| 103501. |
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| 103502. |
- Tiikkaja, S., et al.
(författare)
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Familial risk of premature cardiovascular mortality and the impact of intergenerational occupational class mobility
- 2012
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Ingår i: Social Science & Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 75:10, s. 1883-1890
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Tidskriftsartikel (refereegranskat)abstract
- The negative impact of low social class on cardiovascular disease (CVD) and mortality has been consistently documented. However, less scientific consistency exists in terms of whether a unique health effect of social mobility from childhood to adulthood prevails. This study explored how childhood and adult social class and the transition between them (social mobility), are related to premature CVD mortality when familial aggregation of CVD among siblings is also considered. The study includes nearly 1.9 million Swedish residents born 1939-1959 distributed over 1,044,725 families, of whom 14,667 died prematurely from CVD in 1990-2003. Information on parental class (1960) and own mid-life occupational class (1990) was retrieved from the respective censuses. Odds ratios for premature CVD mortality according to trajectory-specific social mobility, along with pairwise mean odds ratios for sibling resemblance of premature CVD mortality, were calculated by means of alternating logistic regression. This model calculates the remaining dependency of CVD mortality within sibships after accounting for available risk factors (like parental and adult social class) in the population mean model. Results showed that premature CVD mortality was associated with both parental and own adult social class. A clear tendency for the downwardly mobile to have increased, and for the upwardly mobile to experience a decreased risk of premature DID mortality was found, as well as a corresponding unique effect of social mobility per se among the manual and non-manual classes. This effect was verified for men, but not for women, when they were analysed separately. The pairwise mean odds ratios for premature CVD mortality among full siblings were 1.78 (95% CI: 1.52-2.08), and were independent of parental CVD mortality and parental or adult occupational class.
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| 103503. |
- Tiikkaja, Sanna, et al.
(författare)
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Intergenerational class mobility and cardiovascular mortality among Swedish women : a population-based register study
- 2009
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 68, s. 733-739
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Tidskriftsartikel (refereegranskat)abstract
- Class inequalities in cardiovascular disease (CVD) mortality are well documented, but the impact of intergenerational class mobility on CVD mortality among women has not been studied thoroughly. We examined whether women's mobility trajectories might contribute to CVD mortality beyond what could be expected from their childhood and adult social class position. The Swedish Work and Mortality Data Base provided childhood (1960) and adulthood (1990) social indicators. Women born 1945–59 (N = 791 846) were followed up for CVD mortality 1990–2002 (2019 deaths) by means of logistic regression analysis. CVD mortality risks were estimated for 16 mobility trajectories. Gross and net impact of four childhood and four adult classes, based on occupation, were analysed for mortality in ischemic heart disease (IHD), stroke, other CVD, – and all CVD. Differences between the two most extreme trajectories were 10-fold, but the common trajectory of moving from manual to non-manual position was linked to only a slight excess mortality (OR = 1.26) compared to the equally common trajectory of maintaining a stable non-manual position (reference category). Moving into adult manual class resulted in an elevated CVD mortality whatever the childhood position (ORs varied between 1.42 and 2.24). After adjustment for adult class, childhood class had some effect, in particular there was a low risk of coming from a self-employed childhood class on all outcomes (all ORs around = 0.80). A woman's own education had a stronger influence on the mortality estimates than did household income. Social mobility trajectories among Swedish women are linked to their CVD mortality risk. Educational achievement seems to be a key factor for intergenerational continuity and discontinuity in class-related risk of CVD mortality among Swedish women. However, on mutual adjustment, adult class was much more closely related to CVD mortality than was class in childhood.
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| 103504. |
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| 103505. |
- Tiikkaja, Sanna, et al.
