Physicochemical characterization of titanium dioxide pigments using various techniques for size determination and asymmetric flow field flow fractionation hyphenated with inductively coupled plasma mass spectrometry.

PubMed

Helsper, Johannes P F G; Peters, Ruud J B; van Bemmel, Margaretha E M; Rivera, Zahira E Herrera; Wagner, Stephan; von der Kammer, Frank; Tromp, Peter C; Hofmann, Thilo; Weigel, Stefan

2016-09-01

Seven commercial titanium dioxide pigments and two other well-defined TiO2 materials (TiMs) were physicochemically characterised using asymmetric flow field flow fractionation (aF4) for separation, various techniques to determine size distribution and inductively coupled plasma mass spectrometry (ICPMS) for chemical characterization. The aF4-ICPMS conditions were optimised and validated for linearity, limit of detection, recovery, repeatability and reproducibility, all indicating good performance. Multi-element detection with aF4-ICPMS showed that some commercial pigments contained zirconium co-eluting with titanium in aF4. The other two TiMs, NM103 and NM104, contained aluminium as integral part of the titanium peak eluting in aF4. The materials were characterised using various size determination techniques: retention time in aF4, aF4 hyphenated with multi-angle laser light spectrometry (MALS), single particle ICPMS (spICPMS), scanning electron microscopy (SEM) and particle tracking analysis (PTA). PTA appeared inappropriate. For the other techniques, size distribution patterns were quite similar, i.e. high polydispersity with diameters from 20 to >700 nm, a modal peak between 200 and 500 nm and a shoulder at 600 nm. Number-based size distribution techniques as spICPMS and SEM showed smaller modal diameters than aF4-UV, from which mass-based diameters are calculated. With aF4-MALS calculated, light-scattering-based "diameters of gyration" (Øg) are similar to hydrodynamic diameters (Øh) from aF4-UV analyses and diameters observed with SEM, but much larger than with spICPMS. A Øg/Øh ratio of about 1 indicates that the TiMs are oblate spheres or fractal aggregates. SEM observations confirm the latter structure. The rationale for differences in modal peak diameter is discussed.

Asymmetric flow field flow fractionation with light scattering detection - an orthogonal sensitivity analysis.

PubMed

Galyean, Anne A; Filliben, James J; Holbrook, R David; Vreeland, Wyatt N; Weinberg, Howard S

2016-11-18

Asymmetric flow field flow fractionation (AF 4 ) has several instrumental factors that may have a direct effect on separation performance. A sensitivity analysis was applied to ascertain the relative importance of AF 4 primary instrument factor settings for the separation of a complex environmental sample. The analysis evaluated the impact of instrumental factors namely, cross flow, ramp time, focus flow, injection volume, and run buffer concentration on the multi-angle light scattering measurement of natural organic matter (NOM) molar mass (MM). A 2 (5-1) orthogonal fractional factorial design was used to minimize analysis time while preserving the accuracy and robustness in the determination of the main effects and interactions between any two instrumental factors. By assuming that separations resulting in smaller MM measurements would be more accurate, the analysis produced a ranked list of effects estimates for factors and interactions of factors based on their relative importance in minimizing the MM. The most important and statistically significant AF 4 instrumental factors were buffer concentration and cross flow. The least important was ramp time. A parallel 2 (5-2) orthogonal fractional factorial design was also employed on five environmental factors for synthetic natural water samples containing silver nanoparticles (NPs), namely: NP concentration, NP size, NOM concentration, specific conductance, and pH. None of the water quality characteristic effects or interactions were found to be significant in minimizing the measured MM; however, the interaction between NP concentration and NP size was an important effect when considering NOM recovery. This work presents a structured approach for the rigorous assessment of AF 4 instrument factors and optimal settings for the separation of complex samples utilizing efficient orthogonal factional factorial design and appropriate graphical analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

In-house validation of a method for determination of silver nanoparticles in chicken meat based on asymmetric flow field-flow fractionation and inductively coupled plasma mass spectrometric detection.

PubMed

Loeschner, Katrin; Navratilova, Jana; Grombe, Ringo; Linsinger, Thomas P J; Købler, Carsten; Mølhave, Kristian; Larsen, Erik H

2015-08-15

Nanomaterials are increasingly used in food production and packaging, and validated methods for detection of nanoparticles (NPs) in foodstuffs need to be developed both for regulatory purposes and product development. Asymmetric flow field-flow fractionation with inductively coupled plasma mass spectrometric detection (AF(4)-ICP-MS) was applied for quantitative analysis of silver nanoparticles (AgNPs) in a chicken meat matrix following enzymatic sample preparation. For the first time an analytical validation of nanoparticle detection in a food matrix by AF(4)-ICP-MS has been carried out and the results showed repeatable and intermediately reproducible determination of AgNP mass fraction and size. The findings demonstrated the potential of AF(4)-ICP-MS for quantitative analysis of NPs in complex food matrices for use in food monitoring and control. The accurate determination of AgNP size distribution remained challenging due to the lack of certified size standards. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study on steric transition in asymmetrical flow field-flow fractionation and application to characterization of high-energy material.

PubMed

Dou, Haiyang; Lee, Yong-Ju; Jung, Euo Chang; Lee, Byung-Chul; Lee, Seungho

2013-08-23

In field-flow fractionation (FFF), there is the 'steric transition' phenomenon where the sample elution mode changes from the normal to steric/hyperlayer mode. Accurate analysis by FFF requires understanding of the steric transition phenomenon, particularly when the sample has a broad size distribution, for which the effect by combination of different modes may become complicated to interpret. In this study, the steric transition phenomenon in asymmetrical flow FFF (AF4) was studied using polystyrene (PS) latex beads. The retention ratio (R) gradually decreases as the particle size increases (normal mode) and reaches a minimum (Ri) at diameter around 0.5μm, after which R increases with increasing diameter (steric/hyperlayer mode). It was found that the size-based selectivity (Sd) tends to increase as the channel thickness (w) increases. The retention behavior of cyclo-1,3,5-trimethylene-2,4,6-trinitramine (commonly called 'research department explosive' (RDX)) particles in AF4 was investigated by varying experimental parameters including w and flow rates. AF4 showed a good reproducibility in size determination of RDX particles with the relative standard deviation of 4.1%. The reliability of separation obtained by AF4 was evaluated by transmission electron microscopy (TEM). Copyright © 2013 Elsevier B.V. All rights reserved.

Impact of asymmetrical flow field-flow fractionation on protein aggregates stability.

PubMed

Bria, Carmen R M; Williams, S Kim Ratanathanawongs

2016-09-23

The impact of asymmetrical flow field-flow fractionation (AF4) on protein aggregate species is investigated with the aid of multiangle light scattering (MALS) and dynamic light scattering (DLS). The experimental parameters probed in this study include aggregate stability in different carrier liquids, shear stress (related to sample injection), sample concentration (during AF4 focusing), and sample dilution (during separation). Two anti-streptavidin (anti-SA) IgG1 samples composed of low and high molar mass (M) aggregates are subjected to different AF4 conditions. Aggregates suspended and separated in phosphate buffer are observed to dissociate almost entirely to monomer. However, aggregates in citric acid buffer are partially stable with dissociation to 25% and 5% monomer for the low and high M samples, respectively. These results demonstrate that different carrier liquids change the aggregate stability and low M aggregates can behave differently than their larger counterparts. Increasing the duration of the AF4 focusing step showed no significant changes in the percent monomer, percent aggregates, or the average Ms in either sample. Syringe-induced shear related to sample injection resulted in an increase in hydrodynamic diameter (dh) as measured by batch mode DLS. Finally, calculations showed that dilution during AF4 separation is significantly lower than in size exclusion chromatography with dilution occurring mainly at the AF4 channel outlet and not during the separation. This has important ramifications when analyzing aggregates that rapidly dissociate (<∼2s) upon dilution as the size calculated by AF4 theory may be more accurate than that measured by online DLS. Experimentally, the dhs determined by online DLS generally agreed with AF4 theory except for the more well retained larger aggregates for which DLS showed smaller sizes. These results highlight the importance of using AF4 retention theory to understand the impacts of dilution on analytes. Copyright © 2016 Elsevier B.V. All rights reserved.

Study on antidiabetic activity of wheat and barley starch using asymmetrical flow field-flow fractionation coupled with multiangle light scattering.

PubMed

Dou, Haiyang; Zhou, Bing; Jang, Hae-Dong; Lee, Seungho

2014-05-02

The ability of asymmetrical flow field-flow fractionation (AF4) coupled online with multiangle light scattering (MALS) and refractive index detector (RI) (AF4-MALS-RI) for monitoring of change in molecular conformation of wheat and barley starch during germination process was evaluated. AF4 provides separation of starch molecules based on their hydrodynamic sizes, and MALS yields the molar mass and molecular size (radius of gyration, Rg). In vitro and in vivo anti-hyperglycemic effect of germinated wheat and barley was studied. The relationship between antidiabetic activity and molecular conformation was, for the first time, investigated. The ratio of Rg to the hydrodynamic radius (Rh) and the apparent density were proven to be important parameters as they offer an insight into molecular conformation. Results showed that, when geminated, the apparent density and the antidiabetic activity of barley were significantly increased, suggesting germination makes the molecules more compact which could contribute to enhancement of their antidiabetic activity. The information obtained by AF4-MALS-RI is valuable for understanding of germination mechanism, and thus for developing functional foods. Copyright © 2014 Elsevier B.V. All rights reserved.

Asymmetric flow field-flow fractionation of manufactured silver nanoparticles spiked into soil solution.

PubMed

Koopmans, G F; Hiemstra, T; Regelink, I C; Molleman, B; Comans, R N J

2015-05-01

Manufactured metallic silver nanoparticles (AgNP) are intensively utilized in consumer products and this will inevitably lead to their release to soils. To assess the environmental risks of AgNP in soils, quantification of both their concentration and size in soil solution is essential. We developed a methodology consisting of asymmetric flow field-flow fractionation (AF4) in combination with on-line detection by UV-vis spectroscopy and off-line HR-ICP-MS measurements to quantify the concentration and size of AgNP, coated with either citrate or polyvinylpyrrolidone (PVP), in water extracts of three different soils. The type of mobile phase was a critical factor in the fractionation of AgNP by AF4. In synthetic systems, fractionation of a series of virgin citrate- and PVP-coated AgNP (10-90 nm) with reasonably high recoveries could only be achieved with ultrahigh purity water as a mobile phase. For the soil water extracts, 0.01% (w:v) sodium dodecyl sulfate (SDS) at pH 8 was the key to a successful fractionation of the AgNP. With SDS, the primary size of AgNP in all soil water extracts could be determined by AF4, except for PVP-coated AgNP when clay colloids were present. The PVP-coated AgNP interacted with colloidal clay minerals, leading to an overestimation of their primary size. Similar interactions between PVP-coated AgNP and clay colloids can take place in the environment and facilitate their transport in soils, aquifers, and surface waters. In conclusion, AF4 in combination with UV-vis spectroscopy and HR-ICP-MS measurements is a powerful tool to characterize AgNP in soil solution if the appropriate mobile phase is used. Copyright © 2015 Elsevier B.V. All rights reserved.

One-step analysis of DNA/chitosan complexes by field-flow fractionation reveals particle size and free chitosan content.

PubMed

Ma, Pei Lian; Buschmann, Michael D; Winnik, Françoise M

2010-03-08

The composition of samples obtained upon complexation of DNA with chitosan was analyzed by asymmetrical flow field flow fractionation (AF4) with online UV-visible, multiangle light scattering (MALS), and dynamic light scattering (DLS) detectors. A chitosan labeled with rhodamine B to facilitate UV-vis detection of the polycation was complexed with DNA under conditions commonly used for transfection (chitosan glucosamine to DNA phosphate molar ratio of 5). AF4 analysis revealed that 73% of the chitosan-rhodamine remained free in the dispersion and that the DNA/chitosan complexes had a broad size distribution ranging from 20 to 160 nm in hydrodynamic radius. The accuracy of the data was assessed by comparison with data from batch-mode DLS and scanning electron microscopy. The AF4 combined with DLS allowed the characterization of small particles that were not detected by conventional batch-mode DLS. The AF4 analysis will prove to be an important tool in the field of gene therapy because it readily provides, in a single measurement, three important physicochemical parameters of the complexes: the amount of unbound polycation, the hydrodynamic size of the complexes, and their size distribution.

