| 1. |
- Aad, G., et al.
(författare)
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- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :11
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Aad, G., et al.
(författare)
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- 2013
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 11. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Comparisons of Immunoassay and Mass Spectrometry Measurements of Serum Estradiol Levels and Their Influence on Clinical Association Studies in Men
- 2013
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:6
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Tidskriftsartikel (refereegranskat)abstract
- Context: Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known Objective: Our objective was to compare immunoassay and MS measurements of E2 levels in men and Design and Setting: Middle-aged and older male subjects participating in the population-based Main Outcome Measures: Immunoassay and MS measurements of serum E2 were compared and Results: Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately Conclusions: Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a
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| 12. |
- Rutter, M. K., et al.
(författare)
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Epidemiological evidence against a role for C-reactive protein causing leptin resistance
- 2013
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 168:1, s. 101-106
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Tidskriftsartikel (refereegranskat)abstract
- Objective: It has been suggested that elevated levels of C-reactive protein (CRP) might interfere with leptin signalling and contribute to leptin resistance. Our aim was to assess whether plasma levels of CRP influence leptin resistance in humans, and our hypothesis was that CRP levels would modify the cross-sectional relationships between leptin and measures of adiposity. Design and methods: We assessed four measures of adiposity: BMI, waist circumference, fat mass and body fat (%) in 2113 British Regional Heart Study (BRHS) men (mean (S.D.) age 69 (5) years), with replication in 760 (age 69 (6) years) European Male Ageing Study (EMAS) subjects. Results: In BRHS subjects, leptin correlated with CRP (Spearman's r=0.22, P<0.0001). Leptin and CRP correlated with all four measures of adiposity (r value range: 0.22-0.57, all P<0.0001). Age-adjusted mean levels for adiposity measures increased in relation to leptin levels, but CRP level did not consistently influence the beta-coefficients of the regression lines in a CRP-stratified analysis. In BRHS subjects, the BMI vs leptin relationship demonstrated a weak statistical interaction with CRP (P=0.04). We observed no similar interaction in EMAS subjects and no significant interactions with other measures of adiposity in BRHS or EMAS cohorts. Conclusion: We have shown that plasma CRP has little influence on the relationship between measures of adiposity and serum leptin levels in these middle-aged and elderly male European cohorts. This study provides epidemiological evidence against CRP having a significant role in causing leptin resistance. European Journal of Endocrinology 168 101-106
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| 13. |
- Camacho, E. M., et al.
(författare)
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Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study
- 2013
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 168:3, s. 445-455
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Health and lifestyle factors are associated with variations in serum testosterone levels in ageing men. However, it remains unclear how age-related changes in testosterone may be attenuated by lifestyle modifications. The objective was to investigate the longitudinal relationships between changes in health and lifestyle factors with changes in hormones of the reproductive endocrine axis in ageing men. Design: A longitudinal survey of 2736 community-dwelling men aged 40-79 years at baseline recruited from eight centres across Europe. Follow-up assessment occurred mean (+/- S.D.) 4.4 +/- 0.3 years later. Results: Paired testosterone results were available for 2395 men. Mean (+/- S.D.) annualised hormone changes were as follows: testosterone -0.1 +/- 0.95 nmol/l; free testosterone (FT) -3.83 +/- 16.8 pmol/l; sex hormone-binding globulin (SHBG) 0.56 +/- 2.5 nmol/l and LH 0.08 +/- 0.57 U/l. Weight loss was associated with a proportional increase, and weight gain a proportional decrease, in testosterone and SHBG. FT showed a curvilinear relationship to weight change; only those who gained or lost >= 15% of weight showed a significant change (in the same direction as testosterone). Smoking cessation was associated with a greater decline in testosterone than being a non-smoker, which was unrelated to weight change. Changes in number of comorbid conditions or physical activity were not associated with significant alterations in hypothalamic-pituitary-testicular (HPT) axis function. Conclusions: Body weight and lifestyle factors influence HPT axis function in ageing. Weight loss was associated with a rise, and weight gain a fall, in testosterone, FT and SHBG. Weight management appears to be important in maintaining circulating testosterone in ageing men, and obesity-associated changes in HPT axis hormones are reversible following weight reduction. European Journal of Endocrinology 168 445-455
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| 16. |
- Pye, S. R., et al.
(författare)
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Late-Onset Hypogonadism and Mortality in Aging Men
- 2014
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:4, s. 1357-1366
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Tidskriftsartikel (refereegranskat)abstract
- Context: Late-onset hypogonadism (LOH) has recently been defined as a syndrome in middle-aged and elderly men reporting sexual symptoms in the presence of low T. The natural history of LOH, especially its relationship to mortality, is currently unknown. Objective: The aim of this study was to clarify the associations between LOH, low T, and sexual symptoms with mortality in men. Design, Setting, and Participants: Prospective data from the European Male Aging Study (EMAS) on 2599 community-dwelling men aged 40-79 years in eight European countries was used for this study. Main Outcome Measure(s): All-cause, cardiovascular, and cancer-related mortality was measured. Results: One hundred forty-seven men died during a median follow-up of 4.3 years. Fifty-five men (2.1%) were identified as having LOH (31 moderate and 24 severe). After adjusting for age, center, body mass index (BMI), current smoking, and poor general health, compared with men without LOH, those with severe LOH had a 5-fold [hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.7, 11.4] higher risk of all-cause mortality. Compared with eugonadal men, the multivariable-adjusted risk of mortality was 2-fold higher in those with T less than 8 nmol/L (irrespective of symptoms; HR 2.3; 95% CI 1.2, 4.2) and 3-fold higher in those with three sexual symptoms (irrespective of serum T; compared with asymptomatic men; HR 3.2; 95% CI 1.8, 5.8). Similar risks were observed for cardiovascular mortality. Conclusions: Severe LOH is associated with substantially higher risks of all-cause and cardiovascular mortality, to which both the level of T and the presence of sexual symptoms contribute independently. Detecting low T in men presenting with sexual symptoms offers an opportunity to identify a small subgroup of aging men at particularly high risk of dying.