(författare)
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Psychiatric disorder and work life : A longitudinal study of intra-generational social mobility
- 2016
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Ingår i: International Journal of Social Psychiatry. - : SAGE Publications. - 0020-7640 .- 1741-2854. ; 62:2, s. 156-166
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intra-generational social mobility, which describes the mobility within an individual’s own working life, is seldom studied among employees with psychiatric disorders (EPD). There is need of knowledge of the intra-generational mobility patterns, in a broader perspective, among EPD.Aims: To investigate intra-generational social mobility in employed individuals diagnosed with affective disorder, personality disorder, schizophrenia and drug dependence in a national Swedish cohort.Method: We identified a national sample of employed Swedish adults born in 1939–1949 (N = 876, 738), and among them individuals with a first-time hospital admission for affective psychosis, neurosis and personality disorder, alcoholism, drug dependence or schizophrenia in 1964–1980 (N = 18, 998). Employed individuals without hospital admission for such diagnoses were utilised as a comparison group (N = 866, 442). Intra-individual social class changes between 1980 and 1990 among EPD and the comparison group were described through summary statistics and graphs.Results: EPD more often held Low manual occupations at baseline in 1980 than the comparison group (44% vs. 28%), although parental social class was similar. In 1990, 19% of EPD and 4% of the comparison group had lost contact with the labour market. Social stability was less common among EPD (49 %) than in the comparison group (67%). Mobility out of the labour force increased and social stability decreased by number of inpatient admissions. Employees diagnosed with affective psychosis or neurosis and personality disorder fared better in the labour market than employees with schizophrenia.Conclusion: Employees suffering from psychiatric disorder do not maintain their social class or remain in the labour force to the same extent as individuals without those problems, irrespective of their parental class. Our results support the social drift hypothesis that individuals with poor psychiatric health move downward in the social hierarchy.
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| 103506. |
- Tiikkaja, Sanna, et al.
(författare)
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Social Class, Social Mobility and Risk of Psychiatric Disorder - A Population-Based Longitudinal Study
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study explored how adult social class and social mobility between parental and own adult social class is related to psychiatric disorder.Material and Methods: In this prospective cohort study, over 1 million employed Swedes born in 1949-1959 were included. Information on parental class (1960) and own mid-life social class (1980 and 1990) was retrieved from the censuses and categorised as High Non-manual, Low Non-manual, High Manual, Low Manual and Self-employed. After identifying adult class, individuals were followed for psychiatric disorder by first admission of schizophrenia, alcoholism and drug dependency, affective psychosis and neurosis or personality disorder (N=24 659) from the Swedish Patient Register. We used Poisson regression analysis to estimate first admission rates of psychiatric disorder per 100 000 person-years and relative risks (RR) by adult social class (treated as a time-varying covariate). The RRs of psychiatric disorder among the Non-manual and Manual classes were also estimated by magnitude of social mobility.Results: The rate of psychiatric disorder was significantly higher among individuals belonging to the Low manual class as compared with the High Non-manual class. Compared to High Non-manual class, the risk for psychiatric disorder ranged from 2.07 (Low Manual class) to 1.38 (Low Non-manual class). Parental class had a minor impact on these estimates. Among the Non-manual and Manual classes, downward mobility was associated with increased risk and upward mobility with decreased risk of psychiatric disorder. In addition, downward mobility was inversely associated with the magnitude of social mobility, independent of parental class.Conclusions: Independently of parental social class, the risk of psychiatric disorder increases with increased downward social mobility and decreases with increased upward mobility.
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| 103507. |
- Tiiman, Ann, et al.
(författare)
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Amyloidogenic Nanoplaques in Blood Serum of Patients with Alzheimer's Disease Revealed by Time-Resolved Thioflavin T Fluorescence Intensity Fluctuation Analysis
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS PRESS. - 1387-2877 .- 1875-8908. ; 68:2, s. 571-582
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Tidskriftsartikel (refereegranskat)abstract
- Background: Biomarkers are central to current research on molecular mechanisms underlying Alzheimer's disease (AD). Their further development is of paramount importance for understanding pathophysiological processes that eventually lead to disease onset. Biomarkers are also crucial for early disease detection, before clinical manifestation, and for development of new disease modifying therapies. Objective: The overall aim of this work is to develop a minimally invasive method for fast, ultra-sensitive and cost-effective detection of structurally modified peptide/protein self-assemblies in the peripheral blood and in other biological fluids. Specifically, we focus here on using this method to detect structured amyloidogenic oligomeric aggregates in the blood serum of apparently healthy individuals and patients in early AD stage, and measure their concentration and size. Methods: Time-resolved detection of Thioflavin T (ThT) fluorescence intensity fluctuations in a sub-femtoliter observation volume element was used to identify in blood serum ThT-active structured amyloidogenic oligomeric aggregates, hereafter called nanoplaques, and measure with single-particle sensitivity their concentration and size. Results: The concentration and size of structured amyloidogenic nanoplaques are significantly higher in the blood serum of individuals diagnosed with AD than in control subjects. Conclusion: A new method with the ultimate, single-particle sensitivity was successfully developed. The proposed approach neither relies on the use of immune-based probes, nor on the use of radiotracers, signal-amplification or protein separation techniques, and provides a minimally invasive test for fast and cost-effective early determination of structurally modified peptides/proteins in the peripheral blood, as shown here, but also in other biological fluids.
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| 103508. |
- Tiiman, Ann, et al.
