| 1. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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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.
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| 2. |
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| 3. |
- Kurki, MI, et al.
(författare)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Tidskriftsartikel (refereegranskat)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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| 4. |
- Neuvonen, E, et al.
(författare)
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Associations of Depressive Symptoms and Cognition in the FINGER Trial: A Secondary Analysis of a Randomised Clinical Trial
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Depression and cognition are associated, but the role of depressive symptoms in lifestyle interventions to prevent dementia needs further study. We investigated the intervention effect on depressive symptoms and their associations with cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER; NCT01041989), a two-year multidomain lifestyle trial. One thousand two-hundred and sixty individuals (60–77 years) at risk for dementia were randomised into a multidomain intervention (diet, exercise, cognitive training, and vascular/metabolic risk monitoring) or control group (regular health advice). Depressive symptoms (Zung scale) and cognition (modified Neuropsychological Test Battery) were evaluated at baseline, 12, and 24 months. One thousand one-hundred and twenty-five participants had baseline Zung data. Mean Zung score decreased 0.73 (SD 5.6) points in the intervention and 0.36 (5.6) points in the control group, with nonsignificant between-group difference (group × time coefficient −0.006, 95% CI −0.019 to 0.007). Overall, higher baseline Zung score was associated with less improvement in global cognition (−0.140, p = 0.005) and memory (−0.231, p = 0.005). Participants with clinically significant baseline depressive symptoms (Zung ≥ 40 points) had less intervention benefit to executive functioning (group × time × Zung −0.096, 95% CI −0.163 to −0.028). Change in Zung score was not associated with change in cognition. Clinically significant depressive symptoms warrant more attention when designing dementia-prevention interventions.
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| 5. |
- Sindi, S., et al.
(författare)
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Baseline telomere length and effects of a multidomain lifestyle intervention on cognition : The FINGER randomized controlled trial
- 2017
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 59:4, s. 1459-1470
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte telomere length (LTL) is a biomarker of aging, and it is associated with lifestyle. It is currently unknown whether LTL is associated with the response to lifestyle interventions. The goal is to assess whether baseline LTL modified the cognitive benefits of a 2-year multidomain lifestyle intervention (exploratory analyses). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a 2-year randomized controlled trial including 1,260 people at risk of cognitive decline, aged 60-77 years identified from the general population. Participants were randomly assigned to the lifestyle intervention (diet, exercise, cognitive training, and vascular risk management) and control (general health advice) groups. Primary outcome was change in cognition (comprehensive neuropsychological test battery). Secondary outcomes were changes in cognitive domains: Memory, executive functioning, and processing speed. 775 participants (392 control, 383 intervention) had baseline LTL (peripheral blood DNA). Mixed effects regression models with maximum likelihood estimation were used to analyze change in cognition as a function of randomization group, time, baseline LTL, and their interaction. Intervention and control groups did not significantly differ at baseline. Shorter LTL was related to less healthy baseline lifestyle. Intervention benefits on executive functioning were more pronounced among those with shorter baseline LTL (p-value for interaction was 0.010 adjusted for age and sex, and 0.007 additionally adjusted for baseline lifestyle factors). The FINGER intervention cognitive benefits were more pronounced with shorter baseline LTL, particularly for executive functioning, indicating that the multidomain lifestyle intervention was especially beneficial among higher-risk individuals.
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| 6. |
- Sindi, S., et al.
(författare)
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Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline : A Randomized Clinical Trial
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 76:3, s. 491-498
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs). METHODS: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60-77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989). RESULTS: This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was -0.016 (0.19) in the intervention group and -0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI -0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: -0.005 (95% CI -0.010 to -0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI -0.011 to 0.264). CONCLUSIONS: This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits. CLINICAL TRIALS REGISTRATION NUMBER: NCT01041989.
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| 10. |
- Paajanen, T, et al.
