| 1. |
- Peden, John F., et al.
(författare)
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A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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| 2. |
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| 3. |
- Shawki, Ali, et al.
(författare)
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Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese
- 2015
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 309:8, s. G635-G647
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Tidskriftsartikel (refereegranskat)abstract
- Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring membrane-transport protein that serves a critical role in erythroid iron utilization. We have investigated its role in intestinal metal absorption by studying a mouse model lacking intestinal DMT1 (i.e., DMT1(int/int)). DMT1(int/int) mice exhibited a profound hypochromic-microcytic anemia, splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was demonstrated by the following observations in DMT1(int/int) mice: 1) blood iron and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver hepcidin (Hamp1) was depressed; and 3) intraperitoneal iron injection corrected the anemia, and reversed the changes in blood iron, nonheme-iron stores, and hepcidin expression levels. We observed decreased total iron content in multiple tissues from DMT1(int/int) mice compared with DMT1(+/+) mice but no meaningful change in copper, manganese, or zinc. DMT1(int/int) mice absorbed Cu-64 and Mn-54 from an intragastric dose to the same extent as did DMT1(+/+) mice but the absorption of Fe-59 was virtually abolished in DMT1(int/int) mice. This study reveals a critical function for DMT1 in intestinal nonheme-iron absorption for normal growth and development. Further, this work demonstrates that intestinal DMT1 is not required for the intestinal transport of copper, manganese, or zinc.
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| 4. |
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| 5. |
- Westman, Anders, 1946-, et al.
(författare)
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Quality of life and maintenance of improvements after early multimodal rehabilitation : a 5-year follow-up
- 2006
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Ingår i: Disability and Rehabilitation. - London : Taylor & Francis. - 0963-8288 .- 1464-5165. ; 28:7, s. 437-446
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. There is a paucity of long-term evaluations on rehabilitation of musculoskeletal disorders, e.g., neck, shoulder or back pain. The aim of this study was to assess quality of life and the effect of early multimodal rehabilitation on 91 patients with musculoskeletal pain and disability at a 5-year follow-up. Method. The follow-up assessment, which included questions on pain, function, quality of life, perceived health, sick leave and psychosomatic symptoms, was performed 5 years after the assessment of baseline status. Results. Improvements in pain, perceived health and psychosomatic symptoms were maintained at the 5-year follow-up. In addition, improvements in function, quality of life, and level of acceptable pain were significant in comparison to baseline. At the time of the baseline assessment all patients were on sick leave (13% were on partial sick leave). At the 5-year follow-up, 58% of the patients were at work part or full time. The results show that those working differed significantly from those not working at the 5-year follow-up on almost all variables, indicating that those working enjoy better health. The most salient prognostic factors for return to work were perceived health and educational level at the time of the baseline evaluation. Conclusions. These results show that treatment improved quality of life and the effects were basically maintained at 5 years. Work capacity as reflected in return to work increased greatly (81%) at a 1-year follow-up and was substantial (58%) at the 5-year follow-up. Moreover, perceived health and educational levels were important prognostic factors. Finally, the fact that patients working reported better health underscores the probable importance of return to work. Our results imply that it may be feasible to obtain long-term benefits from such a primary care-based intervention.
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| 6. |
- Augustin, K, et al.
(författare)
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Green tea extracts lower serum folates in rats at very high dietary concentrations only and do not affect plasma folates in a human pilot study.
