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- Benetou, V., et al.
(författare)
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Education, marital status, and risk of hip fractures in older men and women : the CHANCES project
- 2015
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 26:6, s. 1733-1746
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Tidskriftsartikel (refereegranskat)abstract
- The role of socioeconomic status in hip fracture incidence is unclear. In a diverse population of elderly, higher education was found to be associated with lower, whereas living alone, compared to being married/cohabiting, with higher hip fracture risk. Educational level and marital status may contribute to hip fracture risk.INTRODUCTION: The evidence on the association between socioeconomic status and hip fracture incidence is limited and inconsistent. We investigated the potential association of education and marital status with hip fracture incidence in older individuals from Europe and USA.METHODS: A total of 155,940 participants (79 % women) aged 60 years and older from seven cohorts were followed up accumulating 6456 incident hip fractures. Information on education and marital status was harmonized across cohorts. Hip fractures were ascertained through telephone interviews/questionnaires or through record linkage with registries. Associations were assessed through Cox proportional hazard regression adjusting for several factors. Summary estimates were derived using random effects models.RESULTS: Individuals with higher education, compared to those with low education, had lower hip fracture risk [hazard ratio (HR) = 0.84, 95 % confidence interval (CI) 0.72-0.95]. Respective HRs were 0.97 (95 % CI 0.82-1.13) for men and 0.75 (95 % CI 0.65-0.85) for women. Overall, individuals living alone, especially those aged 60-69 years, compared to those being married/cohabiting, tended to have a higher hip fracture risk (HR = 1.12, 95 % CI 1.02-1.22). There was no suggestion for heterogeneity across cohorts (P heterogeneity > 0.05).CONCLUSIONS: The combined data from >150,000 individuals 60 years and older suggest that higher education may contribute to lower hip fracture risk. Furthermore, this risk may be higher among individuals living alone, especially among the age group 60-69 years, when compared to those being married/cohabiting.
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| 4. |
- Bellavia, D, et al.
(författare)
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Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis
- 2002
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 99:6, s. 3788-3793
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Tidskriftsartikel (refereegranskat)abstract
- Notch receptors are conserved regulators of cell fate and have been implicated in the regulation of T cell differentiation and lymphomagenesis. However, neither the generality of Notch involvement in leukemia, nor the molecules with which Notch may interact have been clarified. Recently, we showed that transgenic mice expressing the constitutively active intracellular domain of Notch3 in thymocytes and T cells developed early and aggressive T cell neoplasias. Although primarily splenic, the tumors sustained features of immature thymocytes, including expression of pTα, a defining component of the pre T cell receptor, known to be a potent signaling complex provoking thymocyte survival, proliferation, and activation. Thus, enforced expression of Notch3, which is ordinarily down-regulated as thymocytes mature, may sustain pre T cell receptor expression, causing dysregulated hyperplasia. This hypothesis has been successfully tested in this article by the observation that deletion of pTα in Notch3 transgenic mice abrogates tumor development, indicating a crucial role for pTα in T cell leukemogenesis. Parallel observations were made in humans, in that all T cell acute lymphoblastic leukemias examined showed expression of Notch3 and of the Notch target gene HES-1, as well as of pTα a and b transcripts, whereas the expression of all these genes was dramatically reduced or absent in remission. Together, these results suggest that the combined expression of Notch3 and pTα sustains T cell leukemogenesis and may represent pathognomonic molecular features of human T-ALL.
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| 5. |
- Donat-Vargas, C., et al.
(författare)
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Cardiovascular and cancer mortality in relation to dietary polychlorinated biphenyls and marine polyunsaturated fatty acids : a nutritional-toxicological aspect of fish consumption
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:2, s. 197-209
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Tidskriftsartikel (refereegranskat)abstract
- Background: Co-exposure to environmental contaminants present in fish could mitigate the beneficial effects of fish consumption and possibly explain the lack of association observed for mortality in some geographical regions.Objective: To assess the independent associations of dietary exposure to polychlorinated biphenyls (PCBs) and long-chain omega-3 fish fatty acids intake with cardiovascular and cancer mortality.Methods: We used the prospective population-based Swedish Mammography Cohort and the Cohort of Swedish Men comprising 32 952 women and 36 545 men, free from cancer, cardiovascular disease and diabetes at baseline in 1998. Validated estimates of dietary PCBs and long-chain omega-3 fish fatty acids [i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] intake were obtained via a food frequency questionnaire at baseline. Information on death was ascertained through register linkage.Results: During a mean follow-up of 15.5 years, we ascertained 16 776 deaths. We observed for cardiovascular mortality, comparing extreme quintiles in multivariable models mutually adjusted for PCBs and EPA-DHA, dose-dependent associations for dietary PCB exposure, hazard ratio (HR) 1.31 (CI 95%: 1.08 to 1.57; P-trend 0.005) and for dietary EPA-DHA intake, HR 0.79 (CI 95%: 0.66 to 0.95; P-trend 0.041). For cancer mortality, no clear associations were discerned.Conclusion: The beneficial effect of fish consumption on the cardiovascular system seems compromised by co-exposure to PCBs - one likely explanation for the inconsistent associations observed between fish consumption and mortality.
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| 6. |
- Katsoulis, M, et al.
(författare)
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Excess mortality after hip fracture in elderly persons from Europe and the USA : the CHANCES project.