(författare)
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CERAD Neuropsychological Total Scores Reflect Cortical Thinning in Prodromal Alzheimer's Disease
- 2013
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 3:1, s. 446-58
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Sensitive cognitive global scores are beneficial in screening and monitoring for prodromal Alzheimer's disease (AD). Early cortical changes provide a novel opportunity for validating established cognitive total scores against the biological disease markers. <b><i>Methods:</i></b> We examined how two different total scores of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and the Mini-Mental State Examination (MMSE) are associated with cortical thickness (CTH) in mild cognitive impairment (MCI) and prodromal AD. Cognitive and magnetic resonance imaging (MRI) data of 22 progressive MCI, 78 stable MCI, and 98 control subjects, and MRI data of 103 AD patients of the prospective multicenter study were analyzed. <b><i>Results:</i></b> CERAD total scores correlated with mean CTH more strongly (r = 0.34-0.38, p < 0.001) than did MMSE (r = 0.19, p = 0.01). Of those vertex clusters that showed thinning in progressive MCI, 60-75% related to the CERAD total scores and 3% to the MMSE. <b><i>Conclusion:</i></b> CERAD total scores are sensitive to the CTH signature of prodromal AD, which supports their biological validity in detecting early disease-related cognitive changes.
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| 11. |
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| 12. |
- Anttila, M. -R, et al.
(författare)
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Biopsychosocial profiles of patients with cardiac disease in remote rehabilitation processes : Mixed methods grounded theory approach
- 2021
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Ingår i: JMIR Rehabilitation and Assistive Technologies. - : JMIR Publications Inc.. - 2369-2529. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Digital development has caused rehabilitation services and rehabilitees to become increasingly interested in using technology as a part of rehabilitation. This study was based on a previously published study that categorized 4 groups of patients with cardiac disease based on different experiences and attitudes toward technology (e-usage groups): feeling outsider, being uninterested, reflecting benefit, and enthusiastic using. Objective: This study identifies differences in the biopsychosocial profiles of patients with cardiac disease in e-usage groups and deepen the understanding of these profiles in cardiac rehabilitation. Methods: Focus group interviews and measurements were conducted with 39 patients with coronary heart disease, and the mean age was 54.8 (SD 9.4, range 34-77) years. Quantitative data were gathered during a 12-month rehabilitation period. First, we used analysis of variance and Tukey honestly significant difference test, a t test, or nonparametric tests—Mann–Whitney and Kruskal–Wallis tests—to compare the 4 e-usage groups—feeling outsider, being uninterested, reflecting benefit, and enthusiastic using—in biopsychosocial variables. Second, we compared the results of the 4 e-groups in terms of recommended and reference values. This analysis contained 13 variables related to biomedical, psychological, and social functioning. Finally, we formed biopsychosocial profiles based on the integration of the findings by constant comparative analysis phases through classic grounded theory. Results: The biomedical variables were larger for waistline (mean difference [MD] 14.2; 95% CI 1.0-27.5; P=.03) and lower for physical fitness (MD −0.72; 95% CI −1.4 to −0.06; P=.03) in the being uninterested group than in the enthusiastic using group. The feeling outsider group had lower physical fitness (MD −55.8; 95% CI −110.7 to −0.92; P=.047) than the enthusiastic using group. For psychosocial variables, such as the degree of self-determination in exercise (MD −7.3; 95% CI −13.5 to −1.1; P=.02), the being uninterested group had lower values than the enthusiastic using group. Social variables such as performing guided tasks in the program (P=.03) and communicating via messages (P=.03) were lower in the feeling outsider group than in the enthusiastic using group. The feeling outsider and being uninterested groups had high-risk lifestyle behaviors, and adherence to the web-based program was low. In contrast, members of the being uninterested group were interested in tracking their physical activity. The reflecting benefit and enthusiastic using groups had low-risk lifestyle behavior and good adherence to web-based interventions; however, the enthusiastic using group had low self-efficacy in exercise. These profiles showed how individuals reflected their lifestyle risk factors differently. We renamed the 4 groups as building self-awareness, increasing engagement, maintaining a healthy lifestyle balance, and strengthening self-confidence. Conclusions: The results facilitate more effective and meaningful personalization guidance and inform the remote rehabilitation. Professionals can tailor individual web-based lifestyle risk interventions using these biopsychosocial profiles.
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| 13. |
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| 14. |
- Liu, YW, et al.
