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  • 1.
    Bergman, Frida
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wahlström, Viktoria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Otten, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lanthén, Ellen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Renklint, Rebecka
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Waling, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Sörlin, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Levine, James A.
    Department of Endocrinology, The Mayo Clinic, Rochester, MN, USA; Fondation IPSEN, Paris, France.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Treadmill workstations in office workers who are overweight or obese: a randomised controlled trial2018Ingår i: The Lancet Public Health, ISSN 2468-2667, Vol. 3, nr 11, artikel-id e523-e535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Treadmill workstations that enable office workers to walk on a treadmill while working at their computers might increase physical activity in offices, but long-term effects are unknown. We therefore investigated whether treadmill workstations in offices increased daily walking time.

    Methods: We did a randomised controlled trial of healthy office workers who were either overweight or obese. We recruited participants from 13 different companies, which comprised 17 offices, in Umeå, Sweden. We included people who were aged 40-67 years, had sedentary work tasks, and had a body-mass index (BMI) between 25 kg/m2 and 40 kg/m2. After the baseline measurement, we stratified participants by their BMI (25-30 kg/m2 and >30 to 40 kg/m2); subsequently, an external statistician randomly assigned these participants (1:1) to either the intervention group (who received treadmill workstations for optional use) or the control group (who continued to work at their sit-stand desks as usual). Participants in the intervention group received reminders in boosting emails sent out to them at four occasions during the study period. Researchers were masked to group assignment until after analysis of the primary outcome. After the baseline measurement, participants were not masked to group belongings. The primary outcome was total daily walking time at weekdays and weekends, measured at baseline, 2 months, 6 months, 10 months, and 13 months with the accelerometer activPAL (PAL Technologies, Glasgow, UK), which was worn on the thigh of participants for 24 h a day for 7 consecutive days. We used an intention-to-treat approach for our analyses. This trial is registered with ClinicalTrials.gov, number NCT01997970, and is closed to new participants.

    Findings: Between Nov 1, 2013, and June 30, 2014, a total of 80 participants were recruited and enrolled (n=40 in both the intervention and control groups). Daily walking time during total time awake at weekdays increased between baseline and 13 months by 18 min (95% CI 9 to 26) in the intervention group and 1 min (-7 to 9) in the control group (difference 22 min [95% CI 7 to 37], pinteraction=0·00045); for weekend walking, the change from baseline to 13 months was 5 min (-8 to 18) in the intervention group and 8 min (-5 to 21) in the control group (difference -1 min [-19 to 17]; pinteraction=0·00045). Neither measure met our predetermined primary outcome of 30 min difference in total walking time between the intervention and control group, so the primary outcome of the trial was not met. One adverse event was reported in a participant who accidently stepped on their Achilles tendon.

    Interpretation: In a sedentary work environment, treadmill workstations result in a statistically significant but smaller-than-expected increase in daily walking time. Future studies need to investigate how increasing physical activity at work might have potentially compensatory effects on non-work activity.

  • 2.
    Boraxbekk, Carl-Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Centrum för befolkningsstudier (CBS).
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Larsson, Christel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Göteborgs Universitet.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Diet-Induced Weight Loss alters Functional Brain Responses during an Episodic Memory Task2015Ingår i: Obesity Facts, ISSN 1662-4025, E-ISSN 1662-4033, Vol. 8, s. 261-272Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results: Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions: Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.

  • 3. Lebedeva, A
    et al.
    Sundström, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Lindgren, Lenita
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Stomby, A
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Jönköping County Hospital, Region Jönköping County, Jönköping, Sweden.
    Aarsland, D
    Westman, E
    Winblad, B
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus2018Ingår i: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 167, nr 6, s. 491-502Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Depression is associated with accelerated aging and age-related diseases. However, mechanisms underlying this relationship remain unclear. The aim of this study was to longitudinally assess the link between depressive symptoms, brain atrophy, and cortisol levels.

    METHOD: Participants from the Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4-year follow-up. Cortisol levels were measured at baseline in four saliva samples. Cortical and hippocampal atrophy rates were estimated and compared between participants with and without depressive symptoms (n = 81) and correlated with cortisol levels (n = 49).

    RESULTS: Atrophy in the left superior frontal gyrus and right lingual gyrus developed in parallel with depressive symptoms, and in the left temporal pole, superior temporal cortex, and supramarginal cortex after the onset of depressive symptom. Depression-related atrophy was significantly associated with elevated cortisol levels. Elevated cortisol levels were also associated with widespread prefrontal, parietal, lateral, and medial temporal atrophy.

