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| 2. |
- Bakker, M. K., et al.
(author)
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Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
- 2020
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:12, s. 1303-1313
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Journal article (peer-reviewed)abstract
- Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.
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| 6. |
- Niemela, T., et al.
(author)
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Relationship Between Soluble Urokinase Plasminogen Activator Receptor (suPAR) and Disease Outcome in Adult-Onset Asthma
- 2022
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In: Journal of Asthma and Allergy. - 1178-6965. ; 15, s. 579-593
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Journal article (peer-reviewed)abstract
- Background: Soluble urokinase plasminogen activator receptor (suPAR) has emerged as a novel biomarker for various inflammatory conditions and has been proposed to associate with the severity of asthma. However, the relationship between suPAR and clinical asthma features is poorly understood. Objective: To examine associations of serum suPAR levels with clinical characteristics of asthma and to define the phenotype with high suPAR levels in patients with adult-onset asthma. Methods: Serum suPAR levels were measured with ELISA from patients with adult-onset asthma participating in the 12-year followup visit in the Seinajoki Adult Asthma Study. Results: In total, 201 patients were divided into quartiles according to suPAR values. High suPAR patients had more severe asthma symptoms and poorer asthma control. They also had higher levels of interleukin 8 (IL-8), interleukin 6 (IL-6), matrix metalloproteinase 9 (MMP-9), and blood neutrophil counts than those with low suPAR levels. The use of high-dose inhaled and oral corticosteroids was more common in patients with elevated suPAR. Such patients also had visited healthcare more frequently during the follow-up period, had more comorbidities, and were physically less active than those with low suPAR levels. The above-mentioned results remained similar after excluding the patients with co-existing COPD; only association to hospitalizations was lost. In multivariable binary regression analyses, the highest suPAR quartile was associated with higher cumulative dispensed oral corticosteroid use, more severe symptoms, and uncontrolled asthma. Conclusion: High suPAR levels occur in uncontrolled adult-onset asthma patients characterized by neutrophilic inflammation, high corticosteroid use, frequent healthcare visits, and multimorbidity with unhealthy lifestyle. This biomarker could be useful in determining asthma phenotypes and target new asthma treatments.
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- Ilmarinen, P., et al.
(author)
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Long-term prognosis of new adult-onset asthma in obese patients
- 2021
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 57:4
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Journal article (peer-reviewed)abstract
- Background: Obesity has been associated with poor outcomes of asthma in cross-sectional studies, but long-term effect of obesity on asthma remains unknown. Aims: To study the effects of obesity, found at the time of diagnosis of adult-onset asthma, on 12-year prognosis by focusing on oral corticosteroid (OCS) use and respiratory-related hospital admissions. Methods: Patients diagnosed with adult-onset asthma (n=203) were divided into three categories based on diagnostic body mass index (BMI) (<25 kg.m(-2), 25-29.9 kg.m(-2), >= 30 kg.m(-2)) and followed for 12 years as part of the Seinajoki Adult Asthma Study. Self-reported and dispensed OCS were assessed for the 12-year period. Data on hospital admissions were analysed based on medical records. Results: 12 years after diagnosis, 86% of the patients who were obese (BMI.30 kg.m(-2)) at diagnosis remained obese. During the follow-up, no difference was found in weight gain between the BMI categories. During the 12-year follow-up, patients obese at diagnosis reported more frequent use of OCS courses (46.9% versus 23.1%, p=0.028), were dispensed OCS more often (81.6% versus 56.9%, p=0.014) and at higher doses (median 1350 (interquartile range 280-3180) mg versus 600 (0-1650) mg prednisolone, p=0.010) compared to normal-weight patients. Furthermore, patients who were obese had more often one or more respiratory-related hospitalisations compared to normal-weight patients (38.8% versus 16.9%, p=0.033). In multivariate logistic regression analyses, obesity predicted OCS use and hospital admissions. Conclusions: In adult-onset asthma, patients obese at diagnosis mostly remained obese at long-term and had more exacerbations and respiratory-related hospital admissions compared to normal-weight patients during 12-year follow-up. Weight loss should be a priority in their treatment to prevent this outcome.
