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1.
  • Forstner, A. J., et al. (författare)
  • Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression
  • 2019
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578.
  • Tidskriftsartikel (refereegranskat)abstract
    • Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10−4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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2.
  • Carmona-Gutierrez, D., et al. (författare)
  • Guidelines and recommendations on yeast cell death nomenclature
  • 2018
  • Ingår i: Microbial Cell. - 2311-2638. ; 5:1, s. 4-31
  • Forskningsöversikt (refereegranskat)abstract
    • Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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3.
  • Clements, C. C., et al. (författare)
  • Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy
  • 2021
  • Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578.
  • Tidskriftsartikel (refereegranskat)abstract
    • Although large genome-wide association studies (GWAS) of major depressive disorder (MDD) have identified many significant loci, the SNP-based heritability remains notably low, which might be due to etiological heterogeneity in existing samples. Here, we test the utility of targeting the severe end of the MDD spectrum through genome-wide SNP genotyping of 2725 cases who received electroconvulsive therapy (ECT) for a major depressive episode (MDE) and 4035 controls. A subset of cases (n = 1796) met a narrow case definition (MDE occurring in the context of MDD). Standard GWAS quality control procedures and imputation were conducted. SNP heritability and genetic correlations with other traits were estimated using linkage disequilibrium score regression. Results were compared with MDD cases of mild-moderate severity receiving internet-based cognitive behavioral therapy (iCBT) and summary results from the Psychiatric Genomics Consortium (PGC). The SNP-based heritability was estimated at 29-34% (SE: 6%) for the narrow case definition, considerably higher than the 6.5-8.0% estimate in the most recent PGC MDD study. Our severe MDE cases had smaller genetic correlations with neurodevelopmental disorders and neuroticism than PGC MDD cases but higher genetic risk scores for bipolar disorder than iCBT MDD cases. One genome-wide significant locus was identified (rs114583506, P = 5e-8) in an intron of HLA-B in the major histocompatibility locus on chr6. These results indicate that individuals receiving ECT for an MDE have higher burden of common variant risk loci than individuals with mild-moderate MDD. Furthermore, severe MDE shows stronger relations with other severe adult-onset psychiatric disorders but weaker relations with personality and stress-related traits than mild-moderate MDD. These findings suggest a different genetic architecture at the severest end of the spectrum, and support further study of the severest MDD cases as an extreme phenotype approach to understand the etiology of MDD.
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4.
  • Isomura, Kayoko, et al. (författare)
  • Risk of specific cardiovascular diseases in obsessive-compulsive disorder
  • 2020
  • Ingår i: Journal of Psychiatric Research. - : Elsevier. - 0022-3956 .- 1879-1379. ; 135, s. 189-196
  • Tidskriftsartikel (refereegranskat)abstract
    • Individuals with obsessive-compulsive disorder (OCD) may have an increased risk of cardiovascular disease (CVD), but evidence for specific types of CVD is limited. This population-based, sibling-controlled cohort study investigated the risk of specific CVD in individuals with OCD. Linking data from various Swedish population-based registers, we explored the risk of a range of CVD in a cohort of individuals diagnosed with OCD between 1973 and 2013 (n = 33,561), compared to matched (1:10) unaffected individuals (n = 335,610). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using conditional Cox proportional hazards regression models, adjusting for history of somatic diseases. To control for familial confounders, we analyzed 23,263 clusters of full siblings discordant for OCD. Individuals with psychiatric comorbidities were systematically excluded to assess the impact of these comorbidities. Over an average follow-up time of 27 years, OCD was associated with an increased risk of a broad range of CVD (adjusted HR [aHR] for any CVD = 1.25 [95% confidence interval [CI], 1.22-1.29]). These associations were strongest for the subtypes venous thrombo-embolism (aHR = 1.48 [95% CI, 1.38-1.58]) and heart failure (aHR = 1.37 [95% CI, 1.28-1.46]). When comparing OCD-exposed individuals with their non-exposed full siblings, results were largely similar. Exclusion of several groups of psychiatric comorbidities resulted in comparable results, albeit attenuated. Individuals with OCD have a moderately increased risk of CVD-related morbidity, independent from history of somatic diseases, familial confounders, and psychiatric comorbidities. The time may be ripe for the development and evaluation of lifestyle interventions to help reduce the risk of cardiovascular morbidity in OCD.
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5.
