| 1. |
- Keindl, Magdalena, et al.
(författare)
-
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
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 11
-
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.
|
|
| 2. |
- Sjögren, Jakob Jonsson, et al.
(författare)
-
Characteristics and impact of pain from root-filled teeth : A practice-based cross-sectional study comparing painful teeth with and without signs of inflammatory dental disease
- 2024
-
Ingår i: Journal of Oral and Facial Pain and Headache. - : Quintessence Publishing. - 2333-0384 .- 2333-0376. ; 38:1, s. 64-76
-
Tidskriftsartikel (refereegranskat)abstract
- To compare pain characteristics, impact of pain and characteristics of patients with painful root-filled teeth with and without signs of inflammatory dental disease. This cross-sectional study was performed in the Public Dental Health services, Region orebro County, Sweden. Adult patients with >= 1 root-filled tooth identified at their regular check -up were included and assigned to one of two groups; those with >= 1 sign of inflammatory dental disease (DD+) and those without any such sign (DD-). Patients/teeth were compared regarding pain characteristics (intensity, frequency, duration, quality and provoking factors), impact of pain (medication intake, impact on life) and patient characteristics as background factors (general health, other bodily and orofacial pain). Statistics included descriptive data (frequency tables) and group comparisons (Chi-square, Fisher's Exact and Mann-Whitney U-tests). The DD+ group included 27 participants (30 teeth) and the DD- group 22 participants (23 teeth). On average, pain intensity was mild, the frequency most often recurrent, and the impact was low. Average pain duration since onset exceeded 2 years in both groups. The only observed between-group differences were average pain intensity; 3.1 (0-10 Numerical Rating Scale (NRS)) in DD- group compared to 1.6 for DD+ (p = 0.030), and tenderness to apical palpation; only reported in the DD+ group. The similarities in clinical presentation between the two groups underscore the difficulties in correctly distinguishing between pain of odontogenic and non-odontogenic origin in root-filled teeth with a standard clinical investigation. Additional diagnostic methods need to be investigated for their ability to differentiate between tooth pain or discomfort of different origins.
|
|
| 3. |
- Armour, Sarah L., et al.
(författare)
-
Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells
- 2023
-
Ingår i: DIABETES. - 0012-1797 .- 1939-327X. ; 72:10, s. 1446-1459
-
Tidskriftsartikel (refereegranskat)abstract
- Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from alpha-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic alpha-cells remain unclear. Here we show that in alpha-cells, the interaction between fatty acid oxidation and glucose metabolism controls glucagon secretion. The glucose-dependent inhibition of glucagon secretion relies on pyruvate dehydrogenase and carnitine palmitoyl transferase 1a activity and lowering of mitochondrial fatty acid oxidation by increases in glucose. This results in reduced intracellular ATP and leads to membrane repolarization and inhibition of glucagon secretion. These findings provide a new framework for the metabolic regulation of the alpha-cell, where regulation of fatty acid oxidation by glucose accounts for the stimulation and inhibition of glucagon secretion.Article Highlights It has become clear that dysregulation of glucagon secretion and alpha-cell function plays an important role in the development of diabetes, but we do not know how glucagon secretion is regulated. Here we asked whether glucose inhibits fatty acid oxidation in alpha-cells to regulate glucagon secretion. We found that fatty acid oxidation is required for the inhibitory effects of glucose on glucagon secretion through reductions in ATP. These findings provide a new framework for the regulation of glucagon secretion by glucose.
|
|
| 4. |
-
Att välja trä
- 2020. - 10
-
Samlingsverk (redaktörskap) (populärvet., debatt m.m.)
|
|
| 5. |
- Cataldo, Luis Rodrigo, et al.