Semi-preparative asymmetrical flow field-flow fractionation: A closer look at channel dimensions and separation performance.

PubMed

Bria, Carmen R M; Skelly, Patrick W; Morse, James R; Schaak, Raymond E; Williams, S Kim Ratanathanawongs

2017-05-26

The design and performance of a semi-preparative asymmetrical flow field-flow fractionation (SP-AF4) channel are investigated with the objective of better understanding and exploiting the relationship between channel dimensions, sample loading, and resolution. Most size-based separations of nanometer and submicrometer particles are currently limited to analytical scale quantities (<100μg). However, there is a strong need to fractionate and collect larger quantities so that fundamental properties of the more narrowly dispersed fractions can be studied using additional characterization methods and for subsequent applications. In this work, dimensions of the spacer that defines the form of SP-AF4 channels are varied and their performances are assessed with respect to sample focusing position and loading. Separations are performed in aqueous and organic carrier fluids. A critical evaluation of channel dimensions showed that increasing the channel breadth is a practical and effective route to maintaining separation resolution while increasing sample loads to milligram quantities. Good size resolution (∼1.0) is achieved for separations of 10mg of 50 and 100nm silica nanoparticles suspended in water and up to 0.6mg of ∼10 to 35nm inorganic hybrid nanoparticles suspended in tetrahydrofuran. This work represents important advances in the understanding of SP-AF4 separations and extends sample loading capacities in both aqueous and organic solvents. Copyright © 2017 Elsevier B.V. All rights reserved.

High Speed Size Sorting of Subcellular Organelles by Flow Field-Flow Fractionation.

PubMed

Yang, Joon Seon; Lee, Ju Yong; Moon, Myeong Hee

2015-06-16

Separation/isolation of subcellular species, such as mitochondria, lysosomes, peroxisomes, Golgi apparatus, and others, from cells is important for gaining an understanding of the cellular functions performed by specific organelles. This study introduces a high speed, semipreparative scale, biocompatible size sorting method for the isolation of subcellular organelle species from homogenate mixtures of HEK 293T cells using flow field-flow fractionation (FlFFF). Separation of organelles was achieved using asymmetrical FlFFF (AF4) channel system at the steric/hyperlayer mode in which nuclei, lysosomes, mitochondria, and peroxisomes were separated in a decreasing order of hydrodynamic diameter without complicated preprocessing steps. Fractions in which organelles were not clearly separated were reinjected to AF4 for a finer separation using the normal mode, in which smaller sized species can be well fractionated by an increasing order of diameter. The subcellular species contained in collected AF4 fractions were examined with scanning electron microscopy to evaluate their size and morphology, Western blot analysis using organelle specific markers was used for organelle confirmation, and proteomic analysis was performed with nanoflow liquid chromatography-tandem mass spectrometry (nLC-ESI-MS/MS). Since FlFFF operates with biocompatible buffer solutions, it offers great flexibility in handling subcellular components without relying on a high concentration sucrose solution for centrifugation or affinity- or fluorescence tag-based sorting methods. Consequently, the current study provides an alternative, competitive method for the isolation/purification of subcellular organelle species in their intact states.

Asymmetrical flow field-flow fractionation coupled to inductively coupled plasma mass spectrometry for sizing SeNPs for packaging applications

NASA Astrophysics Data System (ADS)

Palomo-Siguero, María; Vera, Paula; Echegoyen, Yolanda; Nerin, Cristina; Cámara, Carmen; Madrid, Yolanda

2017-06-01

This paper describes the application of Asymmetrical Flow Field-Flow Fractionation (AF4) coupled to diode array detector (DAD) and inductively coupled plasma mass spectrometry (AF4-UV-ICP-MS) to characterize selenium nanoparticles (SeNPs) in an aqueous acrylic adhesive to be used in a multilayer food packaging material. SeNPs were synthesized using a solution-phase approach based on the reduction of selenite with ascorbic acid in presence of different stabilizers compatible with food industry such as polysaccharides (chitosan (poly(D-glucosamine) and hydroxyethylcellulose (HEC)) and non-ionic surfactants (Triton X-100 (t-octylphenoxypolyethoxyethanol), 2,4,7,9-tetramethyl 5decyne-4,7-diol ethoxylate, and isotridecanol ethoxylate). Several parameters such as pH, ascorbic acid and stabilizers concentration, and compatibility of the stabilizer with the adhesive were evaluated. SeNPs suspensions with spherical morphology were obtained except when isotridecanol ethoxylate was employed which provides SeNPs with a nanorod morphology. AF4-DAD-ICP-MS was further applied for sizing the different SeNPs preparations. DAD was used as detector for selecting the best AF4 separation conditions before coupling to ICP-MS to ensure unequivocal identification of NPs. AF4 calibration with polystyrene latex (PSL) beads of known sizes allowed size determination of the different SeNPs. The following estimated hydrodynamic sizes (expressed as the mean ± standard deviation, n = 6 replicates) were found: chitosan-SeNPs- (26 ± 3 nm), TritonX100-SeNPs (22 ± 10 nm) HEC- SeNPs (91 ± 8 nm) and 2,4,7,9-tetramethyl 5decyne-4,7-diol ethoxylate- SeNPs (59 ± 4 nm). The proposed methodology was successfully applied to the characterization in terms of size of aqueous acrylic adhesives containing SeNPs Results from AF4-ICP-MS and TEM shown that only those SeNPs obtained with non-ionic surfactants and HEC were compatible with the adhesive. The results reported here evidence the usefulness of AF4-ICP-MS as analytical tool for controlling those manufacturing process involving nanoparticles which opens new frontiers in applicability of AF4-ICP-MS.

Asymmetric flow field-flow fractionation (AF4) for the quantification of nanoparticle release from tablets during dissolution testing.

PubMed

Engel, A; Plöger, M; Mulac, D; Langer, K

2014-01-30

Nanoparticles composed of poly(DL-lactide-co-glycolide) (PLGA) represent promising colloidal drug carriers for improved drug targeting. Although most research activities are focused on intravenous application of these carriers the peroral administration is described to improve bioavailability of poorly soluble drugs. Based on these insights the manuscript describes a model tablet formulation for PLGA-nanoparticles and especially its analytical characterisation with regard to a nanosized drug carrier. Besides physico-chemical tablet characterisation according to pharmacopoeias the main goal of the study was the development of a suitable analytical method for the quantification of nanoparticle release from tablets. An analytical flow field-flow fractionation (AF4) method was established and validated which enables determination of nanoparticle content in solid dosage forms as well as quantification of particle release during dissolution testing. For particle detection a multi-angle light scattering (MALS) detector was coupled to the AF4-system. After dissolution testing, the presence of unaltered PLGA-nanoparticles was successfully proved by dynamic light scattering and scanning electron microscopy. Copyright © 2013 Elsevier B.V. All rights reserved.

Co-elution effects can influence molar mass determination of large macromolecules with asymmetric flow field-flow fractionation coupled to multiangle light scattering.

PubMed

Perez-Rea, Daysi; Zielke, Claudia; Nilsson, Lars

2017-07-14

Starch and hence, amylopectin is an important biomacromolecule in both the human diet as well as in technical applications. Therefore, accurate and reliable analytical methods for its characterization are needed. A suitable method for analyzing macromolecules with ultra-high molar mass, branched structure and high polydispersity is asymmetric flow field-flow fractionation (AF4) in combination with multiangle light scattering (MALS) detection. In this paper we illustrate how co-elution of low quantities of very large analytes in AF4 may cause disturbances in the MALS data which, in turn, causes an overestimation of the size. Furthermore, it is shown how pre-injection filtering of the sample can improve the results. Copyright © 2017 Elsevier B.V. All rights reserved.

Asymmetrical flow field flow fractionation methods to characterize submicron particles: application to carbon-based aggregates and nanoplastics.

PubMed

Gigault, Julien; El Hadri, Hind; Reynaud, Stéphanie; Deniau, Elise; Grassl, Bruno

2017-11-01

In the last 10 years, asymmetrical flow field flow fractionation (AF4) has been one of the most promising approaches to characterize colloidal particles. Nevertheless, despite its potentialities, it is still considered a complex technique to set up, and the theory is difficult to apply for the characterization of complex samples containing submicron particles and nanoparticles. In the present work, we developed and propose a simple analytical strategy to rapidly determine the presence of several submicron populations in an unknown sample with one programmed AF4 method. To illustrate this method, we analyzed polystyrene particles and fullerene aggregates of size covering the whole colloidal size distribution. A global and fast AF4 method (method O) allowed us to screen the presence of particles with size ranging from 1 to 800 nm. By examination of the fractionating power F d , as proposed in the literature, convenient fractionation resolution was obtained for size ranging from 10 to 400 nm. The global F d values, as well as the steric inversion diameter, for the whole colloidal size distribution correspond to the predicted values obtained by model studies. On the basis of this method and without the channel components or mobile phase composition being changed, four isocratic subfraction methods were performed to achieve further high-resolution separation as a function of different size classes: 10-100 nm, 100-200 nm, 200-450 nm, and 450-800 nm in diameter. Finally, all the methods developed were applied in characterization of nanoplastics, which has received great attention in recent years. Graphical Absract Characterization of the nanoplastics by asymmetrical flow field flow fractionation within the colloidal size range.

Asymmetric flow field flow fractionation for the characterization of globule size distribution in complex formulations: A cyclosporine ophthalmic emulsion case.

PubMed

Qu, Haiou; Wang, Jiang; Wu, Yong; Zheng, Jiwen; Krishnaiah, Yellela S R; Absar, Mohammad; Choi, Stephanie; Ashraf, Muhammad; Cruz, Celia N; Xu, Xiaoming

2018-03-01

Commonly used characterization techniques such as cryogenic-transmission electron microscopy (cryo-TEM) and batch-mode dynamic light scattering (DLS) are either time consuming or unable to offer high resolution to discern the poly-dispersity of complex drug products like cyclosporine ophthalmic emulsions. Here, a size-based separation and characterization method for globule size distribution using an asymmetric flow field flow fractionation (AF4) is reported for comparative assessment of cyclosporine ophthalmic emulsion drug products (model formulation) with a wide size span and poly-dispersity. Cyclosporine emulsion formulations that are qualitatively (Q1) and quantitatively (Q2) the same as Restasis® were prepared in house with varying manufacturing processes and analyzed using the optimized AF4 method. Based on our results, the commercially available cyclosporine ophthalmic emulsion has a globule size span from 30 nm to a few hundred nanometers with majority smaller than 100 nm. The results with in-house formulations demonstrated the sensitivity of AF4 in determining the differences in the globule size distribution caused by the changes to the manufacturing process. It is concluded that the optimized AF4 is a potential analytical technique for comprehensive understanding of the microstructure and assessment of complex emulsion drug products with high poly-dispersity. Published by Elsevier B.V.

Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI)

NASA Astrophysics Data System (ADS)

Rigaux, G.; Gheran, C. V.; Callewaert, M.; Cadiou, C.; Voicu, S. N.; Dinischiotu, A.; Andry, M. C.; Vander Elst, L.; Laurent, S.; Muller, R. N.; Berquand, A.; Molinari, M.; Huclier-Markai, S.; Chuburu, F.

2017-02-01

Chitosan CS—tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

Factors affecting measurement of channel thickness in asymmetrical flow field-flow fractionation.

PubMed

Dou, Haiyang; Jung, Euo Chang; Lee, Seungho

2015-05-08

Asymmetrical flow field-flow fractionation (AF4) has been considered to be a useful tool for simultaneous separation and characterization of polydisperse macromolecules or colloidal nanoparticles. AF4 analysis requires the knowledge of the channel thickness (w), which is usually measured by injecting a standard with known diffusion coefficient (D) or hydrodynamic diameter (dh). An accurate w determination is a challenge due to its uncertainties arising from the membrane's compressibility, which may vary with experimental condition. In the present study, influence of factors including the size and type of the standard on the measurement of w was systematically investigated. The results revealed that steric effect and the particles-membrane interaction by van der Waals or electrostatic force may result in an error in w measurement. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimization and evaluation of asymmetric flow field-flow fractionation of silver nanoparticles.