  • Feldt, K., et al. (författare)
  • Change in mitral regurgitation severity impacts survival after transcatheter aortic valve replacement
  • 2019
  • Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 294, s. 32-36
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The impact of a change in mitral regurgitation (MR) following TAVR is unknown. We studied the impact of baseline MR and early post-procedural change in MR on survival following TAVR. Methods: The SWEDEHEART registry included all TAVRs performed in Sweden. Patients were dichotomized into no/mild and moderate/severe MR groups. Vital status, echocardiographic data at baseline and within 7 days after TAVR were analyzed. Results: 1712 patients were included. 1404 (82%) had no/mild MR and 308 (18%) had moderate/severe MR. Baseline moderate/severe MR conferred a higher mortality rate at 5-year follow-up (adjusted HR 1.29, CI 1.01-1.65, p = 0.04). Using persistent <= mild MR as the reference, when moderate/severe MR persisted or if MR worsened from <= mild at baseline to moderate/severe after TAVR, higher 5-year mortality rates were seen (adjusted HR 1.66, CI 1.17-2.34, p = 0.04; adjusted HR 1.97, CI 1.29-3.00, p = 0.002, respectively). If baseline moderate/severe MR improved to = mild after TAVR no excess mortality was seen (HR 1.09, CI 0.75-1.58, p = 0.67). Paravalvular aortic regurgitation (PVL) was inversely associated with MR improvement after TAVR (OR 0.4, 95%: CI 0.17-0.94; p = 0.034). Atrial fibrillation (OR 2.1, 95% CI: 1.27-3.39, p = 0.004), self-expanding valve (OR 3.8, 95% CI: 2.08-7.14, p < 0.0001), and PVL (4.3, 95% CI 2.32-7.78. p < 0.0001) were associated with MR worsening. Conclusions: Moderate/severe baseline MR in patients undergoing TAVR is associated with a mortality increase during 5 years of follow-up. This risk is offset if MR improves to <= mild, whereas worsening of MR after TAVR is associated with a 2-fold mortality increase.
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8.
  • Schiele, Miriam A., et al. (författare)
  • Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders : A meta-analysis
  • 2021
  • Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 44, s. 105-120
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.
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9.
  • Bjursten, H., et al. (författare)
  • Infective endocarditis after transcatheter aortic valve implantation: a nationwide study
  • 2019
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 40:39, s. 3263-3269
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims  Transcatheter aortic valve implantation (TAVI), now a common procedure to treat high-risk patients with severe aortic stenosis, has rapidly been expanding into younger and lower-risk populations, creating a need to better understand long-term outcome after TAVI. The aim of the present investigation was to determine the incidence, risk factors for, clinical presentation of, and outcome after prosthetic valve endocarditis (PVE) in patients treated with TAVI in a nationwide study. Methods and results  Three registries were used: a national TAVI registry, a national diagnosis registry, and a national infective endocarditis registry. Combining these registries made it possible to perform a nationwide, all-comers study with independent and validated reporting of PVE in 4336 patients between 2008 and mid-2018. The risk for PVE after TAVI was 1.4% (95% confidence interval 1.0–1.8%) the first year and 0.8% (0.6–1.1%) per year thereafter. One-year survival after PVE diagnosis was 58% (49–68%), and 5-year survival was 29% (17–41%). Body surface area, estimated glomerular filtration rate <30 mL/min/1.73 m2, critical pre-operative state, mean pre-procedural valve gradient, amount of contrast dye used, transapical access, and atrial fibrillation were identified as independent risk factors for PVE. Staphylococcus aureus was more common in early (<1 year) PVE. Infection with S. aureus, root abscess, late PVE, and non-community acquisition was associated with higher 6-month mortality. Conclusion  The incidence of PVE was similar to that of surgical bioprostheses. Compromised renal function was a strong risk factor for developing PVE. In the context of PVE, TAVI seems to be a safe option for patients.
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10.
  • da Silva, Cristina, et al. (författare)
  • Hemodynamic outcomes of transcatheter aortic valve implantation with the CoreValve system : an early assessment
  • 2015
  • Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 35:3, s. 216-222
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: Transcatheter aortic valve implantation (TAVI) is an established method for the treatment of high-risk patients with aortic stenosis (AS). The beneficial effects of TAVI in cardiac hemodynamics have been described in recent studies, but those investigations were mostly performed after an interval of more than 6 months following aortic valve implantation. The aim of this study is to investigate the acute and short-term alterations in hemodynamic conditions using the echocardiography outcomes in patients undergoing TAVI. Methods and Results: A total of 60 patients (26 males, 34 females; age 84·7 ± 5·8) who underwent TAVI with CoreValve system were included in the study. Echocardiography was performed before hospital discharge and at 3 months follow-up. As expected, TAVI was associated with an immediate significant improvement in aortic valve area (AVA) (from 0·64 ± 0·16 cm2 to 1·67 ± 0·41 cm2, P-value<0·001) and mean gradient (from 51·9 ± 15·4 mmHg to 8·8 ± 3·8 mmHg, P-value<0·001). At 3-month follow-up, systolic LV function was augmented (EF: 50 ± 14% to 54 ± 11%, P-value = 0·024). Left ventricle (LV) mass and left atrium (LA) volume were significantly reduced (LV mass index from 126·5 ± 30·5 g m-2 to 102·4 ± 32·4 g m-2; LA index from 42·9 ± 17·3 ml m-2 to 33·6 ± 10·6 ml m-2; P-value<0·001 for both). Furthermore, a decrement in systolic pulmonary artery pressure (SPAP) from 47·5 ± 13·5 mmHg to 42·5 ± 11·2 mmHg, P-value = 0·02 was also observed. Despite the high incidence of paravalvular regurgitation (PVR) (80%), most of the patients presented mild or trace PVR and no significant progress of the regurgitation grade was seen after 3 months. Conclusion: This study demonstrates that the beneficial effects of TAVI in cardiac function and hemodynamics occur already after a short period following aortic valve implantation.
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