    CONCLUSION: Depressive symptoms and elevated cortisol levels are associated with atrophy of the prefrontal and limbic areas of the brain.

  • 4. Morgan, Ruth A.
    et al.
    Beck, Katharina R.
    Nixon, Mark
    Homer, Natalie Z. M.
    Crawford, Andrew A.
    Melchers, Diana
    Houtman, René
    Meijer, Onno C.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Anderson, Anna J.
    Upreti, Rita
    Stimson, Roland H.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Michoel, Tom
    Cohain, Ariella
    Ruusalepp, Arno
    Schadt, Eric E.
    Björkegren, Johan L. M.
    Andrew, Ruth
    Kenyon, Christopher J.
    Hadoke, Patrick W. F.
    Odermatt, Alex
    Keen, John A.
    Walker, Brian R.
    Carbonyl reductase 1 catalyzes 20 beta-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 10633Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Carbonyl Reductase 1 (CBR1) is a ubiquitously expressed cytosolic enzyme important in exogenous drug metabolism but the physiological function of which is unknown. Here, we describe a role for CBR1 in metabolism of glucocorticoids. CBR1 catalyzes the NADPH-dependent production of 20 beta-dihydrocortisol (20 beta-DHF) from cortisol. CBR1 provides the major route of cortisol metabolism in horses and is up-regulated in adipose tissue in obesity in horses, humans and mice. We demonstrate that 20 beta-DHF is a weak endogenous agonist of the human glucocorticoid receptor (GR). Pharmacological inhibition of CBR1 in diet-induced obesity in mice results in more marked glucose intolerance with evidence for enhanced hepatic GR signaling. These findings suggest that CBR1 generating 20 beta-dihydrocortisol is a novel pathway modulating GR activation and providing enzymatic protection against excessive GR activation in obesity.

  • 5.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Andersson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Ståhl, Jens
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Saleh, Ahmed
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Waling, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hauksson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Department of Radiography and Biomedical Science, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    Svensson, Michael B.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för idrottsmedicin.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Exercise Training Adds Cardiometabolic Benefits of a Paleolithic Diet in Type 2 Diabetes Mellitus2019Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, nr 2, artikel-id e010634Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The accumulation of myocardial triglycerides and remodeling of the left ventricle are common features in type 2 diabetes mellitus and represent potential risk factors for the development of diastolic and systolic dysfunction. A few studies have investigated the separate effects of diet and exercise training on cardiac function, but none have investigated myocardial changes in response to a combined diet and exercise intervention. This 12-week randomized study assessed the effects of a Paleolithic diet, with and without additional supervised exercise training, on cardiac fat, structure, and function.

    Methods and Results: Twenty-two overweight and obese subjects with type 2 diabetes mellitus were randomized to either a Paleolithic diet and standard-care exercise recommendations ( PD ) or to a Paleolithic diet plus supervised exercise training 3 hours per week ( PD - EX ). This study includes secondary end points related to cardiac structure and function, ie, myocardial triglycerides levels, cardiac morphology, and strain were measured using cardiovascular magnetic resonance, including proton spectroscopy, at baseline and after 12 weeks. Both groups showed major favorable metabolic changes. The PD - EX group showed significant decreases in myocardial triglycerides levels (-45%, P=0.038) and left ventricle mass to end-diastolic volume ratio (-13%, P=0.008) while the left ventricle end-diastolic volume and stroke volume increased significantly (+14%, P=0.004 and +17%, P=0.008, respectively). These variables were unchanged in the PD group.

    Conclusions: Exercise training plus a Paleolithic diet reduced myocardial triglycerides levels and improved left ventricle remodeling in overweight/obese subjects with type 2 diabetes mellitus.

    Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01513798.

