| 1. |
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| 2. |
- Kaptoge, S., et al.
(författare)
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World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
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Ingår i: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 3. |
- Gregson, J., et al.
(författare)
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Cardiovascular Risk Factors Associated With Venous Thromboembolism
- 2019
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Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
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| 4. |
- Emerging Risk Factors, Collaboration, et al.
(författare)
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The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases
- 2007
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Ingår i: Eur J Epidemiol. - 0393-2990. ; 22:12, s. 839-69
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Tidskriftsartikel (refereegranskat)abstract
- Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
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| 5. |
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| 6. |
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| 7. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 8. |
- Cesano, A, et al.
(författare)
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Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume II-practical challenges
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- The development of strongly predictive validated biomarkers is essential for the field of immuno-oncology (IO) to advance. The highly complex, multifactorial data sets required to develop these biomarkers necessitate effective, responsible data-sharing efforts in order to maximize the scientific knowledge and utility gained from their collection. While the sharing of clinical- and safety-related trial data has already been streamlined to a large extent, the sharing of biomarker-aimed clinical trial derived data and data sets has been met with a number of hurdles that have impaired the progression of biomarkers from hypothesis to clinical use. These hurdles include technical challenges associated with the infrastructure, technology, workforce, and sustainability required for clinical biomarker data sharing. To provide guidance and assist in the navigation of these challenges, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to outline the challenges that researchers currently face, both at the conceptual level (Volume I) and at the technical level (Volume II). The committee also suggests possible solutions to these problems in the form of professional standards and harmonized requirements for data sharing, assisting in continued progress toward effective, clinically relevant biomarkers in the IO setting.
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| 9. |
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| 10. |
- Nielsen, B. M., et al.
(författare)
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Prediction of fat-free body mass from bioelectrical impedance among 9-to 11-year-old Swedish children
- 2007
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 9:4, s. 521-539
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Predictive equations for estimating body composition from bioelectrical impedance analysis (BIA) among Scandinavian children are lacking. In the present study, equations for estimation of fat-free body mass (FFM) and lean tissue mass (LTM) were developed and cross-validated from BIA using dual-energy X-ray absorptiometry (DXA) as the reference measurement of body composition. Methods: The study population consisted of 49 girls and 52 boys aged 9-11 years from Malmo, Sweden. Bioelectrical impedance was measured between hand and foot at 50 kHz. Predictive equations were developed by multiple linear regression and cross-validated against DXA measurements of body composition. Results: FFM was predicted from BIA and anthropometric variables with an adjusted R-2 = 0.95 and root mean square error (RMSE) = 0.84 kg, and LTM was predicted with an adjusted R-2 = 0.95 and RMSE = 0.87 kg. Cross-validation revealed a mean RMSE = 0.95 kg FFM and a mean RMSE = 0.96 kg LTM. Prediction of body composition from equations developed in previous literature was mixed when applied to the present cohort of children. Conclusions: FFM and LTM are predicted with sufficient accuracy at the population level. We recommend that the predictive equations developed in the present study are used in prepubescent European children aged 9-11 years only in order to minimize confounding of results because of possible differences in population samples.
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| 11. |
- Rutella, S, et al.
(författare)
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Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume I-conceptual challenges
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial and biomarker data, and the conflicts caused by these differing interests represent significant obstacles to effective, widespread sharing of data. Thus, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to identify the current barriers to biomarker data sharing in immuno-oncology (IO) and to help in establishing professional standards for the responsible sharing of clinical trial data. The conclusions of the committee are described in two position papers: Volume I—conceptual challenges and Volume II—practical challenges, the first of which is presented in this manuscript. Additionally, the committee suggests actions by key stakeholders in the field (including organizations and professional societies) as the best path forward, encouraging the cultural shift needed to ensure responsible data sharing in the IO research setting.
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| 12. |
- Sennström, Maria B., et al.
(författare)
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Human cervical ripening, an inflammatory process mediated by cytokines
- 2000
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 6:4, s. 81-375
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Tidskriftsartikel (refereegranskat)abstract
- An extensive remodelling process, referred to as cervical ripening, takes place in the cervical tissue during pregnancy and labour. It is recognized as softening and dilation of the cervical canal, and starts as a slow process during pregnancy, becoming rapid close to partum. In this study we focus on cytokines as possible mediators of this final remodelling. mRNA levels for interleukin (IL)-8, IL-6 and granulocyte colony-stimulating factor (G-CSF) were upregulated in the ripe postpartum cervical tissue (n = 8) compared to the unripe state (n = 9). Likewise, released cytokine concentrations increased from non-pregnant (n = 11) to the term-pregnant group (n = 13) with a further increase at partum (n = 16). IL-8 concentrations increased 4-fold from non-pregnant to term-pregnant (P<0.01), and a further 10-fold to postpartum state (P<0.0001). Concentrations of IL-6 and G-CSF were similarly increased. Specific IL-8 immunostaining was identified in the epithelia of pregnant cervical tissue (n = 7) and was most pronounced in the epithelia and stroma of postpartum tissue (n = 4). In conclusion, IL-8, IL-6 and G-CSF increase in the human cervix during the ripening process, indicating their important role in the cervical remodelling. These data demonstrate that cervical ripening is similar to an inflammatory process.
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| 13. |
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| 14. |
- Arvidsson, Daniel, 1974, et al.