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| 17. |
- Vanderschueren, D., et al.
(författare)
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Gonadal sex steroid status and bone health in middle-aged and elderly European men
- 2010
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 21:8, s. 1331-1339
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Tidskriftsartikel (refereegranskat)abstract
- The influence of sex steroids on calcaneal quantitative ultrasound (QUS) parameters was assessed in a population sample of middle-aged and elderly European men. Higher free and total E-2 though not testosterone, were independently associated with higher QUS parameters. The aim of this study was to investigate the association between QUS parameters and sex steroids in middle-aged and elderly European men. Three thousand one hundred forty-one men aged between 40 and 79 years were recruited from eight European centres for participation in a study of male ageing: the European Male Ageing Study. Subjects were invited by letter to attend for an interviewer-administered questionnaire, blood sample and QUS of the calcaneus (Hologic-SAHARA). Blood was assessed for sex steroids including oestradiol (E-2), testosterone (T), free and bio-available E-2 and T and sex hormone binding globulin (SHBG). Serum total T was not associated with any of the QUS parameters. Free T and both free and total E-2 were positively related to all QUS readings, while SHBG concentrations were negatively associated. These relationships were observed in both older and younger (< 60 years) men. In a multivariate model, after adjustment for age, centre, height, weight, physical activity levels and smoking, free E-2 and SHBG, though not free T, remained independently associated with the QUS parameters. After further adjustment for IGF-1, however, the association with SHBG became non-significant. Higher free and total E-2 are associated with bone health not only among the elderly but also middle-aged European men.
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| 18. |
- Ward, K. A., et al.
(författare)
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Influence of age and sex steroids on bone density and geometry in middle-aged and elderly European men
- 2011
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 22:5, s. 1513-1523
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Tidskriftsartikel (refereegranskat)abstract
- The influence of age and sex steroids on bone density and geometry of the radius was examined in two European Caucasian populations. Age-related change in bone density and geometry was observed. In older men, bioavailable oestradiol may play a role in the maintenance of cortical and trabecular bone mineral density (BMD). To examine the effect of age and sex steroids on bone density and geometry of the radius in two European Caucasian populations. European Caucasian men aged 40-79 years were recruited from population registers in two centres: Manchester (UK) and Leuven (Belgium), for participation in the European Male Ageing Study. Total testosterone (T) and oestradiol (E-2) were measured by mass spectrometry and the free and bioavailable fractions calculated. Peripheral quantitative computed tomography was used to scan the radius at distal (4%) and midshaft (50%) sites. Three hundred thirty-nine men from Manchester and 389 from Leuven, mean ages 60.2 and 60.0 years, respectively, participated. At the 50% radius site, there was a significant decrease with age in cortical BMD, bone mineral content (BMC), cortical thickness, and muscle area, whilst medullary area increased. At the 4% radius site, trabecular and total volumetric BMD declined with age. Increasing bioavailable E-2 (bioE(2)) was associated with increased cortical BMD (50% radius site) and trabecular BMD (4% radius site) in Leuven, but not Manchester, men. This effect was predominantly in those aged 60 years and over. In older Leuven men, bioavailable testosterone (Bio T) was linked with increased cortical BMC, muscle area and SSI (50% radius site) and total area (4% radius site). There is age-related change in bone density and geometry at the midshaft radius in middle-aged and elderly European men. In older men bioE(2) may maintain cortical and trabecular BMD. BioT may influence bone health through associations with muscle mass and bone area.
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| 19. |
- Corona, G, et al.
(författare)
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Thyroid hormones and male sexual function.
- 2012
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Ingår i: International Journal of Andrology. - : Wiley. - 1365-2605 .- 0105-6263. ; 35:5, s. 668-679
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Tidskriftsartikel (refereegranskat)abstract
- The role of thyroid hormones in the control of erectile functioning has been only superficially investigated. The aim of the present study was to investigate the association between thyroid and erectile function in two different cohorts of subjects. The first one derives from the European Male Ageing Study (EMAS study), a multicentre survey performed on a sample of 3369 community-dwelling men aged 40-79 years (mean 60 ± 11 years). The second cohort is a consecutive series of 3203 heterosexual male patients (mean age 51.8 ± 13.0 years) attending our Andrology and Sexual Medicine Outpatient Clinic for sexual dysfunction at the University of Florence (UNIFI study). In the EMAS study all subjects were tested for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Similarly, TSH levels were checked in all patients in the UNIFI study, while FT4 only when TSH resulted outside the reference range. Overt primary hyperthyroidism (reduced TSH and elevated FT4, according to the reference range) was found in 0.3 and 0.2% of EMAS and UNIFI study respectively. In both study cohorts, suppressed TSH levels were associated with erectile dysfunction (ED). Overt hyperthyroidism was associated with an increased risk of severe erectile dysfunction (ED, hazard ratio = 14 and 16 in the EMAS and UNIFI study, respectively; both p < 0.05), after adjusting for confounding factors. These associations were confirmed in nested case-control analyses, comparing subjects with overt hyperthyroidism to age, BMI, smoking status and testosterone-matched controls. Conversely, no association between primary hypothyroidism and ED was observed. In conclusion, erectile function should be evaluated in all individuals with hyperthyroidism. Conversely, assessment of thyroid function cannot be recommended as routine practice in all ED patients.
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| 20. |
- Lee, D. M., et al.