- 2009
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 60:3, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- Green tea catechins (GTC) have been shown to inhibit the activities of enzymes involved in folate uptake. Hence, regular green tea drinkers may be at risk of impaired folate status. The present experiments aimed at studying the impact of dietary GTC on folate concentrations and metabolism. In a human pilot study (parallel design) healthy men consumed for 3 weeks 6 capsules (approximately 670 mg GTC) per day (2 capsules with each principal meal) containing aqueous extracts of the leaves of Camellia sinensis (n=17) or placebo (n=16). No differences in plasma folate concentrations were observed between treatments. We further fed groups of 10 male rats diets fortified with 0, 0.05, 0.5, 1, or 5 g GTC/kg for 6 weeks. Only at the highest intake, GTC significantly decreased serum 5-methyl-tetrahydrofolate concentrations in rats, while mRNA concentrations of reduced folate carrier, proton-coupled folate transporter/heme carrier protein 1, and dihydrofolate reductase (DHFR) remained unchanged in intestinal mucosa. Using an in vitro enzyme activity assay, we observed a time- and dose-dependent inhibition of DHFR activity by epigallocatechin gallate and a green tea extract. Our data suggest that regular green tea consumption is unlikely to impair folate status in healthy males, despite the DHFR inhibitory activity of GTC.
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| 7. |
- Hedberg, P, et al.
(författare)
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Augmented blood pressure response to exercise is associated with improved long-term survival in older people
- 2009
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 95:13, s. 1072-1078
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Studies on the prognostic importance of the systolic blood pressure (SBP) response during exercise report ambiguous results. Most research focuses on younger and middle-aged selected patient groups and rarely includes women. We investigated the prognostic value of SBP response during exercise testing in 75-year-olds. Design: Prospective observational cohort study. Setting: A community-based random sample of 75-yearold men and women (n = 382). Main outcome measures: The prognostic value of SBP change from rest to peak exercise during a symptom-limited cycle test was evaluated for the endpoints all-cause mortality and cardiovascular mortality during long-term follow-up. Results: After a median follow-up of 10.6 years, 140 (37%) of the participants had died, 64 (17%) from cardiovascular causes. The all-cause mortalities for exercise SBP changes of <= 30 mm Hg, 31-55 mm Hg and > 55 mm Hg were 5.1, 4.2 and 2.6 per 100 person-years, respectively (logrank 9.6; p = 0.008). For every 10 mm Hg increase in SBP during exercise the relative hazard for all-cause mortality was reduced by 13% (p = 0.030) and for cardiovascular mortality by 26% (p = 0.004) after adjustment for sex, smoking, waist circumference, total/HDL cholesterol ratio, prevalent ischaemic heart disease, hypertension, diabetes, cardiovascular medication, pre-exercise SBP, exercise capacity, resting left ventricular ejection fraction and left ventricular mass index. Conclusions: Our findings suggest that an augmented SBP response during exercise is associated with an improved long-term survival among community-living 75-year-old individuals.
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| 8. |
- Johansson, Ann-Christin, et al.
(författare)
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Psychosocial stress factors among patients with lumbar disc herniation, scheduled for disc surgery in comparison with patients scheduled for arthroscopic knee surgery
- 2007
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Ingår i: European spine journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 16:7, s. 961-970
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Tidskriftsartikel (refereegranskat)abstract
- Returning to work after disc surgery appears to be more heavily influenced by psychological aspects of work than by MR-identified morphological alterations. It is still not known whether psychosocial factors of importance for outcome after disc surgery are present preoperatively or develop in the postoperative phase. The aim of this study was to investigate the presence of work-related stress, life satisfaction and demanding life events, among patients undergoing first-time surgery for lumbar disc herniation in comparison with patients scheduled for arthroscopic knee surgery. Sixty-nine patients with disc herniation and 162 patients awaiting arthroscopy were included in the study, during the time period March 2003 to May 2005. Sixty-two percent of the disc patients had been on sick leave for an average of 7.8 months and 14 percent of the knee patients had been on sick leave for an average of 4.2 months. The psychosocial factors were investigated preoperatively using a questionnaire, which was a combination of the questionnaire of quality of work competence (QWC), life satisfaction (LiSat9) and life events as a modification of the social readjustment scale. There were no significant differences between the two groups in terms of work-related stress or the occurrence of demanding life events. The disc patients were significantly less satisfied with functions highly inter-related to pain and discomfort, such as present work situation, leisure-time, activities of daily living (ADL) function and sleep. Patients with disc herniation on sick leave were significantly less satisfied with their present work situation than knee patients on sick leave; this sub-group of patients with disc herniation also reported significantly higher expectations in relation to future job satisfaction than knee patients. The results indicate that psychosocial stress is not more pronounced preoperatively in this selected group of disc patients, without co-morbidity waiting for first-time disc surgery, than among knee patients awaiting arthroscopy. It was notable that the disc patients had high expectations in terms of improved job satisfaction after treatment by surgery.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- McLeod, Olga, et al.
