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1.
Rev Sci Instrum ; 91(6): 063303, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611048

RESUMO

The development from single shot basic laser plasma interaction research toward experiments in which repetition rated laser-driven ion sources can be applied requires technological improvements. For example, in the case of radio-biological experiments, irradiation duration and reproducible controlled conditions are important for performing studies with a large number of samples. We present important technological advancements of recent years at the ATLAS 300 laser in Garching near Munich since our last radiation biology experiment. Improvements range from target positioning over proton transport and diagnostics to specimen handling. Exemplarily, we show the current capabilities by performing an application oriented experiment employing the zebrafish embryo model as a living vertebrate organism for laser-driven proton irradiation. The size, intensity, and energy of the laser-driven proton bunches resulted in evaluable partial body changes in the small (<1 mm) embryos, confirming the feasibility of the experimental system. The outcomes of this first study show both the appropriateness of the current capabilities and the required improvements of our laser-driven proton source for in vivo biological experiments, in particular the need for accurate, spatially resolved single bunch dosimetry and image guidance.

2.
J Radiol Prot ; 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32702682

RESUMO

The 'Centre for Advanced Laser Applications' (CALA) is a new research institute for laser-based accelerationelectron beams for brilliant x-ray generation, laser-driven sub-nanosecond bunches of protons and heavy ionsbiomedical applications like imaging and tumour therapy as well as for nuclear and high-field physics. The radiation sources emerging from experiments using the up to 2.5 petawatt laser pulses with 25 femtosecond duration will be mixed particle-species of high intensity, high energy and pulsed, thus posing new challenges compared to conventional radiation protection. Such worldwide pioneering laser experiments result in source characteristics that require careful a-priori radiation safety simulations. The FLUKA Monte-Carlo code was used to model the five CALA experimental caves, including the corridors, halls and air spaces surrounding the caves. Beams of electrons (< 5 GeV), protons (< 200 MeV), C (< 400 MeV/u) and 97Au (< 10 MeV/u) ions were simulated using spectra, divergences and bunch-charges based on expectations from recent scientific progress. Simulated dose rates locally can exceed 1.5 kSv/h inside beam dumps. Vacuum pipes in the cave walls for laser transport and extraction channels for the generated X-rays result in small dose leakage to neighboring areas. Secondary neutrons contribute to most of the prompt dose rate outside caves into which the beam is delivered. This secondary radiation component causes non-negligible dose rates to occur behind walls to which large fluences of secondary particles are directed. By employing adequate beam dumps matched to beam-divergence, magnets, passive shielding and laser pulse repetition limits, average dose rates in- and outside the experimental building stay below design specifications (< 0.5 µSv/hunclassified areas, < 2.5 µSv/h for supervised areas, < 7.5 µSv/h maximum local dose rate) and regulatory limits (< 1 mSv/a for unclassified areas).

3.
Clin Res Cardiol ; 109(8): 1025-1034, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32002633

RESUMO

BACKGROUND: Supraventricular tachycardias induced by dual antegrade conduction via the atrioventricular (AV) node are rare but often misdiagnosed with severe consequences for the affected patients. As long-term follow-up in these patients was not available so far, this study investigates outcomes in patients with dual antegrade conduction in the AV node. METHODS AND RESULTS: In this multicentre observational study, patients from six European centres were studied. Catheter ablation was performed in 17 patients (52 ± 16 years) with dual antegrade conduction via both AV nodal pathways between 2012 and 2018. Patients with the final diagnosis of a manifest dual AV nodal non-re-entrant tachycardia had a mean delay of the correct diagnosis of over 1 year (range 2-31 months). Two patients received prescription of non-indicated oral anticoagulation, two further patients suffered from inappropriate shocks of an implantable cardioverter defibrillator. In 12 patients, a co-existence of dual antegrade and re-entry conduction in the AV node was present. Mean fast pathway conduction time was 138 ± 61 ms and mean slow pathway conduction time was 593 ± 134 ms. Successful radiofrequency catheter ablation was performed in all patients. Post-procedurally oral anticoagulation was discontinued, without detection of cerebrovascular events or atrial fibrillation during a long-term follow-up of median 17 months (range 6-72 months). CONCLUSION: This first multicentre study investigating patients with supraventricular tachycardia and dual antegrade conduction in the AV node demonstrates that catheter ablation is safe and effective while long-term patient outcome is good. Autonomic tone dependent changes in ante- vs. retrograde conduction via slow and/or fast pathway can challenge the diagnosis and therapy in some patients.

