| 1. |
- Avdic, Daniel, et al.
(författare)
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Sex differences in sickness absence and the morbidity-mortality paradox : a longitudinal study using Swedish administrative registers
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Objective To analyse whether gender-specific health behaviour can be an explanation for why women outlive men, while having worse morbidity outcomes, known as the morbidity-mortality or gender paradox. Setting The working population in Sweden. Participants Thirty per cent random sample of Swedish women and men aged 40-59 with a hospital admission in the 1993-2004 period were included. The sample for analysis consists of 233274 individuals (115430 men and 117844 women) and in total 1 867013 observations on sickness absence. Intervention Hospital admission across 18 disease categories. Main outcome measures The main outcome measures were sickness absence (morbidity) and mortality. Longitudinal data at the individual level allow us to study how sickness absence changed after a hospital admission in men and women using a difference-in-differences regression analysis. Cox regression models are used to study differences in mortality after the admission. Results Women increased their sickness absence after a hospital admission by around five more days per year than men (95% CI 5.25 to 6.22). At the same time, men had higher mortality in the 18 diagnosis categories analysed. The pattern of more sickness absence in women was the same across 17 different diagnosis categories. For neoplasm, with a 57% higher risk of death for men (54.18%-59.89%), the results depended on the imputation method of sickness for those deceased. By using the premortality means of sickness absence, men had an additional 14.47 (-16.30- -12.64) days of absence, but with zero imputation women had an additional 1.6 days of absence (0.05-3.20). Analyses with or without covariates revealed a coherent picture. Conclusions The pattern of increased sickness absence (morbidity) and lower mortality in women provides evidence on the more proactive and preventive behaviour of women than of men, which could thus explain the morbidity-mortality paradox.
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| 2. |
- Lundborg, Magnus, et al.
(författare)
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Human skin barrier structure and function analyzed by cryo-EM and molecular dynamics simulation
- 2018
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Ingår i: Journal of Structural Biology. - : Academic Press. - 1047-8477 .- 1095-8657. ; 203:2, s. 149-161
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Tidskriftsartikel (refereegranskat)abstract
- In the present study we have analyzed the molecular structure and function of the human skin's permeability barrier using molecular dynamics simulation validated against cryo-electron microscopy data from near native skin. The skin's barrier capacity is located to an intercellular lipid structure embedding the cells of the superficial most layer of skin - the stratum corneum. According to the splayed bilayer model (Iwai et al., 2012) the lipid structure is organized as stacked bilayers of ceramides in a splayed chain conformation with cholesterol associated with the ceramide sphingoid moiety and free fatty acids associated with the ceramide fatty acid moiety. However, knowledge about the lipid structure's detailed molecular organization, and the roles of its different lipid constituents, remains circumstantial. Starting from a molecular dynamics model based on the splayed bilayer model, we have, by stepwise structural and compositional modifications, arrived at a thermodynamically stable molecular dynamics model expressing simulated electron microscopy patterns matching original cryo-electron microscopy patterns from skin extremely closely. Strikingly, the closer the individual molecular dynamics models' lipid composition was to that reported in human stratum corneum, the better was the match between the models' simulated electron microscopy patterns and the original cryo-electron microscopy patterns. Moreover, the closest-matching model's calculated water permeability and thermotropic behaviour were found compatible with that of human skin. The new model may facilitate more advanced physics-based skin permeability predictions of drugs and toxicants. The proposed procedure for molecular dynamics based analysis of cellular cryo-electron microscopy data might be applied to other biomolecular systems.
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| 3. |
- Narangifard, Ali, et al.
(författare)
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Molecular Reorganization during the Formation of the Human Skin Barrier Studied In Situ
- 2021
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 141:5, s. 1243-1253
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Tidskriftsartikel (refereegranskat)abstract
- In vertebrates, skin upholds homeostasis by preventing body water loss. The skin's permeability barrier is located intercellularly in the stratum corneum and consists of stacked lipid lamellae composed of ceramides, cholesterol, and free fatty acids. We have combined cryo-electron microscopy with molecular dynamics modeling and electron microscopy simulation in our analysis of the lamellae's formation, a maturation process beginning in stratum granulosum and ending in stratum corneum. Previously, we have revealed the lipid lamellae's initial- and end-stage molecular organizations. In this study, we reveal two cryo-electron microscopy patterns representing intermediate stages in the lamellae's maturation process: a single-band pattern with 2.0-2.5 nm periodicity and a two-band pattern with 5.5-6.0 nm periodicity, which may be derived from lamellar lipid structures with 4.0-5.0 nm and 5.5-6.0 nm periodicity, respectively. On the basis of the analysis of the data now available on the four maturation stages identified, we can present a tentative molecular model for the complete skin barrier formation process.
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