(författare)
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Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease
- 2016
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 81, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA = 0.11, P = 6.73E(-5) and chromosome 14, rs4902762, BETA = 0.12, P= 5.76E(-6)) and one for eosinophil count (rs72797327, BETA = -0.10, P = 1.41E(-6)). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA = 0.04, P= 0.2763, I-2 = 24, I-2 - P = 0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2 = 0.93 with rs56183820) BETA = -0.10, P = 8.64E(-6) and rs11739623 (r2 = 0.96 with rs72797327) BETA = -0.23, P = 1.74E(-29), respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNP5 associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels.
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| 13. |
- Nilsson, Göran, et al.
(författare)
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Heart rate recovery is more strongly associated with the metabolic syndrome, waist circumference, and insulin sensitivity in women than in men among the elderly in the general population
- 2007
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 154:3, s. 460.e1-460.e7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low heart rate recovery (HRR) at exercise test and the metabolic syndrome (MetS) are both predictors of cardiovascular morbidity and mortality. We studied in 75-year-old women and men, representative of the general population, the relationship between (1) HRR and the MetS, (2) HRR and the individual components of the MetS, and (3) HRR and insulin sensitivity. Methods: A cross-sectional study of randomly selected 75-year-olds from a general population was performed (191 women and 194 men). The MetS was defined according to the National Cholesterol Education Program criteria. Heart rate was measured as beats per minute immediately after exercise and at 4 minutes into recovery. Results: Heart rate recovery (median and interquartile range, beat/min) was 48 (37-58) for women and 49 (38-58) for men. Thirty-seven percent of the women and 25% of the men had the MetS. Heart rate recovery was 52 (42-61) for women with the MetS and 42 (31-49) for those without. The corresponding values for men was 50 (39-61) and 47 (35-54); the difference between individuals with and without the MetS was significant for women (P < .001) but not for men (P = .084). The following significant correlation coefficients between HRR and MetS components were found: for women, waist circumference (-0.43, P < .001), high-density lipoprotein cholesterol (0.37, P < .001), insulin sensitivity (-0.37, P < .001), fasting plasma glucose (-0.30, P < .001), and triglycerides (-0.24, P = .001); for men, triglycerides (-0.20, P = .005). The sex disparity in the strength of correlation reached statistical significance for insulin sensitivity (P < .001) and waist circumference (P = .042). Conclusion: Among 75-year-olds, the MetS and related components are more strongly correlated to HRR in women than in men.
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| 14. |
- Nilsson, Göran, et al.
(författare)
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Low Psychological General Well-Being (PGWB) is associated with deteriorated 10-year survival in men but not in women among the elderly
- 2011
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 52:2, s. 167-171
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Tidskriftsartikel (refereegranskat)abstract
- We studied Psychological General Well-Being (PGWB) and its relation to 10-year survival in 75-year-olds from the general population. The PGWB global score (sum of six subscale scores) and the subscale scores were transformed to 0-100 scales. Ten-year survival in relation to PGWB global and subscale scores was studied in a cohort of 204 men and 213 women. Global PGWB score (median) was 83 in men and 79 in women (for difference p = 0.001). Significantly higher male scores were found for most PGWB subscales. Global PGWB score was significantly related to better 10-year survival in men (relative risk per ten points of score was 0.80; p = 0.001 and 0.85; p = 0.022 adjusting for chronic diseases and living alone) but not in women (relative risk 0.94; p = 0.478 unadjusted). Among 75-year-olds, PGWB score was significantly higher for men. A high PGWB score was significantly related to better survival in men but not in women.