PubMed

Loeschner, Katrin; Navratilova, Jana; Legros, Samuel; Wagner, Stephan; Grombe, Ringo; Snell, James; von der Kammer, Frank; Larsen, Erik H

2013-01-11

Asymmetric flow field-flow fractionation (AF(4)) in combination with on-line optical detection and mass spectrometry is one of the most promising methods for separation and quantification of nanoparticles (NPs) in complex matrices including food. However, to obtain meaningful results regarding especially the NP size distribution a number of parameters influencing the separation need to be optimized. This paper describes the development of a separation method for polyvinylpyrrolidone-stabilized silver nanoparticles (AgNPs) in aqueous suspension. Carrier liquid composition, membrane material, cross flow rate and spacer height were shown to have a significant influence on the recoveries and retention times of the nanoparticles. Focus time and focus flow rate were optimized with regard to minimum elution of AgNPs in the void volume. The developed method was successfully tested for injected masses of AgNPs from 0.2 to 5.0 μg. The on-line combination of AF(4) with detection methods including ICP-MS, light absorbance and light scattering was helpful because each detector provided different types of information about the eluting NP fraction. Differences in the time-resolved appearance of the signals obtained by the three detection methods were explained based on the physical origin of the signal. Two different approaches for conversion of retention times of AgNPs to their corresponding sizes and size distributions were tested and compared, namely size calibration with polystyrene nanoparticles (PSNPs) and calculations of size based on AF(4) theory. Fraction collection followed by transmission electron microscopy was performed to confirm the obtained size distributions and to obtain further information regarding the AgNP shape. Characteristics of the absorbance spectra were used to confirm the presence of non-spherical AgNP. Copyright © 2012 Elsevier B.V. All rights reserved.

Detection of nanoplastics in food by asymmetric flow field-flow fractionation coupled to multi-angle light scattering: possibilities, challenges and analytical limitations.

PubMed

Correia, Manuel; Loeschner, Katrin

2018-02-06

We tested the suitability of asymmetric flow field-flow fractionation (AF4) coupled to multi-angle light scattering (MALS) for detection of nanoplastics in fish. A homogenized fish sample was spiked with 100 nm polystyrene nanoparticles (PSNPs) (1.3 mg/g fish). Two sample preparation strategies were tested: acid digestion and enzymatic digestion with proteinase K. Both procedures were found suitable for degradation of the organic matrix. However, acid digestion resulted in large PSNPs aggregates/agglomerates (> 1 μm). The presence of large particulates was not observed after enzymatic digestion, and consequently it was chosen as a sample preparation method. The results demonstrated that it was possible to use AF4 for separating the PSNPs from the digested fish and to determine their size by MALS. The PSNPs could be easily detected by following their light scattering (LS) signal with a limit of detection of 52 μg/g fish. The AF4-MALS method could also be exploited for another type of nanoplastics in solution, namely polyethylene (PE). However, it was not possible to detect the PE particles in fish, due to the presence of an elevated LS background. Our results demonstrate that an analytical method developed for a certain type of nanoplastics may not be directly applicable to other types of nanoplastics and may require further adjustment. This work describes for the first time the detection of nanoplastics in a food matrix by AF4-MALS. Despite the current limitations, this is a promising methodology for detecting nanoplastics in food and in experimental studies (e.g., toxicity tests, uptake studies). Graphical abstract Basic concept for the detection of nanoplastics in fish by asymmetric flow field-flow fractionation coupled to multi-angle light scattering.

Application of asymmetric flow field-flow fractionation (AF4) and multiangle light scattering (MALS) for the evaluation of changes in the product molar mass during PVP-b-PAMPS synthesis.

PubMed

Fuentes, Catalina; Castillo, Joel; Vila, Jose; Nilsson, Lars

2018-06-01

The use of polymers for the delivery of drugs has increased dramatically in the last decade. To ensure the desired properties and functionality of such substances, adequate characterization in terms of the molar mass (M) and size is essential. The aim of this study was to evaluate the changes in the M and size of PVP-b-PAMPS when the amounts of the synthesis reactants in the two-step radical reaction were varied. The determination of the M and size distributions was performed by an asymmetric flow field-flow fractionation (AF4) system connected to multiangle light scattering (MALS) and differential refractive index (dRI) detectors. The results show that the M of the polymers varies depending on the relative amounts of the reactants and that AF4-MALS-dRI is a powerful characterization technique for analyzing polymers. Using AF4, it was possible to separate the product of the first radical reaction (PVP-CTA) into two populations. The first population had an elongated, rod-like or random coil conformation, and the second had a conformation corresponding to homogeneous spheres or a microgel structure. PVP-b-PAMPS had only one population, which had a rod-like conformation. The molar masses of PVP-CTA and PVP-b-PAMPS found in this study were higher than those reported in previous studies.

Quantum dot agglomerates in biological media and their characterization by asymmetrical flow field-flow fractionation.

PubMed

Moquin, Alexandre; Neibert, Kevin D; Maysinger, Dusica; Winnik, Françoise M

2015-01-01

The molecular composition of the biological environment of nanoparticles influences their physical properties and changes their pristine physicochemical identity. In order to understand, or predict, the interactions of cells with specific nanoparticles, it is critical to know their size, shape, and agglomeration state not only in their nascent state but also in biological media. Here, we use asymmetrical flow field-flow fractionation (AF4) with on-line multiangle light scattering (MALS), dynamic light scattering (DLS) and UV-Visible absorption detections to determine the relative concentration of isolated nanoparticles and agglomerates in the case of three types of semi-conductor quantum dots (QDs) dispersed in Dulbecco's Modified Eagle Media (DMEM) containing 10% of fetal bovine serum (DMEM-FBS). AF4 analysis also yielded the size and size distribution of the agglomerates as a function of the time of QDs incubation in DMEM-FBS. The preferred modes of internalization of the QDs are assessed for three cell-types, N9 microglia, human hepatocellular carcinoma cells (HepG2) and human embryonic kidney cells (Hek293), by confocal fluorescence imaging of live cells, quantitative determination of the intracellular QD concentration, and flow cytometry. There is an excellent correlation between the agglomeration status of the three types of QDs in DMEM-FBS determined by AF4 analysis and their preferred mode of uptake by the three cell lines, which suggests that AF4 yields an accurate description of the nanoparticles as they encounter cells and advocates its use as a means to characterize particles under evaluation. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of protein formulation and carrier solution on asymmetrical flow field-flow fractionation: a case study of the plant-produced recombinant anthrax protective antigen pp-PA83.

PubMed

Palais, Caroline; Chichester, Jessica A; Manceva, Slobodanka; Yusibov, Vidadi; Arvinte, Tudor

2015-02-01

Asymmetrical flow field-flow fractionation (afFFF) was used to investigate the properties of a plant-produced anthrax toxin protective antigen, pp-PA83. The afFFF fractogram consisted of two main peaks with molar masses similar to the molecular mass of pp-PA83 monomer. afFFF carrier solutions strongly influenced the ratio and the intensity of the two main peaks. These differences indicate that conformation changes in the pp-PA83 molecule occurred during the afFFF analysis. Similar fractograms were obtained for different pp-PA83 formulations when the afFFF carrier solution and the protein formulation were the same (or very similar). The data show that in specific cases, afFFF could be used to study protein conformation and document the importance of studying the influence of the carrier solution on afFFF. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Detection and Quantification of Silver Nanoparticles at ...

EPA Pesticide Factsheets

The presence of silver nanoparticles (AgNPs) in aquatic environments could potentially cause adverse impacts on ecosystems and human health. However, current understanding of the environmental fate and transport of AgNPs is still limited because their properties in complex environmental samples cannot be accurately determined. In this study, the feasibility of using asymmetric flow field-flow fractionation (AF4) connected online with single particle inductively coupled plasma mass spectrometry (spICPMS) to detect and quantify AgNPs at environmentally relevant concentrations was investigated. The AF4 channel had a thickness of 350 μm and its accumulation wall was a 10 kDa regenerated cellulose membrane. A 0.02% FL-70 surfactant solution was used as an AF4 carrier. With 1.2 mL/min AF4 cross-flow rate, 1.5 mL/min AF4 channel flow rate, and 5 ms spICPMS dwell time, the AF4-spICPMS can detect and quantify 40–80 nm AgNPs, as well as Ag-SiO2 core−shell nanoparticles (51.0 nm diameter Ag core and 21.6 nm SiO2 shell), with good recovery within 30 min. This system was not only effective in differentiating and quantifying different types of AgNPs with similar hydrodynamic diameters, such as in mixtures containing Ag-SiO2 core–shell nanoparticles and 40–80 nm AgNPs, but also suitable for differentiating between 40 nm AgNPs and elevated Ag+ content. The study results indicate that AF4-spICPMS is capable of detecting and quantifying AgNPs and other engineered metal n

Asymmetrical flow field-flow fractionation for human serum albumin based nanoparticle characterisation and a deeper insight into particle formation processes.

PubMed

John, C; Langer, K

2014-06-13

Nanoparticles used as drug delivery systems are of growing interest in the pharmaceutical field. Understanding the behaviour and effects of nanosystems in the human body is dependent on comprehensive characterisation of the systems especially with regard to size and size distribution. Asymmetrical flow field-flow fractionation (AF4) is a promising method for this challenge as this technique enables chromatographic separation of particles and solute molecules according to their respective size. Within this study AF4 was used for the characterisation of human serum albumin (HSA) based nanoparticles. In a first part, the most important aspects of method development like the choice of cross flow rate, focusing and the increase of sample concentration via outlet stream splitting on the sample separation were evaluated. Sample fractionation was controlled by inline-coupling of a dynamic light scattering detector (DLS, Zetasizer) and was confirmed by DLS batch mode measurements. In a second part the applicability of field-flow fractionation for characterisation of the HSA particle formation process by a desolvation method was evaluated. A time dependent particle formation was observed which was controlled by the amount of desolvating agent. Furthermore, field-flow fractionation in combination with in-line dynamic light scattering was used to monitor the increase of particle diameter during PEGylation of the resulting HSA nanoparticles. The separation of nanoparticles from dissolved polyethylene glycol (PEG) could successfully be used for determination of the particles' PEGylation degree. Copyright © 2014 Elsevier B.V. All rights reserved.

Asymmetric flow field-flow fractionation in the field of nanomedicine.

PubMed

Wagner, Michael; Holzschuh, Stephan; Traeger, Anja; Fahr, Alfred; Schubert, Ulrich S

2014-06-03

Asymmetric flow field-flow fractionation (AF4) is a widely used and versatile technique in the family of field-flow fractionations, indicated by a rapidly increasing number of publications. It represents a gentle separation and characterization method, where nonspecific interactions are reduced to a minimum, allows a broad separation range from several nano- up to micrometers and enables a superior characterization of homo- and heterogenic systems. In particular, coupling to multiangle light scattering provides detailed access to sample properties. Information about molar mass, polydispersity, size, shape/conformation, or density can be obtained nearly independent of the used material. In this Perspective, the application and progress of AF4 for (bio)macromolecules and colloids, relevant for "nano" medical and pharmaceutical issues, will be presented. The characterization of different nanosized drug or gene delivery systems, e.g., polymers, nanoparticles, micelles, dendrimers, liposomes, polyplexes, and virus-like-particles (VLP), as well as therapeutic relevant proteins, antibodies, and nanoparticles for diagnostic usage will be discussed. Thereby, the variety of obtained information, the advantages and pitfalls of this emerging technique will be highlighted. Additionally, the influence of different fractionation parameters in the separation process is discussed in detail. Moreover, a comprehensive overview is given, concerning the investigated samples, fractionation parameters as membrane types and buffers used as well as the chosen detectors and the corresponding references. The perspective ends up with an outlook to the future.

Core lipid, surface lipid and apolipoprotein composition analysis of lipoprotein particles as a function of particle size in one workflow integrating asymmetric flow field-flow fractionation and liquid chromatography-tandem mass spectrometry

PubMed Central

Jones, Jeffery I.; Gardner, Michael S.; Schieltz, David M.; Parks, Bryan A.; Toth, Christopher A.; Rees, Jon C.; Andrews, Michael L.; Carter, Kayla; Lehtikoski, Antony K.; McWilliams, Lisa G.; Williamson, Yulanda M.; Bierbaum, Kevin P.; Pirkle, James L.; Barr, John R.