(författare)
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A Longitudinal Analysis of the Relationships of Physical Activity and Body Fat With Nerve Growth Factor and Brain-Derived Neural Factor in Children
- 2018
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Ingår i: Journal of Physical Activity & Health. - : Human Kinetics. - 1543-3080 .- 1543-5474. ; 15:8, s. 620-625
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nerve growth factor (NGF) and brain-derived neural factor (BDNF) are important for brain function and detectable in the blood. This study explored the longitudinal associations of physical activity and body fat with serum NGF and BDNF in children. Methods: Two waves of measurements were performed 2 years apart in 8- to 11-year-old children, including physical activity using the ActiGraph model 7164, body composition by dual-energy X-ray absorptiometry, and serum NGF and BDNF determined by multiplex immunoassay. The first wave included 248 children. Full information maximum likelihood estimation with robust standard errors was applied in structural equation modeling. Results: Vigorous physical activity showed a direct positive longitudinal relationship with NGF (standardized coefficient beta = 0.30, P = .01) but not with BDNF (beta = 0.04, P = .84). At the same time, body fat percentage was positively related to both NGF (beta = 0.59, P < .001) and BDNF (beta = 0.17, P = .04). There was an indication of an indirect relationship of vigorous physical activity with NGF (product of unstandardized coefficient beta = -0.18, P = .02) and BDNF (beta = -0.07, P = .05) through the negative relationship with body fat percentage (beta = -0.36, P < .001). Conclusions: Vigorous physical activity is directly related to serum NGF and indirectly through the level of body fat. The relationships with serum BDNF are more complex.
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| 15. |
- Bjornsdottir, Gudlaug, et al.
(författare)
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Longitudinal changes in size and composition of carotid artery plaques using ultrasound: Adaptation and validation of methods (inter-and intraobserver variability)
- 2014
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Ingår i: Journal for Vascular Ultrasound. - : SAGE Publications. - 1544-3175 .- 1544-3167. ; 38:4, s. 198-208
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Tidskriftsartikel (refereegranskat)abstract
- Introduction.—B-mode ultrasonography of the carotid arteries enables quantitative measurements of atherosclerotic plaque area and composition assessed as grayscale median (GSM). The purpose of this study was to set up a standardized ultrasound protocol to measure longitudinal changes in plaque area and composition and to determine the intra-and interobserver variability of the measurements in a longitudinal population based study, the Age Gene/ Environment Susceptibility Reykjavik study. Method.—A total of 219 participants from the Age Gene/Environment Susceptibility Reykjavik study (76 ± 6 years old, 36% males) underwent 2-dimensional, B-mode ultrasound examination of the carotid arteries approximately 5 years apart for a longitudinal assessment of plaque area and composition. Standardized protocol was used to acquire comparable images from both visits. Ultrasound was performed bilaterally on the common carotid artery, internal carotid artery, and bifurcation. An image analysis program was modified and adapted for a longitudinal assessment of plaque area and plaque composition by GSM. Twenty-five subjects were selected from the group of 219 for intra-and interobserver variability assessment. Results.—Intraobserver variability for plaque area ranged from 12.10 to 18.63% and 0.89 to 0.96 for coefficient of variation and correlation (r), respectively, for plaque GSM ranged from 7.77 to 8.04% and 0.86 to 0.90. Interobserver variability for plaque area was 23.29% and 0.81 and 8.55% and 0.87 for plaque GSM. Conclusion.—The results from this study show that ultrasound can be used consistently for assessment of changes in plaque area and GSM over time. This can be achieved by proper training of ultrasound sonographers and by applying and following strict image acquisition and image analysis protocols.
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| 16. |
- Dencker, Magnus, et al.
(författare)
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Aerobic capacity related to cardiac size in young children.
- 2013
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Ingår i: Journal of Sports Medicine and Physical Fitness. - 0022-4707. ; 53:1, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- Aim:Aerobic capacity, defined as peak oxygen uptake (VO2PEAK), is generally considered to be the best single marker for aerobic fitness. We assessed if VO2PEAK is related to different cardiac dimensions in healthy young children on a population base. Methods: In a cross-sectional study, 245 children (137 boys and 108 girls) aged 8-11 years, were recruited from a population based cohort. VO2PEAK (ml/min-1/kg-1) was assessed by indirect calorimetry during a maximal exercise test. DXA-scan was used to measure lean body mass (LBM) and total fat mass (TBF). Echocardiography, with 2-dimensional guided M-mode, was performed in accordance with current guidelines. Left ventricular end-diastolic diameter (LVDD) and left atrial end-systolic diameter (LA) were measured, and left ventricular mass (LVM) was calculated. Results: Univariate correlations were found between VO2PEAK versus LVDD r=0.44 and LA r=0.27 (both P<0.05) and LVM r=-0.06 (NS) in boys. Corresponding values for girls were; 0.55, 0.34 (both P<0.05) and 0.11 (NS). Multiple regression analysis with VO2PEAK as dependent variable and inclusion of LBM, TBF, sex, age, Tanner stage, and maximal heart rate as independent variables showed that 67% of the total variance of VO2PEAK could be explained by these variables. Including LVDD or LA in the model, added 1% additional explained variance. Conclusion: Findings from this population based cohort of young healthy children show that multiple cardiac dimensions at rest are related to VO2PEAK. However, the different cardiac dimensions contributed very little to the added explained variance of VO2PEAK.
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| 17. |
- Dencker, Magnus, et al.
(författare)
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Aerobic fitness related to cardiovascular risk factors in young children.