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| 16. |
- Otero, Jaime, et al.
(author)
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Basin-scale phenology and effects of climate variability on global timing of initial seaward migration of Atlantic salmon (Salmo salar)
- 2014
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 20:1, s. 61-75
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Journal article (peer-reviewed)abstract
- Migrations between different habitats are key events in the lives of many organisms. Such movements involve annually recurring travel over long distances usually triggered by seasonal changes in the environment. Often, the migration is associated with travel to or from reproduction areas to regions of growth. Young anadromous Atlantic salmon (Salmo salar) emigrate from freshwater nursery areas during spring and early summer to feed and grow in the North Atlantic Ocean. The transition from the freshwater ('parr') stage to the migratory stage where they descend streams and enter salt water ('smolt') is characterized by morphological, physiological and behavioural changes where the timing of this parr-smolt transition is cued by photoperiod and water temperature. Environmental conditions in the freshwater habitat control the downstream migration and contribute to within- and among-river variation in migratory timing. Moreover, the timing of the freshwater emigration has likely evolved to meet environmental conditions in the ocean as these affect growth and survival of the post-smolts. Using generalized additive mixed-effects modelling, we analysed spatio-temporal variations in the dates of downstream smolt migration in 67 rivers throughout the North Atlantic during the last five decades and found that migrations were earlier in populations in the east than the west. After accounting for this spatial effect, the initiation of the downstream migration among rivers was positively associated with freshwater temperatures, up to about 10 °C and levelling off at higher values, and with sea-surface temperatures. Earlier migration occurred when river discharge levels were low but increasing. On average, the initiation of the smolt seaward migration has occurred 2.5 days earlier per decade throughout the basin of the North Atlantic. This shift in phenology matches changes in air, river, and ocean temperatures, suggesting that Atlantic salmon emigration is responding to the current global climate changes.
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- Spirin, Viacheslav, et al.
(author)
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The genus Fomitopsis (Polyporales, Basidiomycota) reconsidered
- 2024
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In: STUDIES IN MYCOLOGY. - 0166-0616 .- 1872-9797. ; :107, s. 149-249
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Journal article (peer-reviewed)abstract
- Based on seven- and three-gene datasets, we discuss four alternative approaches for a reclassification of Fomitopsidaceae (Polyporales, Basidiomycota). After taking into account morphological diversity in the family, we argue in favour of distinguishing three genera only, viz. Anthoporia, Antrodia and Fomitopsis. Fomitopsis becomes a large genus with 128 accepted species, containing almost all former Fomitopsis spp. and most species formerly placed in Antrodia, Daedalea and Laccocephalum. Genera Buglossoporus, Cartilosoma, Daedalea, Melanoporia, Neolentiporus, alongside twenty others, are treated as synonyms of Fomitopsis. This generic scheme allows for morphologically distinct genera in Fomitopsidaceae, unlike other schemes we considered. We provide arguments for retaining Fomitopsis and suppressing earlier (Daedalea, Caloporus) or simultaneously published generic names (Piptoporus) considered here as its synonyms. Taxonomy of nine species complexes in the genus is revised based on ITS, ITS + TEF1, ITS + TEF1 + RPB1 and ITS + TEF1 + RPB2 datasets. In total, 17 species are described as new to science, 26 older species are reinstated and 26 currently accepted species names are relegated to synonymy. A condensed identification key for all accepted species in the genus is provided.
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| 22. |
- Takala, J., et al.