(författare)
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Chronic widespread pain is associated with slower cognitive processing speed in middle-aged and older European men
- 2010
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 151:1, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- Evidence from clinic-based studies suggests that the fibromyalgia syndrome (FMS) is associated with impairment in cognitive function though the mechanism is unclear. The aim of this analysis was to determine whether there is a similar association between chronic widespread pain (CWP), a cardinal feature of FMS, and impaired cognition in a community setting. Men (n = 3369, 40-79 years) were recruited from population registers in eight centres for participation in the European Male Ageing Study (EMAS). Subjects completed a pain questionnaire and pain manikin, with the presence of CWP defined using the American College of Rheumatology criteria. The cognitive functions measured were: visuospatial-constructional ability and visual memory (Rey-Osterrieth Complex Figure [ROCF]); visual recognition (Camden Topographical Recognition Memory test [CTRM]); and psychomotor processing speed (Digit-Symbol Substitution test [DSST]). We restricted our analysis to those subjects reporting pain that satisfied the criteria for CWP and those who were pain free. Of these 1539 men [mean (SD) age 60 (11) years], 266 had CWP. All cognitive test scores declined cross-sectionally with age (P < 0.05). In age-adjusted linear regressions men with CWP had a lower DSST score (beta = -2.4, P < 0.001) compared to pain free subjects. After adjustment for lifestyle and health factors the association between pain status and the DSST score was attenuated but remained significant (beta = -1.02, P = 0.04). There was no association between CWP and the ROCF-copy, ROCF-recall or CTRM scores. CWP is associated with slower psychomotor processing speed among community-dwelling European men. Prospective studies are required to confirm this observation and explore possible mechanisms for the association. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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| 21. |
- Moayyeri, Alireza, et al.
(författare)
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Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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| 22. |
- Reed, R. A., et al.
(författare)
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Anthology of the Development of Radiation Transport Tools as Applied to Single Event Effects
- 2013
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Ingår i: IEEE Transactions on Nuclear Science. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9499 .- 1558-1578. ; 60:3, s. 1876-1911
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Tidskriftsartikel (refereegranskat)abstract
- This anthology contains contributions from eleven different groups, each developing and/or applying Monte Carlo-based radiation transport tools to simulate a variety of effects that result from energy transferred to a semiconductor material by a single particle event. The topics span from basic mechanisms for single-particle induced failures to applied tasks like developing websites to predict on-orbit single event failure rates using Monte Carlo radiation transport tools.
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| 23. |
- Al-Hamadany, R., et al.
(författare)
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Impact of tensile strain on the oxygen vacancy migration in SrTiO3 : Density functional theory calculations
- 2013
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 113:22
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Tidskriftsartikel (refereegranskat)abstract
- Strontium titanate is a promising dielectric material for device applications including capacitors and gate dielectrics. However, oxygen vacancies, which are inevitable donor defects mobile under bias at room temperature, lead to undesirable leakage current in SrTiO3 thin films. Epitaxially grown SrTiO3 on lattice mismatched substrates leads to strained SrTiO3, inducing structural phase transitions from a cubosymmetric non-ferroelectric geometry to tetragonal and orthorhombic structures, depending upon the sign of the strain. In this study, density functional calculations have been performed to determine the impact of isotropic biaxial tensile strain in a (001) plane upon the phase of SrTiO3 and the activation energy for the migration of oxygen vacancies in such strained SrTiO3. The phase transition of the host material yields anisotropy in oxygen vacancy diffusion for diffusion within and between planes parallel to the strain. We found a general reduction in the barrier for diffusion within and normal to the plane of tensile strain. The inter-plane diffusion barrier reduces up to 25% at high values of strain. The variation in the barrier corresponding to in-plane diffusion is smaller in comparison to inter-plane diffusion. Finally, we reflect upon how the interplay between lattice strain with native defects plays a crucial role in the conduction mechanism of thin film, strained SrTiO3
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| 24. |
- Alba, M., et al.
(författare)
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Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function
- 2013
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 15:12, s. 1101-1110
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe effects of sitagliptin and pioglitazone, alone and in combination, on - and -cell function were assessed in patients with type 2 diabetes. MethodsFollowing a 6-week diet/exercise period, 211 patients with HbA1c of 6.5-9.0% and fasting plasma glucose of 7.2-14.4mmol/l were randomized (1:1:1:1) to sitagliptin, pioglitazone, sitagliptin+pioglitazone or placebo. At baseline and after 12weeks, patients were given a mixed meal followed by frequent blood sampling for measurements of glucose, insulin, C-peptide and glucagon. ResultsAfter 12weeks, 5-h glucose total area under the curve (AUC) decreased in all active treatments versus placebo; reduction with sitagliptin+pioglitazone was greater versus either monotherapy. The 5-h insulin total AUC increased with sitagliptin versus all other treatments and increased with sitagliptin+pioglitazone versus pioglitazone. The 3-h glucagon AUC decreased with sitagliptin versus placebo and decreased with sitagliptin+pioglitazone versus pioglitazone or placebo. (s), a measure of dynamic -cell responsiveness to above-basal glucose concentrations, increased with either monotherapy versus placebo and increased with sitagliptin+pioglitazone versus either monotherapy. The insulin sensitivity index (ISI), a composite index of insulin sensitivity, improved with pioglitazone and sitagliptin+pioglitazone versus placebo. The disposition index, a measure of the relationship between -cell function and insulin sensitivity, improved with all active treatments versus placebo. ConclusionsSitagliptin and pioglitazone enhanced -cell function (increasing postmeal phi(s)), and sitagliptin improved -cell function (decreasing postmeal glucagon) after 12weeks in patients with type 2 diabetes. Through these complementary mechanisms of action, the combination of sitagliptin and pioglitazone reduced postmeal glucose more than either treatment alone.
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| 25. |
- Baldwin, DS, et al.
(författare)
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Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology
- 2014
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 28:5, s. 403-439
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Tidskriftsartikel (refereegranskat)abstract
- This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.
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| 26. |
- Basabe-Desmonts, L., et al.