4.
J Cardiovasc Electrophysiol ; 31(5): 1051-1061, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32107811

RESUMO

INTRODUCTION: The aim of this study was to investigate electrophysiological findings in patients with arrhythmia recurrence undergoing a repeat ablation procedure using ultra-high-density (UHDx) mapping following an index procedure using either contact-force (CF)-guided radiofrequency current (RFC) pulmonary vein isolation (PVI) or second-generation cryoballoon (CB) PVI for treatment of atrial fibrillation (AF). METHODS AND RESULTS: Fifty consecutive patients with recurrence of AF and/or atrial tachycardia (AT) following index CF-RFC PVI (n = 21) or CB PVI (n = 29) were included. A 64-pole mini-basket mapping catheter in combination with an UHDx-mapping system-guided ablation was used. RFC was applied using a catheter tip with three incorporated mini-electrodes. PV reconnection rates were higher after CF-RFC PVI (CF-RFC: 2.5 ± 1.3 PVs vs CB: 1.4 ± 0.9 PVs; P = .0025) and left PVs were more frequently reconnected (CF-RFC: 64% PVs vs CB: 35% PVs; P = .0077). Fractionated signals along the antral index ablation line (FS) were found in 30% of CB-PVI patients (CF-RFC: 9.5% vs CB:30%; P = .098) targeted for ablation. In five cases, FS were a critical part of maintaining consecutive AT. The main AT mechanism found during reablation (n = 45 ATs) was macroreentry (80% [36/45], CF-RFC: 78.9% vs CB: 80.8%; P = 1.0) with a variety of circuits throughout both atria. CONCLUSION: UHDx mapping is sensitive in detecting conduction gaps along the index ablation line. Left PVs are more frequently reconnected after initial CF-RFC PVI. FS are a common finding after CB PVI and can maintain certain forms of ATs. ATs after index PVI are mostly macroreentries with a broad spectrum of entities.

5.
PLoS One ; 15(1): e0228249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31990942

RESUMO

This ex vivo proof-of-concept study aimed to investigate the effect of nanosilver particles (AgNP) added to a conventional infiltrant resin (Icon) on external penetration into natural proximal enamel caries exceeding into dentin after internal tunnel preparation and internal infiltration. Carious lesions (ICDAS codes 2/3) of extracted human (pre-)molars revealing proximal caries radiographically exceeding into dentin (E2/D1 lesions) were preselected. Then, 48 of those specimens showing demineralized areas transcending the enamel-dentin border as assessed by means of near-infrared light transillumination (DIAGNOcam) were deproteinized (NaOCl, 5%). Using an internal tunnel approach, occlusal cavities central to the marginal ridge were prepared. Excavation of carious dentin, total etch procedure (H3PO4, 40%), and internal resin infiltration (FITC-labeled) followed, along with final restorations (flowable composite resin). Outer lesion surfaces were etched (HCl, 15%) prior to external infiltration (RITC-labeled). Group 1 (control; n = 24) used non-modified infiltrant, while an infiltrant/AgNP mixture (20 nm; 5.5 wt%) was used with experimental Group 2 (n = 24). Non-infiltrated pores of cut lesions were stained (Berberine), and specimens were analyzed using confocal laser scanning microscopy. Compared to the non-filled infiltrant, incorporation of AgNP had no effect on the resin's external penetration. Between the groups, no significant differences regarding internal or external infiltration could be detected, and non-infiltrated lesion areas did not differ significantly (p>0.109; t-test). The internal tunnel preparation in combination with both an internal resin infiltration and an additional external infiltration approach using a nanosilver-modified infiltrant resin leads to increased infiltrated lesion areas, thus occluding and adhesively stabilizing the porous volume of the demineralized enamel. While exerting antimicrobial effects by the nanosilver particles, this approach should have the potential as a viable treatment alternative for proximal lesions extending into dentin, thus avoiding the sacrifice of sound enamel, postponing the frequently inevitable restoration/re-restoration cycle of conventional proximal caries treatment, and improving dental health.