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 281:3, s. 300-310
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly.OBJECTIVE: All-cause mortality after hip fracture was investigated to assess its magnitude.METHODS: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time-dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random-effects meta-analysis.RESULTS: Hip fracture was positively associated with increased all-cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76-2.57, after adjusting for potential confounders. This association was stronger amongst men [HR: 2.39, 95% CI: 1.72-3.31] than amongst women [HR: 1.92, 95% CI: 1.54-2.39], although this difference was not significant. Mortality was higher during the first year after the hip fracture [HR: 2.78, 95% CI: 2.12-3.64], but it remained elevated without major fluctuations after longer time since hip fracture [HR (95% CI): 1.89 (1.50-2.37) after 1-4 years; 2.15 (1.81-2.55) after 4-8 years; 1.79 (1.57-2.05) after 8 or more years].CONCLUSION: In this large population-based sample of older persons across eight cohorts, hip fracture was associated with excess short- and long-term all-cause mortality in both sexes.
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| 7. |
- Rota, M, et al.
(författare)
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Erratum
- 2018
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Ingår i: International journal of cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 143:8, s. E10-E10
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Bellavia, A, et al.
(författare)
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Fish consumption and all-cause mortality in a cohort of Swedish men and women.
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 281:1, s. 86-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological studies of fish consumption and all-cause mortality have provided inconsistent results.OBJECTIVE: We examined the dose-response association between fish consumption and mortality from all causes in a large population-based cohort of Swedish men and women.METHODS: The study included 72 522 participants (33 973 women and 38 549 men), aged 45-83 years, from the Swedish Mammography Cohort and the Cohort of Swedish Men. Information on fish consumption was obtained through a self-administered questionnaire in 1997. Participants were followed for 17 years (1 January 1998 to 31 December 2014), and data on death and causes of death were ascertained through linkage to the Swedish Cause of Death Register. We used Cox proportional hazard regression to estimate hazard ratios (HRs) of death. Fish consumption was evaluated as a continuous predictor, flexibly modelled with restricted cubic splines to assess potential nonlinear associations.RESULTS: During follow-up, 16 730 deaths (7168 women and 9562 men) were recorded. The dose-response association between fish consumption and all-cause mortality was U-shaped. Compared with the median fish consumption (women: 25.0; men: 30.5 g day-1 ), lower levels of consumption were progressively associated with higher mortality risk up to 25% for women [HR 1.25; 95% confidence interval (CI): 1.11, 1.40] and 19% for men (HR 1.19; 95% CI: 1.07, 1.32) with no reported consumption. Increasingly higher levels of fish consumption were associated with higher mortality risk only amongst women, with a 39% higher mortality risk amongst women reporting the highest level of fish consumption (80 g day-1 ; HR 1.39; 95% CI: 1.15, 1.68).CONCLUSION: These results indicate a U-shaped association between fish consumption and all-cause mortality, particularly amongst women.
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| 15. |
- Benetou, Vassiliki, et al.
(författare)
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Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women : The CHANCES Project
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:9, s. 1743-1752
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Tidskriftsartikel (refereegranskat)abstract
- The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of elderly from Europe and United States. A total of 142,018 individuals (among which 116,509 women), aged ≥60 years old, from five cohorts, were followed-up prospectively for 1,911,482 person-years accumulating 5,552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires. Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HR) derived by Cox proportional-hazards regression were estimated for each cohort and subsequently pooled using random-effects meta-analysis. Intake of ≤ 1 servings/day of fruit and vegetables combined was associated with 39% higher hip fracture risk [pooled adjusted HR:1.39, 95% Confidence Intervals (CIs): 1.20, 1.58] in comparison to moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison to the same reference. Associations were more evident among women. We concluded that a daily intake of one or less servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk.
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| 16. |
- Diluvio, G, et al.
(författare)
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NOTCH3 inactivation increases triple negative breast cancer sensitivity to gefitinib by promoting EGFR tyrosine dephosphorylation and its intracellular arrest
- 2018
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 7:5, s. 42-
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Tidskriftsartikel (refereegranskat)abstract
- Notch dysregulation has been implicated in numerous tumors, including triple-negative breast cancer (TNBC), which is the breast cancer subtype with the worst clinical outcome. However, the importance of individual receptors in TNBC and their specific mechanism of action remain to be elucidated, even if recent findings suggested a specific role of activated-Notch3 in a subset of TNBCs. Epidermal growth factor receptor (EGFR) is overexpressed in TNBCs but the use of anti-EGFR agents (including tyrosine kinase inhibitors, TKIs) has not been approved for the treatment of these patients, as clinical trials have shown disappointing results. Resistance to EGFR blockers is commonly reported. Here we show that Notch3-specific inhibition increases TNBC sensitivity to the TKI-gefitinib in TNBC-resistant cells. Mechanistically, we demonstrate that Notch3 is able to regulate the activated EGFR membrane localization into lipid rafts microdomains, as Notch3 inhibition, such as rafts depletion, induces the EGFR internalization and its intracellular arrest, without involving receptor degradation. Interestingly, these events are associated with the EGFR tyrosine dephosphorylation at Y1173 residue (but not at Y1068) by the protein tyrosine phosphatase H1 (PTPH1), thus suggesting its possible involvement in the observed Notch3-dependent TNBC sensitivity response to gefitinib. Consistent with this notion, a nuclear localization defect of phospho-EGFR is observed after combined blockade of EGFR and Notch3, which results in a decreased TNBC cell survival. Notably, we observed a significant correlation between EGFR and NOTCH3 expression levels by in silico gene expression and immunohistochemical analysis of human TNBC primary samples. Our findings strongly suggest that combined therapies of TKI-gefitinib with Notch3-specific suppression may be exploited as a drug combination advantage in TNBC treatment.
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