- 2012
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Ingår i: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 1432-1076 .- 0340-6199. ; 171:4, s. 705-710
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Tidskriftsartikel (refereegranskat)abstract
- Low aerobic fitness (maximum oxygen uptake (VO(2PEAK))) is predictive for poor health in adults. In a cross-sectional study, we assessed if VO(2PEAK) is related to a composite risk factor score for cardiovascular disease (CVD) in 243 children (136 boys and 107 girls) aged 8 to 11 years. VO(2PEAK) was assessed by indirect calorimetry during a maximal exercise test and scaled by body mass (milliliters per minute per kilogram). Total body fat mass (TBF) and abdominal fat mass (AFM) were measured by Dual-energy X-ray absorptiometry. Total body fat was expressed as a percentage of total body mass (BF%) and body fat distribution as AFM/TBF. Systolic and diastolic blood pressure (SDP and DBP) and resting heart rate (RHR) were measured. The mean artery pressure (MAP) and pulse pressure (PP) were calculated. Echocardiography, 2D-guided M-mode, was performed. Left atrial diameter (LA) was measured and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z scores (value for the individual - mean value for group)/SD were calculated by sex. The sum of z scores for DBP, SDP, PP, MAP, RHR, LVM, LA, RWT, BF%, AFM and AFM/TBF were calculated in boys and girls, separately, and used as composite risk factor score for CVD. Pearson correlation revealed significant associations between VO(2PEAK) and composite risk factor score in both boys (r = -0.48 P < 0.05) and in girls (r = -0.42, P < 0.05). One-way ANOVA analysis indicated significant differences in composite risk factor score between the different quartiles of VO(2PEAK) (P < 0.001); thus, higher VO(2PEAK) was associated with lower composite risk factor score for CVD. In conclusion, low VO(2PEAK) is associated with an elevated composite risk factor score for CVD in both young boys and girls.
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| 18. |
- Dencker, Magnus, et al.
(författare)
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BMI and objectively measured body fat and body fat distribution in prepubertal children.
- 2007
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 27:1, s. 12-16
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Tidskriftsartikel (refereegranskat)abstract
- Background Body Mass Index (BMI) is often used as a surrogate estimate of body fat in epidemiological studies. This study explores the association between BMI, body fat and body fat distribution assessed by Dual-Energy X-Ray Absorptiometry (DXA) in younger children. Methods Cross-sectional study of 246 children (138 boys and 108 girls) aged 8-11 years. DXA was used to quantify abdominal fat mass (AFM), total body fat (TBF) and also total body fat as percentage of total body mass (BF%). Body fat distribution was calculated as AFM/TBF. Results We found close correlations between BMI vs. TBF, BF% and AFM (r = 0.94, r = 0.92 and r = 0.93) for boys and (r = 0.95, r = 0.92 and r = 0.95) for girls, respectively (P < 0.05 for all r-values). However, significantly lower correlation (P < 0.001 for difference between the r-values) existed for body fat distribution (r = 0.64 for boys and 0.73 for girls). Conclusion Percentage body fat, TBF and AFM were all closely associated with BMI, suggesting that BMI serves as a good surrogate marker for obesity in population studies. However, a significantly lower correlation existed for BMI vs. body fat distribution, which may be a limitation when BMI is used to study cardiovascular risk factors in epidemiological studies.
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| 19. |
- Dencker, Magnus, et al.
(författare)
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Body Fat, Abdominal Fat, and Body Fat Distribution Is Related to Left Atrial Diameter in Young Children.
- 2012
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Ingår i: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 20, s. 1104-1108
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Tidskriftsartikel (refereegranskat)abstract
- In adults, the size of the left atria (LA) has important prognostic information. In obese adults, adolescents and children enlargement of LA have been observed. This has not been investigated on a population-based level in young children. We therefore assessed if total body fat mass (TBF), abdominal fat, and body fat distribution were related to LA diameter. Cross-sectional study of 244 children (boys = 137 and girls n = 107) aged 8-11 years, recruited from an urban population-based cohort. Dual-energy X-ray absorptiometry (DXA) measured total lean body mass, TBF, and abdominal fat mass (AFM). Body fat was also calculated as a percentage of body mass (BF%). Body fat distribution (AFM/TBF) was calculated. Echocardiography was performed with two-dimensional guided M-mode. LA diameter was measured and left ventricular mass (LVM) was calculated. Systolic blood pressure and diastolic blood pressure were measured and maturity assessed according to Tanner. There were significant (P < 0.05) univariate correlations for all children between TBF (r = 0.40), BF% (r = 0.32), AFM (r = 0.41), and AFM/TBF (r = 0.41) vs. LA diameter. Multiple regression analyses with the inclusion of possible confounders such as lean body mass, blood pressure, gender, age, and Tanner stage revealed that TBF, AFM, and AFM/TBF were all independently related to LA diameter. Differences in the different body fat measurements explained 6-9% of the variance in LA size. These results demonstrated that both total body fat, AFM, and body fat distribution are already at a young age negatively and independently associated to LA diameter.
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| 20. |
- Dencker, Magnus, et al.
(författare)
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Body fat, abdominal fat and body fat distribution related to cardiovascular risk factors in pre-pubertal children.
- 2012
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 101:8
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Tidskriftsartikel (refereegranskat)abstract
- Aim We analysed whether total body fat, abdominal fat and body fat distribution are associated with higher composite risk factor scores for cardiovascular disease (CVD) in young children. Methods Cross-sectional study of 238 children aged 8-11 years. Total body fat (TBF) and abdominal fat mass (AFM) were measured by DXA. TBF was expressed as a percentage of body weight (BF%). Body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO(2PEAK) ), systolic and diastolic blood pressure (SBP, DBP), and resting heart rate (RHR) were measured. Mean artery pressure (MAP) and pulse pressure (PP) were calculated. Left atrial diameter (LA) was measured, and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z-scores were calculated. Sum of z-scores for SBP, DBP, MAP, PP, RHR, LVM, LA, RWT, and -VO(2PEAK) were calculated in boys and girls, separately, and used as composite risk factor score. Results Pearson correlations between ln BF%, ln AFM and AFM/TBF versus composite risk factor score for boys were r=0.56, r=0.59, and r=0.48, all P<0.001, and for girls r=0.45, r=0.50, and r=0.48, all P<0.001. Conclusion Total body fat, abdominal fat and body fat distribution were all associated with higher composite risk factor scores for CVD in young children. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.
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| 21. |
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| 22. |
- Dencker, Magnus, et al.
(författare)
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Body fat, abdominal fat and body fat distribution related to VO(2PEAK) in young children.
