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- Holmqvist, Fredrik, et al.
(author)
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A decade of catheter ablation of cardiac arrhythmias in Sweden : ablation practices and outcomes
- 2019
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:10, s. 820-830
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Journal article (peer-reviewed)abstract
- Aims: Catheter ablation is considered the treatment of choice for many tachyarrhythmias, but convincing 'real-world' data on efficacy and safety are lacking. Using Swedish national registry data, the ablation spectrum, procedural characteristics, as well as ablation efficacy and reported adverse events are reported.Methods and Results: Consecutive patients (≥18 years of age) undergoing catheter ablation in Sweden between 01 January 2006 and 31 December 2015 were included in the study. Follow-up (repeat ablation and vital status) was collected through 31 December 2016. A total of 26 642 patients (57 ± 15 years, 62% men), undergoing a total of 34 428 ablation procedures were included in the study. In total, 4034 accessory pathway/Wolff-Parkinson-White syndrome (12%), 7358 AV-nodal re-entrant tachycardia (21%), 1813 atrial tachycardia (5.2%), 5481 typical atrial flutter (16%), 11 916 atrial fibrillation (AF, 35%), 2415 AV-nodal (7.0%), 581 premature ventricular contraction (PVC, 1.7%), and 964 ventricular tachycardia (VT) ablations (2.8%) were performed. Median follow-up time was 4.7 years (interquartile range 2.7-7.0). The spectrum of treated arrhythmias changed over time, with a gradual increase in AF, VT, and PVC ablation (P < 0.001). Decreasing procedural times and utilization of fluoroscopy with time, were seen for all arrhythmia types. The rates of repeat ablation differed between ablation types, with the highest repeat ablation seen in AF (41% within 3 years). The rate of reported adverse events was low (n = 595, 1.7%). Death in the immediate period following ablation was rare (n = 116, 0.34%).Conclusion: Catheter ablations have shifted towards more complex procedures over the past decade. Fluoroscopy time has markedly decreased and the efficacy of catheter ablation seems to improve for AF.
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| 2. |
- Jin, Jing, et al.
(author)
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An attenuated replication-competent chikungunya virus with a fluorescently tagged envelope
- 2018
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In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 12:7
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Journal article (peer-reviewed)abstract
- Background: Chikungunya virus (CHIKV) is the most common alphavirus infecting humans worldwide, causing acute and chronically debilitating arthralgia at a great economic expense.Methodology/Principal findings: To facilitate our study of CHIKV, we generated a mCherry tagged replication-competent chimeric virus, CHIKV 37997-mCherry. Single particle cryoEM demonstrated icosahedral organization of the chimeric virus and the display of mCherry proteins on virus surface. CHIKV 37997-mCherry is attenuated in both IFN alpha R knockout and wild-type mice. Strong antiCHIKV and anti-mCherry antibody responses were induced in CHIKV 37997-mCherry infected mice.Conclusions/Significance: Our work suggests that chimeric alphaviruses displaying foreign antigen can serve as vaccines against both aphaviruses and other pathogens and diseases.
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| 3. |
- Jin, Jing, et al.
(author)
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Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane
- 2018
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In: Cell Host and Microbe. - : Cell Press. - 1931-3128 .- 1934-6069. ; 24:3, s. 417-
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Journal article (peer-reviewed)abstract
- Neutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. In addition, antibodies can engage Fc receptors (FcRs) on immune cells to activate antiviral responses. We describe a mechanism by which NAbs inhibit chikungunya virus (CHIKV), the most common alphavirus infecting humans, by preventing virus budding from infected human cells and activating IgG-specific Fc gamma receptors. NAbs bind to CHIKV glycoproteins on the infected cell surface and induce glycoprotein coalescence, preventing budding of nascent virions and leaving structurally heterogeneous nucleocapsids arrested in the cytosol. Furthermore, NAbs induce clustering of CHIKV replication spherules at sites of budding blockage. Functionally, these densely packed glycoprotein-NAb complexes on infected cells activate Fc gamma receptors, inducing a strong, antibody-dependent, cell-mediated cytotoxicity response from immune effector cells. Our findings describe a triply functional antiviral pathway for NAbs that might be broadly applicable across virus-host systems, suggesting avenues for therapeutic innovation through antibody design.
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| 4. |
- Schoneberg, Johannes, et al.
(author)
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ATP-dependent force generation and membrane scission by ESCRT-III and Vps4
- 2018
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In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 362:6421, s. 1423-
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Journal article (peer-reviewed)abstract
- The endosomal sorting complexes required for transport (ESCRTs) catalyze reverse topology scission from the inner face of membrane necks in HIV budding, multivesicular endosome biogenesis, cytokinesis, and other pathways. We encapsulated ESCRT-III subunits Snf7, Vps24. and Vps2 and the AAA+ ATPase (adenosine triphosphatase) Vps4 in giant vesicles from which membrane nanotubes reflecting the correct topology of scission could be pulled. Upon ATP release by photo-uncaging, this system generated forces within the nanotubes that led to membrane scission in a manner dependent upon Vps4 catalytic activity and Vps4 coupling to the ESCRT-III proteins. Imaging of scission revealed Snf7 and Vps4 puncta within nanotubes whose presence followed ATP release, correlated with force generation and nanotube constriction, and preceded scission. These observations directly verify long-standing predictions that ATP-hydrolyzing assemblies of ESCRT-Ill and Vps4 sever membranes.
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| 5. |
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- 2019
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Journal article (peer-reviewed)
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