2018-01-01

Lipoproteins are complex molecular assemblies that are key participants in the intricate cascade of extracellular lipid metabolism with important consequences in the formation of atherosclerotic lesions and the development of cardiovascular disease. Multiplexed mass spectrometry (MS) techniques have substantially improved the ability to characterize the composition of lipoproteins. However, these advanced MS techniques are limited by traditional pre-analytical fractionation techniques that compromise the structural integrity of lipoprotein particles during separation from serum or plasma. In this work, we applied a highly effective and gentle hydrodynamic size based fractionation technique, asymmetric flow field-flow fractionation (AF4), and integrated it into a comprehensive tandem mass spectrometry based workflow that was used for the measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E), free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions separated by AF4 was measured by dynamic light scattering. Measuring all major lipids and apolipoproteins in each size fraction and in the whole serum, using total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle numbers and expression of composition in molar analyte per particle number ratios. Measurements in 110 serum samples showed substantive differences between size fractions of HDL and LDL. Lipoprotein composition within size fractions was expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III, FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with combinations of normal and high levels of Total-C and/or Total-TG. The agreement with previous studies indirectly validates the AF4-LC-MS/MS approach and demonstrates the potential of this workflow for characterization of lipoprotein composition in clinical studies using small volumes of archived frozen samples. PMID:29634782

Coupling asymmetric flow-field flow fractionation and fluorescence parallel factor analysis reveals stratification of dissolved organic matter in a drinking water reservoir.

PubMed

Pifer, Ashley D; Miskin, Daniel R; Cousins, Sarah L; Fairey, Julian L

2011-07-08

Using asymmetrical flow field-flow fractionation (AF4) and fluorescence parallel factor analysis (PARAFAC), we showed physicochemical properties of chromophoric dissolved organic matter (CDOM) in the Beaver Lake Reservoir (Lowell, AR) were stratified by depth. Sampling was performed at a drinking water intake structure from May to July 2010 at three depths (3-, 10-, and 18-m) below the water surface. AF4-fractograms showed that the CDOM had diffusion coefficient peak maximums between 3.5 and 2.8 x 10⁻⁶ cm² s⁻¹, which corresponded to a molecular weight range of 680-1950 Da and a size of 1.6-2.5 nm. Fluorescence excitation-emission matrices of whole water samples and AF4-generated fractions were decomposed with a PARAFAC model into five principal components. For the whole water samples, the average total maximum fluorescence was highest for the 10-m depth samples and lowest (about 40% less) for 18-m depth samples. While humic-like fluorophores comprised the majority of the total fluorescence at each depth, a protein-like fluorophore was in the least abundance at the 10-m depth, indicating stratification of both total fluorescence and the type of fluorophores. The results present a powerful approach to investigate CDOM properties and can be extended to investigate CDOM reactivity, with particular applications in areas such as disinfection byproduct formation and control and evaluating changes in drinking water source quality driven by climate change. Copyright © 2010 Elsevier B.V. All rights reserved.

Characterization of cationic polymers by asymmetric flow field-flow fractionation and multi-angle light scattering-A comparison with traditional techniques.

PubMed

Wagner, Michael; Pietsch, Christian; Tauhardt, Lutz; Schallon, Anja; Schubert, Ulrich S

2014-01-17

In the field of nanomedicine, cationic polymers are the subject of intensive research and represent promising carriers for genetic material. The detailed characterization of these carriers is essential since the efficiency of gene delivery strongly depends on the properties of the used polymer. Common characterization methods such as size exclusion chromatography (SEC) or mass spectrometry (MS) suffer from problems, e.g. missing standards, or even failed for cationic polymers. As an alternative, asymmetrical flow field-flow fractionation (AF4) was investigated. Additionally, analytical ultracentrifugation (AUC) and (1)H NMR spectroscopy, as well-established techniques, were applied to evaluate the results obtained by AF4. In this study, different polymers of molar masses between 10 and 120kgmol(-1) with varying amine functionalities in the side chain or in the polymer backbone were investigated. To this end, some of the most successful gene delivery agents, namely linear poly(ethylene imine) (LPEI) (only secondary amines in the backbone), branched poly(ethylene imine) (B-PEI) (secondary and tertiary amino groups in the backbone, primary amine end groups), and poly(l-lysine) (amide backbone and primary amine side chains), were characterized. Moreover, poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA), poly(2-(amino)ethyl methacrylate) (PAEMA), and poly(2-(tert-butylamino)ethyl methacrylate) (PtBAEMA) as polymers with primary, secondary, and tertiary amines in the side chain, have been investigated. Reliable results were obtained for all investigated polymers by AF4. In addition, important factors for all methods were evaluated, e.g. the influence of different elution buffers and AF4 membranes. Besides this, the correct determination of the partial specific volume and the suppression of the polyelectrolyte effect are the most critical issues for AUC investigations. Copyright © 2013 Elsevier B.V. All rights reserved.

Characterization of Silver Nanoparticles under Environmentally Relevant Conditions Using Asymmetrical Flow Field-Flow Fractionation (AF4)

PubMed Central

Jang, Min-Hee; Lee, Seungho; Hwang, Yu Sik

2015-01-01

The development of methods to monitor manufactured nanomaterials in the environment is one of the crucial areas for the assessment of their risk. More specifically, particle size analysis is a key element, because many properties of nanomaterial are size dependent. The sizing of nanomaterials in real environments is challenging due to their heterogeneity and reactivity with other environmental components. In this study, the fractionation and characterization of a mixture of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) of three different sizes were investigated using asymmetrical flow field-flow fractionation (AF4) coupled with UV-Vis spectrophotometry. In particular, the effects of electrolyte composition and natural organic matter (NOM) on the particle size and stability were evaluated. The fractogram peaks (i.e., stability) of three different AgNPs decreased in the presence of both 10 mM NaCl and 10mM CaCl2, while increased with increasing concentration of humic acid (HA). In addition, the hydrodynamic diameters of AgNPs in both electrolytes slightly increased with an increase of HA concentration, suggesting the adsorption (coating) of HA onto the particle surface. It is also interesting to note that an increase in the particle size depended on the types of electrolyte, which could be explained by the conformational characteristics of the adsorbed HA layers. Consistent these results, AgNPs suspended in lake water containing relatively high concentration of organic carbon (TOC) showed higher particle stability and larger particle size (i.e., by approximately 4nm) than those in river water. In conclusion, the application of AF4 coupled with highly sensitive detectors could be a powerful method to characterize nanoparticles in natural waters. PMID:26575993

Using Asymmetric Flow Field-Flow Fractionation (AF4) to Determine C60 Colloidal Size Distributions

EPA Science Inventory

The formation of aqueous fullerene suspensions by solvent exchange, sonication, or extended mixing in water is widely reported. Commonly used methods for determining the size of these aggregates rely on static and dynamic light scattering, electron microscopy (EM), or atomic forc...

Asymmetric Flow-Field Flow Fractionation (AF4) of Aqueous C60 Aggregates with Dynamic Light Scattering Size and LC-MS

EPA Science Inventory

Current methods for the size determination of nanomaterials in aqueous suspension include dynamic or static light scattering and electron or atomic force microscopy techniques. Light scattering techniques are limited by poor resolution and the scattering intensity dependence on p...

Characterization of branched ultrahigh molar mass polymers by asymmetrical flow field-flow fractionation and size exclusion chromatography.

PubMed

Otte, T; Pasch, H; Macko, T; Brüll, R; Stadler, F J; Kaschta, J; Becker, F; Buback, M

2011-07-08

The molar mass distribution (MMD) of synthetic polymers is frequently analyzed by size exclusion chromatography (SEC) coupled to multi angle light scattering (MALS) detection. For ultrahigh molar mass (UHM) or branched polymers this method is not sufficient, because shear degradation and abnormal elution effects falsify the calculated molar mass distribution and information on branching. High temperatures above 130 °C have to be applied for dissolution and separation of semi-crystalline materials like polyolefins which requires special hardware setups. Asymmetrical flow field-flow fractionation (AF4) offers the possibility to overcome some of the main problems of SEC due to the absence of an obstructing porous stationary phase. The SEC-separation mainly depends on the pore size distribution of the used column set. The analyte molecules can enter the pores of the stationary phase in dependence on their hydrodynamic volume. The archived separation is a result of the retention time of the analyte species inside SEC-column which depends on the accessibility of the pores, the residence time inside the pores and the diffusion ability of the analyte molecules. The elution order in SEC is typically from low to high hydrodynamic volume. On the contrary AF4 separates according to the diffusion coefficient of the analyte molecules as long as the chosen conditions support the normal FFF-separation mechanism. The separation takes place in an empty channel and is caused by a cross-flow field perpendicular to the solvent flow. The analyte molecules will arrange in different channel heights depending on the diffusion coefficients. The parabolic-shaped flow profile inside the channel leads to different elution velocities. The species with low hydrodynamic volume will elute first while the species with high hydrodynamic volume elute later. The AF4 can be performed at ambient or high temperature (AT-/HT-AF4). We have analyzed one low molar mass polyethylene sample and a number of narrow distributed polystyrene standards as reference materials with known structure by AT/HT-SEC and AT/HT-AF4. Low density polyethylenes as well as polypropylene and polybutadiene, containing high degrees of branching and high molar masses, have been analyzed with both methods. As in SEC the relationship between the radius of gyration (R(g)) or the molar mass and the elution volume is curved up towards high elution volumes, a correct calculation of the MMD and the molar mass average or branching ratio is not possible using the data from the SEC measurements. In contrast to SEC, AF4 allows the precise determination of the MMD, the molar mass averages as well as the degree of branching because the molar mass vs. elution volume curve and the conformation plot is not falsified in this technique. In addition, higher molar masses can be detected using HT-AF4 due to the absence of significant shear degradation in the channel. As a result the average molar masses obtained from AF4 are higher compared to SEC. The analysis time in AF4 is comparable to that of SEC but the adjustable cross-flow program allows the user to influence the separation efficiency which is not possible in SEC without a costly change of the whole column combination. Copyright © 2011 Elsevier B.V. All rights reserved.

Polysaccharide characterization by hollow-fiber flow field-flow fractionation with on-line multi-angle static light scattering and differential refractometry.

PubMed

Pitkänen, Leena; Striegel, André M

2015-02-06

Accurate characterization of the molar mass and size of polysaccharides is an ongoing challenge, oftentimes due to architectural diversity but also to the broad molar mass (M) range over which a single polysaccharide can exist and to the ultra-high M of many polysaccharides. Because of the latter, many of these biomacromolecules experience on-column, flow-induced degradation during analysis by size-exclusion and, even, hydrodynamic chromatography (SEC and HDC, respectively). The necessity for gentler fractionation methods has, to date, been addressed employing asymmetric flow field-flow fractionation (AF4). Here, we introduce the coupling of hollow-fiber flow field-flow fractionation (HF5) to multi-angle static light scattering (MALS) and differential refractometry (DRI) detection for the analysis of polysaccharides. In HF5, less stresses are placed on the macromolecules during separation than in SEC or HDC, and HF5 can offer a higher sensitivity, with less propensity for system overloading and analyte aggregation, than generally found in AF4. The coupling to MALS and DRI affords the determination of absolute, calibration-curve-independent molar mass averages and dispersities. Results from the present HF5/MALS/DRI experiments with dextrans, pullulans, and larch arabinogalactan were augmented with hydrodynamic radius (RH) measurements from off-line quasi-elastic light scattering (QELS) and by RH distribution calculations and fractogram simulations obtained via a finite element analysis implementation of field-flow fractionation theory by commercially available software. As part of this study, we have investigated analyte recovery in HF5 and also possible reasons for discrepancies between calculated and simulated results vis-à-vis experimentally determined data. Published by Elsevier B.V.

Application of asymmetric flow-field flow fractionation to the characterization of colloidal dispersions undergoing aggregation.

PubMed

Lattuada, Marco; Olivo, Carlos; Gauer, Cornelius; Storti, Giuseppe; Morbidelli, Massimo

2010-05-18

The characterization of complex colloidal dispersions is a relevant and challenging problem in colloidal science. In this work, we show how asymmetric flow-field flow fractionation (AF4) coupled to static light scattering can be used for this purpose. As an example of complex colloidal dispersions, we have chosen two systems undergoing aggregation. The first one is a conventional polystyrene latex undergoing reaction-limited aggregation, which leads to the formation of fractal clusters with well-known structure. The second one is a dispersion of elastomeric colloidal particles made of a polymer with a low glass transition temperature, which undergoes coalescence upon aggregation. Samples are withdrawn during aggregation at fixed times, fractionated with AF4 using a two-angle static light scattering unit as a detector. We have shown that from the analysis of the ratio between the intensities of the scattered light at the two angles the cluster size distribution can be recovered, without any need for calibration based on standard elution times, provided that the geometry and scattering properties of particles and clusters are known. The nonfractionated samples have been characterized also by conventional static and dynamic light scattering to determine their average radius of gyration and hydrodynamic radius. The size distribution of coalescing particles has been investigated also through image analysis of cryo-scanning electron microscopy (SEM) pictures. The average radius of gyration and the average hydrodynamic radius of the nonfractionated samples have been calculated and successfully compared to the values obtained from the size distributions measured by AF4. In addition, the data obtained are also in good agreement with calculations made with population balance equations.