(author)
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Documentation of smoking in scheduled asthma contacts in primary health care: a 12-year follow-up study
- 2022
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In: Npj Primary Care Respiratory Medicine. - : Springer Science and Business Media LLC. - 2055-1010. ; 32:1
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Journal article (peer-reviewed)abstract
- Smoking among asthmatics is common and associates with poorer asthma control, more rapid lung function decline and higher health care costs in dose-dependent manner. No previous real-life studies exist, however, on how smoking status and pack-years are documented in scheduled asthma contacts in primary health care (PHC) during long-term follow-up, and how often patients are advised to quit smoking. In this real-life 12-year follow-up study, we showed that out of all scheduled PHC asthma contacts (n = 603) smoking was mentioned only in 17.2% and pack-years only in 6.5%. Smoking data was not recorded even once in 70.9% of never smokers, 64.7% of ex-smokers and 27.3% of current smokers. Smoking including pack-years were mentioned more often if nurse took part on the scheduled contact. For current smokers, smoking cessation was recommended only in 21.7% of their scheduled contacts. Current smokers used more antibiotics and had more unscheduled health care contacts during follow-up.
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| 23. |
- Takala, J., et al.
(author)
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Participation in scheduled asthma follow-up contacts and adherence to treatment during 12-year follow-up in patients with adult-onset asthma
- 2022
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In: Bmc Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Poor treatment compliance is a common problem in the treatment of asthma. To our knowledge, no previous long-term follow-up studies exist on how scheduled asthma follow-up contacts occur in primary health care (PHC) versus secondary care and how these contacts relate to adherence to medication and in participation to further scheduled asthma contacts. The aim of this study was to evaluate occurrence of scheduled asthma contacts and treatment compliance in PHC versus secondary care, and to identify the factors associated with non-participation to scheduled contacts. Methods: Patients with new adult-onset asthma (n = 203) were followed for 12 years in a real-life asthma cohort of the Seinajoki Adult Asthma Study (SAAS). The first contacts were mainly carried out in secondary care and therefore the actual follow-up time including PHC visits was 10 years. Results: A majority (71%) of the patients had >= 2 scheduled asthma contacts during 10-year follow-up and most of them (79%) mainly in PHC. Patients with follow-up contacts mainly in PHC had better adherence to inhaled corticosteroid (ICS) medication during the whole 12-year period compared to patients in secondary care. In the study population, 29% of the patients had only 0-1 scheduled asthma contacts during the follow-up. Heavy alcohol consumption predicted poor participation in scheduled contacts. Conclusions: Patients with mainly PHC scheduled asthma contacts were more adherent to ICS medication than patients in the secondary care. Based on our results it is necessary to pay more attention to actualization of asthma follow-up visits and systematic assessment of asthma patients including evaluation of alcohol consumption.
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| 26. |
- Vahatalo, I., et al.
(author)
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Long-term adherence to inhaled corticosteroids and asthma control in adult-onset asthma
- 2021
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In: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:1
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Journal article (peer-reviewed)abstract
- Background: In short-term studies, poor adherence to inhaled corticosteroids (ICS) has been associated with worse asthma control, but the association of long-term adherence and disease control remains unclear. Objective: To assess the relationship between 12-year adherence to ICS and asthma control in patients with adult-onset asthma. Methods: As part of the Seinajoki Adult Asthma Study, 181 patients with clinically confirmed new-onset adult asthma and regular ICS medication were followed-up for 12 years. Adherence (%) to ICS was assessed individually ((mu g dispensed/mu g prescribed)x100) during the follow-up. Asthma control was evaluated after 12 years of treatment according to the Global Initiative for Asthma 2010 guideline. Results: Asthma was controlled in 31% and not controlled ( partly controlled or uncontrolled) in 69% of the patients. Patients with not-controlled asthma were more often male, older, nonatopic and used higher doses of ICS than those with controlled disease. The mean +/- SD 12-year adherence to ICS was 63 +/- 38% in patients with controlled asthma and 76 +/- 40% in patients with not-controlled disease (p=0.042). Among patients with not-controlled asthma, those with lower 12-year adherence (<80%) had more rapid decline in forced expiratory volume in 1 s (-47 mL.year(-1)) compared to patients with better adherence (.80%) (-40 mL.year(-1)) (p=0.024). In contrast, this relationship was not seen in patients with controlled asthma. Conclusions: In adult-onset asthma, patients with not-controlled disease showed better 12-year adherence to ICS treatment than those with controlled asthma. In not-controlled disease, adherence >= 80% was associated with more rapid lung function decline, underscoring the importance of early recognition of such patients in routine clinical practice.