(författare)
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Single-Step Separation of Platelets from Whole Blood Coupled with Digital Quantification by Interfacial Platelet Cytometry (iPC)
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:18, s. 14700-14706
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Tidskriftsartikel (refereegranskat)abstract
- We report the efficient single-step separation of individual platelets from unprocessed whole blood, enabling digital quantification of platelet function using interfacial platelet cytometry (iPC) on a chip iPC is accomplished by the precision micropatterning of platelet-specific protein surfaces on solid substrates By separating platelets From whole blood using specific binding to protein spots of a defined size. iPC implements a simple incubate-and-rinse approach, without sample preparation, that enables (I) the study of platelets in the physiological situation of interaction with a protein surface, (2) the choice of the number of platelets bound on each protein spot, from one to many, (3) control of the platelet platelet distance, including the possibility to study noninteracting single platelets, (4) digital quantification (counting) of platelet adhesion to selected protein matrices, enabling statistical characterization of platelet subpopuladons from meaningfully large numbers of single platelets, (5) the study of platelet receptor expression and spatial distribution, and (6) a detailed study of the morphology of isolated single platelets at activation levels that can be manipulated To date, we have demonstrated 1-4 of the above list Platelets were separated from whole blood using tPC with fibrinogen, von Willebrand factor (VWF), and anti-CD42b antibody printed "spots" ranging from a fraction of one to several platelet diameters (2-24 full) The number of platelets captured per spot depends strongly on the protein matrix and the surface area of the spot, together with the platelet volume, morphology, and activation state Blood samples from healthy donors, a May-Hegglin-anomaly patient, and a Glanzmann's Thrombasthenia patient were analyzed via iPC to confirm the specificity of the interaction between protein matrices and platelets For example, the results indicate that platelets interact with fibrinogen spots only through the fibrinogen receptor (aIlb beta 3) and, relevant to diagnostic applications, platelet adhesion correlates strongly with normal versus abnormal platelet function A critical function of platelets is to adhere to regions of damage on blood vessel walls, in contrast to conventional flow cytometry, where platelets are suspended in solution, iPC enables physiologically relevant platelet bioassays based on platelet/protein-matrix inter actions on surfaces. This technology should be inexpensive to implement in clinical assay format, is readily integrable into fluidic microdevices, and paves the way for high-throughput platelet assays from microliter volumes of whole blood.
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| 27. |
- Bentmar Holgersson, Magdalena, et al.
(författare)
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Androgen receptor polymorphism dependent variation in prostate specific antigen concentrations of European men.
- 2014
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 23:10, s. 2048-2056
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Tidskriftsartikel (refereegranskat)abstract
- Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds of 3 or 4 ng/mL in men without PCa. Methods Men without PCa history (n=1744) were selected from the European Male Ageing Study (EMAS) cohort of 40-80 year old men from 8 different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR-variants (CAG repeat-length and/or SNP genotype) were associated with having serum PSA concentrations above 3 or 4 ng/mL, which often are set as cut-off concentrations for further investigation of PCa. Results Carriers of the SNP rs1204038 A-allele (16% of the men) were more likely to have PSA>3 and 4 ng/mL (OR; 95%CI 1.65; 1.13-2.40 and 1.87; 1.18-2.96, respectively) than G-allele carriers. They also had shorter CAG-repeats (median 20 vs. 23, p<0.0005), but CAG repeat length per se did not affect the PSA concentrations. Conclusion The A-allele of the SNP rs1204038 gives a 65% higher risk of having PSA above 3 ng/mL than the G-allele in men without PCa, and thereby an increased risk of being referred for further examination on suspicion of PCa. Impact Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.
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| 28. |
- Boonen, Steven, et al.
(författare)
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Influence of bone remodelling rate on quantitative ultrasound parameters at the calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European men: the European Male Ageing Study (EMAS)
- 2011
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 165:6, s. 977-986
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men. Design: A cross-sectional population-based survey. Methods: Men aged 40-79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (beta C-terminal cross-linked telopeptide (beta-cTX)), total testosterone, total oestradiol (E-2), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dualenergy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres. Results: A total of 3120, mean age 59.9 years (S.D. = 11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E-2 were negatively associated with beta-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both beta-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine. Conclusions: E-2, SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health.
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| 29. |
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| 30. |
- Corona, Giovanni, et al.
(författare)
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Age-Related Changes in General and Sexual Health in Middle-Aged and Older Men: Results from the European Male Ageing Study (EMAS)
- 2010
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Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 7:4, s. 1362-1380
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Limited information is available concerning the general and sexual health status of European men. Aim. To investigate the age-related changes in general and sexual health in middle-aged and older men from different countries of the European Union. Methods. This is a cross-sectional multicenter survey performed on a sample of 3,369 community-dwelling men aged 40-79 years old (mean 60 +/- 11 years). Subjects were randomly selected from eight European centers including centers from nontransitional (Florence [Italy], Leuven [Belgium], Malmo [Sweden], Manchester [United Kingdom], Santiago de Compostela [Spain]) and transitional countries (Lodz [Poland], Szeged [Hungary], Tartu [Estonia]). Main Outcome Measures. Different parameters were evaluated including the Beck's Depression Inventory for the quantification of depressive symptoms, the Short Form-36 Health Survey for the assessment of the quality of life (QoL), the International Prostate Symptom Score for the evaluation of lower urinary tract symptoms, and the European Male Ageing Study sexual function questionnaire for the study of sexual function. Results. More than 50% of subjects reported the presence of one or more common morbidities. Overall, hypertension (29%), obesity (24%), and heart diseases (16%) were the most prevalent conditions. Around 30% of men reported erectile dysfunction (ED) and 6% reported severe orgasmic impairment, both of which were closely associated with age and concomitant morbidities. Only 38% of men reporting ED were concerned about it. Furthermore, concern about ED increased with age, peaking in the 50-59 years age band, but decreased thereafter. Men in transitional countries reported a higher prevalence of morbidities and impairment of sexual function as well as a lower QoL. Conclusion. Sexual health declined while concomitant morbidities increased in European men as a function of age. The burden of general and sexual health is higher in transitional countries, emphasizing the need to develop more effective strategies to promote healthy aging for men in these countries. Corona G, Lee DM, Forti G, O'Connor DB, Maggi M, O'Neill TW, Pendleton N, Bartfai G, Boonen S, Casanueva FF, Finn JD, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean MEJ, Punab M, Silman AJ, Vanderschueren D, Wu FCW, and EMAS Study Group. Age-related changes in general and sexual health in middle-aged and older men: Results from the European Male Ageing Study (EMAS). J Sex Med 2010;7:1362-1380.