- 2011
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Ingår i: International Journal of Pediatric Obesity. - : Informa UK Limited. - 1747-7174 .- 1747-7166. ; 6:2-2, s. 597-602
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Aerobic fitness, defined as maximum oxygen uptake (VO(2PEAK)), and body fat measurements represent two known risk factors for disease. The purpose of this study was to investigate the relationship between VO(2PEAK) and body fat measurements in young children at a population-based level. Methods. Cross-sectional study of 225 children (128 boys and 97 girls) aged 8-11 years, recruited from a population-based cohort. Total lean body mass (LBM), total fat mass (TBF), and abdominal fat mass (AFM) were measured by dual-energy x-ray absorptiometry. Body fat was also calculated as a percentage of body mass (BF%) and body fat distribution as AFM/TBF. VO(2PEAK) was assessed by indirect calorimetry during maximal exercise test. Results. Significant relationships existed between body fat measurements and VO(2PEAK) in both boys and girls, with Pearson correlation coefficients for absolute values of VO(2PEAK) (0.22-0.36, P< 0.05), and for VO(2PEAK) scaled by body mass (-0.38 - -0.70, P<0.05). No relationships were detected for VO(2PEAK) scaled to LBM (-0.17-0.04, all not significant). Boys and girls in the lowest quartile according to body fat measurements had higher absolute values of VO(2PEAK) and lower values of VO(2PEAK) scaled by body mass, compared with those in the highest quartile. No differences were found for VO(2PEAK) scaled to LBM. Conclusions. Our findings document the coexistence of two known risk factors for disease at a young age and confirms that VO(2PEAK) was scaled to LBM may be a better, body fat independent way of expressing fitness.
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| 23. |
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| 24. |
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| 25. |
- Dencker, Magnus, et al.
(författare)
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Cystatin B, cathepsin L and D related to surrogate markers for cardiovascular disease in children
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study investigated potential associations between novel biomarkers for cardiovascular disease and other surrogate markers for health. Methods: Community sample of 170 (92 boys and 78 girls) children aged 8–11 years. Total fat mass (TBF) and abdominal fat (AFM) were measured by Dual-energy x-ray absorptiometry (DXA). Total body fat was also expressed as percentage of total body mass (BF%), and body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO2PEAK), systolic and diastolic blood pressure (SBP and DBP) and pulse pressure (PP) were measured. Echocardiography was performed. Left atrial size (LA) and left ventricular mass (LVM) were measured. A follow-up DXA scan was available in 152 children (84 boys and 68 girls). Frozen serum samples were analyzed for cystatin B, cathepsin L and cathepsin D. Results: Partial correlations between cystatin B versus lnTBF, lnBF%, lnAFM, AFM/TBF, VO2PEAK and PP were; r = 0.38, 0.36, 0.38, 0.29, -0.25 and 0.25, P = 0.001 or less for all. Weaker predominantly non-significant correlations were found for cathepsin L, whereas cathepsin D was not related to any surrogate markers for health. No significant correlations were found between biomarkers and change in body fat over 2 years. Conclusion: Findings from this community-based cohort of young children show that surrogate markers for cardiovascular disease such as total fat mass, percent body fat, abdominal fat, body fat distribution, maximal oxygen uptake and pulse pressure were all associated with cystatin B. This was not found for cathepsin L or cathepsin D.
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| 26. |
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| 27. |
- Dencker, Magnus, et al.
(författare)
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Daily physical activity related to aerobic fitness and body fat in an urban sample of children.
- 2008
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Ingår i: Scandinavian Journal of Medicine & Science in Sports. - : Wiley. - 1600-0838 .- 0905-7188. ; 18, s. 728-735
-
Tidskriftsartikel (refereegranskat)abstract
- This study evaluates associations between objectively measured daily physical activity vs aerobic fitness and body fat in children aged 8-11 years. A cross-sectional study of 225 children aged 7.9-11.1 years was performed. Abdominal fat mass (AFM) and total body fat (TBF) were quantified by dual-energy x-ray absorptiometry. TBF was calculated as percentage of total body mass (BF%). Body fat distribution was calculated as AFM/TBF. Aerobic fitness was measured by indirect calorimetry during a maximal cycle ergometer exercise test. Daily physical activity was assessed by accelerometers for 4 days and daily accumulation of moderate-to-vigorous and vigorous activity was calculated. Significant relationships (P<0.05) existed for vigorous activity vs ln BF% (r=-0.40), ln AFM (r=-0.35), TBF/AFM (r=-0.22) and aerobic fitness (r=0.38), whereas moderate-to-vigorous activity displayed weaker relationships (-0.22, -0.18, -0.12 NS, and 0.25). Multiple regression analyses with inclusion of possible confounders concluded that vigorous activity was independently related to aerobic fitness and ln BF% or ln AFM. Moderate-to-vigorous activity was only independently related to aerobic fitness. In this population, low daily accumulation of vigorous activity was, already in children aged 8-11 years, associated with more body fat and lower aerobic fitness. A similar relation was not found for daily accumulation of moderate-to-vigorous activity.
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| 28. |
- Dencker, Magnus, et al.
(författare)
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Daily physical activity related to body fat in children aged 8-11 years
- 2006
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Ingår i: Journal of Pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 149:1, s. 38-42
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the association between objectively measured daily Study design Cross-sectional, observational, study of 248 children aged 7.9 to 11.1 years. Abdominal fat mass and total body fat mass were measured by dual-energy X-ray absorptiometry. Daily physical activity was assessed by accelerometers for 4 days. Results Total body fat expressed as a percentage of body mass was inversely related to minutes of vigorous physical activity per day, for all children r = -0.38 (P < .05). Children, both boys and girls, in the highest quartile of body fat performed on average 12 minutes less vigorous activity per day compared with their counterparts in the lowest quartile. Multiple regression analysis revealed that independent factors for body fat were number of minutes of vigorous activity per day and sex. Conclusion Low physical activity can be a contributing factor in childhood obesity. Only longitudinal studies, however, can give more definitive information about the relation between daily physical activity and obesity.