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| 27. |
- Vahatalo, I., et al.
(author)
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Long-Term Use of Short-Acting beta(2)-Agonists in Patients With Adult-Onset Asthma
- 2022
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In: Journal of Allergy and Clinical Immunology-in Practice. - : Elsevier BV. - 2213-2198. ; 10:8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Short-term studies have associated high use of short-acting beta(2)-agonists (SABA) with increased risk of exacerbations, emergency visits, and asthma-related costs. However, no studies exist on long-term SABA use, and previous studies on the topic have not included information about adherence to inhaled corticosteroids (ICS) nor disease control, both affecting the need of SABA. OBJECTIVE: To evaluate the clinical characteristics of SABA and ICS usage in newly diagnosed adult-onset asthma patients during a 12-year follow-up period. METHODS: In the Seinajoki Adult Asthma Study, 203 patients with adult-onset asthma were followed for 12 years. Information on dispensed SABA and ICS during the follow-up was obtained from the Finnish Social Insurance Institution. High SABA use was defined as >= 36 canisters in 12 years, corresponding to an average of >= 3 dispensed canisters/y. RESULTS: Patients were dispensed median 6 (interquartile range: 3-16) SABA canisters and 48 (18-67) ICS canisters over 12 years, corresponding to 2 (1-4) and 11 (5-16) puffs/week, respectively. Only 10% of the patients were classified as high SABA users during this period. Obesity (body mass index >= 30) and high Airways Questionnaire 20 symptom scores at baseline predicted high long-term SABA use (incidence rate ratio: 1.53 [1.01-2.30] and 1.04 [1.00-1.08], respectively). High SABA users had higher ICS adherence, higher blood neutrophil counts, more comorbidities, and used more oral corticosteroid and antibiotic courses versus low SABA users. CONCLUSION: High SABA use was infrequent in patients with confirmed adult-onset asthma. However, as high SABA use is associated with more severe asthma, these patients should be recognized in clinical practice. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
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| 28. |
- Wijns, W, et al.
(author)
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Myocardial revascularization
- 2011
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In: REVISTA PORTUGUESA DE CARDIOLOGIA. - : Elsevier BV. - 0870-2551 .- 2174-2049. ; 30:12, s. 951-1005
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Journal article (other academic/artistic)
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| 29. |
- Yau, Anthony C. Y., et al.
(author)
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Inflammation and neutrophil extracellular traps in cerebral cavernous malformation
- 2022
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In: Cellular and Molecular Life Sciences (CMLS). - : Springer Nature. - 1420-682X .- 1420-9071. ; 79:4
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Journal article (peer-reviewed)abstract
- Cerebral Cavernous Malformation (CCM) is a brain vascular disease with various neurological symptoms. In this study, we describe the inflammatory profile in CCM and show for the first time the formation of neutrophil extracellular traps (NETs) in rodents and humans with CCM. Through RNA-seq analysis of cerebellum endothelial cells from wild-type mice and mice with an endothelial cell-specific ablation of the Ccm3 gene (Ccm3(iECKO)), we show that endothelial cells from Ccm3(iECKO) mice have an increased expression of inflammation-related genes. These genes encode proinflammatory cytokines and chemokines, as well as adhesion molecules, which promote recruitment of inflammatory and immune cells. Similarly, immunoassays showed elevated levels of these cytokines and chemokines in the cerebellum of the Ccm3(iECKO) mice. Consistently, both flow cytometry and immunofluorescence analysis showed infiltration of different subsets of leukocytes into the CCM lesions. Neutrophils, which are known to fight against infection through different strategies, including the formation of NETs, represented the leukocyte subset within the most pronounced increase in CCM. Here, we detected elevated levels of NETs in the blood and the deposition of NETs in the cerebral cavernomas of Ccm3(iECKO) mice. Degradation of NETs by DNase I treatment improved the vascular barrier. The deposition of NETs in the cavernomas of patients with CCM confirms the clinical relevance of NETs in CCM.
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