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| 31. |
- Han, Thang S., et al.
(författare)
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Impaired quality of life and sexual function in overweight and obese men: the European Male Ageing Study
- 2011
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 164:6, s. 1003-1011
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few published data link overweight and obesity with measures of quality of life (QoL) including sexual health in men. Objective: To assess the association of overweight/obesity with impairment of physical and psychological QoL and sexual functions in men. Design and setting: Cross-sectional, multicentre survey of 3369 community-dwelling men aged 40-79 (mean +/- S.D., 60 +/- 11) years randomly selected from eight European centres. Outcomes: Adiposity was assessed by body mass index (BMI) and waist circumference (WC), QoL and functional impairments by physical and psychological function domains of the Short Form-36 questionnaire, Beck's Depression Inventory and the European Male Ageing Study sexual function questionnaire. Results: Complete data on sexual activities and erectile function were available in 2734 (92%) and 3193 (95%) of the participants respectively. From the population studied, 814 men were obese (BMI >= 30 kg/m(2)) and 1171 had WC >= 102 cm, 25% of all men were unable to do vigorous activity and 2-13% reported depressive symptoms. Symptoms of sexual dysfunction ranged between 22% (low sexual desire) and 40% (infrequent morning erections) of the participants. Among obese men with both BMI >= 30 kg/m(2) and WC >= 102 cm, at least one symptom of impaired physical, psychological and sexual function was reported by 41, 43 and 73% of the participants respectively. Compared with the reference group of non-obese men (BMI < 30 kg/m(2) and WC < 102cm), men with BMI >= 30 kg/m(2) and WC >= 102 cm more frequently reported at least one symptom of impaired physical function (odds ratio (OR)=2.67; confidence interval (CI): 2.07-3.45, P < 0.001), impaired psychological function (OR=1.48; CI: 1.14-1.90, P < 0.01) and impaired sexual function (OR=1.45; CI: 1.14-1.85, P < 0.01). These functional impairments were also more prevalent in men who had WC >= 102 cm even with BMI < 30 kg/m(2), but those with BMI >= 30 kg/m(2) and WC < 102 cm generally did not suffer from increased impaired physical or sexual health. Men with high BMI and WC were at even greater likelihood of having a composite of two or more or three or more symptoms compared with those with normal BMI and WC. Conclusions: Men with high WC, including those who are 'non-obese' with BMI < 30 kg/m(2), have poor QoL with symptoms of impaired physical, psychological and sexual functions. Health promotion to improve QoL should focus on prevention of obesity and central fat accumulation.
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| 32. |
- Holliday, Kate L., et al.
(författare)
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The ESR1 (6q25) Locus Is Associated with Calcaneal Ultrasound Parameters and Radial Volumetric Bone Mineral Density in European Men
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. Methods: Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. Results: 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. Conclusions: Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.
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| 33. |
- Huhtaniemi, Ilpo T., et al.
(författare)
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Comparison of serum testosterone and estradiol measurements in 3174 European men using platform immunoassay and mass spectrometry; relevance for the diagnostics in aging men
- 2012
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 166:6, s. 983-991
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Tidskriftsartikel (refereegranskat)abstract
- Background: The limitations of serum testosterone and estradiol (E-2) measurements using nonextraction platform immunoassays (IAs) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated, but directly comparative data on the two methods are scarce. Methods: We compared serum testosterone and E-2 measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects from the European Male Aging Study (n = 3174; age 40-79 years), peripheral serum testosterone and E-2 were analyzed using established commercial platform IAs (Roche Diagnostics E170) and in-house GC MS methods. Results: Over a broad concentration range, serum testosterone concentration measured by IA and MS showed high correlation (R=0.93, P<0.001), which was less robust in the hypogonadal range (<11 nmol/l; R=0.72, P<0.001). The IA/MS correlation was weaker in E-2 measurements (R=0.32, P<0.001, at E-2 <40.8 pmol/l, and R=0.74, P<0.001, at E-2 >40.8 pmol/l). Using MS as the comparator method, IA ascertained low testosterone compatible with hypogonadism (<11 nmol/l), with 75% sensitivity and 96.3% specificity. The same parameters with IA for the detection of low E-2 (<40.7 pmol/l) were 13.3 and 99.3%, and for high E-2 (>120 pmol/l) 88.4 and 88.6%. Conclusion: A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis of male hypogonadism. The IA used for E-2 measurements showed poor correlation with MS and may only be suitable for the detection of high E-2 in men.
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| 34. |
- Huhtaniemi, Ilpo T, et al.
(författare)
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Effect of Polymorphisms in Selected Genes Involved in Pituitary-Testicular Function on Reproductive Hormones and Phenotype in Aging Men.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 1898-1908
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Tidskriftsartikel (refereegranskat)abstract
- Context: Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men. Objective: We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status. Design and Setting: Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men. Participants: A total of 2748 men, aged 40-79 (mean +/- SD, 60.2 + 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5alpha-reductase type II (SRD5A2), 17alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR). Main Outcome Measures: We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. Results: Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition). Conclusion: In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.
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| 35. |
- Lee, David M., et al.