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| 15. |
- Nilsson, Göran, et al.
(författare)
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QTc interval and survival in 75-year-old men and women from the general population
- 2006
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 8:4, s. 233-240
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The study concerns the relationship of the corrected QT (QTc) interval to 6.4 years of survival and to measures of cardiac function, such as echocardiographic variables and plasma levels of brain natriuretic peptide (BNP), in 75-year-old people. Methods and results: QTc was measured in a 12-lead electrocardiogram (ECG) in 210 men and 223 women, comprising a randomly selected sample from the general population (70% participation rate). The Sicard 440/740 computer-analysis program, with Hodges' formula for heart rate-based QT correction, was used. The optimal cut-off point for predicting survival according to the receiver operating characteristic curve was found between 429 and 430 ms. Individuals with a QTc interval of ≥430 ms (n = 115) had decreased survival when compared with those with shorter QTc interval (n = 318); the relative risk was 2.4 (95% confidence interval 1.5-3.7). The predictive ability of QTc reflects an association between QTc and the following variables: BNP, left ventricular mass, and left ventricular ejection fraction (but not diastolic filling patterns). Both Hodges' and Bazett's formulae for heart rate correction of the QT interval were useful for predicting survival. The median QTc was 415 ms using Hodges' formula and 430 ms with Bazett's formula. The QRS component of QTc predicted survival better than the rest of the QTc interval and was approximately as useful as the QTc interval itself. Conclusion: The computer-derived QTc obtained from the ordinary 12-lead ECG identifies high-risk individuals among elderly people from the general population.
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| 16. |
- Nilsson, G, et al.
(författare)
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White blood cell counts associate more strongly to the metabolic syndrome in 75-year-old women than in men : a population based study.
- 2007
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Ingår i: Metabolic Syndrome and Related Disorders. - : Mary Ann Liebert Inc. - 1540-4196 .- 1557-8518. ; 5:4, s. 359-364
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Tidskriftsartikel (refereegranskat)abstract
- Background: A positive relation between the metabolic syndrome (MetS) and inflammatoryactivity has been reported. The purpose of this investigation was to study the relationshipsbetween 1) white blood cell (WBC) count and MetS, 2) WBC count and the individual com-ponents of MetS and 3) WBC count and insulin sensitivity in 75-year-old women and menfrom the general population. Methods: The study included 200 women and 196 men comprising 64% of the 75-year oldpeople from the city of Västerås in Sweden. MetS was defined according to the National Cho-lesterol Education Program (NCEP). Results: WBC count (109/L; median and interquartile range) was 5.7 (4.9–6.8) for women and6.3 (5.4–7.2) for men, P Ͻ .001 for gender difference. For women with and without MetS, WBCcount was 6.3 (5.3–7.3) and 5.4(4.7–6.3), respectively. For men the corresponding figures were6.7 (5.9–7.6) and 6.1 (5.4–7.1).The difference in WBC count between individuals with and with-out MetS was significant (P Ͻ .001 for women; P ϭ .014 for men). All individual componentsof MetS (with exception of blood pressure) were more strongly associated with WBC countfor women than for men. Insulin sensitivity, measured as HOMA-IR (HOmeostasis ModelAssessment-Insulin Resistance) index, was significantly associated with WBC count in wo-men but not in men. Conclusions: In this elderly population, individuals with MetS had a higher WBC countthan those without. Women had a lower WBC count and stronger relationship between WBCcount and insulin sensitivity than did men.
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| 17. |
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| 18. |
- Nohlert, Eva, et al.
