| 51. |
- Davidsson, P., et al.
(författare)
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No effect of sleep on the generalization of fear learning
- 2014
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Ingår i: Journal of sleep research. - : Wiley-Blackwell. - 1365-2869. ; 23, s. 7-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Sleep has been shown to be involved both in emotion regulation and in the active processing of information. We combined these two concepts and tested if sleep affected the generalization of fear learning.Methods: In a fear conditioning paradigm, participants were shown images of a small and a big circle where one of them was paired with an aversive sound, making it the CS+. Fear was measured with skin conductance responses. Participants were then randomly divided into a sleep or a wake group. The sleep group took a 2 h nap while the wake group rested for 2 h. Participants were then exposed to the two circles seen before, combined with 8 novel circles that gradually varied in size from the small one to the big one. We looked at how many circle sizes away from the CS+ that participants still exhibited a fear response, and if this differed between the sleep and the wake group.Results: We found no effect of sleep on the slope of the generalization across the different circles. There was a main effect of circle size, F(1,25) = 10.42, P = 0.01, but no main effect of sleep/wake, F (1,25) = 0.40, P = 0.54, and no interaction between sleep/wake X circle size, F(1,25) = 0.62, P = 0.44.Conclusions: The fear conditioning manipulation worked, with a gradual increase of fear depending on the stimuli’s similarity to the CS+. However, there was no effect of sleep or wake, which could possibly be explained by that just a 2 h nap not being a sufficient sleep manipulation to detect any differences.
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| 52. |
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| 53. |
- Elksnis, Andris, et al.
(författare)
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Pharmacological Inhibition of NOX4 Improves Mitochondrial Function and Survival in Human Beta-Cells
- 2021
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have reported beneficial effects of NADPH oxidase 4 (NOX4) inhibition on beta-cell survival in vitro and in vivo. The mechanisms by which NOX4 inhibition protects insulin producing cells are, however, not known. The aim of the present study was to investigate the effects of a pharmacological NOX4 inhibitor (GLX7013114) on human islet and EndoC-beta H1 cell mitochondrial function, and to correlate such effects with survival in islets of different size, activity, and glucose-stimulated insulin release responsiveness. We found that maximal oxygen consumption rates, but not the rates of acidification and proton leak, were increased in islets after acute NOX4 inhibition. In EndoC-beta H1 cells, NOX4 inhibition increased the mitochondrial membrane potential, as estimated by JC-1 fluorescence; mitochondrial reactive oxygen species (ROS) production, as estimated by MitoSOX fluorescence; and the ATP/ADP ratio, as assessed by a bioluminescent assay. Moreover, the insulin release from EndoC-beta H1 cells at a high glucose concentration increased with NOX4 inhibition. These findings were paralleled by NOX4 inhibition-induced protection against human islet cell death when challenged with high glucose and sodium palmitate. The NOX4 inhibitor protected equally well islets of different size, activity, and glucose responsiveness. We conclude that pharmacological alleviation of NOX4-induced inhibition of beta-cell mitochondria leads to increased, and not decreased, mitochondrial ROS, and this was associated with protection against cell death occurring in different types of heterogeneous islets. Thus, NOX4 inhibition or modulation may be a therapeutic strategy in type 2 diabetes that targets all types of islets.
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| 54. |
- Elksnis, Andris, et al.
(författare)
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The selective NOX4 inhibitor GLX7013159 decreases blood glucose concentrations and human beta-cell apoptotic rates in diabetic NMRI nu/nu mice transplanted with human islets
- 2023
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Ingår i: Free radical research. - : Taylor & Francis. - 1071-5762 .- 1029-2470. ; 57:6-12, s. 460-469
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Tidskriftsartikel (refereegranskat)abstract
- NADPH oxidase 4 (NOX4) inhibition has been reported to mitigate diabetes-induced beta-cell dysfunction and improve survival in vitro, as well as counteract high-fat diet-induced glucose intolerance in mice. We investigated the antidiabetic effects of the selective NOX4 inhibitor GLX7013159 in vivo in athymic diabetic mice transplanted with human islets over a period of 4 weeks. The GLX7013159-treated mice achieved lower blood glucose and water consumption throughout the treatment period. Furthermore, GLX7013159 treatment resulted in improved insulin and c-peptide levels, better insulin secretion capacity, as well as in greatly reduced apoptotic rates of the insulin-positive human cells, measured as colocalization of insulin and cleaved caspase-3. We conclude that the antidiabetic effects of NOX4 inhibition by GLX7013159 are observed also during a prolonged study period in vivo and are likely to be due to an improved survival and function of the human beta-cells.
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| 55. |
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| 56. |
- Funk, Eva, 1953-, et al.
(författare)
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Patient-initiated breath-holds in MRI : an alternative for reducing respiratory artifacts and improving image quality
- 2015
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Ingår i: Clinical imaging. - : Elsevier. - 0899-7071 .- 1873-4499. ; 39:4, s. 619-622
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate MRI image quality using two different breath-hold techniques.Materials and methods: Thirty patients remitted for MRI, 2D-dual gradient echo acquisition of the liver conducted two separate breath-hold acquisitions in randomized order, operator-instructed and patient-initiated. The images were reviewed by two radiologists.Results: There were no significant differences in image quality between the two breath-hold techniques either in overall image quality or respiratory motion artifacts. This assessment was equal and concordant for both radiologists.Conclusion: In terms of image quality, the patient self-initiated breath-hold was shown to be an equal alternative to conventional breath-hold imaging.
