| 1. |
- Bartels, M., et al.
(författare)
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Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3-16years from multiple raters in six cohorts in the EU-ACTION project
- 2018
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Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 27:9, s. 1105-1121
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.
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| 2. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 3. |
- de Mello, V. D. F., et al.
(författare)
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Link between plasma ceramides, inflammation and insulin resistance : association with serum IL-6 concentration in patients with coronary heart disease
- 2009
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 52:12, s. 2612-2615
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Ceramides and IL-6 have a role in immune-inflammatory responses and cardiovascular diseases, and are suggested to be involved in insulin and glucose metabolism. We sought to assess the associations of circulating levels of IL-6, TNF-alpha and high-sensitivity C reactive protein (hsCRP), which are inflammatory markers related to insulin resistance (IR), with the plasma lipid metabolites ceramides and diacylglycerols (DAG) in patients with CHD.METHODS: Cross-sectional analyses were carried out on data from 33 patients with CHD. Serum levels of the inflammatory markers and plasma lipid metabolites (lipidomics approach performed by ultra-performance liquid chromatography coupled to electrospray ionisation MS) were measured at the same time point as insulin resistance (IR) (HOMA-IR index).RESULTS: Serum circulating levels of IL-6 were strongly correlated with plasma ceramide concentrations (r = 0.59, p < 0.001). Adjustments for serum TNF-alpha or hsCRP levels, smoking, BMI, age, sex or HOMA-IR did not change the results (p < 0.001). After adjustments for the effect of serum inflammatory markers (TNF-alpha or hsCRP), HOMA-IR and BMI the correlation between plasma DAG and serum IL-6 (r = 0.33) was also significant (p < 0.03). In a linear regression model, circulating levels of both ceramides and TNF-alpha had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation (p < 0.001).CONCLUSIONS/INTERPRETATION: Our results strongly suggest that the link between ceramides, IR and inflammation is related to the inflammatory marker IL-6. Ceramides may contribute to the induction of inflammation involved in IR states that frequently coexist with CHD.
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| 4. |
- Sundén, Henrik, 1978, et al.
(författare)
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Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators
- 2015
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 1520-4804 .- 0022-2623. ; 58:3, s. 1569-1574
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Tidskriftsartikel (refereegranskat)abstract
- To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.
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| 5. |
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| 6. |
- Bergh, Camilla, et al.
(författare)
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Increased risk of revision in patients with non-traumatic femoral head necrosis.
- 2014
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Ingår i: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 85:1, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Previous studies of patients who have undergone total hip arthroplasty (THA) due to femoral head necrosis (FHN) have shown an increased risk of revision compared to cases with primary osteoarthritis (POA), but recent studies have suggested that this procedure is not associated with poor outcome. We compared the risk of revision after operation with THA due to FHN or POA in the Nordic Arthroplasty Register Association (NARA) database including Denmark, Finland, Norway, and Sweden. Patients and methods 427,806 THAs performed between 1995 and 2011 were included. The relative risk of revision for any reason, for aseptic loosening, dislocation, deep infection, and periprosthetic fracture was studied before and after adjustment for covariates using Cox regression models. Results 416,217 hips with POA (mean age 69 (SD 10), 59% females) and 11,589 with FHN (mean age 65 (SD 16), 58% females) were registered. The mean follow-up was 6.3 (SD 4.3) years. After 2 years of observation, 1.7% in the POA group and 3.0% in the FHN group had been revised. The corresponding proportions after 16 years of observation were 4.2% and 6.1%, respectively. The 16-year survival in the 2 groups was 86% (95% CI: 86-86) and 77% (CI: 74-80). After adjusting for covariates, the relative risk (RR) of revision for any reason was higher in patients with FHN for both periods studied (up to 2 years: RR = 1.44, 95% CI: 1.34-1.54; p < 0.001; and 2-16 years: RR = 1.25, 1.14-1.38; p < 0.001). Interpretation Patients with FHN had an overall increased risk of revision. This increased risk persisted over the entire period of observation and covered more or less all of the 4 most common reasons for revision.
