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- Björk, Anne, et al.
(författare)
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Variations in the vitamin D receptor gene are not associated with measures of muscle strength, physical performance, or falls in elderly men : Data from MrOS Sweden
- 2019
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 187, s. 160-165
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Tidskriftsartikel (refereegranskat)abstract
- The vitamin D receptor (VDR) has been proposed as a candidate gene for several musculoskeletal phenotypes. However, previous results on the associations between genetic variants of the VDR with muscle strength and falls have been contradictory. The MrOS Sweden survey, a prospective population-based cohort study of 3014 elderly men (mean age 75 years, range 69-81) offered the opportunity to further investigate these associations. At baseline, data were collected on muscle strength and also the prevalence of falls during the previous 12 months. Genetic association analysis was performed for 7 Single Nucleotide Polymorphisms (SNPs), covering the genetic region surrounding the VDR gene in 2924 men with available samples of DNA. Genetic variations in the VDR were not associated with five different measurements of muscle strength or physical performance (hand grip strength right and left, 6 m walking test (easy and narrow) and timed-stands test). However, one of the 7 SNPs of the gene for the VDR receptor, rs7136534, was associated with prevalence of falls (33.6% of the AA, 14.6% of the AG and 16.5% of the GG allele). In conclusion, VDR genetic variants are not related to muscle strength or physical performance in elderly Swedish men. The role of the rs7136534 SNP for the occurrence of falls is not clear.
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- Cawthon, P. M., et al.
(författare)
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Putative Cut-Points in Sarcopenia Components and Incident Adverse Health Outcomes: AnSDOCAnalysis
- 2020
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Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 68:7, s. 1429-1437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES Analyses performed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) identified cut-points in several metrics of grip strength for consideration in a definition of sarcopenia. We describe the associations between the SDOC-identified metrics of low grip strength (absolute or standardized to body size/composition); low dual-energy x-ray absorptiometry (DXA) lean mass as previously defined in the literature (appendicular lean mass [ALM]/ht(2)); and slowness (walking speed <.8 m/s) with subsequent adverse outcomes (falls, hip fractures, mobility limitation, and mortality). DESIGN Individual-level, sex-stratified pooled analysis. We calculated odds ratios (ORs) or hazard ratios (HRs) for incident falls, mobility limitation, hip fractures, and mortality. Follow-up time ranged from 1 year for falls to 8.8 +/- 2.3 years for mortality. SETTING Eight prospective observational cohort studies. PARTICIPANTS A total of 13,421 community-dwelling men and 4,828 community-dwelling women. MEASUREMENTS Grip strength by hand dynamometry, gait speed, and lean mass by DXA. RESULTS Low grip strength (absolute or standardized to body size/composition) was associated with incident outcomes, usually independently of slowness, in both men and women. ORs and HRs generally ranged from 1.2 to 3.0 for those below vs above the cut-point. DXA lean mass was not consistently associated with these outcomes. When considered together, those who had both muscle weakness by absolute grip strength (<35.5 kg in men and <20 kg in women) and slowness were consistently more likely to have a fall, hip fracture, mobility limitation, or die than those without either slowness or muscle weakness. CONCLUSION Older men and women with both muscle weakness and slowness have a higher likelihood of adverse health outcomes. These results support the inclusion of grip strength and walking speed as components in a summary definition of sarcopenia.
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- Cronholm, Felix, et al.
(författare)
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The fracture predictive ability of a musculoskeletal composite score in old men - data from the MrOs Sweden study
- 2019
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Ingår i: BMC Geriatr. - : Springer Science and Business Media LLC. - 1471-2318. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDetection of high-risk individuals for fractures are needed. This study assessed whether level of physical activity (PA) and a musculoskeletal composite score could be used as fracture predictive tools, and if the score could predict fractures better than areal bone mineral density (aBMD).MethodsMrOs Sweden is a prospective population-based observational study that at baseline included 3014 men aged 69-81years. We assessed femoral neck bone mineral content (BMC), bone area, aBMD and total body lean mass by dual energy X-ray absorptiometry, calcaneal speed of sound by quantitative ultrasound and hand grip strength by a handheld dynamometer. PA was assessed by the Physical Activity Scale for the Elderly (PASE) questionnaire. We followed the participants until the date of first fracture, death or relocation (median 9.6years). A musculoskeletal composite score was calculated as mean Z-score of the five measured traits. A Cox proportional hazards model was used to analyze the association between the musculoskeletal traits, the composite score and incident fractures (yes/no) during the follow-up period. Data are presented as hazard ratios (HR) with 95% confidence intervals (95% CI) for fracture for a+1 standard deviation (SD) change (+1 Z-score) in the various musculoskeletal traits as well as the composite score. We used a linear regression model to estimate the association between level of PA, measured as PASE-score and the different musculoskeletal traits as well as the composite score.ResultsA+1 SD higher composite score was associated with an incident fracture HR of 0.61 (0.54, 0.69), however not being superior to aBMD in fracture prediction. A+1 SD higher PASE-score was associated with both a higher composite score and lower fracture incidence (HR 0.83 (0.76, 0.90)).ConclusionsThe composite score was similar to femoral neck aBMD in predicting fractures, and also low PA predicted fractures. This highlights the need of randomized controlled trials to evaluate if PA could be used as a fracture preventive strategy.