  • 6.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Hauksson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Effects of a paleolithic diet with and without supervised exercise on liver fat and insulin sensitivity: a randomised controlled trial in individuals with type 2 diabetes2016Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, s. S10-S10Artikel i tidskrift (Refereegranskat)
  • 7.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waling, M.
    Umeå universitet.
    Chorell, E.
    Umeå universitet.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Svensson, M.
    Umeå universitet.
    Holst, J. J.
    Umeå universitet.
    Olsson, T.
    Umeå universitet.
    The liver-alpha-cell axis during weight loss in type 2 diabetes2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S97-S98Artikel i tidskrift (Övrigt vetenskapligt)
  • 8.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waling, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Isaksson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Söderström, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Hauksson, Jón
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    A heterogeneous response of liver and skeletal muscle fat to the combination of a Paleolithic diet and exercise in obese individuals with type 2 diabetes: a randomised controlled trial2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 7, s. 1548-1559Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis: The aim of the study was to investigate ectopic fat deposition and insulin sensitivity, in a parallel single-blinded randomised controlled trial, comparing Paleolithic diet alone with the combination of Paleolithic diet and exercise in individuals with type 2 diabetes. Methods: Thirty-two individuals with type 2 diabetes with BMI 25-40 kg/m(2) and 30-70 years of age followed a Paleolithic diet ad libitum for 12 weeks. In addition, study participants were randomised by computer program to either supervised combined exercise training (PD-EX group) or standard care exercise recommendations (PD group). Staff performing examinations and assessing outcomes were blinded to group assignment. Thirteen participants were analysed in each group: hepatic and peripheral insulin sensitivity were measured using the hyperinsulinaemic-euglycaemic clamp technique combined with [6,6-H-2(2)]glucose infusion, and liver fat was assessed by proton magnetic resonance spectroscopy; both analyses were secondary endpoints. Intramyocellular lipid (IMCL) content was measured by magnetic resonance spectroscopy as a secondary analysis. All examinations were performed at Umca University Hospital, Umca, Sweden. Results: Both study groups showed a median body weight loss of 7 kg. Fat mass decreased by 5.7 kg in the PD group and by 6.5 kg in the PD-EX group. Maximum oxygen uptake increased in the PD-EX group only. Liver fat showed a consistent reduction (74% decrease) in the PD group, while the response in the PD-EX group was heterogeneous (p < 0.05 for the difference between groups). IMCL content of the soleus muscle decreased by 40% in the PD group and by 22% in the PD-EX group (p < 0.05 for the difference between groups). Both groups improved their peripheral and adipose tissue insulin sensitivity, but not their hepatic insulin sensitivity. Plasma fetuin-A decreased by 11% in the PD group (p < 0.05) and remained unchanged in the PD-EX group. Liver fat changes during the intervention were correlated with changes in fetuin-A (r(S) = 0.63, p < 0.01). Participants did not report any important adverse events caused by the intervention. Conclusions/interpretation: A Paleolithic diet reduced liver fat and IMCL content, while there was a tissue-specific heterogeneous response to added exercise training.

  • 9.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waling, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Isaksson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Söderström, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Hauksson, Jón
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Exercise training reverses the effect of a Paleolithic diet on liver fat and intramyocellular lipid content in patients with type 2 diabetes2017Konferensbidrag (Refereegranskat)
  • 10.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waling, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Isaksson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Söderström, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Hauksson, Jón
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Exercise training reverses the effect of a Paleolithic diet on liver fat and intramyocellular lipid content in patients with type 2 diabetes2017Konferensbidrag (Refereegranskat)
  • 11.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waling, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Isaksson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Tellström, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Lundin-Olsson, Lillemor
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Brage, Soren
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Effects of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: a randomized controlled trial in individuals with type 2 diabetes2016Konferensbidrag (Refereegranskat)
  • 12.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waling, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Isaksson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Tellström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundin-Olsson, Lillemor
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Brage, Søren
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Benefits of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: a randomized controlled trial in individuals with type 2 diabetes2017Ingår i: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 33, nr 1, artikel-id e2828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Means to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed.

    Methods

    Thirty-two patients with type 2 diabetes (age 59 ± 8 years) followed a Paleolithic diet for 12 weeks. Participants were randomized to either standard care exercise recommendations (PD) or 1-h supervised exercise sessions (aerobic exercise and resistance training) three times per week (PD-EX).

    Results

    For the within group analyses, fat mass decreased by 5.7 kg (IQR: −6.6, −4.1; p < 0.001) in the PD group and by 6.7 kg (−8.2, −5.3; p < 0.001) in the PD-EX group. Insulin sensitivity (HOMA-IR) improved by 45% in the PD (p < 0.001) and PD-EX (p < 0.001) groups. HbA1c decreased by 0.9% (−1.2, −0.6; p < 0.001) in the PD group and 1.1% (−1.7, −0.7; p < 0.01) in the PD-EX group. Leptin decreased by 62% (p < 0.001) in the PD group and 42% (p < 0.001) in the PD-EX group. Maximum oxygen uptake increased by 0.2 L/min (0.0, 0.3) in the PD-EX group, and remained unchanged in the PD group (p < 0.01 for the difference between intervention groups). Male participants decreased lean mass by 2.6 kg (−3.6, −1.3) in the PD group and by 1.2 kg (−1.3, 1.0) in the PD-EX group (p < 0.05 for the difference between intervention groups).

