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| 2. |
- Dreifaldt, Mats, et al.
(författare)
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The ‘‘no-touch’’ harvesting technique for vein grafts in coronary artery bypass surgery preserves an intact vasa vasorum
- 2011
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Ingår i: The Internet Journal of Thoracic and Cardiovascular Surgery. - New York, USA : Elsevier. - 1524-0274 .- 0022-5223. ; 141:1, s. 145-150
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Our objective was to evaluate the impact of vein graft harvesting technique on structure and function of vasa vasorum.Methods: Paired segments of great saphenous veins harvested either with conventional harvesting technique or no-touch technique were obtained from 9 consecutive patients undergoing coronary artery bypass grafting. Quantitative measurements, using immunohistochemistry and morphometry, were performed. Ultrastructural analyses of vasa vasorum were performed with electron microscopy. Video footage of superficial vasa vasorum in an implanted saphenous vein graft harvested with the no-touch technique was captured during a coronary bypass operation and is presented for online viewing.Results: The total area of vasa vasorum in vein grafts harvested with the conventional technique was significantly reduced both in the media (P¼.007) and in the adventitia (P¼.014) compared with vein grafts harvested with the no-touch technique. Ultrastructural findings indicated that the no-touch technique preserved an intact vasa vasorum whereas the conventional technique did not. Video footage showed retrograde flow in the vasa vasorum in vein graft harvested with the no-touch technique.Conclusions: These findings showthat the no-touch technique for saphenous vein graft harvesting for coronary bypass grafting preserves an intact vasa vasorum. This could represent one of the mechanisms underlying the improved patency of saphenous vein grafts harvested with this technique.
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| 3. |
- Tate, A. E., et al.
(författare)
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A genetically informed prediction model for suicidal and aggressive behaviour in teens
- 2022
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal and aggressive behaviours cause significant personal and societal burden. As risk factors associated with these behaviours frequently overlap, combined approaches in predicting the behaviours may be useful in identifying those at risk for either. The current study aimed to create a model that predicted if individuals will exhibit suicidal behaviour, aggressive behaviour, both, or neither in late adolescence. A sample of 5,974 twins from the Child and Adolescent Twin Study in Sweden (CATSS) was broken down into a training (80%), tune (10%) and test (10%) set. The Netherlands Twin Register (NTR; N = 2702) was used for external validation. Our longitudinal data featured genetic, environmental, and psychosocial predictors derived from parental and self-report data. A stacked ensemble model was created which contained a gradient boosted machine, random forest, elastic net, and neural network. Model performance was transferable between CATSS and NTR (macro area under the receiver operating characteristic curve (AUC) [95% CI] AUC(CATSS(test set)) = 0.709 (0.671-0.747); AUC(NTR) = 0.685 (0.656-0.715), suggesting model generalisability across Northern Europe. The notable exception is suicidal behaviours in the NTR, which was no better than chance. The 25 highest scoring variable importance scores for the gradient boosted machines and random forest models included self-reported psychiatric symptoms in mid-adolescence, sex, and polygenic scores for psychiatric traits. The model's performance is comparable to current prediction models that use clinical interviews and is not yet suitable for clinical use. Moreover, genetic variables may have a role to play in predictive models of adolescent psychopathology.
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| 4. |
- Baldwin, J. R., et al.
(författare)
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A genetically informed Registered Report on adverse childhood experiences and mental health
- 2023
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 7:2, s. 269-290
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Tidskriftsartikel (refereegranskat)abstract
- Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene-environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene-environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.
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| 5. |
- Fritz, Tomas, et al.
(författare)
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Low-intensity exercise increases skeletal muscle protein expression of PPARdelta and UCP3 in type 2 diabetic patients
- 2006
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 22:6, s. 492-498
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Physical exercise provides health benefits for people with type 2 diabetes mellitus, partly by enhancing skeletal muscle insulin action. We tested the hypothesis that changes in expression of key genes in skeletal muscles relate to exercise-induced improvements in type 2 diabetic patients. METHODS: We determined mRNA expression of 20 selected genes following a self-supervised program of walking (> 150 min per week) over a 4-month period. RESULTS: This level of physical activity improved clinical parameters in approximately half the participants, as determined by reduced hypertension and enhanced insulin sensitivity (defined by reduced plasma-insulin levels and improved homeostasis model assessment (HOMA)). Skeletal muscle mRNA expression of Cbl-associated protein (CAP), diacylglycerol kinase (DGK)delta, uncoupling protein (UCP) 3, nuclear respiratory factor (NRF)-1, and peroxisome proliferator-activated receptor (PPAR)delta tended to increase in type 2 diabetic patients with an improved clinical profile. Skeletal muscle protein expression of PPARdelta and UCP3 was increased significantly after physical exercise in patients with an improved clinical profile, but were unchanged in patients who did not show exercise-mediated improvements in clinical parameters. CONCLUSIONS: This study provides clinical evidence that improvements in insulin sensitivity can be achieved in type 2 diabetic patients after individually executed low-intensity exercise training. Moreover, the positive clinical response to exercise is correlated with changes in skeletal muscle proteins involved in the regulation of mitochondrial biogenesis and metabolism. These changes in skeletal muscle gene expression offer a possible molecular explanation for the improvements in clinical outcomes.