(författare)
-
The human batokine EPDR1 regulates β-cell metabolism and function
- 2022
-
Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 66
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Ependymin-Related Protein 1 (EPDR1) was recently identified as a secreted human batokine regulating mitochondrial respiration linked to thermogenesis in brown fat. Despite that EPDR1 is expressed in human pancreatic β-cells and that glucose-stimulated mitochondrial metabolism is critical for stimulus-secretion coupling in β-cells, the role of EPDR1 in β-cell metabolism and function has not been investigated. Methods: EPDR1 mRNA levels in human pancreatic islets from non-diabetic (ND) and type 2 diabetes (T2D) subjects were assessed. Human islets, EndoC-βH1 and INS1 832/13 cells were transfected with scramble (control) and EPDR1 siRNAs (EPDR1-KD) or treated with human EPDR1 protein, and glucose-stimulated insulin secretion (GSIS) assessed by ELISA. Mitochondrial metabolism was investigated by extracellular flux analyzer, confocal microscopy and mass spectrometry-based metabolomics analysis. Results: EPDR1 mRNA expression was upregulated in human islets from T2D and obese donors and positively correlated to BMI of donors. In T2D donors, EPDR1 mRNA levels negatively correlated with HbA1c and positively correlated with GSIS. EPDR1 silencing in human islets and β-cell lines reduced GSIS whereas treatment with human EPDR1 protein increased GSIS. Epdr1 silencing in INS1 832/13 cells reduced glucose- and pyruvate- but not K+-stimulated insulin secretion. Metabolomics analysis in Epdr1-KD INS1 832/13 cells suggests diversion of glucose-derived pyruvate to lactate production and decreased malate-aspartate shuttle and the tricarboxylic acid (TCA) cycle activity. The glucose-stimulated rise in mitochondrial respiration and ATP/ADP-ratio was impaired in Epdr1-deficient cells. Conclusion: These results suggests that to maintain glucose homeostasis in obese people, upregulation of EPDR1 may improve β-cell function via channelling glycolysis-derived pyruvate to the mitochondrial TCA cycle.
|
|
| 6. |
- Cooper, Steven J., et al.
(författare)
-
Exploring Snowfall Variability through the High-Latitude Measurement of Snowfall (HiLaMS) Field Campaign
- 2022
-
Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 103:8, s. E1762-E1780
-
Tidskriftsartikel (refereegranskat)abstract
- The High-Latitude Measurement of Snowfall (HiLaMS) campaign explored variability in snowfall properties and processes at meteorologically distinct field sites located in Haukeliseter, Norway, and Kiruna, Sweden, during the winters of 2016/17 and 2017/18, respectively. Campaign activities were founded upon the sensitivities of a low-cost, core instrumentation suite consisting of Micro Rain Radar, Precipitation Imaging Package, and Multi-Angle Snow Camera. These instruments are highly portable to remote field sites and, considered together, provide a unique and complementary set of snowfall observations including snowflake habit, particle size distributions, fall speeds, surface snowfall accumulations, and vertical profiles of radar moments and snow water content. These snow-specific parameters, used in combination with existing observations from the field sites such as snow gauge accumulations and ambient weather conditions, allow for advanced studies of snowfall processes. HiLaMS observations were used to 1) successfully develop a combined radar and in situ microphysical property retrieval scheme to estimate both surface snowfall accumulation and the vertical profile of snow water content, 2) identify the predominant snowfall regimes at Haukeliseter and Kiruna and characterize associated macrophysical and microphysical properties, snowfall production, and meteorological conditions, and 3) identify biases in the HARMONIE-AROME numerical weather prediction model for forecasts of snowfall accumulations and vertical profiles of snow water content for the distinct snowfall regimes observed at the mountainous Haukeliseter site. HiLaMS activities and results suggest value in the deployment of this enhanced snow observing instrumentation suite to new and diverse high-latitude locations that may be underrepresented in climate and weather process studies.
|
|
| 7. |
- Eliasson, Gabriella, et al.