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| 29. |
- Dencker, Magnus, et al.
(författare)
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Galectin-3 levels relate in children to total body fat, abdominal fat, body fat distribution, and cardiac size
- 2018
-
Ingår i: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 0340-6199 .- 1432-1076. ; 177:3, s. 461-467
-
Tidskriftsartikel (refereegranskat)abstract
- Galectin-3 has recently been proposed as a novel biomarker for cardiovascular disease in adults. The purpose of this investigation was to assess relationships between galectin-3 levels and total body fat, abdominal fat, body fat distribution, aerobic fitness, blood pressure, left ventricular mass, left atrial size, and increase in body fat over a 2-year period in a population-based sample of children. Our study included 170 children aged 8–11 years. Total fat mass and abdominal fat were measured by dual-energy x-ray absorptiometry (DXA). Body fat distribution was expressed as abdominal fat/total fat mass. Maximal oxygen uptake was assessed by indirect calorimetry during a maximal exercise test and scaled to body mass. Systolic and diastolic blood pressure and pulse pressure were measured. Left atrial size, left ventricular mass, and relative wall thickness were measured by echocardiography. Frozen serum samples were analyzed for galectin-3 by the Proximity Extension Assay technique. A follow-up DXA scan was performed in 152 children 2 years after the baseline exam. Partial correlations, with adjustment for sex and age, between galectin-3 versus body fat measurements indicated weak to moderate relationships. Moreover, left atrial size, left ventricular mass, and relative wall thickness and pulse pressure were also correlated with galectin-3. Neither systolic blood pressure nor maximal oxygen uptake was correlated with galectin-3. There was also a correlation between galectin-3 and increase in total body fat over 2 years, while no such correlations were found for the other fat measurements. Conclusion: More body fat and abdominal fat, more abdominal body fat distribution, more left ventricular mass, and increased left atrial size were all associated with higher levels of galectin-3. Increase in total body fat over 2 years was also associated with higher levels of galectin-3.(Table presented.)
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| 30. |
- Dencker, Magnus, et al.
(författare)
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Maximal oxygen uptake versus maximal power output in children
- 2008
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Ingår i: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 26:13, s. 1397-1402
-
Tidskriftsartikel (refereegranskat)abstract
- Maximal oxygen uptake ([Vdot]O2max) is considered the optimal method to assess aerobic fitness. The measurement of [Vdot]O2max, however, requires special equipment and training. Maximal exercise testing with determination of maximal power output offers a more simple approach. This study explores the relationship between [Vdot]O2max and maximal power output in 247 children (139 boys and 108 girls) aged 7.9-11.1 years. Maximal oxygen uptake was measured by indirect calorimetry during a maximal ergometer exercise test with an initial workload of 30W and 15Wmin-1 increments. Maximal power output was also measured. A sample (n=124) was used to calculate reference equations, which were then validated using another sample (n=123). The linear reference equation for both sexes combined was: [Vdot]O2max (mlmin-1)=96 + 10.6maximal power + 3.5body mass. Using this reference equation, estimated [Vdot]O2max per unit of body mass (mlmin-1kg-1) calculated from maximal power correlated closely with the direct measurement of [Vdot]O2max (r=0.91, P0.001). Bland-Altman analysis gave a mean limits of agreement of 0.22.9 (mlmin-1kg-1) (1s). Our results suggest that maximal power output serves as a good surrogate measurement for [Vdot]O2max in population studies of children aged 8-11 years.
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| 31. |
- Dencker, Magnus, et al.
(författare)
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Objectively measured daily physical activity related to cardiac size in young children.
- 2009
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Ingår i: Scandinavian Journal of Medicine & Science in Sports. - : Wiley. - 1600-0838 .- 0905-7188. ; Aug 5, s. 664-668
-
Tidskriftsartikel (refereegranskat)abstract
- Training studies in children have suggested that endurance training can give enlargement of cardiac dimensions. This relationship has not been studied on a population-based level in young children with objective methods. A cross-sectional study was made of 248 children (140 boys and 108 girls), aged 8-11 years, from a population-based cohort. Left ventricular end-diastolic diameter (LVDD) and left atrial end-systolic diameter (LA) were measured with echocardiography and indexed for body surface area (BSA). Physical activity was assessed by accelerometry, and the duration of vigorous physical activity per day (VPA) was calculated. Acceptable accelerometer and echocardiography measurements were obtained in 228 children (boys=127, girls=101). Univariate correlations between VPA and LVDD were indexed for BSA in boys (r=0.27, P<0.05) and in girls (r=0.10, NS). Multiple regression analysis showed that independent factors for LVDD, indexed for BSA for boys, were age and VPA. LA indexed for BSA was not related to physical activity variables in either gender. No clear relationship exists between cardiac size and daily physical activity in children aged 8-11 years. This suggests that significant cardiac remodelling due to volume exposure secondary to a high amount of physical activity begins later in life.
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| 32. |
- Dencker, Magnus, et al.