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| 6. |
- Souza, Domingos S. R., et al.
(författare)
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Harvesting the saphenous vein with surrounding tissue for CABG provides long-term graft patency comparable to the left internal thoracic artery : results of a randomized longitudinal trial
- 2006
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 132:2, s. 373-U75
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Conventional harvesting of the saphenous vein in coronary artery bypass surgery produces vessel damage that contributes to graft failure. A novel "no touch" technique provides high short- and long-term patency rates.Method: This randomized longitudinal trial compares graft patency of two patient groups undergoing coronary artery bypass surgery. Conventional: 52 patients had their veins stripped, distended, and stored in saline solution. No-touch: 52 patients had veins removed with surrounding tissue, not distended, and stored in heparinized blood. Angiographic assessment was performed at mean time 18 months after the operation in 46 patients in the conventional group and 45 patients in the no-touch group and repeated at mean time 8.5 years in 37 patients from both groups.Results: The distribution of the grafts to the recipient coronary arteries regarding their size and quality was similar in both groups. The angiographic assessment at 18 months postoperatively showed 89% conventional versus 95% no-touch grafts were patent. Repeated angiography at 8.5 years showed a patency rate for the conventional group of 76% and 90% for the no- touch group ( P =.01). The multivariate analysis showed that the most important surgical factors for graft patency were the technique of harvesting ( odds ratio = 3.7, P =.007) for the no- touch versus the conventional technique and the vein quality before implantation ( odds ratio = 3.2, P =.007) for veins that were of good quality. By comparison the patency of the thoracic artery grafts was 90%.Conclusion: Harvesting the saphenous vein with surrounding tissue provides high short- and long-term patency rates comparable to the left internal thoracic artery.
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| 7. |
- Steinz, Maarten M, et al.
(författare)
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Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis
- 2019
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Ingår i: JCI Insight. - : American Society for Clinical Investigation (ASCI). - 2379-3708 .- 2324-7703 .- 2325-4556. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle weakness in patients suffering from rheumatoid arthritis (RA) adds to their impaired working abilities and reduced quality of life. However, little molecular insight is available on muscle weakness associated with RA. Oxidative stress has been implicated in the disease pathogenesis of RA. Here, we show that oxidative posttranslational modifications of the contractile machinery targeted to actin result in impaired actin polymerization and reduced force production. Using mass spectrometry, we identified the actin residues targeted by oxidative 3-nitrotyrosine (3-NT) or malondialdehyde (MDA) adduct modifications in weakened skeletal muscle from mice with arthritis and patients afflicted by RA. The residues were primarily located in 3 distinct regions positioned at matching surface areas of the skeletal muscle actin molecule from arthritic mice and patients with RA. Moreover, molecular dynamics simulations revealed that these areas, here coined "hotspots," are important for the stability of the actin molecule and its capacity to generate filaments and interact with myosin. Together, these data demonstrate how oxidative modifications on actin promote muscle weakness in RA patients and may provide novel leads for targeted therapeutic treatment to improve muscle function.
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| 8. |
- Tsui, Janice C. S., et al.
(författare)
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Localization of nitric oxide synthase in saphenous vein grafts harvested with a novel "no-touch" technique : potential role of nitric oxide contribution to improved early graft patency rates.