(författare)
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Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men
- 2014
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 1468-2834 .- 0002-0729. ; 43:4, s. 528-535
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Tidskriftsartikel (refereegranskat)abstract
- Setting: prospective cohort analysis within the European Male Ageing Study. Participants: 2,816 community-dwelling men aged 40-79 years at baseline. Methods: Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)(2)D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models. Results: a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)(2)D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D < 25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04). Conclusion: lower 25(OH)D and 1,25(OH)(2)D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here.
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| 36. |
- Lee, David M., et al.
(författare)
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Association of hypogonadism with vitamin D status: the European Male Ageing Study
- 2012
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 166:1, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Interrelationships between hormones of the hypothalamic-pituitary-testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men. Design and methods: Cross-sectional survey of 3369 community-dwelling men aged 40-79 years in eight European centres. Testosterone (T), oestradiol (E(2)) and dihydrotestosterone were measured by gas chromatography-mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with vitamin D using multinomial logistic regression. Results: In univariate analyses, free T levels were lower (P=0.02) and E(2) and LH levels were higher (P<0.05) in men with vitamin D deficiency (25(OH)D <50 nmol/l). 25(OH)D was positively associated with total and free T and negatively with E(2) and LH in age- and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, vitamin D deficiency was significantly associated with compensated (relative risk ratio (RRR)=1.52, P=0.03) and secondary hypogonadism (RRR=1.16, P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001). Conclusions: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.
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| 37. |
- Lee, David M, et al.
(författare)
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Cohort Profile: The European Male Ageing Study.
- 2013
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 42:2, s. 391-401
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Tidskriftsartikel (refereegranskat)abstract
- The European Male Ageing Study (EMAS) was designed to examine the hypothesis that inter-individual and regional variability in symptomatic dysfunctions, alterations in body composition and health outcomes in ageing men can be explained by different rates of decline in anabolic hormones, the most important of which being testosterone. Between 2003 and 2005, 3369 community-dwelling men, aged between 40 and 79 years, were recruited from population-based registers in eight European centres to participate in the baseline survey, with follow-up investigations performed a median of 4.3 years later. Largely, identical questionnaire instruments and clinical investigations were used in both phases to capture contemporaneous data on general health (including cardiovascular diseases and chronic conditions), physical and cognitive functioning, mental health, sexual function, quality of life, bone health, chronic pain, disease biomarkers, hormones (sex hormones and metabolic hormones) and genetic polymorphisms. EMAS actively encourages new collaborations, data sharing for validation studies and participation in genetic study consortia. Potential collaborators should contact the principal investigator (F.C.W.W.) in the first instance.
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| 38. |
- Lee, David M., et al.
(författare)
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Endogenous hormones, androgen receptor CAG repeat length and fluid cognition in middle-aged and older men: results from the European Male Ageing Study
- 2010
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 162:6, s. 1155-1164
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Data remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men. Design: Community-based, cross-sectional study of 3369 men aged 40-79 years. Methods: Cognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE2) and 5 alpha-dihydrotestosterone were measured by gas chromatography-mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE2 were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping. Results: Total testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (beta=-0.011, P=0.02), although this was driven by subjects with DHEAS levels > 10 mu mol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (beta=-0.007, P=0.06), nor any interaction effect between CAG repeat length and hormones. Conclusion: Our results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether 'high' DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.
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| 39. |
- Lee, David M., et al.
(författare)
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Frailty and Sexual Health in Older European Men
- 2013
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Ingår i: Journals of Gerontology - Series B Psychological Sciences and Social Sciences. - : Oxford University Press (OUP). - 1079-5014. ; 68:7, s. 837-844
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Tidskriftsartikel (refereegranskat)abstract
- Background. There has been little research on how late-life frailty interrelates with sexual health. Our objective was to examine the association of frailty with sexual functioning and satisfaction among older men. Methods. The study population consisted of 1,504 men aged 60 to 79 years, participating in the European Male Aging Study. Self-report questionnaires measured overall sexual functioning, sexual function related distress, and erectile dysfunction. Frailty status was defined using a phenotype (FP) or index (FI). Associations between frailty and sexual function were explored using regression models. Results. Based on the frailty phenotype, 5% of men were classified as frail, and the mean frailty index was 0.18 (SD = 0.12). Frailty was associated with decreasing overall sexual functioning and increasing sexual function related distress in multiple linear regressions adjusted for age, smoking, alcohol consumption, living arrangements, comorbidities, and depression. Frailty was also associated with an increased odds of erectile dysfunction after adjustment for the same confounders: odds ratio = 1.99 (95% confidence interval = 1.14, 3.48) and 4.08 (95% confidence interval = 2.63, 6.36) for frailty phenotype and frailty index, respectively. Conclusions. Frailty was associated with impaired overall sexual functioning, sexual function related distress, and erectile dysfunction. Individuals assessed for frailty-related deficits may also benefit from an appraisal of sexual health as an important aspect of well-being and quality of life.
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| 40. |
- Lee, David M., et al.
(författare)
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Lower vitamin D levels are associated with depression among community-dwelling European men
- 2011
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 25:10, s. 1320-1328
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Tidskriftsartikel (refereegranskat)abstract
- Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH) Levels have been linked with depressive symptoms among adults in various clinical settings. Data in generally healthy, community-dwelling individuals remain inconclusive. We investigated whether depression was associated with 25(OH)D and/or PTH in a sample of middle-aged and older men (n = 3369; mean age 60 +/- 11) participating in the European Male Ageing Study, and whether any associations were explained by lifestyle and health factors. The Beck Depression Inventory-II (BDI-II) was used to screen for depression, and serum 25(OH)D and PTH levels measured by radioimmunoassay. Univariate analysis revealed that 25(OH)D levels were lower (p < 0.001) and PTH higher (p = 0.004) in people with depression. In age- and centre-adjusted linear regressions a higher BDI-II score was significantly associated with tower levels of 25(OH)D (p = 0.004). After adjustment for lifestyle and health factors this relationship was attenuated but remained significant (p = 0.01). Using multivariable logistic regression the odds for depression increased approximately 70% across decreasing 25(OH)D quartiles (p(trend) = 0.04). There was no independent association between PIN and depression in any of the muttivariable regressions. Our results reveal an inverse association between 25(OH)D levels and depression, largely independent of several lifestyle and health factors. Further studies are required to determine whether higher levels of vitamin D have an antidepressant effect in older adults.