(författare)
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Total body fat, abdominal fat, body fat distribution and surrogate markers for health related to adipocyte fatty acid-binding protein (FABP4) in children
- 2017
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Ingår i: Journal of Pediatric Endocrinology and Metabolism. - : Walter de Gruyter GmbH. - 0334-018X .- 2191-0251. ; 30:4, s. 375-382
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to assess possible relationships between adipocyte fatty acid-binding protein (FABP4) and total body fat (TBF), abdominal fat, body fat distribution, aerobic fitness, blood pressure, cardiac dimensions and the increase in body fat over 2 years in a community sample of children. A cross-sectional study was used in a community sample of 170 (92 boys and 78 girls) children aged 8-11 years. TBF and abdominal fat (AFM) were measured by dual-energy X-ray absorptiometry (DXA). TBF was also expressed as percentage of total body mass (BF%), and body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO2PEAK) was assessed by indirect calorimetry during a maximal exercise test and scaled to body mass. Systolic and diastolic blood pressure (SBP and DBP) and pulse pressure (PP) were measured. Echocardiography was performed. Left atrial (LA) size was measured, and left ventricular mass (LVM) was calculated. A follow-up DXA scan was available in 152 children (84 boys and 68 girls). Frozen serum samples were analyzed for FABP4. Partial correlations, with adjustment for sex, between FABP4 vs. ln TBF, ln BF%, ln AFM, AFM/TBF and VO2PEAK were (r=0.69, 0.68, 0.69, 0.49 and -0.39, p<0.05 for all). Moreover, SBP, PP, LVM and LA were also weakly correlated with FABP4 (r=0.23, 0.22, 0.28 and 0.21, p<0.05 for all). Correlations between FABP4 vs. increase in TBF and AFM over 2 years were 0.29 and 0.26, p<0.05, for both. (Increase in percent body fat or change in fat distribution were not correlated.) Findings from this community-based cohort of young children show that increased body fat and abdominal fat, more abdominal body fat distribution, low fitness, more LVM and increased LA, increased SBP and PP were all associated with increased levels of FABP4. Increase in TBF and abdominal fat over 2 years were also associated with increased levels of FABP4.
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| 33. |
- Falconer, C, et al.
(författare)
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Different organization of collagen fibrils in stress-incontinent women of fertile age
- 1998
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 77, s. 87-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective was to test the hypothesis that stress urinary incontinence in women is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism.METHODS: Transvaginal biopsies were obtained from the paraurethral connective tissue in women of fertile age with stress urinary incontinence and in matched continent controls. All the stress-incontinent women were characterized with urodynamic investigation. In the biopsies, collagen concentration, measured as hydroxyproline, and the degree of extraction by pepsin digestion were quantified. Proteoglycan composition and concentration were analyzed using Alcian blue precipitation, followed by electrophoretic separation and quantification. Using Northern blots mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen organization was examined with transmission electron microscopy and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron).RESULTS: The biochemical and morphological analyses exposed a significant difference in the paraurethral connective tissue between stress urinary incontinent women before menopause and comparable controls. The collagen concentration was almost 30% higher and the diameters of the collagen fibrils were 30% larger in the incontinent group of women. Also the organization of the collagen fibrils differed, with considerably higher cross-linking. A higher level of mRNA for collagen I and III in the incontinent group indicates that the differences can be related to an altered collagen metabolism. No change of proteoglycan amount or composition was observed, resulting in a significantly lower proteoglycan/collagen ratio in the incontinent group of women.CONCLUSION: Stress urinary incontinence in fertile women is associated with a change in collagen metabolism resulting in an increased concentration of collagen and larger collagen fibrils. These alterations should result in a more rigid form of extracellular matrix, suggesting a connective tissue with impaired mechanical function.
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| 34. |
- Falconer, C, et al.
(författare)
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Paraurethral connective tissue in stress-incontinent women after menopause
- 1998
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349. ; 77:1, s. 95-100
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study whether stress urinary incontinence after menopause is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism.METHODS: Transvaginal biopsies were obtained from the paraurethral connective tissue in stress urinary incontinent women after menopause with and without estrogen replacement therapy, and from comparable controls. All the stress-incontinent women underwent urodynamic investigation. In the specimens, collagen concentration, measured as hydroxyproline, and the degree of extractability by pepsin digestion, were quantified. Proteoglycan composition and concentration were analyzed using Alcian Blue precipitation, followed by electro-phoretic separation and quantification. Using Northern blots, mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen structure was examined with transmission electron microscopy, and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron).RESULTS: No significant difference in paraurethral connective tissue biochemistry or ultrastructure was registered between women with stress incontinence and controls. Estrogen replacement therapy resulted in a lower collagen concentration both between the controls (p = 0.02) and between the incontinent women (0.02). In the women with stress incontinence also the extractability by pepsin digestion was higher in the group with estrogen treatment (p = 0.004), indicating a decrease in cross-linking. The proteoglycan/collagen ratio was higher in the control group with estrogen treatment compared to untreated (p = 0.02), but no difference was found between estrogen treated and untreated incontinent women. The median collagen fibril diameter was 15% larger in the incontinent group of women without estrogen therapy compared to the control group and 5% larger when comparing the incontinent group on estrogen replacement therapy to the corresponding control group.CONCLUSION: The extracellular matrix of paraurethral connective tissue in stress urinary incontinent women after menopause reacted differently to estrogen replacement therapy compared to continent controls. In contrast to incontinent women of fertile age no major changes in collagen metabolism were found in stress urinary incontinent women after menopause.
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| 35. |
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| 36. |
- Hedblom, Marcus, et al.
(författare)
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Reduction of physiological stress by urban green space in a multisensory virtual experiment
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Although stress is an increasing global health problem in cities, urban green spaces can provide health benefits. There is, however, a lack of understanding of the link between physiological mechanisms and qualities of urban green spaces. Here, we compare the effects of visual stimuli (360 degree virtual photos of an urban environment, forest, and park) to the effects of congruent olfactory stimuli (nature and city odours) and auditory stimuli (bird songs and noise) on physiological stress recovery. Participants (N = 154) were pseudo-randomised into participating in one of the three environments and subsequently exposed to stress (operationalised by skin conductance levels). The park and forest, but not the urban area, provided significant stress reduction. High pleasantness ratings of the environment were linked to low physiological stress responses for olfactory and to some extent for auditory, but not for visual stimuli. This result indicates that olfactory stimuli may be better at facilitating stress reduction than visual stimuli. Currently, urban planners prioritise visual stimuli when planning open green spaces, but urban planners should also consider multisensory qualities.
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| 37. |
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| 38. |
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| 39. |
- Juhasz, P., et al.