(författare)
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APOE ε2 allele is associated with larger regional cortical thicknesses and volumes
- 2010
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 30:3, s. 229-237
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> The protective effect of the apolipoprotein E (APOE) Ε2 allele against Alzheimer’s disease (AD) is controversial. <i>Objective:</i> Our purpose was to clarify if the Ε2 allele affects regional cortical thicknesses and volumes. <i>Methods:</i> Regional cortical thicknesses and volumes were measured with an automated pipeline in 109 subjects with mild cognitive impairment, 114 AD patients and 105 age-matched healthy controls. <i>Results:</i> In the mild cognitive impairment group, the Ε2 carriers had thicker regional cortices at the transverse temporal cortex and parahippocampal gyrus than the subjects with Ε3/Ε3, and a larger cerebral gray matter and smaller lateral ventricles than the Ε3/Ε3 and Ε4 carriers. In the AD group, the Ε2 carriers had significantly thicker entorhinal and transverse temporal cortices, a larger whole cerebral gray matter, and smaller lateral ventricles than the subjects with the Ε3/Ε3 genotype, and a significantly thicker entorhinal cortex and larger cerebral gray matter than Ε4 carriers. No APOE2 effect was found in the control group. <i>Conclusion:</i> The APOE Ε2 allele is associated with larger regional cortical thicknesses and volumes in mild cognitive impairment and AD.
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| 19. |
- Ollila, H, et al.
(författare)
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Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma
- 2022
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 870352-
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Tidskriftsartikel (refereegranskat)abstract
- Pleural mesothelioma (MPM) is an aggressive malignancy with an average patient survival of only 10 months. Interestingly, about 5%–10% of the patients survive remarkably longer. Prior studies have suggested that the tumor immune microenvironment (TIME) has potential prognostic value in MPM. We hypothesized that high-resolution single-cell spatial profiling of the TIME would make it possible to identify subpopulations of patients with long survival and identify immunophenotypes for the development of novel treatment strategies.MethodsWe used multiplexed fluorescence immunohistochemistry (mfIHC) and cell-based image analysis to define spatial TIME immunophenotypes in 69 patients with epithelioid MPM (20 patients surviving ≥ 36 months). Five mfIHC panels (altogether 21 antibodies) were used to classify tumor-associated stromal cells and different immune cell populations. Prognostic associations were evaluated using univariate and multivariable Cox regression, as well as combination risk models with area under receiver operating characteristic curve (AUROC) analyses.ResultsWe observed that type M2 pro-tumorigenic macrophages (CD163+pSTAT1−HLA-DRA1−) were independently associated with shorter survival, whereas granzyme B+ cells and CD11c+ cells were independently associated with longer survival. CD11c+ cells were the only immunophenotype increasing the AUROC (from 0.67 to 0.84) when added to clinical factors (age, gender, clinical stage, and grade).ConclusionHigh-resolution, deep profiling of TIME in MPM defined subgroups associated with both poor (M2 macrophages) and favorable (granzyme B/CD11c positivity) patient survival. CD11c positivity stood out as the most potential prognostic cell subtype adding prediction power to the clinical factors. These findings help to understand the critical determinants of TIME for risk and therapeutic stratification purposes in MPM.
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| 20. |
- Paajanen, Antti, et al.
(författare)
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FDS2FEM - A tool for coupling fire and structural analyses
- 2013
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Konferensbidrag (refereegranskat)abstract
- Computational modelling of fire-structural response requires interoperability of various models describing different physical phenomena. Typically, the most advanced sub-models are found within independent simulation software incapable of interoperability. To address this issue, we have developed a tool for coupling two of such programs: Fire Dynamics Simulator and ABAQUS. We present the main features and theory behind the coupling approach and use an example case to demonstrate how a coupled fire-structural analysis is set up. We also discuss potential applications and present limitations of our approach.
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| 21. |
- Paajanen, L, et al.
(författare)
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Homogenization of milk has no effect on milk-specific antibodies in healthy adults
- 2005
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Ingår i: Milchwissenschaft. - 0026-3788. ; 60:3, s. 239-241
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Tidskriftsartikel (refereegranskat)abstract
- It has been claimed that some consumers tolerate unhomogenized cow's milk better than homogenized cow's milk. The aim of this study was to compare the effect of homogenized and unhomogenized milk on the production of specific antibodies against cow's milk proteins (casein, beta-lactoglobulin) and bovine insulin. Thirty-six milk-tolerant volunteers were challenged with homogenized and unhomogenized cow's milk for 28 days in a randomized, open, cross-over study (>400 ml of milk daily). From serum samples taken at baseline and at the end of both milk challenges IgG and IgA were measured by ELISA against casein, beta-lactoglobulin and bovine insulin, and IgE against casein. The antibody production of the subjects remained constant for over 2 months, with no differences between the challenges with homogenized and unhomogenized milk. Inter-individual variation was greater than the intra-individual variation or the variation between the milk challenges. The order of the milk challenges did not affect the results. In conclusion, there seems to be no difference in the immunological responses to homogenized and unhomogenized milk in healthy adults with a good tolerance of milk.
