| 1. |
- Glasbey, JC, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Bravo, L, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 5. |
- Tabiri, S, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- de Rojas, I., et al.
(author)
-
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
|
|
| 9. |
|
|
| 10. |
- Brevini, T, et al.
(author)
-
FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
- 2023
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7950, s. 134-
-
Journal article (peer-reviewed)abstract
- Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Lindberg, I., et al.
(author)
-
Direct healthcare cost of atopic dermatitis in the Swedish population
- 2021
-
In: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 141:5 Suppl., s. S45-S45
-
Journal article (other academic/artistic)abstract
- Data quantifying population-based direct healthcare costs (DHCC) for atopic dermatitis (AD) by severity are limited. This study was designed to provide estimates for these costs. Patients were identified at first AD diagnosis in the National Patient Registry (secondary care) or in primary care (national coverage: 31%) (International Classification of Diseases-10 L20) or first dispensation of topical calcineurin inhibitor or topical corticosteroid (Anatomical Therapeutic Chemical code D11AH01/02 once; D07 twice in a year) in the Prescribed Drug Registry in 2007-17 (index) and followed until death, emigration, 31 Dec 2018 or adulthood. Patients without AD diagnosis with a record of diagnoses/treatment for other non-AD skin conditions were excluded. Patients were matched 1:1 on age, gender and region to controls. 1-year DHCC for secondary and primary care visits and filled prescriptions were compared with controls (2020€). Disease severity (mild-to-moderate [M2M] vs severe) using AD treatment and visits as proxies was assessed between index to 30 days after. 187,338 M2M (48% female; mean age 4) and 46,754 severe children (51%; 8), while 445,317 M2M (55%; 55) and 11,640 severe adults (57%; 53) were included. In children vs. controls, 1-year DHCC for secondary care, primary care and medications were respectively €72, €23, €33 million (mn) higher in M2M and €26, €4, €13 mn higher in severe; in adults vs. controls, €353, €68, €182 mn higher in M2M and €21, €2, €17 mn higher in severe (all comparisons significant, p<0.05). On population level, AD is associated with substantial economic burden, which is higher in M2M vs severe AD partially due to higher prevalence of M2M.
|
|
| 15. |
|
|
| 16. |
- Vandaele, Ann Carine, et al.
(author)
-
Martian dust storm impact on atmospheric H2O and D/H observed by ExoMars Trace Gas Orbiter
- 2019
-
In: Nature. - : Springer. - 1476-4687 .- 1476-4687 .- 0028-0836. ; 568:7753, s. 521-525
-
Journal article (other academic/artistic)abstract
- Global dust storms on Mars are rare1,2 but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere3, primarily owing to solar heating of the dust3. In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars4. Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes5,6, as well as a decrease in the water column at low latitudes7,8. Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H2O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H2O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals3. The observed changes in H2O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere.
|
|
| 17. |
- von Kobyletzki, L., et al.
(author)
-
Care pathways in atopic dermatitis : a retrospective population-based cohort study
- 2022
-
In: Journal of the European Academy of Dermatology and Venereology. - : John Wiley & Sons. - 0926-9959 .- 1468-3083. ; 36:9, s. 1456-1466
-
Journal article (peer-reviewed)abstract
- Background Atopic dermatitis (AD) is a complex disease with variations in severity and healthcare utilization. Examining patient pathways through analyses of longitudinal patient data provides an opportunity to describe real-world clinical patient care and evaluate healthcare access and treatment. Objective To describe longitudinal care pathways including health care management, treatment patterns and disease progression (by proxy measures) in patients with AD. Materials and methods This was a longitudinal observational study, which used linked data from national and regional healthcare registers in Sweden. Patients with AD were identified through diagnosis in primary or secondary care or by dispensed medications. Descriptive statistics for number of healthcare visits, type of dispensed drug class, rate of - and time to - referral to secondary care and treatment escalation were calculated. Results A total of 341 866 patients with AD distributed as 197 959 paediatric (age < 12), 36 133 adolescent (age >= 12- < 18) and 107 774 adult (age >= 18) patients were included in this study. Healthcare visits to primary and secondary care and dispensation of AD-indicated treatments were more common during the year in which managed AD care was initiated. Topical corticosteroids (TCSs) and emollients were the most frequently used treatments across all age cohorts while systemic treatment was uncommon in all age cohorts. Among patients who initiated treatment with TCSs, 18.2% escalated to TCSs with higher potency following the start of managed AD care. Conclusions We found that healthcare contacts and use of AD-indicated treatments were concentrated in the year during which managed AD care was initiated and decreased significantly thereafter. Since a significant proportion of patients with AD have flares and persistent AD, our results suggest that patients with AD may be monitored infrequently and are undertreated. There is a need to inform practitioners about adequate treatment options to provide individualized care, in particular for patients with persistent severe AD.
|
|