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| 41. |
- McBeth, John, et al.
(författare)
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Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the European Male Ageing Study
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:8, s. 1448-1452
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A study was undertaken to test the hypothesis that musculoskeletal pain is associated with low vitamin D levels but the relationship is explained by physical inactivity and/or other putative confounding factors. Methods Men aged 40-79 years completed a postal questionnaire including a pain assessment and attended a clinical assessment (lifestyle questionnaire, physical performance tests, 25-hydroxyvitamin D3 (25-(OH) D) levels from fasting blood sample). Subjects were classified according to 25-(OH) D levels as 'normal' (>= 15 ng/ml) or 'low' (<15 ng/ml). The relationship between pain status and 25-(OH) D levels was assessed using logistic regression. Results are expressed as ORs and 95% CIs. Results 3075 men of mean (SD) age 60 (11) years were included in the analysis. 1262 (41.0%) subjects were pain-free, 1550 (50.4%) reported 'other pain' that did not satisfy criteria for chronic widespread pain (CWP) and 263 (8.6%) reported CWP. Compared with patients who were pain-free, those with 'other pain' and CWP had lower 25-(OH) D levels (n = 239 (18.9%), n = 361 (23.3) and n = 67 (24.1%), respectively, p < 0.05). After adjusting for age, having 'other pain' was associated with a 30% increase in the odds of having low 25-(OH) D while CWP was associated with a 50% increase. These relationships persisted after adjusting for physical activity levels. Adjusting for additional lifestyle factors (body mass index, smoking and alcohol use) and depression attenuated these relationships, although pain remained moderately associated with increased odds of 20% of having low vitamin D levels. Conclusions These findings have implications at a population level for the long-term health of individuals with musculoskeletal pain.
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| 42. |
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| 43. |
- O'Connor, Daryl B, et al.
(författare)
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The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men.
- 2011
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96, s. 1577-1587
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Tidskriftsartikel (refereegranskat)abstract
- Context: Limited data are available exploring the associations between sex hormones, multiple domains of sexual functioning, and sexual function-related distress in nonpatient samples in Europe. Objectives: The aim of the study was to investigate the relationships between serum testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) and sexual function in a multicenter population-based study of aging in men. Design: Using stratified random sampling, 2838 men aged 40-79 yr completed the European Male Ageing Study-Sexual Function Questionnaire and provided a blood sample for hormone measurements. T, E2, and DHT were measured using gas chromatography-mass spectrometry. Setting: We conducted a community-based population survey in eight European centers. Main Outcome Measures: Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured. Results: Total and free T, but not E2 or DHT, was associated with overall sexual function in middle-aged and older men. E2 was the only hormone associated with sexual function-related distress such that higher levels were related to greater distress. Free T levels were associated with masturbation frequency and erectile dysfunction in the fully adjusted models, such that higher T was associated with less dysfunction and greater frequency. Moreover, there was a T threshold for the relationship between total T, sexual function, and erectile dysfunction. At T concentrations of 8 nmol/liter or less, T was associated with worse sexual functioning, whereas at T levels over 8 nmol/liter, the relationship came to a plateau. Conclusions: These findings suggest that different hormonal mechanisms may regulate sexual functioning (T) vs. the psychological aspects (E2) of male sexual behavior. Moreover, there was a T threshold for overall sexual function such that at levels greater than 8 nmol/liter the relationship between T and sexual function did not become stronger.
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| 44. |
- Pye, Stephen R., et al.
(författare)
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Influence of Insulin-Like Growth Factor Binding Protein (IGFBP)-1 and IGFBP-3 on Bone Health: Results from the European Male Ageing Study
- 2011
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 88:6, s. 503-510
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine the influence of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3, and IGF-I on calcaneal ultrasound parameters in middle-aged and elderly European men. Men aged 40-79 years were recruited from population registers for participation in the European Male Ageing Study (EMAS). Subjects were invited by letter to complete a postal questionnaire and to attend for an interviewer-assisted questionnaire, quantitative ultrasound (QUS) of the calcaneus, and a fasting blood sample from which serum levels of IGFBP-1, IGFBP-3, IGF-I, estradiol (E-2), and SHBG were assayed. The questionnaires included the Physical Activity Scale for the Elderly (PASE) and questions about smoking and alcohol consumption. Estimated bone mineral density (eBMD) was derived as a function of the QUS parameters speed of sound and broadband ultrasound attenuation. Height and weight were measured in all subjects. 3057 men, mean age 59.7 years (standard deviation 11.0) were included in the analysis. After adjusting for age, center, and BMI, higher levels of IGFBP-1 were associated with lower eBMD. Higher levels of both IGFBP-3 and IGF-I were associated with higher eBMD. After further adjustment for PASE score, current smoking, alcohol consumption, free E-2, and SHBG, IGFBP-3 and IGF-I, though not IGFBP-1, remained significantly associated with eBMD. IGFBP-1 was associated with bone health, though the effect could be explained by other factors. IGFBP-3 and IGF-I were independent determinants of bone health in middle-aged and elderly European men.
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| 45. |
- Pye, Stephen R., et al.
