| 1. |
- Bossini-Castillo, Lara, et al.
(författare)
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Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population.
- 2011
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 1976-1981
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population.Methods. A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay.Results. The MIF -173 SNP showed association with SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173*C allele was significantly higher in the dcSSc group compared with controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173*C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR = 0.83, 95% CI 0.73, 0.94)].Conclusion. Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker.
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| 2. |
- Caton, Summer A., et al.
(författare)
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Evolution of the sources of TTG and associated rocks during the Archean from in-situ 87Sr/86Sr isotope analysis of apatite by LA-MC-ICPMS
- 2022
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Ingår i: Lithos. - : Elsevier BV. - 0024-4937 .- 1872-6143. ; 428-429
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Tidskriftsartikel (refereegranskat)abstract
- Radiogenic isotopes provide an important means towards elucidating Archean crustal evolution. The global Hf and Nd isotope record of Archean crustal fragments has been instrumental to unveiling the history of ancient crustal growth and differentiation. The Rb-Sr system could provide valuable complementary constraints in this regard, as this system is particularly sensitive to magmatic fractionation processes, and the chemical and isotopic evolution of magma sources. Application of this system has so far been complicated, however, by its susceptibility to isotope re-equilibration or alteration of the Rb/Sr parent-daughter ratio. In-situ Sr isotope analysis of primary igneous minerals with very low Rb/Sr, such as apatite, provides a new means to determine the initial 87Sr/86Sr (87Sr/86Sri) values for igneous rocks directly. In this study, we apply in-situ Sr isotope analysis of apatite by LA-MC-ICPMS to tonalite-trondhjemite-granodiorite (TTG) rocks and end-member sanukitoids from Archean cratons worldwide. The 87Sr/86Sri values of sanukitoids are relatively radiogenic, supporting the model in which such rocks are formed by flux melting of a mantle strongly enriched by metasomatism, possibly by slab-derived fluids. The 87Sr/86Sri values for TTGs formed between 3.72 and 3.45 Ga are generally radiogenic, indicating aged amphibolite sources. The 87Sr/86Sri values of younger TTGs are systematically lower and were derived from mafic sources that had an average age of ≤0.2 Gyr. This evolution matches with observations from Hf isotopes for TTGs of similar age and indicates a systematic change in the nature or efficiency of TTG crust formation during the Paleoarchean. In-situ Sr isotope analysis of apatite provides a useful method to uncover the Sr record of the early continental crust, and enables constraints on local source evolution and the general two-step evolutionary process of Archean crust formation.
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| 3. |
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| 4. |
- Gold, Michael R, et al.
(författare)
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Impact of atrial prevention pacing on atrial fibrillation burden: primary results of the Study of Atrial Fibrillation Reduction (SAFARI) trial.
- 2009
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Ingår i: Heart rhythm : the official journal of the Heart Rhythm Society. - : Elsevier BV. - 1556-3871. ; 6:3, s. 295-301
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of atrial-based pacing algorithms in preventing atrial fibrillation (AF) remains controversial. The inconsistent results noted in previous trials may be due in part to differences in endpoints, pacing algorithms, and study design. SAFARI, a worldwide, prospective, randomized clinical trial, was designed to address these issues and to evaluate the safety and efficacy of a suite of prevention pacing therapies (PPTs) among patients with paroxysmal AF. METHODS AND RESULTS: Patients who met standard pacemaker indications and documented symptomatic AF were implanted with a pacemaker (Vitatron Selection 9000). At 4 months, only patients with documented AF despite dual-chamber pacing were randomized to PPTs ON or PPTs OFF and followed for 6 months. Incidence of permanent AF and change in AF burden were compared between the two groups. Among the 555 patients enrolled, 240 had AF burden at 4 months and were randomized. The risk of developing permanent AF was similar in both groups (0 in the PPTs ON group vs. 3 in the OFF group). However, there was a significant reduction in AF burden between baseline and 10-month follow-up in the ON group compared with the OFF group (median decrease of 0.08 hours/day vs no change, P = .03). CONCLUSION: Among patients with paroxysmal AF and standard bradycardia indications, PPTs are safe and associated with less AF burden compared with conventional pacing.