Assuntos
Cárie Dentária/metabolismo , Dentina/metabolismo , Nanopartículas Metálicas/química , Resinas Sintéticas/química , Resinas Sintéticas/metabolismo , Prata/química , Ouro/química , Teste de Materiais
6.
J Cardiovasc Electrophysiol ; 31(1): 61-69, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31701589

RESUMO

AIMS: Catheter contact and local tissue characteristics are relevant information for successful radiofrequency current (RFC)-ablation. Local impedance (LI) has been shown to reflect tissue characteristics and lesion formation during RFC-ablation. Using a novel ablation catheter incorporating three mini-electrodes, we investigated LI in relation to generator impedance (GI) in patients with ventricular tachycardia (VT) and its applicability as an indicator of effective RFC-ablation. METHODS AND RESULTS: Baseline impedance, Δimpedance during ablation and drop rate (Δimpedance/time) were analyzed for 625 RFC-applications in 28 patients with recurrent VT undergoing RFC-ablation. LI was lower in scarred (87.0 Ω [79.0-95.0]) compared to healthy myocardium (97.5 Ω ([82.75-111.50]; P = .03) while GI did not differ between scarred and healthy myocardium. ΔLI was higher (18 Ω [9.4-26.0]) for VT-terminating as compared to non-terminating RFC-ablation (ΔLI 13 Ω [8.85-18.0]; P = .03), but did not differ for ΔGI between terminating vs nonterminating RFC-ablation. Correspondingly, LI drop rate was higher for RFC-ablation terminating the VT compared with RFC-ablation not terminating the VT (0.63 Ω/s [0.52-0.76] vs 0.32 Ω [0.20-0.58]; P = .008) while there was no difference for GI drop rate. ΔLI was higher in patients with nonischemic cardiomyopathy vs patients with ischemic cardiomyopathy (16 Ω [11.0-20.0] vs 11.0 Ω [7.85-17.00]; P = .003). CONCLUSION: Our findings suggest that LI is a sensitive parameter to guide RFC-ablation in patients with VT. LI indicates differences in tissue characteristics and generally is higher in patients with nonischemic cardiomyopathy. Hence, the etiology of the underlying cardiomyopathy needs to be considered when adopting LI for monitoring catheter ablation of VT.

7.
Blood Purif ; 49(1-2): 33-43, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31509822

RESUMO

BACKGROUND/AIMS: Cytokines are among the main target substances that have to be removed effectively in order to improve the patient's health status in the treatment of sepsis, septic shock, and liver diseases. Although there are various medical devices commercially available, the success of their clinical use is limited. The aim of this in vitro study was to compare 3 different medical devices with respect to their clearance for the cytokines interleukin-6 (IL-6), IL-8, IL-1ß, and tumor necrosis factor alpha. The medical devices that were tested are the whole blood adsorbent CytoSorb, the high cutoff filter EMiC2, and the hemofilter HemofeelCH 1.8. METHODS: The study was carried out on the multiFiltrate machine with 1 L human plasma for 8 h. Samples for cytokine quantification were taken at defined time points from the plasma pool. Each experiment was conducted in triplicates, and clearance was calculated for all tested cytokines. RESULTS: All 3 medical devices showed good cytokine removal. The highest clearance for all cytokines was achieved by hemoperfusion with Cytosorb. IL-8 and IL-6 clearance were higher with Hemofeel (continuous venovenous hemodiafiltration) than with EMiC2 (continuous venovenous hemodialysis) because the polymethyl methacrylate (PMMA)-based membrane Hemofeel is able to remove these 2 cytokines by adsorption. Protein and albumin loss was highest withCytosorb and lowest with EMiC2. CONCLUSION: The mechanisms of cytokine removal by blood purification include convection, diffusion, and adsorption. PMMA-based filters are able to combine all 3 mechanisms for certain cytokines. Cytosorb showed the best adsorption kinetics, while dialysis with polystyrene-based membranes offers the best biocompatibility because they do not show any unspecific adsorption of other plasma components.