Size Determination of Aqueous C60 by Asymmetric Flow Field-Flow Fractionation (AF4) and in-Line Dynamic Light Scattering

EPA Science Inventory

To date, studies on the environmental behaviour of aggregated aqueous fullerene nanomaterials have used the entire size distribution of fullerene aggregates and do not distinguish between different aggregate size classes. This is a direct result of the lack of analytical methods ...

Characterization of the molar mass distribution of macromolecules in beer for different mashing processes using asymmetric flow field-flow fractionation (AF4) coupled with multiple detectors.

PubMed

Choi, Jaeyeong; Zielke, Claudia; Nilsson, Lars; Lee, Seungho

2017-07-01

The macromolecular composition of beer is largely determined by the brewing and the mashing process. It is known that the physico-chemical properties of proteinaceous and polysaccharide molecules are closely related to the mechanism of foam stability. Three types of "American pale ale" style beer were prepared using different mashing protocols. The foam stability of the beers was assessed using the Derek Rudin standard method. Asymmetric flow field-flow fractionation (AF4) in combination with ultraviolet (UV), multiangle light scattering (MALS) and differential refractive index (dRI) detectors was used to separate the macromolecules present in the beers and the molar mass (M) and molar mass distributions (MD) were determined. Macromolecular components were identified by enzymatic treatments with β-glucanase and proteinase K. The MD of β-glucan ranged from 10 6 to 10 8  g/mol. In addition, correlation between the beer's composition and foam stability was investigated (increased concentration of protein and β-glucan was associated with increased foam stability).

Development and evaluation of methods for starch dissolution using asymmetrical flow field-flow fractionation. Part II: Dissolution of amylose.

PubMed

Perez-Rea, Daysi; Bergenståhl, Björn; Nilsson, Lars

2016-02-01

In this paper, we investigate whether dissolution in water under autoclaving conditions (140 °C, 20 min) or in dimethyl sulfoxide, DMSO (100 °C, 1 h), is preferable for characterization of amylose. Two types of amylose, potato and maize, were dissolved either in water using an autoclave or in DMSO. On the aqueous solutions obtained, the extent of molecular dissolution of the sample (referred to as the dissolution yield) was determined by enzymatic analysis as well as the molecular properties, such as molar mass and root-mean-square radius, obtained with asymmetrical flow field-flow fractionation coupled to multi-angle light scattering and differential refractive index detection (AF4-MALS-dRI). The results showed that both dissolution methods are efficient at dissolving amylose. However, AF4-MALS-dRI analysis revealed substantial differences. Amylose aqueous solutions obtained by dissolution in DMSO were relatively stable over time, but the dissolution method in autoclave caused some degradation of the molecules, and their solutions display a high tendency to retrograde.

An alternative method for calibration of flow field flow fractionation channels for hydrodynamic radius determination: The nanoemulsion method (featuring multi angle light scattering).

PubMed

Bolinsson, Hans; Lu, Yi; Hall, Stephen; Nilsson, Lars; Håkansson, Andreas

2018-01-19

This study suggests a novel method for determination of the channel height in asymmetrical flow field-flow fractionation (AF4), which can be used for calibration of the channel for hydrodynamic radius determinations. The novel method uses an oil-in-water nanoemulsion together with multi angle light scattering (MALS) and elution theory to determine channel height from an AF4 experiment. The method is validated using two orthogonal methods; first, by using standard particle elution experiments and, secondly, by imaging an assembled and carrier liquid filled channel by x-ray computed tomography (XCT). It is concluded that the channel height can be determined with approximately the same accuracy as with the traditional channel height determination technique. However, the nanoemulsion method can be used under more challenging conditions than standard particles, as the nanoemulsion remains stable in a wider pH range than the previously used standard particles. Moreover, the novel method is also more cost effective. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of oxidized tannins: comparison of depolymerization methods, asymmetric flow field-flow fractionation and small-angle X-ray scattering.

PubMed

Vernhet, Aude; Dubascoux, Stéphane; Cabane, Bernard; Fulcrand, Hélène; Dubreucq, Eric; Poncet-Legrand, Céline

2011-09-01

Condensed tannins are a major class of plant polyphenols. They play an important part in the colour and taste of foods and beverages. Due to their chemical reactivity, tannins are not stable once extracted from plants. A number of chemical reactions can take place, leading to structural changes of the native structures to give so-called derived tannins and pigments. This paper compares results obtained on native and oxidized tannins with different techniques: depolymerization followed by high-performance liquid chromatography analysis, small-angle X-ray scattering (SAXS) and asymmetric flow field-flow fractionation (AF4). Upon oxidation, new macromolecules were formed. Thioglycolysis experiments showed no evidence of molecular weight increase, but thioglycolysis yields drastically decreased. When oxidation was performed at high concentration (e.g., 10 g L(-1)), the weight average degree of polymerization determined from SAXS increased, whereas it remained stable when oxidation was done at low concentration (0.1 g L(-1)), indicating that the reaction was intramolecular, yet the conformations were different. Differences in terms of solubility were observed; ethanol being a better solvent than water. We also separated soluble and non-water-soluble species of a much oxidized fraction. Thioglycolysis showed no big differences between the two fractions, whereas SAXS and AF4 showed that insoluble macromolecules have a weight average molecular weight ten times higher than the soluble ones.

Role of rain intensity and soil colloids in the retention of surfactant-stabilized silver nanoparticles in soil.

PubMed

Makselon, Joanna; Siebers, Nina; Meier, Florian; Vereecken, Harry; Klumpp, Erwin

2018-07-01

Undisturbed outdoor lysimeters containing arable loamy sand soil were used to examine the influence of either heavy rain events (high frequency of high rain intensity), steady rain (continuous rainfall of low rain intensity), and natural rainfall on the transport and retention of surfactant-stabilized silver nanoparticles (AgNP). In addition, the AgNP-soil associations within the A p horizon were analyzed by means of particle-size fractionation, asymmetrical flow field-flow fractionation coupled with UV/Vis-detection and inductively coupled plasma mass spectrometer (AF4-UV/Vis-ICP-MS), and transmission electron microscopy coupled to an energy-dispersive X-ray (TEM-EDX) analyzer. The results showed that AgNP breakthrough for all rain events was less than 0.1% of the total AgNP mass applied, highlighting that nearly all AgNP were retained in the soil. Heavy rain treatment and natural rainfall revealed enhanced AgNP transport within the A p horizon, which was attributed to the high pore water flow velocities and to the mobilization of AgNP-soil colloid associations. Particle-size fractionation of the soil revealed that AgNP were present in each size fraction and therefore indicated strong associations between AgNP and soil. In particular, water-dispersible colloids (WDC) in the size range of 0.45-0.1 μm were found to exhibit high potential for AgNP attachment. The AF4-UV/Vis-ICP-MS and TEM-EDX analyses of the WDC fraction confirmed that AgNP were persistent in soil and associated to soil colloids (mainly composed of Al, Fe, Si, and organic matter). These results confirm the particularly important role of soil colloids in the retention and remobilization of AgNP in soil. Furthermore, AF4-UV/Vis-ICP-MS results indicated the presence of single, homo-aggregated, and small AgNP probably due to dissolution. Copyright © 2018 Elsevier Ltd. All rights reserved.

On-line miniaturized asymmetrical flow field-flow fractionation-electrospray ionization-tandem mass spectrometry with selected reaction monitoring for quantitative analysis of phospholipids in plasma lipoproteins.

PubMed

Yang, Iseul; Kim, Ki Hun; Lee, Ju Yong; Moon, Myeong Hee

2014-01-10

A direct analytical method for high speed quantitative analysis of lipids in human blood plasma using on-line chip-type asymmetrical flow field-flow fractionation-electrospray ionization-tandem mass spectrometry (cAF4-ESI-MS/MS) with selected reaction monitoring (SRM) is described in this study. Utilizing a miniaturized cAF4 channel, high speed size separation of high density lipoproteins (HDL) and low density lipoproteins (LDL) from plasma samples can be accomplished at a microflow rate along with simultaneous desalting of lipoproteins, both of which are conducive to direct ESI of lipids in lipoproteins. This study demonstrates that the SRM method to monitor phospholipids during cAF4-ESI-MS/MS can be successfully applied to the quantitation of lipid molecules in plasma lipoproteins without the need of a separate lipid extraction process. For quantitation of lipids in HDL and LDL during cAF4-ESI-MS/MS runs, a protein standard (carbonic anhydrase, 29 kDa) was added to each plasma sample as an internal standard such that a peak intensity of y67(+5) ions, which are high abundant SRM product ions of CA, could be utilized to calculate the relative intensity of each lipid molecule. The developed method was applied to plasma samples from 10 patients with coronary artery disease (CAD) and 10 healthy control samples, and quantitative analysis of 39 lipid molecules including phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, phosphatidylglycerols, and phosphatidylinositols, resulted in the selection of 13 PL species showing more than 2.5 fold difference in relative abundance (p<0.01) between the groups. The present study demonstrates a high speed analytical method for determining plasma lipid content and distribution without an organic solvent extraction of lipids from plasma. Copyright © 2013 Elsevier B.V. All rights reserved.

Iron-rich colloids as carriers of phosphorus in streams: A field-flow fractionation study.

PubMed

Baken, Stijn; Regelink, Inge C; Comans, Rob N J; Smolders, Erik; Koopmans, Gerwin F

2016-08-01

Colloidal phosphorus (P) may represent an important fraction of the P in natural waters, but these colloids remain poorly characterized. In this work, we demonstrate the applicability of asymmetric flow field-flow fractionation (AF4) coupled to high resolution ICP-MS for the characterization of low concentrations of P-bearing colloids. Colloids from five streams draining catchments with contrasting properties were characterized by AF4-ICP-MS and by membrane filtration. All streams contain free humic substances (2-3 nm) and Fe-bearing colloids (3-1200 nm). Two soft water streams contain primary Fe oxyhydroxide-humic nanoparticles (3-6 nm) and aggregates thereof (up to 150 nm). In contrast, three harder water streams contain larger aggregates (40-1200 nm) which consist of diverse associations between Fe oxyhydroxides, humic substances, clay minerals, and possibly ferric phosphate minerals. Despite the diversity of colloids encountered in these contrasting streams, P is in most of the samples predominantly associated with Fe-bearing colloids (mostly Fe oxyhydroxides) at molar P:Fe ratios between 0.02 and 1.5. The molar P:Fe ratio of the waters explains the partitioning of P between colloids and truly dissolved species. Waters with a high P:Fe ratio predominantly contain truly dissolved species because the Fe-rich colloids are saturated with P, whereas waters with a low P:Fe ratio mostly contain colloidal P species. Overall, AF4-ICP-MS is a suitable technique to characterize the diverse P-binding colloids in natural waters. Such colloids may increase the mobility or decrease the bioavailability of P, and they therefore need to be considered when addressing the transport and environmental effects of P in catchments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Asymmetric flow field-flow fractionation coupled to inductively coupled plasma mass spectrometry for the quantification of quantum dots bioconjugation efficiency.

PubMed

Menéndez-Miranda, Mario; Encinar, Jorge Ruiz; Costa-Fernández, José M; Sanz-Medel, Alfredo

2015-11-27

Hyphenation of asymmetric flow field-flow fractionation (AF4) to an on-line elemental detection (inductively coupled plasma-mass spectrometry, ICP-MS) is proposed as a powerful diagnostic tool for quantum dots bioconjugation studies. In particular, conjugation effectiveness between a "model" monoclonal IgG antibody (Ab) and CdSe/ZnS core-shell Quantum Dots (QDs), surface-coated with an amphiphilic polymer, has been monitored here by such hybrid AF4-ICP-MS technique. Experimental conditions have been optimized searching for a proper separation between the sought bioconjugates from the eventual free reagents excesses employed during the bioconjugation (QDs and antibodies). Composition and pH of the carrier have been found to be critical parameters to ensure an efficient separation while ensuring high species recovery from the AF4 channel. An ICP-MS equipped with a triple quadropole was selected as elemental detector to enable sensitive and reliable simultaneous quantification of the elemental constituents, including sulfur, of the nanoparticulated species and the antibody. The hyphenated technique used provided nanoparticle size-based separation, elemental detection, and composition analysis capabilities that turned out to be instrumental in order to investigate in depth the Ab-QDs bioconjugation process. Moreover, the analytical strategy here proposed allowed us not only to clearly identify the bioconjugation reaction products but also to quantify nanoparticle:antibodies bioconjugation efficiency. This is a key issue in future development of analytical and bioanalytical photoluminescent QDs applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of Asymmetric Flow Field-Flow Fractionation hyphenations for liposome-antimicrobial peptide interaction.