(författare)
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Long-term follow-up of a high- and a low-intensity smoking cessation intervention in a dental setting- a randomized trial
- 2013
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 13:9, s. Article number: 592-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Achieving lifelong tobacco abstinence is an important public health goal. Most studies use 1-year follow-ups, but little is known about how good these are as proxies for long-term and life-long abstinence. Also, intervention intensity is an important issue for development of efficient and cost-effective cessation treatment protocols.The study aims were to assess the long-term effectiveness of a high- and a low-intensity treatment (HIT and LIT) for smoking cessation and to analyze to what extent 12-month abstinence predicted long-term abstinence. Methods. 300 smokers attending dental or general health care were randomly assigned to HIT or LIT at the public dental clinic. Main outcome measures were self-reported point prevalence, continuous abstinence (≥6 months), and sustained abstinence. The study was a follow-up after 5-8 years of a previously performed 12-month follow-up, both by postal questionnaires. Results: Response rate was 85% (n=241) of those still alive and living in Sweden. Abstinence rates were 8% higher in both programs at the long-term than at the 12-month follow-up. The difference of 7% between HIT and LIT had not change, being 31% vs. 24% for point prevalence and 26% vs. 19% for 6-month continuous abstinence, respectively. Significantly more participants in HIT (12%) than in LIT (5%) had been sustained abstinent (p=0.03). Logistic regression analyses showed that abstinence at 12-month follow-up was a strong predictor for abstinence at long-term follow-up. Conclusions: Abstinence at 12-month follow-up is a good predictor for long-term abstinence. The difference in outcome between HIT and LIT for smoking cessation remains at least 5-8 years after the intervention. Trial registration number. NCT00670514.
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| 19. |
- Olofsson, P. S., et al.
(författare)
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Genetic variants of TNFSF4 and risk for carotid artery disease and stroke
- 2009
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Ingår i: Journal of Molecular Medicine. - New York : Springer. - 0946-2716 .- 1432-1440. ; 87:4, s. 337-346
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Tidskriftsartikel (refereegranskat)abstract
- In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730∈±∈30 vs 330∈±∈65 arbitrary units, p∈<∈0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-α; 460∈±∈110 vs 133∈±∈8 arbitrary units, p∈<∈0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.
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| 20. |
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| 21. |
- Westman, Anders, 1946-, et al.
(författare)
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Controlled 3-year follow-up of a multidisciplinary pain rehabilitation program in primary health care
- 2010
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Ingår i: Disability and Rehabilitation. - Oxon, United Kingdom : Taylor & Francis. - 0963-8288 .- 1464-5165. ; 32:4, s. 307-316
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The high prevalence of musculoskeletal pain generates significant costs for primary health care and the whole of society. The development of appropriate interventions is therefore necessary. The aim of this effectiveness study was to assess the long-term effects of a primary health care multidisciplinary rehabilitation program in Sweden.Methods: An experimental group comprising 89 patients from two primary health care units received individualised treatment interventions after a multidisciplinary investigation. A control group of 69 patients with the same inclusion criteria from four other primary health care units were treated according to routine. All participants completed questionnaires measuring pain, sick leave, quality of life, health care utilisation, drug consumption and psychosocial factors at baseline and at 3-year follow-up.Results: After 3 years, utilisation of primary health care was significantly lower in the experimental group and work capacity was slightly but not significantly higher. The control group showed a trend of having a higher risk of high consumption after 3 years compared to the intervention group. There was no significant difference between the two groups concerning remaining variables such as function, catastrophising and pain.Conclusion: Both groups demonstrated considerable improvement over the course of 3 years. The experimental group had lower health care utilisation and a reduced risk of using large amounts of medication at the 3-year follow-up, indicating that compared with participants in the control group they were coping in a better way with pain.
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| 22. |
- Westman, Anders, et al.
