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Stomby, A., Salami, A., Dahlqvist, P., Evang, J. A., Ryberg, M., Bollerslev, J., . . . Ragnarsson, O. (2019). Elevated resting-state connectivity in the medial temporal lobe and the prefrontal cortex among patients with Cushing's syndrome in remission. European Journal of Endocrinology, 180(5), 329-338
Open this publication in new window or tab >>Elevated resting-state connectivity in the medial temporal lobe and the prefrontal cortex among patients with Cushing's syndrome in remission
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2019 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 180, no 5, p. 329-338Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Bioscientifica, 2019
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-159205 (URN)10.1530/EJE-19-0028 (DOI)000466509100003 ()30939453 (PubMedID)
Available from: 2019-05-21 Created: 2019-05-21 Last updated: 2019-05-21Bibliographically approved
Otten, J., Andersson, J., Ståhl, J., Stomby, A., Saleh, A., Waling, M., . . . Olsson, T. (2019). Exercise Training Adds Cardiometabolic Benefits of a Paleolithic Diet in Type 2 Diabetes Mellitus. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 8(2), Article ID e010634.
Open this publication in new window or tab >>Exercise Training Adds Cardiometabolic Benefits of a Paleolithic Diet in Type 2 Diabetes Mellitus
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2019 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 2, article id e010634Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
Keywords
cardiovascular magnetic resonance imaging, diet, exercise, myocardial metabolism, type 2 diabetes mellitus
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-157046 (URN)10.1161/JAHA.118.010634 (DOI)000460105800010 ()30652528 (PubMedID)
Available from: 2019-03-07 Created: 2019-03-07 Last updated: 2019-03-27Bibliographically approved
Otten, J., Stomby, A., Waling, M., Isaksson, A., Söderström, I., Ryberg, M., . . . Olsson, T. (2018). 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 trial. Diabetologia, 61(7), 1548-1559
Open this publication in new window or tab >>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 trial
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2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 7, p. 1548-1559Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Exercise, Hyperinsulinaemic-euglycaemic clamp, Insulin sensitivity, Intramyocellular fat, Liver fat, Nutrition, Obesity, Paleolithic diet, Proton magnetic resonance spectroscopy, Weight loss
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-150764 (URN)10.1007/s00125-018-4618-y (DOI)000434250500007 ()29696296 (PubMedID)
Available from: 2018-08-27 Created: 2018-08-27 Last updated: 2018-08-27Bibliographically approved
Lebedeva, A., Sundström, A., Lindgren, L., Stomby, A., Stomby, A., Aarsland, D., . . . Nyberg, L. (2018). Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus. Acta Psychiatrica Scandinavica, 167(6), 491-502
Open this publication in new window or tab >>Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus
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2018 (English)In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 167, no 6, p. 491-502Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
depressive symptomatology, neuroimaging, superior temporal gyrus, superior frontal gyrus, MRI
National Category
Nursing Psychiatry
Identifiers
urn:nbn:se:umu:diva-146479 (URN)10.1111/acps.12860 (DOI)000433560700006 ()29457245 (PubMedID)
Available from: 2018-04-10 Created: 2018-04-10 Last updated: 2019-05-21Bibliographically approved
Otten, J., Stomby, A., Waling, M., Chorell, E., Ryberg, M., Svensson, M., . . . Olsson, T. (2018). The liver-alpha-cell axis during weight loss in type 2 diabetes. Paper presented at 54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY. Diabetologia, 61, S97-S98
Open this publication in new window or tab >>The liver-alpha-cell axis during weight loss in type 2 diabetes
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2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S97-S98Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-152243 (URN)000443556001192 ()
Conference
54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY
Funder
Swedish Diabetes AssociationSwedish Heart Lung Foundation
Available from: 2018-10-04 Created: 2018-10-04 Last updated: 2018-10-04Bibliographically approved
Bergman, F., Wahlström, V., Stomby, A., Otten, J., Lanthén, E., Renklint, R., . . . Olsson, T. (2018). Treadmill workstations in office workers who are overweight or obese: a randomised controlled trial. The Lancet Public Health, 3(11), Article ID e523-e535.
Open this publication in new window or tab >>Treadmill workstations in office workers who are overweight or obese: a randomised controlled trial
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2018 (English)In: The Lancet Public Health, ISSN 2468-2667, Vol. 3, no 11, article id e523-e535Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
The Lancet Publishing Group, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public health
Identifiers
urn:nbn:se:umu:diva-152709 (URN)10.1016/S2468-2667(18)30163-4 (DOI)000451514600013 ()30322782 (PubMedID)
Available from: 2018-10-19 Created: 2018-10-19 Last updated: 2019-05-20Bibliographically approved
Stomby, A., Otten, J., Ryberg, M., Nyberg, L., Olsson, T. & Boraxbekk, C.-J. (2017). A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes. Frontiers in Aging Neuroscience, 9, Article ID 391.
Open this publication in new window or tab >>A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes
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2017 (English)In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, article id 391Article in journal (Refereed) Published
Keywords
type 2 diabetes, paleolithic diet, exercise, magnetic resonance imaging, episodic memory
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-142120 (URN)10.3389/fnagi.2017.00391 (DOI)000416906800001 ()29255413 (PubMedID)
Available from: 2017-11-22 Created: 2017-11-22 Last updated: 2018-06-09Bibliographically approved
Otten, J., Stomby, A., Waling, M., Isaksson, A., Tellström, A., Lundin-Olsson, L., . . . Olsson, T. (2017). 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 diabetes. Diabetes/Metabolism Research Reviews, 33(1), Article ID e2828.
Open this publication in new window or tab >>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 diabetes
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2017 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 33, no 1, article id e2828Article in journal (Refereed) Published
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.

Keywords
type 2 diabetes, Paleolithic diet, diet intervention, exercise, glycosyl-ated haemoglobin A, insulin sensitivity, leptin
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-126188 (URN)10.1002/dmrr.2828 (DOI)000397102800010 ()
Available from: 2016-10-03 Created: 2016-10-03 Last updated: 2019-03-14Bibliographically approved
Morgan, R. A., Beck, K. R., Nixon, M., Homer, N. Z. M., Crawford, A. A., Melchers, D., . . . Walker, B. R. (2017). Carbonyl reductase 1 catalyzes 20 beta-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity. Scientific Reports, 7, Article ID 10633.
Open this publication in new window or tab >>Carbonyl reductase 1 catalyzes 20 beta-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10633Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-139790 (URN)10.1038/s41598-017-10410-1 (DOI)000409439900051 ()
Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2018-06-09Bibliographically approved
Ragnarsson, O., Stomby, A., Dahlqvist, P., Evang, J. A., Ryberg, M., Olsson, T., . . . Johannsson, G. (2017). Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission. Psychoneuroendocrinology, 82, 117-125
Open this publication in new window or tab >>Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission
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2017 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 82, p. 117-125Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Cushing's syndrome, Cognitive function, Hippocampus, Prefrontal cortex, Functional magnetic resonance imaging
National Category
Neurology Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-137931 (URN)10.1016/j.psyneuen.2017.05.010 (DOI)000405254700015 ()28544904 (PubMedID)
Available from: 2017-08-04 Created: 2017-08-04 Last updated: 2018-06-09Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-9169-1059

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