(författare)
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ESI and MALDI LC/MS-MS approaches for large scale protein, identification and quantification : Are they equivalent?
- 2002
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Ingår i: ; , s. 55-56
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Konferensbidrag (refereegranskat)abstract
- An approach for large scale protein identification and quantification was described. The peptide mixtures from the strong cation exchange (SCX) fractionated protein digests were separated and analyzed by HPLC MS/MS. The human fibrobalst nuclei were purified from stimulated and non-stimulated cells. The quantification results with MALDI and ESI LC/MS were shown to be identical within experimental error.
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| 40. |
- Mani, K, et al.
(författare)
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Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside preferentially inhibits growth of transformed cells
- 1998
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Ingår i: Cancer Research. - 0008-5472. ; 58:6, s. 104-1099
-
Tidskriftsartikel (refereegranskat)abstract
- Xylose forms the direct carbohydrate-protein link in extra- or pericellular proteoglycans (PGs) that are substituted with either chondroitin sulfate (CS)/dermatan sulfate (DS) and/or heparan sulfate (HS). Cell surface PGs carrying HS are important regulators of cell growth. Xylose coupled to an aromatic compound can enter cells and initiate either CS/DS synthesis or both HS and CS/DS synthesis, depending on the nature of the aromatic adduct. Here, we show that 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside, which can prime both types of glycan chains, inhibits growth of a set of normal and transformed cells. Transformed cells are preferentially inhibited, and at a concentration of 0.15-0.20 mM xyloside, transformed cells are totally growth arrested, whereas normal cells are only < or = 50% inhibited. No inhibition of growth is observed with the stereoisomeric 2-(6-hydroxynaphthyl)-O-beta-L-xylopyranoside, which does not prime glycosaminoglycan synthesis at all; with the nonhydroxylated 2-naphthyl-O-beta-D-xylopyranoside, which only primes CS/DS synthesis under these conditions; or with p-nitrophenyl-O-beta-D-xylopyranoside, which is known to prime only CS/DS synthesis. We conclude that growth inhibition is due to priming of HS and/or CS/DS synthesis, which may either lead to the formation of specific antiproliferative glycans or glycan fragments or to interference with endogenous PG synthesis and turnover.
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| 41. |
- Müller, Catharina, et al.
(författare)
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Early extracellular matrix changes are associated with later development of bronchiolitis obliterans syndrome after lung transplantation
- 2017
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 4:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic lung allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS) is the main cause of death beyond 1-year post-lung transplantation. The disease-initiating triggers as well as the molecular changes leading to fibrotic alterations in the transplanted lung are largely unknown. The aim of this study was to identify potential early changes in the extracellular matrix (ECM) in different compartments of the transplanted lung prior to the development of BOS.METHODS: Transbronchial biopsies from a cohort of 58 lung transplantation patients at the Copenhagen University hospital between 2005 and 2006, with or without development of BOS in a 5-year follow-up, were obtained 3 and 12 months after transplantation. Biopsies were assessed for total collagen, collagen type IV and biglycan in the alveolar and small airway compartments using Masson's Trichrome staining and immunohistochemistry.RESULTS: A time-specific and compartment-specific pattern of ECM changes was detected. Alveolar total collagen (p=0.0190) and small airway biglycan (p=0.0199) increased between 3 and 12 months after transplantation in patients developing BOS, while collagen type IV (p=0.0124) increased in patients without BOS. Patients with early-onset BOS mirrored this increase. Patients developing grade 3 BOS showed distinct ECM changes already at 3 months. Patients with BOS with treated acute rejections displayed reduced alveolar total collagen (p=0.0501) and small airway biglycan (p=0.0485) at 3 months.CONCLUSIONS: Patients with future BOS displayed distinct ECM changes compared with patients without BOS. Our data indicate an involvement of alveolar and small airway compartments in post-transplantation changes in the development of BOS.
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| 42. |
- Olafsson, S, et al.
(författare)
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Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
- 2017
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Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 2, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10−7, 4.3 × 10−9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.
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| 43. |
- Onomura, Shiho, 1985, et al.
(författare)
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Meteorological forcing data for urban outdoor thermal comfort models from a coupled convective boundary layer and surface energy balance scheme
- 2015
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Ingår i: Urban Climate. - : Elsevier BV. - 2212-0955. ; 11, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- Site-specific meteorological forcing appropriate for applications such as urban outdoor thermal comfort simulations can be obtained using a newly coupled scheme that combines a simple slab convective boundary layer (CBL) model and urban land surface model (ULSM) (here two ULSMs are considered). The former simulates daytime CBL height, air temperature and humidity, and the latter estimates urban surface energy and water balance fluxes accounting for changes in land surface cover. The coupled models are tested at a suburban site and two rural sites, one irrigated and one unirrigated grass, in Sacramento, U.S.A. All the variables modelled compare well to measurements (e.g. coefficient of determination = 0.97 and root mean square error = 1.5 °C for air temperature). The current version is applicable to daytime conditions and needs initial state conditions for the CBL model in the appropriate range to obtain the required performance. The coupled model allows routine observations from distant sites (e.g. rural, airport) to be used to predict air temperature and relative humidity in an urban area of interest. This simple model, which can be rapidly applied, could provide urban data for applications such as air quality forecasting and building energy modelling, in addition to outdoor thermal comfort.
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| 44. |
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| 45. |
- Tanha, Tina, et al.
(författare)
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Lack of physical activity in young children is related to higher composite risk factor score for cardiovascular disease.