    Conclusions

    A Paleolithic diet improves fat mass and metabolic balance including insulin sensitivity, glycemic control, and leptin in subjects with type 2 diabetes. Supervised exercise training may not enhance the effects on these outcomes, but preserves lean mass in men and increases cardiovascular fitness.

  • 13. Ragnarsson, Oskar
    et al.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Ryhov County Hospital, Jönköping, Sweden.
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Evang, Johan A.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bollerslev, Jens
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Johannsson, Gudmundur
    Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission2017Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 82, s. 117-125Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 commis matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p < 0.001) and in the right inferior occipital gyrus (p < 0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p = 0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p < 0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p < 0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function.

  • 14.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Brain function and glucocorticoids in obesity and type 2 diabetes including effects of lifestyle interventions2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background Obesity and associated metabolic dysregulation are linked to impaired cognitive function and alterations in brain structure, which increases the risk of age-related dementia. Increased glucocorticoid (GC) exposure may be a potential mediator of these negative effects on the brain.

    Methods and results In paper 1, we tested the relationship between cortisol levels, brain morphology and cognitive function in 200 women and men. Salivary cortisol levels were negatively related to cortical surface areas in prefrontal brain regions in both sexes. In participants with type 2 diabetes, high salivary cortisol levels were associated with lower memory performance. In paper 2, we tested in 70 overweight women the effects on tissue-specific GC metabolism of a Paleolithic diet or a diet following the Nordic nutrition recommendations. The 24-month interventions led to decreased expression of the GC-activating enzyme 11βHSD1 in adipose tissue, interpreted as a normalization of an obesity-related disturbance in GC metabolism. Furthermore, GC metabolism by 5α-reductase increased substantially after 2 years, an unexpected and novel result. The outcomes did not differ by diet. In paper 3, 20 women included in paper 2 were examined with functional magnetic resonance imaging (fMRI) while performing a memory task at baseline and after 6 months. Memory performance improved and functional brain responses increased in the hippocampus. Once again, the results were similar in both diet groups. In paper 4, 24 overweight participants with type 2 diabetes were examined with fMRI, using the same memory test as in paper 3, at baseline and after 12 weeks of intervention with a Paleolithic diet with or without exercise training. Functional brain response increased in the hippocampus, but memory was not improved. The addition of physical exercise did not alter the results.

    Conclusion Cortisol levels are linked to prefrontal brain structure and, at least in type 2 diabetes, lower memory performance. Furthermore, the dysregulated GC metabolism in obesity can be reversed by long-term diet- induced weight loss. Finally, dietary interventions with associated metabolic improvements alter functional brain responses during memory testing, including increased activation of the hippocampus. Whether these changes are linked to alterations in GC exposure and mediate improved cognition requires further study. 

  • 15.
    Stomby, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Andrew, Ruth
    Walker, Brian R.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Tissue-specific dysregulation of cortisol regeneration by 11 beta HSD1 in obesity: has it promised too much?2014Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr 6, s. 1100-1110Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Cushing's syndrome, caused by increased production of cortisol, leads to metabolic dysfunction including visceral adiposity, hypertension, hyperlipidaemia and type 2 diabetes. The similarities with the metabolic syndrome are striking and major efforts have been made to find obesity-associated changes in the regulation of glucocorticoid action and synthesis, both at a systemic level and tissue level. Obesity is associated with tissue-specific alterations in glucocorticoid metabolism, with increased activity of the glucocorticoid-regenerating enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) in subcutaneous adipose tissue and decreased conversion of cortisone to cortisol, interpreted as decreased 11 beta HSD1 activity, in the liver. In addition, genetic manipulation of 11 beta HSD1 activity in rodents can either induce (by overexpression of Hsd11b1, the gene encoding 11 beta HSD1) or prevent (by knocking out Hsd11b1) obesity and metabolic dysfunction. Taken together with earlier evidence that non-selective inhibitors of 11 beta HSD1 enhance insulin sensitivity, these results led to the hypothesis that inhibition of 11 beta HSD1 might be a promising target for treatment of the metabolic syndrome. Several selective 11 beta HSD1 inhibitors have now been developed and shown to improve metabolic dysfunction in patients with type 2 diabetes, but the small magnitude of the glucose-lowering effect has precluded their further commercial development. This review focuses on the role of 11 beta HSD1 as a tissue-specific regulator of cortisol exposure in obesity and type 2 diabetes in humans. We consider the potential of inhibition of 11 beta HSD1 as a therapeutic strategy that might address multiple complications in patients with type 2 diabetes, and provide our thoughts on future directions in this field.