8.
Int J Mol Sci ; 20(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683553

RESUMO

Acylation of antimicrobial peptides mimics the structure of the natural lipopeptide polymyxin B, and increases antimicrobial and endotoxin-neutralizing activities. In this study, the antimicrobial properties of lactoferrin-based LF11 peptides as well as blood compatibility as a function of acyl chain length were investigated. Beyond the classical hemolysis test, the biocompatibility was determined with human leukocytes and platelets, and the influence of antimicrobial peptides (AMPs) on the plasmatic coagulation and the complement system was investigated. The results of this study show that the acylation of cationic peptides significantly reduces blood tolerance. With increasing acyl chain length, the cytotoxicity of LF11 peptides to human blood cells also increased. This study also shows that acylated cationic antimicrobial peptides are inactivated by the presence of heparin. In addition, it could be shown that the immobilization of LF11 peptides leads to a loss of their antimicrobial properties.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Materiais Biocompatíveis/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Acilação , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/química , Materiais Biocompatíveis/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Hemólise/efeitos dos fármacos , Humanos , Leucócitos/citologia , Lipopolissacarídeos/farmacologia , Testes de Sensibilidade Microbiana , Ativação Plaquetária/efeitos dos fármacos
9.
Cardiovasc Diagn Ther ; 9(Suppl 2): S247-S263, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31737533

RESUMO

Background: Ultra-high density mapping (HDM) is a promising tool in the treatment of patients with complex arrhythmias. In adults with congenital heart disease (CHD), rhythm disorders are among the most common complications but catheter ablation can be challenging due to heterogenous anatomy and complex arrhythmogenic substrates. Here, we describe our initial experience using HDM in conjunction with novel automated annotation algorithms in patients with moderate to great CHD complexity. Methods: We studied a series of consecutive adult patients with moderate to great CHD complexity and an indication for catheter ablation due to symptomatic arrhythmia. HDM was conducted using the Rhythmia™ mapping system and a 64-electrode mini-basket catheter for identification of anatomy, voltage, activation pattern and critical areas of arrhythmia for ablation guidance. To investigate novel advanced mapping strategies, postprocedural signal processing using the Lumipoint™ software was applied. Results: In 19 patients (53±3 years; 53% male), 21 consecutive ablation procedures were conducted. Procedures included ablation of atrial fibrillation (n=7; 33%), atrial tachycardia (n=11; 52%), atrioventricular accessory pathway (n=1; 5%), the atrioventricular node (n=1; 5%) and ventricular arrhythmias (n=4; 19%). A total of 23 supraventricular and 8 ventricular arrhythmias were studied with the generation of 56 complete high density maps (atrial n=43; ventricular n=11, coronary sinus n=2) and an average of 12,043±1,679 mapping points. Multiple arrhythmias were observed in n=7 procedures (33% of procedures; range of arrhythmias detected 2-4). A total range of 1-4 critical areas were defined per procedure and treated within a radiofrequency application time of 16 (interquartile range 12-45) minutes. Postprocedural signal processing using Lumipoint™ allowed rapid annotation of fractionated signals within specific windows of interest. This supported identification of a practical critical isthmus in 20 out of 27 completed atrial and ventricular tachycardia activation maps. Conclusions: Our findings suggest that HDM in conjunction with novel automated annotation algorithms provides detailed insights into arrhythmia mechanisms and might facilitate tailored catheter ablation in patients with moderate to great CHD complexity.

10.
Sci Rep ; 9(1): 10450, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31320731

RESUMO

Calcium (Ca) is an essential element for almost all living organisms. Here, we examined global variation and controls of freshwater Ca concentrations, using 440 599 water samples from 43 184 inland water sites in 57 countries. We found that the global median Ca concentration was 4.0 mg L-1 with 20.7% of the water samples showing Ca concentrations ≤ 1.5 mg L-1, a threshold considered critical for the survival of many Ca-demanding organisms. Spatially, freshwater Ca concentrations were strongly and proportionally linked to carbonate alkalinity, with the highest Ca and carbonate alkalinity in waters with a pH around 8.0 and decreasing in concentrations towards lower pH. However, on a temporal scale, by analyzing decadal trends in >200 water bodies since the 1980s, we observed a frequent decoupling between carbonate alkalinity and Ca concentrations, which we attributed mainly to the influence of anthropogenic acid deposition. As acid deposition has been ameliorated, in many freshwaters carbonate alkalinity concentrations have increased or remained constant, while Ca concentrations have rapidly declined towards or even below pre-industrial conditions as a consequence of recovery from anthropogenic acidification. Thus, a paradoxical outcome of the successful remediation of acid deposition is a globally widespread freshwater Ca concentration decline towards critically low levels for many aquatic organisms.