(författare)
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Do psychosocial factors predict disability and health at a 3-year follow-up for patients with non-acute musculoskeletal pain? : A validation of the Örebro Musculoskeletal Pain Screening Questionnaire
- 2008
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 12:5, s. 641-649
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Early identification and intervention with those that run the risk of developing long-term disability would offer a great opportunity for reducing costs and personal suffering associated with long-term work absenteeism. The Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) has been used and validated in several studies for participants with mainly acute pain problems. The aim of this study was to validate the ÖMPSQ for patients with non-acute pain problems (e.g. 1–6 months sick leave) and compare to other relevant questionnaires. Method One hundred and fifty-eight patients with musculoskeletal pain and disability recruited to a multidisciplinary rehabilitation project completed a battery of questionnaires at baseline and at 3-year follow-up visits. The main analysis involved the relationship between risk levels in the questionnaire and sick leave and perceived health after 3 years. Results The ÖMSPQ predicted future sick leave and health and was found to have six factors. The function and pain factors were the best predictors of sick leave after 3 years, while the distress factor was the best predictor of perceived mental health and return to work-expectancy was borderline significant. Perceived physical health at 3 years was best predicted by the function and pain factors with the fear-avoidance factor being marginally significant. Conclusion The results demonstrate that psychosocial factors as measured by ÖMPSQ are related to work disability and perceived health even 3 years after treatment for patients with non-acute pain problems. The ÖMSPQ was a good predictor of outcome.
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| 23. |
- Öhrvik, Helena, et al.
(författare)
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Cathepsin Protease Controls Copper and Cisplatin Accumulation via Cleavage of the Ctr1 Metal-binding Ectodomain
- 2016
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 291:27, s. 13905-13916
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Tidskriftsartikel (refereegranskat)abstract
- Copper is an essential metal ion for embryonic development, iron acquisition, cardiac function, neuropeptide biogenesis, and other critical physiological processes. Ctr1 is a high affinity Cu+ transporter on the plasma membrane and endosomes that exists as a full-length protein and a truncated form of Ctr1 lacking the methionine- and histidine-rich metal-binding ectodomain, and it exhibits reduced Cu+ transport activity. Here, we identify the cathepsin L/B endolysosomal proteases functioning in a direct and rate-limiting step in the Ctr1 ectodomain cleavage. Cells and mice lacking cathepsin L accumulate full-length Ctr1 and hyper-accumulate copper. As Ctr1 also transports the chemotherapeutic drug cisplatin via direct binding to the ectodomain, we demonstrate that the combination of cisplatin with a cathepsin L/B inhibitor enhances cisplatin uptake and cell killing. These studies identify a new processing event and the key protease that cleaves the Ctr1 metal-binding ectodomain, which functions to regulate cellular Cu+ and cisplatin acquisition.
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| 24. |
- Öhrvik, Helena, et al.
(författare)
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Ctr2 Regulates Mast Cell Maturation by Affecting the Storage and Expression of Tryptase and Proteoglycans
- 2015
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 195:8, s. 3654-3664
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Tidskriftsartikel (refereegranskat)abstract
- Copper (Cu) is essential for multiple cellular functions. Cellular uptake of Cu+ is carried out by the Ctr1 high-affinity Cu transporter. The mobilization of endosomal Cu pools is regulated by a protein structurally similar to Ctr1, called Ctr2. It was recently shown that ablation of Ctr2 caused an increase in the concentration of Cu localized to endolysosomes. However, the biological significance of excess endolysosomal Cu accumulation has not been assessed. In this study, we addressed this issue by investigating the impact of Ctr2 deficiency on mast cells, a cell type unusually rich in endolysosomal organelles (secretory granules). We show that Ctr2(-/-) mast cells have increased intracellular Cu concentrations and that the absence of Ctr2 results in increased metachromatic staining, the latter indicating an impact of Ctr2 on the storage of proteoglycans in the secretory granules. In agreement with this, the absence of Ctr2 caused a skewed ratio between proteoglycans of heparin and chondroitin sulfate type, with increased amounts of heparin accompanied by a reduction of chondroitin sulfate. Moreover, transmission electron microscopy analysis revealed a higher number of electron-dense granules in Ctr2(-/-) mast cells than in wild-type cells. The increase in granular staining and heparin content is compatible with an impact of Ctr2 on mast cell maturation and, in support of this, the absence of Ctr2 resulted in markedly increased mRNA expression, storage, and enzymatic activity of tryptase. Taken together, the present study introduces Ctr2 and Cu as novel actors in the regulation of mast cell maturation and granule homeostasis.
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