| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
- Schijven, Dick, et al.
(författare)
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Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
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Tidskriftsartikel (refereegranskat)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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| 4. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 5. |
- Dore, Riccardo, et al.
(författare)
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Resistance to thyroid hormone induced tachycardia in RTHα syndrome
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.
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| 6. |
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| 7. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 8. |
- Olander, Julia, 1984, et al.
(författare)
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Implant-Supported Single Crowns with Titanium or Zirconia Abutments: A Retrospective Up-to-5-year Follow-up Study.
- 2022
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Ingår i: The International journal of prosthodontics. - : Quintessence Publishing. - 1942-4426 .- 0893-2174. ; 35:4, s. 387-395
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Tidskriftsartikel (refereegranskat)abstract
- To compare the clinical outcomes of single implants with titanium (Ti) or zirconia (Zr) abutments after up to 5 years in function.This study was a retrospective analysis on single implants with screw-retained abutments (Zr or Ti) covered with porcelain veneer placed between 2011 and 2013 at one referral specialist clinic. Clinical data from patient records were collected from 132 patients and 174 implants. Technical complications such as fractures, chipping, and abutment screw loosening were registered. Radiographs were analyzed comparing both annual bone loss and accumulated bone loss at 5 years. In 57 patients with 85 implants, the values of accumulated bone loss at 5 years were compared to baseline.Technical complications occurred in 16 (9%) of the implants, most often during the first year. The following complications were found: fracture of the abutment (n = 1); loosening of the abutment screws (n = 5); and chipping of the porcelain veneer (n = 11). Ti abutments had more complications than Zr abutments (79%). Of all the implants, 45% had an annual bone loss ranging between 0.05 and 2.15 mm, and 59% had an accumulated bone loss at 5 years ranging between 0.05 and 4.25 mm. Zr abutments had a statistically significantly higher amount of yearly and accumulated bone loss at 5 years.Abutment material affected marginal bone loss. The Zr group displayed statistically more bone loss both yearly and after 5 years compared to the Ti group. Technical complications were not affected by abutment material but were affected by age of the patient.
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| 9. |
- Olander, Julia, 1984, et al.
(författare)
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Inflammatory Gene Profile and Particle Presence in Peri-Implant Mucosa: a Pilot Study on 9 Patients
- 2023
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Ingår i: Jomr-Journal of Oral & Maxillofacial Research. - 2029-283X. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this pilot study is to compare gene expression in mucosa around dental implants with zirconia abutment to titanium and investigate presence of particles in mucosa samples and on implant heads. Material and Methods: Ten patients with a single implant supported prosthesis connected to zirconia or titanium abutments were invited at the five-year control. A clinical examination and a survey on experience of function and appearance were conducted. A mucosa biopsy taken in close vicinity to the implant were analysed by real-time polymerase chain reaction (qPCR) and presence of particles in a scanning electron microscope/energy-dispersive X-ray spectroscope (SEM/EDX). Cytological smear samples were collected and analysed through inductively coupled plasma mass spectrometry (ICP-MS) to investigate presence of particles on implant heads. Results: In total, 9 patients participated in the study, five with titanium abutments and four with zirconia abutments. All patients were satisfied with function and aesthetics. Titanium and iron particles were detected in mucosa biopsies. The ICP -MS analysis demonstrated presence of zirconia and titanium. Several proinflammatory genes were upregulated in the zirconia abutment group. Conclusions: Around zirconia abutments a slight increase in proinflammatory response and amount of wear particles was seen as compared to titanium. Wear particles of titanium were present in all soft tissue samples, however zirconia particles only in the samples from implants heads/mucosa with zirconia abutments.
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| 10. |
- Olander, Julia, 1984, et al.
(författare)
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Wear particle release at the interface of dental implant components: Effects of different material combinations. An in vitro study
- 2022
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Ingår i: Dental Materials. - : Elsevier BV. - 0109-5641. ; 38:3, s. 508-516
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Particle generation from implant components caused by frictional wear affect the surrounding peri-implant tissues. The objective of this study was to evaluate the effect of combining implant and abutment materials on wear and particle release in a dynamical loading setup. Methods: A customized dynamical loading machine was used to subject two implant materials (Titanium and Titanium- Zirconium alloy) paired with two different abutment materials (Titanium and Zirconia) to a cyclic loading set of 240.000 cycles (simulating 1 year of clinical use). The implant and abutment complex was immersed in corrosive liquid to collect particle debris and measure the release of corroded ions. Scanning electron microscopy was used to analyze signs of wear on the components after testing and evaluate the size and composition of particle debris. Results: Wear signs were evident in all material couplings. Particle debris was found on top, inside the implants, and on the abutment heads. The particle size ranged between 0.6 and 16.9 µm, with larger particles composed of Ti. Smaller-sized particles were found in the container liquid ranging from 0.253 to 1.7 µm compared to inside the implants ranging from 3.25 to 95.3 µm. Larger particles were found inside Tizr implants compared to Ti implants. Low levels of ions released due to corrosion were found when measuring content in surrounding liquid. Significance: Particle generation is evident when subjecting dental implant and abutment couplings in a dynamic loading setup. Internally connected implants hinder the release of larger particles to surrounding container liquid. © 2022 The Authors
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