  • 16.
    Stomby, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Region Jönköping County, Jönköping, Sweden.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Department of Psychology, Stockholm University, Stockholm, Sweden.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women2016Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 175, nr 2, s. 117-126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Elevated cortisol levels with aging have been associated with atrophy of the hippocampus and prefrontal cortex (PFC), as well as with impaired cognitive functions in men. However, coexisting diseases have confounded many studies examining these relationships. Studies in women are lacking. Our objective was to test whether salivary cortisol levels were related to morphology of the hippocampus and the PFC, and to cognitive performance. Design: A cross-sectional study including 200 elderly (55-80 years old) men and women. Method: We used magnetic resonance imaging, tests of episodic-, semantic-, and working memory, visuospatial ability, and cortisol levels in four saliva samples collected during 1 day. Results: Area under the curve (AUC) for cortisol levels was negatively related to cortical surface area of the left anterior cingulate gyrus (caudal P < 0.001; rostral P = 0.006), right lateral orbitofrontal cortex (P = 0.004), and right rostral middle frontal gyrus (P = 0.003). In women, there was also a negative relationship with cortical surface area in the left rostral middle frontal gyrus (P = 0.006). No relationship was found between cortisol levels and hippocampal volume. Conclusion: This study suggests that the structure of the medial PFC is related to cortisol levels in both elderly women and men.

  • 17.
    Stomby, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Demografiska databasen.
    Nilsson, Lars-Göran
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in women and menManuskript (preprint) (Övrigt vetenskapligt)
  • 18.
    Stomby, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Otten, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Demografiska databasen.
    A Paleolithic diet alters functional brain responses during an episodic memory task in type 2 diabetesManuskript (preprint) (Övrigt vetenskapligt)
  • 19.
    Stomby, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Jönköping County Hospital, Region Jönköping County, Jönköping, Sweden.
    Otten, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes2017Ingår i: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, artikel-id 391Artikel i tidskrift (Refereegranskat)
  • 20.
    Stomby, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Region Jönköping County, Jönköping, Sweden.
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Evang, Johan Arild
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Bollerslev, Jens
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Johannsson, Gudmundur
    Ragnarsson, Oskar
    Elevated resting-state connectivity in the medial temporal lobe and the prefrontal cortex among patients with Cushing's syndrome in remission2019Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 180, nr 5, s. 329-338Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Cushing's syndrome is associated with long-term cognitive deficits and affective symptoms such as depression and anxiety. The alterations in brain function under lying these deficits after Cushing's syndrome are unclear and therefore we aimed to explore alterations in resting-state functional connectivity in patients with Cushing's syndrome in remission. Design: Cross-sectional case-control study. Methods: Nineteen women with Cushing's syndrome in remission for a median time of 7 years (IQR: 6-10) and a mean age of 45 years were included at three university clinics. These patients and 38 age-matched female controls underwent brain imaging at a single center. The main outcome measure was functional connectivity at rest, measured with functional magnetic resonance imaging. Results: The medial temporal lobe (MTL) and prefrontal cortex networks, exhibited elevated functional connectivity among patients compared to controls. The degree of elevated functional connectivity in the MTL was negatively associated with time in remission. Conclusions: Resting-state functional connectivity within glucocorticoid receptor-rich regions, particularly the MTL and medial prefrontal cortex, was increased in patients. These differences in connectivity may provide a neural basis for the cognitive deficits and affective symptoms commonly experienced by patients with Cushing's syndrome in remission.

  • 21.
    Stomby, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Simonyte, Kotryna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stimson, R H
    Larsson, Christel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap. Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Andrew, R
    Walker, B R
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women2015Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 39, nr 5, s. 814-819Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Objectives: Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women.

    Subjects/Methods: Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied.

    Results: Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11βHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months.

    Conclusions: Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

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