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| 22. |
- Paajanen, L, et al.
(författare)
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Intestinal cytokine mRNA expression in delayed-type cow's milk allergy
- 2006
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Ovid Technologies (Wolters Kluwer Health). - 0277-2116 .- 1536-4801. ; 43:4, s. 470-476
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the study was to investigate the characteristics of intestinal immune activation (ie, a chemokine receptor and cytokine expression profile) in delayed-type cow's milk allergy (CMA) appearing in the form of gastrointestinal symptoms. PATIENTS AND METHODS: In all biopsy samples taken from the duodenum and/or the terminal ileum, 30 were studied for the expression of interferon-gamma, transforming growth factor-beta, chemokine receptor (CCR)-4, CCR-5, IL-2, IL-6, IL-10, IL-12p35, IL-12p40 and IL-18 specific mRNA by real-time quantitative reverse transcriptase-polymerase chain reaction in 26 children ages 3 to 15 years: 10 with untreated delayed-type CMA, 6 with celiac disease (CD) and 10 controls. RESULTS: The children with delayed-type CMA showed lower IL-2 and IL-18 mRNA expression in the duodenum (both P = 0.055) and higher CCR-4 and IL-6 mRNA expression in the terminal ileum (P = 0.055, P = 0.016) compared with the controls. The children with CD exhibited slightly higher expression of interferon-gamma and CCR-4 mRNA (P = 0.054, P = 0.053) and lower expression of IL-18 mRNA (P = 0.004) in the duodenal samples compared with the controls. The mRNA expression levels of regulatory cytokines, transforming growth factor-beta and IL-10 remained similar in all 3 groups. CONCLUSIONS: The children with delayed-type gastrointestinal CMA showed a unique pattern of local intestinal hypersensitivity with Th2 response-related characteristics, a profile differing clearly from the children with CD. © 2006 Lippincott Williams & Wilkins, Inc.
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| 23. |
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| 24. |
- Sheen, A. J., et al.
(författare)
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Randomized clinical trial of open suture repair versus totally extraperitoneal repair for treatment of sportsman's hernia
- 2019
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 106:7, s. 837-844
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sportsman's hernia/athletic pubalgia is a recognized cause of chronic groin pain in athletes. Both open and laparoscopic surgical repairs have been described for treatment, but there are no comparative studies. The hypothesis here was that relief of pain would be achieved earlier in patients treated with open minimal suture repair than totally extraperitoneal repair. Methods: A randomized multicentre trial in four European countries was conducted to compare open minimal suture repair with totally extraperitoneal repair. The primary endpoint was complete relief of pain (visual analogue scale (VAS) score 20 or less on a scale from 0 to 100 mm) at 1 month. Secondary endpoints included complications, time to return to sporting activity, and number of patients returning to sport within 1 year. Results: A total of 65 athletes (92 per cent men) with a median age of 29 years were enrolled (31 open repair, 34 totally extraperitoneal repair). By 4 weeks after surgery, median preoperative VAS scores had dropped from 70–80 to 10–20 in both groups (P < 0·001). Relief of pain (VAS score 20 or less) during sports activity 4 weeks after surgery was achieved in 14 of 31 patients after open repair and 24 of 34 after totally extraperitoneal repair (P = 0·047). Return to full sporting activity was achieved by 16 and 18 patients respectively after 1 month (P = 0·992), and by 25 versus 31 after 3 months (P = 0·408). Conclusion: Totally extraperitoneal repair was less painful than open repair in the first month, but otherwise both procedures were similarly effective in treating chronic pain due to sportsman's hernia. Registration number: NCT02297711 (http://www.clinical.trials.gov).
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