- 2011
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Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 100, s. 717-721
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study evaluates if accelerometer measured physical activity is related to higher composite risk factor scores for cardiovascular disease (CVD) in children. Methods: Cross-sectional study that included 223 children aged 7.9-11.1 years (boys n=123, girls n=100). Daily physical activity was assessed by accelerometers for four days. Body fat was quantified by dual x-ray absorptiometry. Maximal oxygen uptake was measured during a maximal exercise test. Resting heart rate and blood pressure were measured. Z-scores [(value for the individual-mean value for group)/SD] were calculated for each variable and the sum of different risk factor z-scores used as an index of composite risk factors score for CVD. Results: Partial correlations, from General Linear Model, between moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA) and general physical activity (GPA) versus index of composite risk factor score were in boys -0.29, -0.33 and -0.30 (all p<0.05). The corresponding correlations in girls were -0.28, -0.32 (both p<0.05), and -0.18, (NS). Conclusion: Low amounts of MVPA and VPA were related to higher composite risk factor scores for CVD in children aged 8-11 years.
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| 46. |
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| 47. |
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| 48. |
- Tiedemann, K, et al.
(författare)
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Regulation of the chondroitin/dermatan fine structure by transforming growth factor-beta 1 through effects on polymer-modifying enzymes
- 2005
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 15:12, s. 1277-1285
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Tidskriftsartikel (refereegranskat)abstract
- The chondroitin/dermatan sulfate proteoglycans (CS/DSPGs), biglycan, decorin, and versican play several important roles in extracellular matrix influencing matrix organization, cell proliferation, and recruitment. Moreover, they bind and regulate growth factors in the extracellular matrix. We have previously shown that cultured human lung fibroblasts treated with transforming growth factor-beta (TGF-beta) alone or in combination with epidermal growth factor and platelet-derived growth factor, increase the production of these PGs. In this report, we describe that the structure of their galactosaminoglycan side chains is altered, albeit there is no alteration of polysaccharide length. The findings showed that iduronic acid content is reduced by 50% in decorin and biglycan, whereas 4-O-sulfation is increased 2-fold in versican. To unravel the mechanism behind these changes, the activities of chondroitin C-5 epimerase and of O-sulfotransferases in cellular fractions prepared from fibroblasts were quantitated, and transcript levels of the relevant sulfotransferases were measured by real time polymerase chain reaction (RT-PCR). The C-5 epimerase activity was reduced by 25% in TGF-beta 1 treated cells and 50% in fibroblasts treated with the growth factor combination. No change in activity in dermatan 4-O sulfotransferase was observed, and only a minor decrease in dermatan 4-O-sulfotransferase-1 (D4ST-1) mRNA was observed. On the other hand, chondroitin 4-O sulfotransferase activity increased 2-fold upon TGF-beta 1 treatment and 3-fold upon treatment with the growth factor combination. This is in agreement with a 2-fold up-regulation of chondroitin-4-O-sulfotransferase 1 (C4ST-1) mRNA, and no changes in chondroitin-4-O-sulfotransferase 2 (C4ST-2) mRNA. Thus, cellular activity and transcript level correlated well with the changes in the structure of the dermatan/chondroitin sulfate chains.
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| 49. |
- Westergren-Thorsson, G, et al.
(författare)
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Altered expression of small proteoglycans, collagen, and transforming growth factor-beta 1 in developing bleomycin-induced pulmonary fibrosis in rats
- 1993
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 92:2, s. 7-632
-
Tidskriftsartikel (refereegranskat)abstract
- The development of bleomycin-induced pulmonary fibrosis in rats was studied over a period of 21 d after an intratracheal instillation of bleomycin. The expression of three small proteoglycans (biglycan, decorin, and fibromodulin), collagen III and TGF-beta 1 was studied by RNA-transfer blot analysis. The proteoglycans were also studied by SDS-polyacrylamide gel electrophoresis and Western blots. TGF-beta 1 mRNA increased threefold already on day 3 and remained elevated until day 10. After the increase of TGF-beta 1 mRNA the messages for biglycan and collagen III steadily increased to reach a maximum 10 d after bleomycin instillation. The mRNA for biglycan increased maximally fourfold and that of collagen III 2.5-fold. Decorin mRNA, in contrast to biglycan decreased and reached 20% of control on day 10. The message for fibromodulin remained constant throughout the study period. The amounts of biglycan and decorin in the tissue changed in accordance with the mRNA levels. The results corroborate and extend previous in vitro studies concerning the effect of TGF-beta 1 on the metabolism of small proteoglycans and show that these macromolecules are regulated differently also in vivo. The marked alterations of biglycan and decorin during the development of fibrosis suggests that these proteoglycans have a regulating role in this process.
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| 50. |
- Westergren-Thorsson, G, et al.
(författare)
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TGF-beta enhances the production of hyaluronan in human lung but not in skin fibroblasts
- 1990
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 186:1, s. 5-192
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor-beta (TGF-beta) enhances the production of extracellular matrix components, such as type I and type III collagen, fibronectin, proteoglycans, in various cell types. The effect on hyaluronan synthesis in relation to proteoglycan synthesis has not been investigated. Human lung or skin fibroblast cultures were treated with TGF-beta in serum-free medium for various periods of time. 35SO4 or [3H]glucosamine was then added to the cultures in the absence of TGF-beta for up to 48 h. Hyaluronan and proteoglycans were isolated by ion-exchange chromatography and quantitated. TGF-beta induced a three- to fourfold increase in hyaluronan production by lung cells but had no effect on skin fibroblasts. In contrast, proteoglycan synthesis was enhanced in both cell types, although skin fibroblasts responded at lower concentrations of TGF-beta. Increased accumulation of hyaluronan was noted only in the cell medium, whereas proteoglycan accumulation was observed both in the medium and in the cell layer. The ED50 for TGF-beta on hyaluronan accumulation in lung cells was the same as that for proteoglycan accumulation, i.e., 40 pM. In skin fibroblasts the ED50 was considerably lower (4 pM). The induction time needed to attain full effect of TGF-beta was 6 h for both hyaluronan and proteoglycan synthesis. These results indicate that TGF-beta has tissue-specific effects on matrix production which may be of importance for control of cell proliferation in various disease states.
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