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| 57. |
- Gebre-Medhin, Maria, et al.
(författare)
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ARTSCAN III : A randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 39:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P 5 .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P 5 .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.
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| 58. |
- Grimberg, Åsa, et al.
(författare)
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Transitions in wheat endosperm metabolism upon transcriptional induction of oil accumulation by oat endosperm WRINKLED1
- 2020
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Ingår i: BMC Plant Biology. - : Springer Science and Business Media LLC. - 1471-2229. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Background Cereal grains, including wheat (Triticum aestivum L.), are major sources of food and feed, with wheat being dominant in temperate zones. These end uses exploit the storage reserves in the starchy endosperm of the grain, with starch being the major storage component in most cereal species. However, oats (Avena sativa L.) differs in that the starchy endosperm stores significant amounts of oil. Understanding the control of carbon allocation between groups of storage compounds, such as starch and oil, is therefore important for understanding the composition and hence end use quality of cereals. WRINKLED1 is a transcription factor known to induce triacylglycerol (TAG; oil) accumulation in several plant storage tissues. Results An oat endosperm homolog of WRI1 (AsWRI1) expressed from the endosperm-specific HMW1Dx5 promoter resulted in drastic changes in carbon allocation in wheat grains, with reduced seed weight and a wrinkled seed phenotype. The starch content of mature grain endosperms of AsWRI1-wheat was reduced compared to controls (from 62 to 22% by dry weight (dw)), TAG was increased by up to nine-fold (from 0.7 to 6.4% oil by dw) and sucrose from 1.5 to 10% by dw. Expression of AsWRI1 in wheat grains also resulted in multiple layers of elongated peripheral aleurone cells. RNA-sequencing, lipid analyses, and pulse-chase experiments using C-14-sucrose indicated that futile cycling of fatty acids could be a limitation for oil accumulation. Conclusions Our data show that expression of oat endosperm WRI1 in the wheat endosperm results in changes in metabolism which could underpin the application of biotechnology to manipulate grain composition. In particular, the striking effect on starch synthesis in the wheat endosperm indicates that an important indirect role of WRI1 is to divert carbon allocation away from starch biosynthesis in plant storage tissues that accumulate oil.
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| 59. |
- Gudjonsdottir, Hrafnhildur, et al.
(författare)
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Cohort Profile : The Stockholm Diabetes Prevention Programme (SDPP)
- 2022
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 51:6, s. e401-e413
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Tidskriftsartikel (refereegranskat)abstract
- The Stockholm Diabetes Prevention Programme (SDPP) was established in the mid-1990s as a baseline for a community-based intervention aimed at primary prevention of type 2 diabetes (T2D). The intervention was found to be ineffective, but the cohort continues to contribute to our understanding of the pathogenesis of T2D and cardiometabolic risk factors.The cohort comprises 15 070 men and 19 416 women, born between 1938 and 1961, resident in five municipalities in Stockholm County, Sweden, at baseline. A sub-cohort answered a screening survey (10 236 men and 16 481 women), and a sub-cohort of those participated in a clinical examination (3128 men and 4821 women) at baseline (clinical cohort).The clinical cohort has been followed up after 10 years, when 2383 men and 3329 women participated, and after 20 years, when 1752 men and 2545 women participated.Socioeconomic, demographic and health-related register information was collected for all. The screening survey contains self-reported information on own and familial T2D. For the clinical cohort, we conducted oral glucose tolerance tests, drew blood and took blood pressures and anthropometric measurements. The participants also filled in questionnaires on lifestyle and psychosocial conditions.Data are available on request after ethical approval; information is available on the study webpage [Stockholm-Diabetes-Prevention-Programme-(SDPP)(regionstockholm.se)].
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| 60. |
- Gummesson, Anders, 1973, et al.
(författare)
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Relations of Adipose Tissue Cell Death-Inducing DFFA-like Effector A Gene Expression to Basal Metabolic Rate, Energy Restriction and Obesity: Population-based and Dietary Intervention Studies.
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4759-65
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Tidskriftsartikel (refereegranskat)abstract
- Context: Cell death-inducing DFFA-like effector A (CIDEA) could be a potential target for the treatment of obesity via the modulation of metabolic rate, based on the findings that CIDEA inhibits the brown adipose tissue uncoupling process in rodents. Objective: To investigate the putative link between CIDEA and basal metabolic rate in humans, and to further elucidate the role of CIDEA in human obesity. Design: We have explored CIDEA gene expression in adipose tissue in two different human studies: A cross-sectional and population-based study assessing body composition and metabolic rate (Mölndal Metabolic study, n=92), and a longitudinal intervention-study of obese subjects treated with a very low calorie diet (VLCD study, n=24). Results: The CIDEA gene was predominantly expressed in adipocytes as compared to other human tissues. CIDEA gene expression in adipose tissue was inversely associated with basal metabolic rate independently of body composition, age and gender (p=0.014). VLCD induced an increase in adipose tissue CIDEA expression (p<0.0001) with a subsequent decrease in response to refeeding (p<0.0001). Reduced CIDEA gene expression was associated with a high body fat content (p<0.0001) and with high insulin levels (p<0.01). No dysregulation of CIDEA expression was observed in individuals with the metabolic syndrome when compared with BMI-matched controls. In a separate sample of VLCD-treated subjects (n=10), uncoupling protein 1 expression was reduced during diet (p=0.0026) and inversely associated with CIDEA expression (p=0.0014). Conclusion: The findings are consistent with the concept that CIDEA plays a role in adipose tissue energy expenditure.
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