| 1. |
- Sliz, E., et al.
(författare)
-
Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
|
|
| 2. |
- Alenius, M, et al.
(författare)
-
Cognitive Performance at Time of AD Diagnosis: A Clinically Augmented Register-Based Study
- 2022
-
Ingår i: Frontiers in psychology. - : Frontiers Media SA. - 1664-1078. ; 13, s. 901945-
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to evaluate the feasibility of using real-world register data for identifying persons with mild Alzheimer’s disease (AD) and to describe their cognitive performance at the time of diagnosis. Patients diagnosed with AD during 2010–2013 (aged 60–81 years) were identified from the Finnish national health registers and enlarged with a smaller private sector sample (total n = 1,268). Patients with other disorders impacting cognition were excluded. Detailed clinical and cognitive screening data (the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery [CERAD-nb]) were obtained from local health records. Adequate cognitive data were available for 389 patients with mild AD (31%) of the entire AD group. The main reasons for not including patients in analyses of cognitive performance were AD diagnosis at a moderate/severe stage (n = 266, 21%), AD diagnosis given before full register coverage (n = 152, 12%), and missing CERAD-nb data (n = 139, 11%). The cognitive performance of persons with late-onset AD (n = 284), mixed cerebrovascular disease and AD (n = 51), and other AD subtypes (n = 54) was compared with that of a non-demented sample (n = 1980) from the general population. Compared with the other AD groups, patients with late-onset AD performed the worst in word list recognition, while patients with mixed cerebrovascular disease and AD performed the worst in constructional praxis and clock drawing tests. A combination of national registers and local health records can be used to collect data relevant for cognitive screening; today, the process is laborious, but it could be improved in the future with refined search algorithms and electronic data.
|
|
| 3. |
- Alenius, M, et al.
(författare)
-
Education-Based Cutoffs for Cognitive Screening of Alzheimer's Disease
- 2022
-
Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 51:1, s. 42-55
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer’s disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. <b><i>Methods:</i></b> CERAD-nb scores were obtained from AD patients (<i>n</i> = 389, 58% women, mean age 74.0 years) and from controls (<i>n</i> = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden’s J was calculated for the overall performance and accuracy of each of the measures. <b><i>Results:</i></b> Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. <b><i>Conclusions:</i></b> Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test.
|
|
| 4. |
- Oudin Åström, Daniel, et al.
(författare)
-
Temperature effects on incidence of surgery for acute type A aortic dissection in the Nordics
- 2022
-
Ingår i: Global health action. - : Informa UK Limited. - 1654-9880 .- 1654-9880 .- 1654-9716. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (<=-5 degrees C) and hot temperatures (>= 21 degrees C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Wikström, A. M., et al.
(författare)
-
Are adolescent boys with Klinefelter syndrome androgen deficient? A longitudinal study of Finnish 47,XXY boys
- 2006
-
Ingår i: Pediatr Res. - : Springer Science and Business Media LLC. - 0031-3998. ; 59:6, s. 854-9
-
Tidskriftsartikel (refereegranskat)abstract
- Testosterone (T)-substitution therapy is widely used in adult patients with Klinefelter syndrome (KS) to prevent symptoms and sequels of androgen deficiency, but it is currently unknown if adolescent boys with KS benefit from early T therapy. To evaluate the optimal age to start T substitution, we searched for signs of androgen deficiency in pubertal boys with KS. 14 nonmosaic 47,XXY boys, aged 10-13.9 y, were followed up for 4-37 mo with staging of puberty and frequent reproductive hormone measurements. Furthermore, indices reflecting androgen action (serum SHBG, leptin, and prostate-specific antigen (PSA) levels) were studied. Both onset and progression of puberty according to Tanner stages were normal in boys with KS. Consistently, serum T concentrations increased as expected and remained normal throughout follow-up. Changes in the indices of androgen action (decreases in serum SHBG and leptin, and increase in serum PSA concentrations) occurred normally, except that average leptin levels were higher in the boys with KS (KS boys 11.8 +/- 7.0 microg/L; controls 7.6 +/- 4.7 microg/L; p = 0.033). Despite normal T concentrations, the KS boys displayed from the age of 13 y elevated serum FSH and LH levels, and exaggerated gonadotropin responses to gonadotropin-releasing hormone. These data do not demonstrate an unequivocal androgen deficiency in adolescent boys with KS that would necessitate androgen supplementation therapy during early puberty.
|
|