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| 5. |
- Heidbüchel, Hein, et al.
(författare)
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Recommendations for participation in leisure-time physical activity and competitive sports in patients with arrhythmias and potentially arrhythmogenic conditions - Part 1 : Supraventricular arrhythmias and pacemakers
- 2006
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Oxford University Press (OUP). - 1741-8267 .- 1741-8275. ; 13:4, s. 475-484
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Tidskriftsartikel (refereegranskat)abstract
- This document by the Study Group on Sports Cardiology of the European Society of Cardiology extends on previous recommendations for sports participation for competitive athletes by also incorporating guidelines for those who want to perform recreational physical activity. For different supraventricular arrhythmias and arrhythmogenic conditions, a description of the relationship between the condition and physical activity is given, stressing how arrhythmias can be influenced by exertion or can be a reflection of the (patho)physiological cardiac adaptation to sports participation itself. The following topics are covered in this text: sinus bradycardia; atrioventricular nodal conduction disturbances; pacemakers; atrial premature beats; paroxysmal supraventricular tachycardia without pre-excitation; pre-excitation, asymptomatic or with associated arrhythmias (i.e. Wolff -Parkinson-White syndrome); atrial fibrillation; and atrial flutter. A related document discusses ventricular arrhythmias, channelopathies and implantable cardioverter defibrillators.
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| 6. |
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| 7. |
- Kowal-Bielecka, Otylia, et al.
(författare)
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Update of EULAR recommendations for the treatment of systemic sclerosis
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 1327-1339
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
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| 8. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 9. |
- Yildiz, Yildiz, et al.
(författare)
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Functional and genetic characterization of the non-lysosomal glucosylceramidase 2 as a modifier for Gaucher disease
- 2013
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gaucher disease (GD) is the most common inherited lysosomal storage disorder in humans, caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA1). GD is clinically heterogeneous and although the type of GBA1 mutation plays a role in determining the type of GD, it does not explain the clinical variability seen among patients. Cumulative evidence from recent studies suggests that GBA2 could play a role in the pathogenesis of GD and potentially interacts with GBA1. Methods: We used a framework of functional and genetic approaches in order to further characterize a potential role of GBA2 in GD. Glucosylceramide (GlcCer) levels in spleen, liver and brain of GBA2-deficient mice and mRNA and protein expression of GBA2 in GBA1-deficient murine fibroblasts were analyzed. Furthermore we crossed GBA2-deficient mice with conditional Gba1 knockout mice in order to quantify the interaction between GBA1 and GBA2. Finally, a genetic approach was used to test whether genetic variation in GBA2 is associated with GD and/or acts as a modifier in Gaucher patients. We tested 22 SNPs in the GBA2 and GBA1 genes in 98 type 1 and 60 type 2/3 Gaucher patients for single-and multi-marker association with GD. Results: We found a significant accumulation of GlcCer compared to wild-type controls in all three organs studied. In addition, a significant increase of Gba2-protein and Gba2-mRNA levels in GBA1-deficient murine fibroblasts was observed. GlcCer levels in the spleen from Gba1/Gba2 knockout mice were much higher than the sum of the single knockouts, indicating a cross-talk between the two glucosylceramidases and suggesting a partially compensation of the loss of one enzyme by the other. In the genetic approach, no significant association with severity of GD was found for SNPs at the GBA2 locus. However, in the multi-marker analyses a significant result was detected for p.L444P (GBA1) and rs4878628 (GBA2), using a model that does not take marginal effects into account. Conclusions: All together our observations make GBA2 a likely candidate to be involved in GD etiology. Furthermore, they point to GBA2 as a plausible modifier for GBA1 in patients with GD.
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