- 2002
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Ingår i: Journal of Vascular Surgery. - New York, USA : Elsevier. - 0741-5214 .- 1097-6809. ; 35:2, s. 356-362
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The use of the saphenous vein in coronary artery bypass graft surgery is associated with high 1-year occlusion rates of as much as 30%. A new "no-touch" technique of saphenous vein harvesting in which the vein is harvested with a pedicle of surrounding tissue and not distended may result in improved early patency rates. We hypothesize that nitric oxide synthase is better preserved with the no-touch technique, and the aim of this study was the investigation of whether nitric oxide synthase distribution and quantity in saphenous veins harvested with the no-touch technique differ from those veins harvested with the conventional technique. The separate contribution of perivascular tissue removal and distension to alterations in nitric oxide synthase was also studied.Methods: Segments of 10 saphenous veins were harvested from 10 patients who underwent coronary artery bypass grafting surgery with the no-touch and conventional techniques. Samples were also taken from segments that were stripped of surrounding tissue but not distended. Nitric oxide synthase distribution was studied with reduced nicotinamide adenine dinucleotide phosphate--diaphorase histochemistry, and staining was quantified with image analysis. Immunohistochemistry was used for the identification of specific nitric oxide synthase isoforms, and immunomarkers were used for the identification of associated cell types.Results: Nitric oxide synthase content was higher in no-touch vessels as compared with conventionally harvested vessels (35.5%; P <.05, with analysis of variance). This content was associated with endothelial nitric oxide synthase on the lumen while all three isoforms were present in the media. In the intact adventitia of no-touch vessels, all three isoforms of nitric oxide synthase were also present, associated with microvessels and perivascular nerves. Perivascular tissue stripping and venous distension both contribute to the reduced nitric oxide synthase in conventionally harvested veins.Conclusion: The new no-touch technique of saphenous vein harvesting preserves nitric oxide synthase, which suggests that improved nitric oxide availability may be an important mechanism in the success of this technique.
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| 9. |
- Bakoyan, Zaki, et al.
(författare)
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Childhood atopic disorders in relation to placental changes-A systematic review and meta-analysis
- 2024
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Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Munksgaard Forlag. - 0905-6157 .- 1399-3038. ; 35:5, s. 1-17
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Forskningsöversikt (refereegranskat)abstract
- Fetal programming may arise from prenatal exposure and increase the risk of diseases later in life, potentially mediated by the placenta. The objective of this systematic review was to summarize and critically evaluate publications describing associations between human placental changes and risk of atopic disorders during childhood. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The inclusion criteria were original research articles or case reports written in English describing a human placental change in relation to disease occurring in offspring during childhood. The MEDLINE and EMBASE databases were searched for eligible studies. Risk of bias (RoB) was assessed using the ROBINS-I tool. The results were pooled both in a narrative way and by a meta-analysis. Nineteen studies were included (n = 12,997 participants). All studies had an overall serious RoB, and publication bias could not be completely ruled out. However, five studies showed that histological chorioamnionitis in preterm-born children was associated with asthma-related problems (pooled odds ratio = 3.25 (95% confidence interval = 2.22-4.75)). In term-born children, a large placenta (≥750 g) increased the risk of being prescribed anti-asthma medications during the first year of life. Placental histone acetylation, DNA methylation, and gene expression differences were found to be associated with different atopic disorders in term-born children. There is some evidence supporting the idea that the placenta can mediate an increased risk of atopic disorders in children. However, further studies are needed to validate the findings, properly control for confounders, and examine potential mechanisms.
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| 10. |
- Baldwin, Jessie R., et al.
(författare)
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Adverse Childhood Experiences and Mental Health : A Genetically Informed Study
- 2021
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 51:6, s. 691-692
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Children exposed to adverse childhood experiences (ACEs) have an elevated risk of mental health problems, but it is unclear whether these associations reflect genetic confounding. We tested (1) whether children with genetic liability to psychopathology are more likely to experience ACEs, and (2) the extent to which the associations between ACEs and mental health are genetically confounded. Par-ticipants were 6411 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). ACEs (including maltreatment, domestic violence, and parental psychopathology, substance abuse, criminality, and separation) were prospectively measured through parent reports at multiple assessments between birth and age 9. Internalizing and externalizing problems at age 9 were assessed through parent reports on the Development and Wellbeing Assessment. We derived polygenic scores for a range of psychiatric disorders. Children with greater genetic liability to psychopathology had a small elevation in risk of ACEs (pooled odds ratio = 1.05, 95% CI 1.01–1.09). Measured polygenic scores accounted for a very small proportion of the associations between ACEs with internalizing problems (pooled average across ACEs = 3.6%) and externalizing problems (pooled average = 4.8%). However, latent polygenic scores capturing SNP heritability in mental health outcomes explained a larger proportion of the associations between ACEs with internalizing problems (pooled average = 63%) and externalizing problems (pooled average = 17%). Risk of mental health problems in children exposed to ACEs is partly, but not completely driven by pre-existing genetic liability to psychopathology. Assuming the absence of nongenetic confounding, these findings are consistent with a partly causal effect of ACEs on mental health.
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