PubMed

Iavicoli, Patrizia; Urbán, Patricia; Bella, Angelo; Ryadnov, Maxim G; Rossi, François; Calzolai, Luigi

2015-11-27

Asymmetric Flow Field-Flow Fractionation (AF4) combined with multidetector analysis form a promising technique in the field of nanoparticle characterization. This system is able to measure the dimensions and physicochemical properties of nanoparticles with unprecedented accuracy and precision. Here, for the first time, this technique is optimized to characterize the interaction between an archetypal antimicrobial peptide and synthetic membranes. By using charged and neutral liposomes it is possible to mimic some of the charge characteristics of biological membranes. The use of AF4 system allows determining, in a single analysis, information regarding the selectivity of the peptides, the quantity of peptides bound to each liposome, the induced change in the size distribution and morphology of the liposomes. The results obtained provide relevant information for the study of structure-activity relationships in the context of membrane-induced antimicrobial action. This information will contribute to the rational design of potent antimicrobial agents in the future. Moreover, the application of this method to other liposome systems is straightforward and would be extremely useful for a comprehensive characterization with regard to size distribution and protein interaction in the nanomedicine field. Copyright © 2015. Published by Elsevier B.V.

Top-down and bottom-up lipidomic analysis of rabbit lipoproteins under different metabolic conditions using flow field-flow fractionation, nanoflow liquid chromatography and mass spectrometry.

PubMed

Byeon, Seul Kee; Kim, Jin Yong; Lee, Ju Yong; Chung, Bong Chul; Seo, Hong Seog; Moon, Myeong Hee

2015-07-31

This study demonstrated the performances of top-down and bottom-up approaches in lipidomic analysis of lipoproteins from rabbits raised under different metabolic conditions: healthy controls, carrageenan-induced inflammation, dehydration, high cholesterol (HC) diet, and highest cholesterol diet with inflammation (HCI). In the bottom-up approach, the high density lipoproteins (HDL) and the low density lipoproteins (LDL) were size-sorted and collected on a semi-preparative scale using a multiplexed hollow fiber flow field-flow fractionation (MxHF5), followed by nanoflow liquid chromatography-ESI-MS/MS (nLC-ESI-MS/MS) analysis of the lipids extracted from each lipoprotein fraction. In the top-down method, size-fractionated lipoproteins were directly infused to MS for quantitative analysis of targeted lipids using chip-type asymmetrical flow field-flow fractionation-electrospray ionization-tandem mass spectrometry (cAF4-ESI-MS/MS) in selected reaction monitoring (SRM) mode. The comprehensive bottom-up analysis yielded 122 and 104 lipids from HDL and LDL, respectively. Rabbits within the HC and HCI groups had lipid patterns that contrasted most substantially from those of controls, suggesting that HC diet significantly alters the lipid composition of lipoproteins. Among the identified lipids, 20 lipid species that exhibited large differences (>10-fold) were selected as targets for the top-down quantitative analysis in order to compare the results with those from the bottom-up method. Statistical comparison of the results from the two methods revealed that the results were not significantly different for most of the selected species, except for those species with only small differences in concentration between groups. The current study demonstrated that top-down lipid analysis using cAF4-ESI-MS/MS is a powerful high-speed analytical platform for targeted lipidomic analysis that does not require the extraction of lipids from blood samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of aggregates of surface modified fullerenes by asymmetrical flow field-flow fractionation with multi-angle light scattering detection.

PubMed

Astefanei, Alina; Kok, Wim Th; Bäuerlein, Patrick; Núñez, Oscar; Galceran, Maria Teresa; de Voogt, Pim; Schoenmakers, Peter J

2015-08-21

Fullerenes are carbon nanoparticles with widespread biomedical, commercial and industrial applications. Attributes such as their tendency to aggregate and aggregate size and shape impact their ability to be transported into and through the environment and living tissues. Knowledge of these properties is therefore valuable for their human and environmental risk assessment as well as to control their synthesis and manufacture. In this work, asymmetrical flow-field flow fractionation (AF4) coupled to multi-angle light scattering (MALS) was used for the first time to study the size distribution of surface modified fullerenes with both polyhydroxyl and carboxyl functional groups in aqueous solutions having different pH (6.5-11) and ionic strength values (0-200mM) of environmental relevance. Fractionation key parameters such as flow rates, flow programming, and membrane material were optimized for the selected fullerenes. The aggregation of the compounds studied appeared to be indifferent to changes in solution pH, but was affected by changes in the ionic strength. Polyhydroxy-fullerenes were found to be present mostly as 4nm aggregates in water without added salt, but showed more aggregation at high ionic strength, with an up to 10-fold increase in their mean hydrodynamic radii (200mM), due to a decrease in the electrostatic repulsion between the nanoparticles. Carboxy-fullerenes showed a much stronger aggregation degree in water (50-100nm). Their average size and recoveries decreased with the increase in the salt concentration. This behavior can be due to enhanced adsorption of the large particles to the membrane at high ionic strength, because of their higher hydrophobicity and much larger particle sizes compared to polyhydroxy-fullerenes. The method performance was evaluated by calculating the run-to-run precision of the retention time (hydrodynamic radii), and the obtained RSD values were lower than 1%. MALS measurements showed aggregate sizes that were in good agreement with the AF4 data. A comparison of the scattering radii from the MALS with the hydrodynamic radii obtained from the retention times in AF4 indicated that the aggregate shapes are far from spherical. TEM images of the fullerenes in the dry state also showed branched and irregular clusters. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantitative characterization of gold nanoparticles by field-flow fractionation coupled online with light scattering detection and inductively coupled plasma mass spectrometry.

PubMed

Schmidt, Bjørn; Loeschner, Katrin; Hadrup, Niels; Mortensen, Alicja; Sloth, Jens J; Koch, Christian Bender; Larsen, Erik H

2011-04-01

An analytical platform coupling asymmetric flow field-flow fractionation (AF(4)) with multiangle light scattering (MALS), dynamic light scattering (DLS), and inductively coupled plasma mass spectrometry (ICPMS) was established and used for separation and quantitative determination of size and mass concentration of nanoparticles (NPs) in aqueous suspension. Mixtures of three polystyrene (PS) NPs between 20 and 100 nm in diameter and mixtures of three gold (Au) NPs between 10 and 60 nm in diameter were separated by AF(4). The geometric diameters of the separated PS NPs and the hydrodynamic diameters of the Au and PS NPs were determined online by MALS and DLS, respectively. The three separated Au NPs were quantified by ICPMS and recovered at 50-95% of the injected masses, which ranged between approximately 8-80 ng of each nanoparticle size. Au NPs adhering to the membrane in the separation channel was found to be a major cause for incomplete recoveries. The lower limit of detection (LOD) ranged between 0.02 ng Au and 0.4 ng Au, with increasing LOD by increasing nanoparticle diameter. The analytical platform was applied to characterization of Au NPs in livers of rats, which were dosed with 10 nm, 60 nm, or a mixture of 10 and 60 nm nanoparticles by intravenous injection. The homogenized livers were solubilized in tetramethylammonium hydroxide (TMAH), and the recovery of Au NPs from the livers amounted to 86-123% of their total Au content. In spite of successful stabilization with bovine serum albumin even in alkaline medium, separation of the Au NPs by AF(4) was not possible due to association with undissolved remains of the alkali-treated liver tissues as demonstrated by electron microscopy images.

Elemental ratios for characterization of quantum-dots populations in complex mixtures by asymmetrical flow field-flow fractionation on-line coupled to fluorescence and inductively coupled plasma mass spectrometry.

PubMed

Menendez-Miranda, Mario; Fernandez-Arguelles, Maria T; Costa-Fernandez, Jose M; Encinar, Jorge Ruiz; Sanz-Medel, Alfredo

2014-08-11

Separation and identification of nanoparticles of different composition, with similar particle diameter, coexisting in heterogeneous suspensions of polymer-coated CdSe/ZnS quantum dots (QDs) have been thoroughly assessed by asymmetric flow field-flow fractionation (AF4) coupled on-line to fluorescence and inductively coupled plasma mass spectrometry (ICPMS) detectors. Chemical characterization of any previously on-line separated nanosized species was achieved by the measurement of the elemental molar ratios of every element involved in the synthesis of the QDs, using inorganic standards and external calibration by flow injection analysis (FIA). Such elemental molar ratios, strongly limited so far to pure single nanoparticles suspensions, have been achieved with adequate accuracy by coupling for the first time an ICP-QQQ instrument to an AF4 system. This hyphenation turned out to be instrumental to assess the chemical composition of the different populations of nanoparticles coexisting in the relatively complex mixtures, due to its capabilities to detect the hardly detectable elements involved in the synthesis. Interestingly such information, complementary to that obtained by fluorescence, was very valuable to detect and identify unexpected nanosized species, present at significant level, produced during QDs synthesis and hardly detectable by standard approaches. Copyright © 2014. Published by Elsevier B.V.

Complex analysis of concentrated antibody-gold nanoparticle conjugates' mixtures using asymmetric flow field-flow fractionation.

PubMed

Safenkova, Irina V; Slutskaya, Elvira S; Panferov, Vasily G; Zherdev, Anatoly V; Dzantiev, Boris B

2016-12-16

Conjugates of gold nanoparticles (GNPs) with antibodies are powerful analytical tools. It is crucial to know the conjugates' state in both the concentrated and mixed solutions used in analytical systems. Herein, we have applied asymmetrical flow field-flow fractionation (AF4) to identify the conjugates' state. The influence of a conjugate's composition and concentration on aggregation was studied in a true analytical solution (a concentrated mixture with stabilizing components). GNPs with an average diameter of 15.3±1.2nm were conjugated by adsorption with eight antibodies of different specificities. We found that, while the GNPs have a zeta potential of -31.6mV, the conjugates have zeta potentials ranging from -5.8 to -11.2mV. Increased concentrations (up to 184nM, OD 520 =80) of the mixed conjugate (mixture of eight conjugates) did not change the form of fractograms, and the peak areas' dependence on concentration was strongly linear (R 2 values of 0.99919 and 0.99845 for absorption signal and light scattering, respectively). Based on the gyration (R g ) and hydrodynamic (R h ) radii measured during fractionation, we found that the nanoparticles were divided into two populations: (1) those with constant radii (R g =9.9±0.9nm; R h =14.3±0.5nm); and (2) those with increased radii from 9.9 to 24.4nm for R g and from 14.3 to 28.1nm for R h . These results confirm that the aggregate state of the concentrated and mixed conjugates' preparations is the same as that of diluted preparations and that AF4 efficiently characterizes the conjugates' state in a true analytical solution. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of a protein conjugate using an asymmetrical-flow field-flow fractionation and a size-exclusion chromatography with multi-detection system.

PubMed

Rebolj, Katja; Pahovnik, David; Zagar, Ema

2012-09-04

In this study we present detailed characterization of a protein-PEG conjugate using two separation techniques, that is, asymmetrical-flow field-flow fractionation (AF4) and size-exclusion chromatography (SEC), which were online coupled to a series of successively connected detectors: an ultraviolet, a multiangle light-scattering, a quasi-elastic light-scattering, and a refractive-index detector (UV-MALS(QELS)-RI). Matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used as a complementary characterization technique. The results of AF4 as well as SEC on two columns connected in series, with both separation techniques coupled to a multidetection system, indicate the uniform molar mass and chemical composition of the conjugate, that is, the molar ratio of protein to PEG is 1/1, the presence of minute amounts of residual unreacted protein and the aggregates with the same chemical composition as that of the conjugate. Since the portion of aggregated species is smaller in the acetate buffer solution containing 5% sorbitol than in the acetate buffer solution with 200-mM sodium chloride, the former buffer solution is more suitable for conjugate storage. The separation using only one SEC column results in poorly resolved peaks of the PEGylated protein conjugate and the aggregates, whereas MALDI-TOF MS analysis reveal the presence of the residual protein, but not the aggregates.