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| 7. |
- de Mello, Vanessa D. F., et al.
(författare)
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The effect of fatty or lean fish intake on inflammatory gene expression in peripheral blood mononuclear cells of patients with coronary heart disease
- 2009
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Ingår i: European Journal of Nutrition. - : Steinkopff-Verlag. - 1436-6207 .- 1436-6215. ; 48:8, s. 447-455
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the effect of fish consumption on gene expression of inflammation-related genes in immune cells in coronary heart disease (CHD).AIM OF THE STUDY: We sought to evaluate the effect of a fatty fish (FF) or a lean fish (LF) diet on the modulation of inflammatory and endothelial function-related genes in peripheral blood mononuclear cells (PBMCs) of subjects with CHD, and its association with serum fatty acid (FA) profile and lipid metabolic compounds.METHODS: Data from 27 patients randomized into an 8-week FF (n = 10; mean +/- SD: 4.3 +/- 0.4 portions of fish per week), LF (n = 11; 4.7 +/- 1.1 portions of fish per week), or control diet (n = 6; 0.6 +/- 0.4 portions of fish per week) were analyzed. The mRNA expression was measured using real-time PCR.RESULTS: The effect of the intervention on the mRNA expression of the genes studied did not differ among groups. In the FF group, however, the decrease in arachidonic acid to eicosapentaenoic acid (AA:EPA) ratio in cholesterol ester and phospholipid fractions strongly correlated with the change in IL1B mRNA levels (r (s) = 0.60, P = 0.06 and r (s) = 0.86, P = 0.002, respectively). In the LF group, the decrease in palmitic acid and total saturated FAs in cholesterol esters correlated with the change in intercellular cell adhesion molecule-1 (ICAM1) expression (r (s) = 0.64, P = 0.04 for both). Circulating levels of soluble ICAM-1 decreased only in the LF group (P < 0.05).CONCLUSIONS: The intake of FF or LF diet did not alter the expression of inflammatory and endothelial function-related genes in PBMCs of patients with CHD. However, the decrease in AA:EPA ratio in serum lipids in the FF group may induce an anti-inflammatory response at mRNA levels in PBMCs. A LF diet might benefit endothelial function, possibly mediated by the changes in serum FA composition.
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| 8. |
- Kumar, Anmol, et al.
(författare)
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GDNF Overexpression from the Native Locus Reveals its Role in the Nigrostriatal Dopaminergic System Function
- 2015
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Ingår i: PLOS Genetics. - : PLoS. - 1553-7390 .- 1553-7404. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Degeneration of nigrostriatal dopaminergic system is the principal lesion in Parkinson's disease. Because glial cell line-derived neurotrophic factor (GDNF) promotes survival of dopamine neurons in vitro and in vivo, intracranial delivery of GDNF has been attempted for Parkinson's disease treatment but with variable success. For improving GDNF-based therapies, knowledge on physiological role of endogenous GDNF at the sites of its expression is important. However, due to limitations of existing genetic model systems, such knowledge is scarce. Here, we report that prevention of transcription of Gdnf 3'UTR in Gdnf endogenous locus yields GDNF hypermorphic mice with increased, but spatially unchanged GDNF expression, enabling analysis of postnatal GDNF function. We found that increased level of GDNF in the central nervous system increases the number of adult dopamine neurons in the substantia nigra pars compacta and the number of dopaminergic terminals in the dorsal striatum. At the functional level, GDNF levels increased striatal tissue dopamine levels and augmented striatal dopamine release and re-uptake. In a proteasome inhibitor lactacystin-induced model of Parkinson's disease GDNF hypermorphic mice were protected from the reduction in striatal dopamine and failure of dopaminergic system function. Importantly, adverse phenotypic effects associated with spatially unregulated GDNF applications were not observed. Enhanced GDNF levels up-regulated striatal dopamine transporter activity by at least five fold resulting in enhanced susceptibility to 6-OHDA, a toxin transported into dopamine neurons by DAT. Further, we report how GDNF levels regulate kidney development and identify microRNAs miR-9, miR-96, miR-133, and miR-146a as negative regulators of GDNF expression via interaction with Gdnf 3'UTR in vitro. Our results reveal the role of GDNF in nigrostriatal dopamine system postnatal development and adult function, and highlight the importance of correct spatial expression of GDNF. Furthermore, our results suggest that 3'UTR targeting may constitute a useful tool in analyzing gene function.