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- Cöster, Marcus E., et al.
(författare)
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Physical function tests predict incident falls : A prospective study of 2969 men in the Swedish Osteoporotic Fractures in Men study
- 2020
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 48:4, s. 436-441
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Falls are common in the elderly population, and fall-related injuries are a major health issue. We investigated the ability of simple physical tests to predict incident falls. Methods: The Swedish Osteoporotic Fractures in Men (MrOS) study includes 3014 population-based men aged 69–81 years at the start of the study. These men performed five different physical tests at baseline: right-hand grip strength, left-hand grip strength, timed stand test, 6 m walking test (time and steps) and narrow walking test. During the first study year, we asked participants to fill out questionnaires regarding falls 4, 8 and 12 months after baseline. A total of 2969 men completed at least one questionnaire and were included in this study. We used generalised estimating equations and logarithmic regression models to estimate odds ratios for fallers and recurrent fallers (more than one fall during the one-year examination period) in each quartile of men for each physical test. Results: The proportions of fallers and recurrent fallers were higher in the lowest quartile of the physical tests than in the other three quartiles combined for all physical tests. A reduction of one standard deviation in respective physical test resulted in a 13–21% higher risk of becoming a faller and a 13–31% higher risk of becoming a recurrent faller. Conclusions: Low results on simple physical tests is a risk factor for incident falls in elderly Swedish men and may facilitate identification of high-risk individuals suitable for fall-intervention programs.
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- Danfors, Torsten, et al.
(författare)
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Epileptic seizures and survival in early disease of grade 2 gliomas
- 2009
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 16:7, s. 823-831
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeThe aims of this study were (i) to determine the correlation between seizure activity and the metabolic rate of the tumour measured by 11Cmethionine PET (MET PET) in patients with grade 2 gliomas, and (ii) to assess the prognostic impact of early seizure manifestations on patient survival.MethodsIn this retrospective review, early seizure manifestations were studied in 101 patients with supratentorial grade 2 gliomas subjected to MET PET as part of the pretreatment tumour investigation. Seizure manifestations as a variable was then used in multivariate survival analyses, together with established prognostic factors for this patient group.ResultsOf all 101 cases, 88 patients had seizures at tumour presentation. Fortyseven were seizure free at the early stage of the disease, whereas 54 had recurrent seizures. Patients with seizures at tumour presentation had a more favourable outcome before and after (P = 0.006) adjustment for conventional prognostic factors. However, for those who continued to have seizures early in the disease, the outcome was worse (P = 0.003). We found no significant correlation between MET PET and the seizure manifestations of the patients.ConclusionThe presence and termination of early seizure manifestations may be favourable prognostic factors in patients with low-grade gliomas.
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- Elsir, Tamador, et al.
(författare)
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A study of embryonic stem cell-related proteins in human astrocytomas : Identification of Nanog as a predictor of survival
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:5, s. 1123-1131
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies suggest that the regulatory networks controlling the functions of stem cells during development may be abnormally active in human cancers. An embryonic stem cell (ESC) gene signature was found to correlate with a more undifferentiated phenotype of several human cancer types including gliomas, and associated with poor prognosis in breast cancer. In the present study, we used tissue microarrays of 80 low-grade (WHO grade II) and 98 high-grade human gliomas (WHO grade III and IV) to investigate the presence of the ESC-related proteins Nanog, Klf4, Oct4, Sox2 and c-Myc by immunohistochemistry. While similar patterns of co-expressed proteins between low- and high-grade gliomas were present, we found up-regulated protein levels of Nanog, Klf4, Oct4 and Sox2 in high-grade gliomas. Survival analysis by Kaplan-Meier analysis revealed a significant shorter survival in the subgroups of low-grade astrocytomas (n=42) with high levels of Nanog protein (p=0.0067) and of Klf4 protein (p=0.0368), in high-grade astrocytomas (n=85) with high levels of Nanog (p=0.0042), Klf4 (p=0.0447), and c-Myc (p=0.0078) and in glioblastomas only (n=71) with high levels of Nanog (p=0.0422) and of c-Myc (p= 0.0256). In the multivariate model, Nanog was identified as an independent prognostic factor in the subgroups of low-grade astrocytomas (p=0.0039), high-grade astrocytomas (p=0.0124) and glioblastomas only (p=0.0544), together with established clinical variables in these tumors. These findings provide further evidence for the joint regulatory pathways of ESC-related proteins in gliomas and identify Nanog as one of the key players in determining clinical outcome of human astrocytomas.
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| 10. |
- Elsir, T., et al.
(författare)
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PROX1 is a predictor of survival for gliomas WHO grade II
- 2011
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 104:11, s. 1747-1754
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Tidskriftsartikel (refereegranskat)abstract
- Background:The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcription factor that has a critical role in the development of various organs. PROX1 has been ascribed both oncogenic and tumour suppressive functions in human cancers. We have recently shown that PROX1 may act as a diagnostic marker for high-grade gliomas. The aim of this study was to address the prognostic value of PROX1 in grade II gliomas.Methods:A total of 116 samples were evaluated for the presence of PROX1 protein. The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.Results:Higher PROX1 protein was associated with poor outcome. In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.Conclusion:PROX1 is a novel predictor of survival for grade II gliomas.
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