Optimisation of asymmetric flow field-flow fractionation for the characterisation of nanoparticles in coated polydisperse TiO2 with applications in food and feed.

PubMed

Omar, J; Boix, A; Kerckhove, G; von Holst, C

2016-12-01

Titanium dioxide (TiO 2 ) has various applications in consumer products and is also used as an additive in food and feeding stuffs. For the characterisation of this product, including the determination of nanoparticles, there is a strong need for the availability of corresponding methods of analysis. This paper presents an optimisation process for the characterisation of polydisperse-coated TiO 2 nanoparticles. As a first step, probe ultrasonication was optimised using a central composite design in which the amplitude and time were the selected variables to disperse, i.e., to break up agglomerates and/or aggregates of the material. The results showed that high amplitudes (60%) favoured a better dispersion and time was fixed in mid-values (5 min). In a next step, key factors of asymmetric flow field-flow fraction (AF4), namely cross-flow (CF), detector flow (DF), exponential decay of the cross-flow (CF exp ) and focus time (Ft), were studied through experimental design. Firstly, a full-factorial design was employed to establish the statistically significant factors (p < 0.05). Then, the information obtained from the full-factorial design was utilised by applying a central composite design to obtain the following optimum conditions of the system: CF, 1.6 ml min -1 ; DF, 0.4 ml min -1 ; Ft, 5 min; and CF exp , 0.6. Once the optimum conditions were obtained, the stability of the dispersed sample was measured for 24 h by analysing 10 replicates with AF4 in order to assess the performance of the optimised dispersion protocol. Finally, the recovery of the optimised method, particle shape and particle size distribution were estimated.

Optimisation of asymmetric flow field-flow fractionation for the characterisation of nanoparticles in coated polydisperse TiO2 with applications in food and feed

PubMed Central

Omar, J.; Boix, A.; Kerckhove, G.; von Holst, C.

2016-01-01

ABSTRACT Titanium dioxide (TiO2) has various applications in consumer products and is also used as an additive in food and feeding stuffs. For the characterisation of this product, including the determination of nanoparticles, there is a strong need for the availability of corresponding methods of analysis. This paper presents an optimisation process for the characterisation of polydisperse-coated TiO2 nanoparticles. As a first step, probe ultrasonication was optimised using a central composite design in which the amplitude and time were the selected variables to disperse, i.e., to break up agglomerates and/or aggregates of the material. The results showed that high amplitudes (60%) favoured a better dispersion and time was fixed in mid-values (5 min). In a next step, key factors of asymmetric flow field-flow fraction (AF4), namely cross-flow (CF), detector flow (DF), exponential decay of the cross-flow (CFexp) and focus time (Ft), were studied through experimental design. Firstly, a full-factorial design was employed to establish the statistically significant factors (p < 0.05). Then, the information obtained from the full-factorial design was utilised by applying a central composite design to obtain the following optimum conditions of the system: CF, 1.6 ml min–1; DF, 0.4 ml min–1; Ft, 5 min; and CFexp, 0.6. Once the optimum conditions were obtained, the stability of the dispersed sample was measured for 24 h by analysing 10 replicates with AF4 in order to assess the performance of the optimised dispersion protocol. Finally, the recovery of the optimised method, particle shape and particle size distribution were estimated. PMID:27650879

Size determination and quantification of engineered cerium oxide nanoparticles by flow field-flow fractionation coupled to inductively coupled plasma mass spectrometry.

PubMed

Sánchez-García, L; Bolea, E; Laborda, F; Cubel, C; Ferrer, P; Gianolio, D; da Silva, I; Castillo, J R

2016-03-18

Facing the lack of studies on characterization and quantification of cerium oxide nanoparticles (CeO2 NPs), whose consumption and release is greatly increasing, this work proposes a method for their sizing and quantification by Flow Field-flow Fractionation (FFFF) coupled to Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Two modalities of FFFF (Asymmetric Flow- and Hollow Fiber-Flow Field Flow Fractionation, AF4 and HF5, respectively) are compared, and their advantages and limitations discussed. Experimental conditions (carrier composition, pH, ionic strength, crossflow and carrier flow rates) are studied in detail in terms of NP separation, recovery, and repeatability. Size characterization of CeO2 NPs was addressed by different approaches. In the absence of feasible size standards of CeO2 NPs, suspensions of Ag, Au, and SiO2 NPs of known size were investigated. Ag and Au NPs failed to show a comparable behavior to that of the CeO2 NPs, whereas the use of SiO2 NPs provided size estimations in agreement to those predicted by the theory. The latter approach was thus used for characterizing the size of CeO2 NPs in a commercial suspension. Results were in adequate concordance with those achieved by transmission electron microscopy, X-ray diffraction and dynamic light scattering. The quantification of CeO2 NPs in the commercial suspension by AF4-ICP-MS required the use of a CeO2 NPs standards, since the use of ionic cerium resulted in low recoveries (99 ± 9% vs. 73 ± 7%, respectively). A limit of detection of 0.9 μg L(-1) CeO2 corresponding to a number concentration of 1.8 × 1012 L(-1) for NPs of 5 nm was achieved for an injection volume of 100 μL. Copyright © 2016 Elsevier B.V. All rights reserved.

Analytical Characterization of the Hydrolysis of Barley Malt Macromolecules During Enzymatic Degradation Over Time Using AF4/MALS/RI.

PubMed

Rübsam, Heinrich; Becker, Thomas; Gastl, Martina

2017-06-01

The changes on the molecular weight distribution (MWD) and particle size distribution (PSD) during hydrolysis of barley malt in isothermal mashing procedures were determined using asymmetrical flow field flow fractionation coupled to multiangle laser light scattering and refractive index (AF4/MALS/RI). Mash/trials were focused on amylolytic starch degradation. Therefore, temperatures (65, 70, and 75 °C) were selected according to α- and β-amylases range of activity. Samples were produced by triplicate, tracking amylolytic processes over time periods from 10 to 90 min in each mash/trial. AF4/MALS/RI analysis demonstrated significant differences on the values of the MWD and PSD according to the temperature/time profile used. At mashing times over 30 min at a temperature of 65 °C, when α- and β-amylase are both active, the decrease over time of the MWD and PSD was significantly higher (P < 0.005) than at 70 °C when mainly α-amylase is active. At 75 °C, also the activity of α-amylase decreased and the MWD and PSD were significantly lower (P < 0.005) than at 70 or 65 °C at any time of the procedure. The MWD and PSD of beer components influence beer palate fullness, thus AF4/ MALS/RI would be a powerful tool for breweries to adapt their technological processes to obtain beers with particular sensorial attributes. © 2017 Institute of Food Technologists®.

Asymmetrical flow field-flow fractionation hyphenated to Orbitrap high resolution mass spectrometry for the determination of (functionalised) aqueous fullerene aggregates.

PubMed

Herrero, P; Bäuerlein, P S; Emke, E; Pocurull, E; de Voogt, P

2014-08-22

In this short communication we report on the technical implementations of coupling an asymmetric flow field-flow fractionation (AF4) instrument to a high resolution mass spectrometer (Orbitrap) using an atmospheric photoionisation interface. This will allow for the first time online identification of different fullerenes in aqueous samples after their aggregates have been fractionated in the FFF channel. Quality parameters such as limits of detection (LODs), limits of quantification (LOQs) or linear range were evaluated and they were in the range of hundreds ng/L for LODs and LOQs and the detector response was linear in the range tested (up to ∼20 μg/L). The low detection and quantification limits make this technique useful for future environmental or ecotoxicology studies in which low concentration levels are expected for fullerenes and common on-line detectors such as UV or MALS do not have enough sensitivity and selectivity. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Assessment of the removal of side nanoparticulated populations generated during one-pot synthesis by asymmetric flow field-flow fractionation coupled to elemental mass spectrometry.

PubMed

Bouzas-Ramos, Diego; García-Cortes, Marta; Sanz-Medel, Alfredo; Encinar, Jorge Ruiz; Costa-Fernández, José M

2017-10-13

Coupling of asymmetric flow field-flow fractionation (AF4) to an on-line elemental detection (inductively coupled plasma-mass spectrometry, ICP-MS) has been recently proposed as a powerful diagnostic tool for characterization of the bioconjugation of CdSe/ZnS core-shell Quantum Dots (QDs) to antibodies. Such approach has been used herein to demonstrate that cap exchange of the native hydrophobic shell of core/shell QDs with the bidentate dihydrolipoic acid ligands directly removes completely the eventual side nanoparticulated populations generated during simple one-pot synthesis, which can ruin the subsequent final bioapplication. The critical assessment of the chemical and physical purity of the surface-modified QDs achieved allows to explain the transmission electron microscopy findings obtained for the different nanoparticle surface modification assayed. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuroprotective and Anti-Inflammatory Effects of the Flavonoid-Enriched Fraction AF4 in a Mouse Model of Hypoxic-Ischemic Brain Injury

PubMed Central

Keddy, Paul G. W.; Dunlop, Kate; Warford, Jordan; Samson, Michel L.; Jones, Quinton R. D.; Rupasinghe, H. P. Vasantha; Robertson, George S.

2012-01-01

We report here neuroprotective and anti-inflammatory effects of a flavonoid-enriched fraction isolated from the peel of Northern Spy apples (AF4) in a mouse of model of hypoxic-ischemic (HI) brain damage. Oral administration of AF4 (50 mg/kg, once daily for 3 days) prior to 50 min of HI completely prevented motor performance deficits assessed 14 days later that were associated with marked reductions in neuronal cell loss in the dorsal hippocampus and striatum. Pre-treatment with AF4 (5, 10, 25 or 50 mg/kg, p.o.; once daily for 3 days) produced a dose-dependent reduction in HI-induced hippocampal and striatal neuron cell loss, with 25 mg/kg being the lowest dose that achieved maximal neuroprotection. Comparison of the effects of 1, 3 or 7 doses of AF4 (25 mg/kg; p.o.) prior to HI revealed that at least 3 doses of AF4 were required before HI to reduce neuronal cell loss in both the dorsal hippocampus and striatum. Quantitative RT-PCR measurements revealed that the neuroprotective effects of AF4 (25 mg/kg; p.o.; once daily for 3 days) in the dorsal hippocampus were associated with a suppression of HI-induced increases in the expression of IL-1β, TNF-α and IL-6. AF4 pre-treatment enhanced mRNA levels for pro-survival proteins such as X-linked inhibitor of apoptosis and erythropoietin following HI in the dorsal hippocampus and striatum, respectively. Primary cultures of mouse cortical neurons incubated with AF4 (1 µg/ml), but not the same concentrations of either quercetin or quercetin-3-O-glucose or its metabolites, were resistant to cell death induced by oxygen glucose deprivation. These findings suggest that the inhibition of HI-induced brain injury produced by AF4 likely involves a transcriptional mechanism resulting from the co-operative actions of various phenolics in this fraction which not only reduce the expression of pro-inflammatory mediators but also enhance pro-survival gene signalling. PMID:23251498

The use of asymmetrical flow field-flow fractionation with on-line detection in the study of drug retention within liposomal nanocarriers and drug transfer kinetics.

PubMed

Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith; Brandl, Martin

2016-05-30

Due to their solubilizing capabilities, liposomes (phospholipid vesicles) are suited for designing formulations for intravenous administration of drug compounds which are poorly water-soluble. Despite the good in-vitro stability of such formulations with minimal drug leakage, upon i.v. injection there is a risk of premature drug loss due to drug transfer to plasma proteins and cell membranes. Here we report on the refinement of a recently introduced simple in vitro predictive tool by Hinna and colleagues in 2014, which brings small drug loaded (donor) liposomes in contact with large acceptor liposomes, the latter serving as a model mimicking biological sinks in the body. The donor- and acceptor-liposomes were subsequently separated using asymmetrical flow field-flow fractionation (AF4), during which the sample is exposed to a large volume of eluent which corresponds to a dilution factor of approximately 600. The model drug content in the donor- and acceptor fraction was quantified by on-line UV/VIS extinction measurements with correction for turbidity and by off-line HPLC measurements of collected fractions. The refined method allowed for (near) baseline separation of donor and acceptor vesicles as well as reliable quantification of the drug content not only of the donor- but now also of the acceptor-liposomes due to their improved size-homogeneity, colloidal stability and reduced turbidity. This improvement over the previously reported approach allowed for simultaneous quantification of both drug transfer and drug release to the aqueous phase. By sampling at specific incubation times, the release and transfer kinetics of the model compound p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl)21H,23H-porphine) was determined. p-THPP is structurally closely related to the photosensitizer temoporfin, which is in clinical use and under evaluation in liposomal formulations. The transfer of p-THPP to the acceptor vesicles followed 1st order kinetics with a half-life of approximately 300 min. As expected, equilibrium distribution between donor- and acceptor vesicles was proportional to the lipid mass ratio. An initial rapid transfer of p-THPP was found (∼ 5%) and investigated further by determining the extent of transfer between donor and acceptor during separation. The donor- and acceptor phase were found to be separated within few minutes and only minor (≤ 2%) transfer could be detected within the AF4 channel under the conditions applied for fractionation. These results demonstrates the potential of our AF4 based method as an in vitro tool to determine retention properties of lipophilic compounds within liposomal carriers in particular, but also within a variety of nano-particulate carriers provided that they exhibit a sufficient size difference compared to the applied colloidal acceptor phase. Copyright © 2016 Elsevier B.V. All rights reserved.