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| 9. |
- Laari, S., et al.
(författare)
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Memory decline in young stroke survivors during a 9-year follow-up: A cohort study
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionA decade after stroke, young stroke survivors continue to suffer from cognitive impairment. However, it is not known whether this long-term cognitive outcome is caused in part by further cognitive decline or solely by incomplete recovery from the acute effects of ischemic stroke. We studied changes in three cognitive domains over a 9-year follow-up period after first-ever and only ischemic stroke. Patients and methodsIn this prospective, two-center cohort study, we recruited consecutive 18-65 year-old patients with acute stroke between 2007 and 2009, along with demographically matched stroke-free controls. We performed comprehensive neuropsychological assessments at 3 months, 2, and 9 years after stroke, and we also performed neurological examinations at the time of inclusion and at the 9-year follow-up. We assessed the associations among stroke, follow-up time and long-term cognitive outcomes using repeated-measures analysis of variance. ResultsThe subjects comprised 85 patients who had had their first-ever and only ischemic stroke (mean age 53 years at inclusion), along with 31 stroke-free demographic controls. We compared the cognitive changes in patients to those in controls over a 9-year follow-up. After initial recovery between 3 months and 2 years after stroke, patients showed a decline in memory between 2 and 9 years after stroke compared to controls within the same time interval (immediate recall p < 0.001; delayed recall p < 0.001; list learning p < 0.001). Other than memory, we found no difference in cognitive changes between poststroke patients and controls. DiscussionOur main finding was memory decline over a decade in young first-ever stroke patients with no further stroke or neurodegenerative disease. Our study extends the previous results of further memory decline in elderly stroke survivors to young stroke survivors. ConclusionYoung stroke survivors might be at risk of memory decline over the decade following the stroke.
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| 10. |
- Makela, K. T., et al.
(författare)
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Countrywise results of total hip replacement An analysis of 438,733 hips based on the Nordic Arthroplasty Register Association database
- 2014
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 85:2, s. 107-116
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose An earlier Nordic Arthroplasty Register Association (NARA) report on 280,201 total hip replacements (THRs) based on data from 1995-2006, from Sweden, Norway, and Denmark, was published in 2009. The present study assessed THR survival according to country, based on the NARA database with the Finnish data included. Material and methods 438,733 THRs performed during the period 1995-2011 in Sweden, Denmark, Norway, and Finland were included. Kaplan-Meier survival analysis was used to calculate survival probabilities with 95% confidence interval (CI). Cox multiple regression, with adjustment for age, sex, and diagnosis, was used to analyze implant survival with revision for any reason as endpoint. Results The 15-year survival, with any revision as an endpoint, for all THRs was 86% (CI: 85.7-86.9) in Denmark, 88% (CI: 87.6-88.3) in Sweden, 87% (CI: 86.4-87.4) in Norway, and 84% (CI: 82.9-84.1) in Finland. Revision risk for all THRs was less in Sweden than in the 3 other countries during the first 5 years. However, revision risk for uncemented THR was less in Denmark than in Sweden during the sixth (HR = 0.53, CI: 0.34-0.82), seventh (HR = 0.60, CI: 0.37-0.97), and ninth (HR = 0.59, CI: 0.36-0.98) year of follow-up. Interpretation The differences in THR survival rates were considerable, with inferior results in Finland. Brand-level comparison of THRs in Nordic countries will be required.
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