(författare)
-
Comorbid conditions as predictors of mortality in severe COPD - an eight-year follow-up cohort study
- 2023
-
Ingår i: European Clinical Respiratory Journal. - : Taylor & Francis. - 2001-8525. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Co-morbidities are common in chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. The aim of the present study was to explore the prevalence of several comorbid conditions in severe COPD, and to investigate and compare their associations with long-term mortality.Methods: In May 2011 to March 2012, 241 patients with COPD stage 3 or 4 were included in the study. Information was collected on sex, age, smoking history, weight and height, current pharmacological treatment, number of exacerbations the recent year and comorbid conditions. At December 31st, 2019, mortality data (all-cause and cause specific) were collected from the National Cause of Death Register. Data were analyzed using Cox-regression analysis with gender, age, previously established predictors of mortality and comorbid conditions as independent variables, and all-cause mortality and cardiac and respiratory mortality, respectively, as dependent variables.Results: Out of 241 patients, 155 (64%) were deceased at the end of the study period; 103 patients (66%) died of respiratory disease and 25 (16%) of cardiovascular disease. Impaired kidney function was the only comorbid condition independently associated with increased all-cause mortality (HR (95% CI) 3.41 (1.47-7.93) p=0.004) and respiratory mortality (HR (95%CI) 4.63 (1.61 to 13.4), p = 0.005). In addition, age >= 70, BMI <22 and lower FEV1 expressed as %predicted were significantly associated with increased all-cause and respiratory mortality.Conclusion: In addition to the risk factors high age, low BMI and poor lung function; impaired kidney function appears to be an important risk factor for mortality in the long term, which should be taken into account in the medical care of patients with severe COPD.
|
|
| 8. |
- Eliasson, Thomas, et al.
(författare)
-
Epiphytic microbiota in Swedish grass-clover herbage and the effect of silage additives on fermentation profiles and bacterial community compositions of the resulting silages
- 2023
-
Ingår i: Journal of Applied Microbiology. - 1364-5072 .- 1365-2672. ; 134
-
Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate the epiphytic microbiota in grass-clover herbage harvested at different sites and occasions and to explore the effect of different silage additives on the resulting silage microbiota.Methods and results Herbage was harvested from grass-clover leys at geographically distributed sites in a long-term field experiment in Sweden, in early and late season of two consecutive years. Different silages were made from the herbage using: (1) no additive, (2) acid-treatment, and (3) inoculation by starter culture. Herbages were analysed for botanical and chemical composition, and the resulting silages for products of fermentation. Bacterial DNA was extracted from herbage and silage samples, followed by sequencing using Illumina 16S rRNA amplicon sequencing. Herbage microbiota showed no clear correlation to site or harvesting time. Silage additives had a major effect on the ensiling process; inoculation resulted in well fermented silages comprising a homogenous microbiota dominated by the genera Lactobacillus and Pediococcus. A minor effect of harvest time was also observed, with generally a more diverse microbiota in second-harvest silages. Untreated silages showed a higher relative abundance (RA) from non-lactic acid bacteria compared to acid-treated silages. In most silages, only a few bacterial amplicon sequence variants contributed to most of the RA.Conclusions The epiphytic microbiota in grass-clover herbage were found to be random and not dependent on site. From a microbial point of view, the most predictable and preferable silage outcome was obtained by inoculation with a starter culture. Acid-treatment with formic- and propionic acid surprisingly resulted in a less preferable silage. Silage making without additives cannot be recommended based on our results.
|
|
| 9. |
|
|
| 10. |
- Glynn, Linn, et al.
(författare)
-
Trends in Survival After First Myocardial Infarction in People With Diabetes
- 2024
-
Ingår i: JOURNAL OF THE AMERICAN HEART ASSOCIATION. - 2047-9980. ; 13:10
-
Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes.Methods and Results Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all-cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo-observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62 +/- 12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75 +/- 10.8 years; women, 38.1%), and individuals without diabetes (73 +/- 13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change -0.48% [95% CI, -0.52% to -0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, -0.33% [95% CI, -0.43% to -0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, -0.18% [95% CI, -0.53% to 0.17%]). Similar trends were observed with regard to 1-year death, cardiovascular death, and major adverse cardiovascular events.Conclusions During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.
|
|