11.
Rev Sci Instrum ; 90(5): 053903, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31153295

RESUMO

A new custom-designed ultrahigh vacuum (UHV) apparatus combining molecular beam techniques and in situ surface spectroscopy for reactivity measurements on complex nanostructured model surfaces is described. It has been specifically designed to study the mechanisms, kinetics, and dynamics of heterogeneously catalyzed reactions over well-defined model catalysts consisting of metal nanoparticles supported on thin oxide films epitaxially grown on metal single crystals. The reactivity studies can be performed in a broad pressure range starting from UHV up to the ambient pressure conditions. The UHV system includes (i) a preparation chamber providing the experimental techniques required for the preparation and structural characterization of single-crystal based model catalysts such as oxide supported metal particles or ordered oxide surfaces and (ii) the reaction chamber containing three molecular beams-two effusive and one supersonic, which are crossed at the same point on the sample surface, infrared reflection-absorption spectroscopy for the detection of surface-adsorbed species, and quadrupole mass spectrometry for gas phase analysis. The supersonic beam is generated in a pulsed supersonic expansion and can be modulated via a variable duty-cycle chopper. The effusive beams are produced by newly developed compact differentially pumped sources based on multichannel glass capillary arrays. Both effusive sources can be modulated by a vacuum-motor driven chopper and are capable of providing high flux and high purity beams. The apparatus contains an ambient pressure cell, which is connected to the preparation chamber via an in situ sample transfer system and provides an experimental possibility to study the reactivity of well-defined nanostructured model catalysts in a broad range of pressure conditions-up to ambient pressure-with the gas phase analysis based on gas chromatography. Additionally, a dedicated deposition chamber is connected to the preparation chamber, which is employed for the in situ functionalization of model surfaces with large organic molecules serving as promoters or modifiers of chemical reactions. We present a general overview of the apparatus as well as a description of the individual components and their interplay. The results of the test measurements involving the most important components are presented and discussed.

12.
Sci Rep ; 9(1): 6714, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31040311

RESUMO

The shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens' principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. This novel method, which we refer to as Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a refinement of the ionoacoustic approach. With its capability of completely monitoring a single, focused proton bunch with prompt readout and high repetition rate, I-BEAT is a promising approach to meet future requirements of experiments and applications in the field of laser-based ion acceleration. We demonstrate its functionality at two laser-driven ion sources for quantitative online determination of the kinetic energy distribution in the focus of single proton bunches.

13.
Sci Rep ; 9(1): 7697, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118430

RESUMO

Today's high-power laser systems are capable of reaching photon intensities up to 1022 W cm-2, generating plasmas when interacting with material. The high intensity and ultrashort laser pulse duration (fs) make direct observation of plasma dynamics a challenging task. In the field of laser-plasma physics and especially for the acceleration of ions, the spatio-temporal intensity distribution is one of the most critical aspects. We describe a novel method based on a single-shot (i.e. single laser pulse) chirped probing scheme, taking nine sequential frames at frame rates up to THz. This technique, to which we refer as temporally resolved intensity contouring (TRIC) enables single-shot measurement of laser-plasma dynamics. Using TRIC, we demonstrate the reconstruction of the complete spatio-temporal intensity distribution of a high-power laser pulse in the focal plane at full pulse energy with sub-picosecond resolution.

14.
Science ; 364(6436): 126-127, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30975875

Assuntos
Carbono , Clima , Planeta Terra
15.
Oncol Res Treat ; 42(5): 283-288, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30995669

RESUMO

Bone marrow biopsies are standard hematology procedures. We report the case of a patient with acute myeloid leukemia who developed retroperitoneal hematoma after the procedure. The bleeding was stopped with endovascular embolization and coiling. This case raises several issues about the standards for bone marrow biopsies and discusses the approach to patients with bleeding risk factors. We also provide a literature review.


