum (ER) morphology and intracellular vacuolisation; with a maximum (worst) aggregate total score of 12. In the Validation cohort, a trend towards higher scores was observed for tail versus head regions (nucleus score following donation after brainstem death [DBD]: head 0.67 ± 0.19; tail 0.86 ± 0.11; p = 0.027) and donation after circulatory death (DCD) versus DBD (mitochondrial score: DCD (head + tail) 2.59 ± 0.16; DBD (head + tail) 2.38 ± 0.21; p = 0.004). Significant mitochondrial changes were seen ubiquitously even with short cold ischaemia, whereas nuclear and vacuolisation changes remained mild even after prolonged ischaemia. ER score correlated with cold ischaemia time (CIT) following DBD (pancreatic tail region: r = 0.796; p = 0.018). No relationships between CIT and EM scores were observed following DCD. In conclusion, we have developed and validated a novel EM score providing standardised quantitative assessment of subcellular ultrastructural morphology in pancreatic acinar cells. This provides a robust novel tool for gold standard measurement of acute cellular stress in studies evaluating surrogate measures of peri-transplant ischaemia, organ preservation technologies and in samples obtained for detailed pathological examination of underlying pancreatic pathology.
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| 47. |
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| 48. |
- Liakopoulos, Vasileios, et al.
(författare)
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Renal and Cardiovascular Outcomes After Weight Loss From Gastric Bypass Surgery in Type 2 Diabetes: Cardiorenal Risk Reductions Exceed Atherosclerotic Benefits
- 2020
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Ingår i: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:6, s. 1276-1284
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE We examined detailed renal and cardiovascular (CV) outcomes after gastric bypass (GBP) surgery in people with obesity and type 2 diabetes mellitus (T2DM), across several renal function categories, in a nationwide cohort study. RESEARCH DESIGN AND METHODS We linked data from the National Diabetes Register and the Scandinavian Obesity Surgery Register with four national databases holding information on socioeconomic variables, medications, hospitalizations, and causes of death and matched 5,321 individuals with T2DM who had undergone GBP with 5,321 who had not (age 18-65 years, mean BMI >40 kg/m(2), mean follow-up >4.5 years). The risks of postoperative outcomes were assessed with Cox regression models. RESULTS During the first years postsurgery, there were small reductions in creatinine and albuminuria and stable estimated glomerular filtration rate (eGFR) in the GBP group. The incidence rates of most outcomes relating to renal function, CV disease, and mortality were lower after GBP, being particularly marked for heart failure (hazard ratio [HR] 0.33 [95% CI 0.24, 0.46]) and CV mortality (HR 0.36 [(95% CI 0.22, 0.58]). The risk of a composite of severe renal disease or halved eGFR was 0.56 (95% CI 0.44, 0.71), whereas nonfatal CV risk was lowered less (HR 0.82 [95% CI 0.70, 0.97]) after GBP. Risks for key outcomes were generally lower after GBP in all eGFR strata, including in individuals with eGFR CONCLUSIONS Our data suggest robust benefits for renal outcomes, heart failure, and CV mortality after GBP in individuals with obesity and T2DM. These results suggest that marked weight loss yields important benefits, particularly on the cardiorenal axis (including slowing progression to end-stage renal disease), whatever the baseline renal function status.
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| 49. |
- Lieber, Ingrid, et al.
(författare)
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Lithium-associated hypothyroidism : Reversible after lithium discontinuation?
- 2021
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Ingår i: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 64:S1, s. S76-S76
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The association between lithium and thyroid dysfunction has long been known. Yet it is not known whether lithium-associated hypothyroidism is reversible, once lithium treatment has been stopped.ObjectivesTo determine whether lithium-associated hypothyroidism was reversible in patients who subsequently discontinued lithium.MethodsRetrospective cohort study in the Swedish region of Norrbotten into the effects and side- effects of lithium treatment and other drugs for relapse prevention (LiSIE). For this particular study, we reviewed medical records between 1997 and 2015 of patients treated with lithium.ResultsOf 1340 patients screened, we identified 90 patients with lithium-associated hypothyroidism who subsequently discontinued lithium. Of these, 27% had overt hypothyroidism at the time when thyroid replacement therapy was initiated. The mean delay from lithium start to thyroid replacement therapy start was 2.3 (SD 4.7) years. Fifty percent received thyroid replacement therapy within 10 months of starting lithium. Of 85 patients available for follow up, 35 (41%) stopped thyroid replacement therapy after lithium discontinuation. Six patients reinstated thyroid replacement therapy subsequently. Only one of these had overt hypothyroidism, occurring 13 days after stopping lithium and 11 days after stopping thyroid replacement therapy.ConclusionsLithium-associated hypothyroidism seems reversible in most patients, once lithium has been discontinued. In such cases, thyroid replacement therapy discontinuation could be attempted much more often than currently done. Based on the limited evidence of our study, we can expect hypothyroidism to recur early after discontinuation of thyroid replacement therapy if at all.DisclosureMO: scient adv. board member Astra Zeneca Sweden; UW: educ. activities Norrbotten Region: Astra Zeneca, Eli Lilly, Janssen, Novartis, Otsuka/Lundbeck, Servier, Shire and Sunovion. All others: none.
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- Lindqvist, Andreas, et al.
(författare)
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GPR162 is a beta cell CART receptor
- 2023
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Ingår i: iScience. - 2589-0042. ; 26:12
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Tidskriftsartikel (refereegranskat)abstract
- Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knockdown (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established using proximity ligation assay, radioactive binding, and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding. Gpr162 KD cells had blunted CARTp-induced exocytosis, and reduced CARTp-induced insulin secretion. Furthermore, we identified a hitherto undescribed GPR162-dependent role of CART as a regulator of cytoskeletal arrangement. Thus, our findings provide mechanistic insight into the effect of CART on insulin secretion and show that GPR162 is the CART receptor in beta cells.
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