(författare)
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Heterogeneity and Turnover of Intermediates during Amyloid-beta (A beta) Peptide Aggregation Studied by Fluorescence Correlation Spectroscopy
- 2015
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 54:49, s. 7203-7211
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Tidskriftsartikel (refereegranskat)abstract
- Self-assembly of amyloid beta (A beta) peptide molecules into large aggregates is a naturally occurring process driven in aqueous solution by a dynamic interplay between hydrophobic interactions among A beta molecules, which promote aggregation, and steric and overall electrostatic hindrance, which stifles it. A beta self-association is entropically unfavorable, as it implies order increase in the system, but under favorable kinetic conditions, the process proceeds at appreciable rates, yielding A beta aggregates of different sizes and structures. Despite the great relevance and extensive research efforts, detailed kinetic mechanisms underlying A beta aggregation remain only partially understood. In this study, fluorescence correlation spectroscopy (FCS) and Thioflavin T (ThT) were used to monitor the time dependent growth of structured aggregates and characterize multiple components during the aggregation of A beta peptides in a heterogeneous aqueous solution. To this aim, we collected data during a relatively large number of observation periods, 30 consecutive measurements lasting 10 s each, at what we consider to be a constant time point in the slow aggregation process. This approach enabled monitoring the formation of nanomolar concentrations of structured amyloid aggregates and demonstrated the changing distribution of amyloid aggregate sizes throughout the aggregation process. We identified aggregates of different sizes with molecular weight from 260 to more than 1 x 10(6) kDa and revealed the hitherto unobserved kinetic turnover of intermediates during A beta aggregation. The effect of different A beta concentrations, A beta:ThT ratios, differences between the 40 (A beta 40) and 42 (A beta 42) residue long variants of A beta, and the effect of stirring were also examined.
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| 103509. |
- Tiiman, Ann, et al.
(författare)
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In vitro fibrillization of Alzheimer's amyloid-beta peptide (1-42)
- 2015
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Ingår i: AIP Advances. - : AIP Publishing. - 2158-3226. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid deposition in the form of extracellular fibrillar aggregates of amyloid-beta (A beta) peptide is a critical pathological event in Alzheimer's disease. Here, we report a systematic investigation of the effects of environmental factors on the kinetics of A beta fibrillization in vitro. The effects of A beta 42 peptide concentration, temperature, pH, added solvents and the ratio of A beta 40 and A beta 42 on the peptide fibrillization under agitated conditions was studied. The analysis show that the rate of fibril growth by monomer addition is not limited by diffusion but by rearrangement in the monomer structure, which is enhanced by low concentrations of fluorinated alcohols and characterized by the activation energy of 12 kcal/ mol. Fibrillization rate decreases at pH values below 7.0 where simultaneous protonation of His 13 and 14 inhibits fibril formation. The lag period for A beta 42 was only twofold shorter and the fibril growth rate twofold faster than those of A beta 40. Lag period was shortened and the fibrillization rate was increased only at 90% content of A beta 42.
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| 103510. |
- Tiiman, Ann, et al.
(författare)
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Specific Binding of Cu(II) Ions to Amyloid-Beta Peptides Bound to Aggregation-Inhibiting Molecules or SDS Micelles Creates Complexes that Generate Radical Oxygen Species
- 2016
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 54:3, s. 971-982
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Tidskriftsartikel (refereegranskat)abstract
- Aggregation of the amyloid-beta (A beta) peptide into insoluble plaques is a major factor in Alzheimer's disease (AD) pathology. Another major factor in AD is arguably metal ions, as metal dyshomeostasis is observed in AD patients, metal ions modulate A beta aggregation, and AD plaques contain numerous metals including redox-active Cu and Fe ions. In vivo, A beta is found in various cellular locations including membranes. So far, Cu(II)/A beta interactions and ROS generation have not been investigated in a membrane environment. Here, we study Cu(II) and Zn(II) interactions with A beta bound to SDS micelles or to engineered aggregation-inhibiting molecules (the cyclic peptide CP-2 and the Z(A beta 3)(12-58) Y18L Affibody molecule). In all studied systems the A beta N-terminal segment was found to be unbound, unstructured, and free to bind metal ions. In SDS micelles, A beta was found to bind Cu(II) and Zn(II) with the same ligands and the same K-D as in aqueous solution. ROS was generated in all Cu(II)/A beta complexes. These results indicate that binding of A beta to membranes, drugs, and other entities that do not interact with the A beta N-terminal part, appears not to compromise the N-terminal segment's ability to bind metal ions, nor impede the capacity of N-terminally bound Cu(II) to generate ROS.
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