(författare)
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Influence of Lifestyle Factors on Quantitative Heel Ultrasound Measurements in Middle-Aged and Elderly Men
- 2010
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 86:3, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- We examined the distribution of quantitative heel ultrasound (QUS) parameters in population samples of European men and looked at the influence of lifestyle factors on the occurrence of these parameters. Men aged between 40 and 79 years were recruited from eight European centers and invited to attend for an interviewer-assisted questionnaire, assessment of physical performance, and quantitative ultrasound (QUS) of the calcaneus (Hologic; Sahara). The relationships between QUS parameters and lifestyle variables were assessed using linear regression with adjustments for age, center, and weight. Three thousand two hundred fifty-eight men, mean age 60.0 years, were included in the analysis. A higher PASE score (upper vs. lower tertile) was associated with a higher BUA (beta coefficient = 2.44 dB/Mhz), SOS (beta = 6.83 m/s), and QUI (beta = 3.87). Compared to those who were inactive, those who walked or cycled more than an hour per day had a higher BUA (beta = 3.71 dB/Mhz), SOS (beta = 6.97 m/s), and QUI (beta = 4.50). A longer time to walk 50 ft was linked with a lower BUA (beta = -0.62 dB/Mhz), SOS (beta = -1.06 m/s), and QUI (beta = -0.69). Smoking was associated with a reduction in BUA, SOS, and QUI. There was a U-shaped association with frequency of alcohol consumption. Modification of lifestyle, including increasing physical activity and stopping smoking, may help optimize bone strength and reduce the risk of fracture in middle-aged and elderly European men.
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| 46. |
- Ravindrarajah, Rathi, et al.
(författare)
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The ability of three different models of frailty to predict all-cause mortality: Results from the European Male Aging Study (EMAS)
- 2013
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Ingår i: Archives of Gerontology and Geriatrics. - : Elsevier BV. - 1872-6976 .- 0167-4943. ; 57:3, s. 360-368
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have directly compared the ability of the most commonly used models of frailty to predict mortality among community-dwelling individuals. Here, we used a frailty index (FI), frailty phenotype (FP), and FRAIL scale (FS) to predict mortality in the EMAS. Participants were aged 40-79 years (n = 2929) at baseline and 6.6% (n = 193) died over a median 4.3 years of follow-up. The FI was generated from 39 deficits, including self-reported health, morbidities, functional performance and psychological assessments. The FP and FS consisted of five phenotypic criteria and both categorized individuals as robust when they had 0 criteria, prefrail as 1-2 criteria and frail as 3+ criteria. The mean FI increased linearly with age (r(2) = 0.21) and in Cox regression models adjusted for age, center, smoking and partner status the hazard ratio (HR) for death for each unit increase of the FI was 1.49. Men who were prefrail or frail by either the FP or FS definitions, had a significantly increased risk of death compared to their robust counterparts. Compared to robust men, those who were FP frail at baseline had a HR for death of 3.84, while those who were FS frail had a HR of 3.87. All three frailty models significantly predicted future mortality among community-dwelling, middle-aged and older European men after adjusting for potential confounders. Our data suggest that the choice of frailty model may not be of paramount importance when predicting future risk of death, enabling flexibility in the approach used. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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| 47. |
- Roshandel, Delnaz, et al.
(författare)
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A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study
- 2011
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: A number of single nucleotide polymorphisms (SNPs) have been associated with broadband ultrasound attenuation (BUA) and speed of sound (SOS) as measured by quantitative ultrasound (QUS) at the calcaneus in the Framingham 100K genome-wide association study (GWAS) but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA) was also tested. Methods: Men aged 40-79 years (N = 2960) were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS). QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS), femoral neck (FN) and total hip (TH) BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p < 10(-4) were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD) bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p < 0.05 indicated replication. Results: Thirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (beta(SD) = 0.07, p = 0.032) but not BUA (beta(SD) = 0.02, p = 0.505) and is located in the 3'UTR of WDR77 (WD repeat domain 77) also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (beta(SD) = -0.22, p = 0.014), FN (beta(SD) = -0.31, p = 0.001) and TH (beta(SD) = -0.36, p = 0.002) in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL. Conclusions: We found suggestive evidence of association between a single SNP located in the 3'UTR of WDR77 with calcaneal ultrasound parameters. The majority of SNPs, associated with QUS parameters
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| 48. |
- Roshandel, Delnaz, et al.
(författare)
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Genetic Variation in the RANKL/RANK/OPG Signaling Pathway Is Associated With Bone Turnover and Bone Mineral Density in Men
- 2010
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:8, s. 1830-1838
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r(2) >= 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMDa) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (beta = 1.83, p = .004) and CTX-I (beta = 17.59, p = 4.74 x 10(-4)), and lower lumbar spine BMDa (beta = -0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (beta = -1.84, p = .003) and CTX-I (beta = -27.02, p = 6.06 x 10(-8)) and higher ultrasound BMD at the calcaneus (beta = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. (c) 2010 American Society for Bone and Mineral Research.
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| 49. |
- Roshandel, Delnaz, et al.
(författare)
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Influence of Polymorphisms in the RANKL/RANK/OPG Signaling Pathway on Volumetric Bone Mineral Density and Bone Geometry at the Forearm in Men
- 2011
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 89:6, s. 446-455
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Tidskriftsartikel (refereegranskat)abstract
- We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) a parts per thousand yen 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (beta [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (beta [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (beta [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (beta [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (beta [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (beta [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (beta [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (beta [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.
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| 50. |
- Roshandel, Delnaz, et al.
(författare)
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Polymorphisms in Genes Involved in the NF-kappa B Signalling Pathway Are Associated with Bone Mineral Density, Geometry and Turnover in Men
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-kappa B cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods: Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r(2) >= 0.8) within MAP3K14 (+/-10 kb) were genotyped in 2359 men aged 40-79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre. Results: We validated the associations between SNPs in GPR177 and BMDa previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMDa, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMDa, vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS. Conclusion: Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-kappa B signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health.
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