Assuntos
Biópsia/efeitos adversos , Hematoma/etiologia , Idoso , Medula Óssea/patologia , Embolização Terapêutica , Feminino , Hematoma/diagnóstico , Hematoma/diagnóstico por imagem , Hematoma/terapia , Humanos
16.
J Cardiovasc Electrophysiol ; 30(5): 679-687, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30821012

RESUMO

INTRODUCTION: Long-term efficacy and safety are uncertain in patients with cardiac implantable electronic devices (CIED) and transvenous leads (TVL) undergoing radiofrequency catheter ablation of atrial fibrillation (AF). Thus, we assessed the outcome of AF ablation in those patients during long-term follow-up using continuous atrial rhythm monitoring (CARM). METHODS AND RESULTS: A total of 190 patients (71.3 ± 10.7 years; 108 (56.8% men) were included in this study. At index procedure 81 (42.6%) patients presented with paroxysmal AF and 109 (57.4%) with persistent AF. The ablation strategy included pulmonary vein isolation in all patients and biatrial ablation of complex fractionated electrograms with additional ablation lines, if appropriate. AF recurrences were assessed by CARM- and CIED-related complications by device follow-up. After a mean follow-up of 55.4 ± 38.1 months, freedom of AF was found in 86 (61.4%) and clinical success defined as an AF burden less than or equal to 1% in 101 (72.1%) patients. Freedom of AF was reported in 74.6% and 51.9% (P = 0.006) and clinical success in 89.8% and 59.3% (P < 0.001) of patients with paroxysmal and persistent AF, respectively. In 3 of 408 (0.7%) ablation procedures, a TVL malfunction occurred within 90 days after catheter ablation. During long-term follow-up 9 (4.7%) patients showed lead dislodgement, 2 (1.1%) lead fracture, and 2 (1.1%) lead insulation defect not related to the ablation procedure. CONCLUSION: Our findings using CARM demonstrate long-term efficacy and safety of radiofrequency catheter ablation of AF in patients with CIED and TVL.

17.
Europace ; 21(Supplement_1): i34-i42, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30801126

RESUMO

AIMS: A novel measure of local impedance (LI) has been found to predict lesion formation during radiofrequency current (RFC) catheter ablation. The aim of this study was to investigate the utility of this novel approach, while comparing LI to the well-established generator impedance (GI). METHODS AND RESULTS: In 25 consecutive patients with a history of atrial fibrillation, catheter ablation was guided by a 3D-mapping system measuring LI in addition to GI via an ablation catheter tip with three incorporated mini-electrodes. Local impedance and GI before and during RFC applications were studied. In total, 381 RFC applications were analysed. The baseline LI was higher in high-voltage areas (>0.5 mV; LI: 110.5 ± 13.7 Ω) when compared with intermediate-voltage sites (0.1-0.5 mV; 90.9 ± 10.1 Ω, P < 0.001), low-voltage areas (<0.1 mV; 91.9 ± 16.4 Ω, P < 0.001), and blood pool LI (91.9 ± 9.9 Ω, P < 0.001). During ablation, mean LI drop (△LI; 13.1 ± 9.1 Ω) was 2.15 times higher as mean GI drop (△GI) (6.1 ± 4.2 Ω, P < 0.001). Baseline LI correlated with △LI: a mean LI of 99.9 Ω predicted a △LI of 12.9 Ω [95% confidence interval (12.1-13.6), R2 0.41; P < 0.001]. This relationship was weak for baseline GI predicting △GI (R2 0.06, P < 0.001). Catheter movements were represented by rapid LI changes. The duration of an RFC application was not predictive for catheter-tissue coupling with no further change of △LI (P = 0.247) nor △GI (P = 0.376) during prolonged ablation. CONCLUSION: Local impedance can be monitored during ablation. Compared with the sole use of GI, baseline LI is a better predictor of impedance drops during ablation and may provide useful insights regarding lesion formation. However, further studies are needed to investigate if this novel approach is useful to guide catheter ablation.

18.
Sci Rep ; 8(1): 14809, 2018 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-30287836

RESUMO

Evidence for relationships between seismotectonic activity and dissolved weathering fluxes remains limited. Motivated by the occurrence of new springs emerging after the 2016 Kumamoto earthquake and supported by historical groundwater data, this study focuses on the long-term effect of near-surface structural deformation on the contribution of deep, highly saline fluids to the solute fluxes from the Aso caldera, Kyushu, Japan. Available hydrologic and structural data suggest that concentrated, over-pressured groundwaters migrate to the surface when new hydraulic pathways open during seismic deformation. These new springs have a hydrochemical fingerprint (including δDH2O, δ18OH2O, δ7Li, δ11B, δ18OSO4, and δ34SSO4) indistinguishable from long-established confined groundwater that likely reflects a mixture of infiltrated meteoric water with high-sulfate hydrothermal fluids. A comparison of historical hydrochemistry data and patterns of past seismicity suggests that discharge of deep fluids is associated with similar deformation structures to those observed during the Kumamoto earthquake, and that seismic activity plays an important role over historic timescales in delivering the majority of the solutes to the caldera outlet, sustaining fluxes that are amongst the world's highest. This upwelling mechanism might be relevant for other systems too, and could contribute to the over-proportional share of active volcanic areas in global weathering fluxes.

19.
Cell Death Dis ; 9(8): 814, 2018 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-30050105

RESUMO

Hematopoiesis, the formation of blood cells from hematopoietic stem cells (HSC), is a highly regulated process. Since the discovery of microRNAs (miRNAs), several studies have shown their significant role in the regulation of the hematopoietic system. Impaired expression of miRNAs leads to disrupted cellular pathways and in particular causes loss of hematopoietic ability. Here, we report a previously unrecognized function of miR-143 in granulopoiesis. Hematopoietic cells undergoing granulocytic differentiation exhibited increased miR-143 expression. Overexpression or ablation of miR-143 expression resulted in accelerated granulocytic differentiation or block of differentiation, respectively. The absence of miR-143 in mice resulted in a reduced number of mature granulocytes in blood and bone marrow. Additionally, we observed an association of high miR-143 expression levels with a higher probability of survival in two different cohorts of patients with acute myeloid leukemia (AML). Overexpression of miR-143 in AML cells impaired cell growth, partially induced differentiation, and caused apoptosis. Argonaute2-RNA-Immunoprecipitation assay revealed ERK5, a member of the MAPK-family, as a target of miR-143 in myeloid cells. Further, we observed an inverse correlation of miR-143 and ERK5 in primary AML patient samples, and in CD34+ HSPCs undergoing granulocytic differentiation and we confirmed functional relevance of ERK5 in myeloid cells. In conclusion, our data describe miR-143 as a relevant factor in granulocyte differentiation, whose expression may be useful as a prognostic and therapeutic factor in AML therapy.


Assuntos
Leucemia Mieloide Aguda/patologia , MicroRNAs/metabolismo , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Apoptose , Diferenciação Celular , Proliferação de Células , Granulócitos/citologia , Granulócitos/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteína Quinase 7 Ativada por Mitógeno/química , Proteína Quinase 7 Ativada por Mitógeno/genética , Prognóstico , Taxa de Sobrevida
20.
PLoS One ; 13(6): e0199204, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29898003

RESUMO

BACKGROUND: Regional citrate anticoagulation has been associated with enhanced biocompatibility in hemodialysis, but the optimal dose of citrate remains to be established. Here, we compared parameters related to cellular activation during in vitro dialysis, using two doses of citrate. METHODS: Human whole blood, anticoagulated with either 3 mM or 4 mM of citrate, was recirculated in an in vitro miniaturized dialysis setup. Complement (C3a-desArg), soluble platelet factor 4 (PF4), thromboxane B2 (TXB2), myeloperoxidase (MPO), as well as platelet- and red blood cell-derived extracellular vesicles (EV) were quantified during recirculation. Dialyzer fibers were examined by scanning electron microscopy after recirculation to assess the activation of clotting and the deposition of blood cells. RESULTS: Increases in markers of platelet and leukocyte activation, PF4, TXB2, and MPO were comparable between both citrate groups. Complement activation tended to be lower at higher citrate concentration, but the difference between the two citrate groups did not reach significance. A strong increase in EVs, particularly platelet-derived EVs, was observed during in vitro dialysis for both citrate groups, which was significantly less pronounced in the high citrate group at the end of the experiment. Assessment of dialyzer clotting scores after analysis of individual fibers by scanning electron microscopy revealed significantly lower scores in the high citrate group. CONCLUSIONS: Our data indicate that an increase in the citrate concentration from 3 mM to 4 mM further dampens cellular activation, thereby improving biocompatibility. A concentration of 4 mM citrate might therefore be optimal for use in clinical practice.


Assuntos
Anticoagulantes/farmacologia , Células Sanguíneas/efeitos dos fármacos , Citratos/farmacologia , Adulto , Células Sanguíneas/metabolismo , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Complemento C3a/metabolismo , Diálise , Vesículas Extracelulares/metabolismo , Humanos , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Microscopia Eletrônica de Varredura , Peroxidase/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Fator Plaquetário 4/metabolismo , Tromboxano B2/metabolismo
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