Catabolic Effects of Endothelial Cell-Derived Microparticles on Disc Cells: Implications in Intervertebral Disc Neovascularization and Degeneration

PubMed Central

Pohl, Pedro H. I.; Lozito, Thomas P.; Cuperman, Thais; Yurube, Takashi; Moon, Hong J.; Ngo, Kevin; Tuan, Rocky S.; Croix, Claudette St.; Sowa, Gwendolyn A.; Rodrigues, Luciano M. R.; Kang, James D.; Vo, Nam V.

2017-01-01

Neovascularization of intervertebral discs, a phenomenon considered pathological since normal discs are primarily avascular structures, occurs most frequently in annulus fibrosus (AF) of degenerated discs. Endothelial cells (ECs) are involved in this process, but the mechanism of the interaction between AF and endothelial cells is unclear. In this study we evaluated the effects on matrix catabolic activity of AF cells by the extracellular endothelial microparticles (EMPs) and soluble protein factors (SUP fraction) produced from ECs. Passage 1 human AF cells grown in monolayer cultures were treated for 72 hours with 250μg of EMPs or SUP fraction isolated from culture of the microvascular endothelial cell line, HEMC-I. Live-cell imaging revealed uptake of EMPs by AF cells. RT-PCR analysis demonstrated increased mRNA expression of MMP-1 (50.3 fold), MMP-3 (4.5 fold) and MMP-13 (5.5 fold) in AF cell cultures treated with EMPs compared to untreated control. Western analysis also demonstrated increased MMP protein expression in EMP-treated AF cells. AF cells treated with the SUP fraction also exhibited a dramatic increase in MMP mRNA and protein expression. Increased MMP expression is primarily due to EMP or SUP stimulation of AF cells since EMPs or SUP fraction alone contained negligible amount of MMPs. Interestingly, MMP activity was elevated in AF cell cultures treated with EMPs but not with SUP. This study revealed enhanced matrix catabolism as a molecular consequence of action of ECs on AF cells via EMPs, which might be expected during neo-angiogenesis of degenerating disc. PMID:27246627

Comparison of Left Atrial Voltage between Sinus Rhythm and Atrial Fibrillation in Association with Electrogram Waveform.

PubMed

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Ohashi, Takuya; Uematsu, Masaaki

2017-05-01

The efficacy of low-voltage-guided ablation in addition to pulmonary vein (PV) isolation for atrial fibrillation (AF) has been reported with voltage mapping being performed during sinus rhythm (SR) or AF. The study aimed to compare the left atrial voltage between SR and AF in association with the electrogram waveform. This prospective observational study included 30 consecutive patients with persistent AF. After completion of PV isolation, electrogram points were taken during both SR and AF at the identical locations evenly throughout the left atrium. Electrograms were divided into two types: normal (sharp electrogram with ≤3 peaks or duration <50 ms) and fractionated (>3 peaks and duration ≥50 ms). During SR, 14 (47%) patients had low-voltage (0.5 mV) substrate with an area of 6.8 ± 4.5 cm 2 . In a total of 1,063 point pairs, 135 (13%) demonstrated a fractionated electrogram during SR and 483 (45%) during AF. The locations with fractionated electrograms during AF more frequently showed fractionation during SR compared to those with normal electrograms during AF (23% vs 5%, P < 0.0001), and had lower amplitude during SR (1.47 ± 1.29 mV vs 2.03 ± 1.19 mV, P < 0.0001). Electrogram amplitude was higher during SR than that during AF (1.77 ± 1.27 mV vs 0.96 ± 0.77 mV, P < 0.0001) with a weak correlation (r = 0.56, P < 0.0001). Subgroup analyses revealed that the correlation was relatively strong (r = 0.73, P < 0.0001) among the electrogram amplitudes with normal waveform during SR and AF. Significant differences in electrogram voltage and fractionation degree may exist between SR and AF at the same locations in patients with persistent AF. © 2017 Wiley Periodicals, Inc.

Distinguishing dissolved organic matter at its origin: size and optical properties of leaf-litter leachates.

PubMed

Cuss, C W; Guéguen, C

2013-09-01

Dissolved organic matter (DOM) was leached from eight distinct samples of leaves taken from six distinct trees (red maple, bur oak at three times of the year, two sugar maple and two white spruce trees from disparate soil types). Multiple samples were taken over 72-96h of leaching. The size and optical properties of leachates were assessed using asymmetrical flow field-flow fractionation (AF4) coupled to diode-array ultraviolet/visible absorbance and excitation-emission matrix fluorescence detectors (EEM). The fluorescence of unfractionated samples was also analyzed. EEMs were analyzed using parallel factor analysis (PARAFAC) and principal component analysis (PCA) of proportional component loadings. Both the unfractionated and AF4-fractionated leachates had distinct size and optical properties. The 95% confidence ranges for molecular weight distributions were determined as: 210-440Da for spruce, 540-920Da for sugar maple, 630-800Da for spring oak leaves, 930-950Da for senescent oak, 1490-1670 for senescent red maple, and 3430-4270Da for oak leaves that were collected from the ground after spring thaw. In most cases the fluorescence properties of leachates were different for individuals from different soil types and across seasons; however, PCA of PARAFAC loadings revealed that the observed distinctiveness was chiefly species-based. Strong correlations were found between the molecular weight distribution of both unfractionated and fractionated leachates and their principal component loadings (R(2)=0.85 and 0.95, respectively). It is concluded that results support a species-based origin for differences in optical properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter Phase III study.

PubMed

Sanguineti, Giuseppe; Richetti, Antonella; Bignardi, Mario; Corvo', Renzo; Gabriele, Pietro; Sormani, Maria Pia; Antognoni, Paolo

2005-03-01

To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx. Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a "biphasic concomitant boost" schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis. From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% +/- 4% for CF and 78% +/- 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% +/- 5% for CF and 64% +/- 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% +/- 4% and 27% +/- 6% for CF and AF, respectively (p = 0.10). Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT.

Catabolic effects of endothelial cell-derived microparticles on disc cells: Implications in intervertebral disc neovascularization and degeneration.

PubMed

Pohl, Pedro H I; Lozito, Thomas P; Cuperman, Thais; Yurube, Takashi; Moon, Hong J; Ngo, Kevin; Tuan, Rocky S; St Croix, Claudette; Sowa, Gwendolyn A; Rodrigues, Luciano M R; Kang, James D; Vo, Nam V

2016-08-01

Neovascularization of intervertebral discs, a phenomenon considered pathological since normal discs are primarily avascular structures, occurs most frequently in annulus fibrosus (AF) of degenerated discs. Endothelial cells (ECs) are involved in this process, but the mechanism of the interaction between AF and endothelial cells is unclear. In this study, we evaluated the effects on matrix catabolic activity of AF cells by the extracellular endothelial microparticles (EMPs) and soluble protein factors (SUP fraction) produced from ECs. Passage 1 human AF cells grown in monolayer cultures were treated for 72 h with 250 µg of EMPs or SUP fraction isolated from culture of the microvascular endothelial cell line, HEMC-I. Live-cell imaging revealed uptake of EMPs by AF cells. RT-PCR analysis demonstrated increased mRNA expression of MMP-1 (50.3-fold), MMP-3 (4.5-fold) and MMP-13 (5.5-fold) in AF cell cultures treated with EMPs compared to untreated control. Western analysis also demonstrated increased MMP protein expression in EMP-treated AF cells. AF cells treated with the SUP fraction also exhibited a dramatic increase in MMP mRNA and protein expression. Increased MMP expression is primarily due to EMP or SUP stimulation of AF cells since EMPs or SUP fraction alone contained negligible amount of MMPs. Interestingly, MMP activity was elevated in AF cell cultures treated with EMPs but not with SUP. This study revealed enhanced matrix catabolism as a molecular consequence of action of ECs on AF cells via EMPs, which might be expected during neo-angiogenesis of degenerating disc. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1466-1474, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Co-elution phenomena in polymer mixtures studied by asymmetric flow field-flow fractionation.

PubMed

Zielke, Claudia; Fuentes, Catalina; Piculell, Lennart; Nilsson, Lars

2018-01-12

Most polymers generally have complex characteristics. Analysis and understanding of these characteristics is crucial as they, for instance, influence functionality. Separation and analysis of samples of polymers, biopolymers in particular, is challenging since they often display broad distributions in size, structure and molar mass (M) and/or a tendency to form aggregates. Only few analytical techniques are suitable for the task. AF4-MALS-dRI is highly suited for the task, but the analysis can nevertheless be especially challenging for heterogeneous mixtures of polymers that exhibit wide size distributions or aggregation. For such systems, systematic and thorough method development is clearly a requirement. This is the purpose of the present work, where we approach the problem of heterogeneous polymer samples systematically by analyzing mixtures of two different polymers which are also characterized individually. An often observed phenomenon in AF4 of samples with a high polydispersity is a downturn in M vs. elution time, especially common at high retention. This result is often dismissed as an artifact attributed to various errors in detection and data processing. In this work, we utilize AF4-MALS-dRI to separate and analyze binary mixtures of the well-known polysaccharides pullulan and glycogen, or pullulan and poly(ethylene oxide), respectively, in solution. The results show that an observed downturn - or even an upturn - in M can be a correct result, caused by inherent properties of the analyzed polymers. Copyright © 2017 Elsevier B.V. All rights reserved.

A review of exosome separation techniques and characterization of B16-F10 mouse melanoma exosomes with AF4-UV-MALS-DLS-TEM.

PubMed

Petersen, Kevin E; Manangon, Eliana; Hood, Joshua L; Wickline, Samuel A; Fernandez, Diego P; Johnson, William P; Gale, Bruce K

2014-12-01

Exosomes participate in cancer metastasis, but studying them presents unique challenges as a result of their small size and purification difficulties. Asymmetrical field flow fractionation with in-line ultraviolet absorbance, dynamic light scattering, and multi-angle light scattering was applied to the size separation and characterization of non-labeled B16-F10 exosomes from an aggressive mouse melanoma cell culture line. Fractions were collected and further analyzed using batch mode dynamic light scattering, transmission electron microscopy and compared with known size standards. Fractogram peak positions and computed radii show good agreement between samples and across fractions. Ultraviolet absorbance fractograms in combination with transmission electron micrographs were able to resolve subtle heterogeneity of vesicle retention times between separate batches of B16-F10 exosomes collected several weeks apart. Further, asymmetrical field flow fractionation also effectively separated B16-F10 exosomes into vesicle subpopulations by size. Overall, the flow field flow fractionation instrument combined with multiple detectors was able to rapidly characterize and separate exosomes to a degree not previously demonstrated. These approaches have the potential to facilitate a greater understanding of exosome function by subtype, as well as ultimately allow for "label-free" isolation of large scale clinical exosomes for the purpose of developing future exosome-based diagnostics and therapeutics.

A review of exosome separation techniques and characterization of B16-F10 mouse melanoma exosomes with AF4-UV-MALS-DLS-TEM

PubMed Central

Manangon, Eliana; Hood, Joshua L.; Wickline, Samuel A.; Fernandez, Diego P.; Johnson, William P.; Gale, Bruce K.

2015-01-01

Exosomes participate in cancer metastasis, but studying them presents unique challenges as a result of their small size and purification difficulties. Asymmetrical field flow fractionation with in-line ultraviolet absorbance, dynamic light scattering, and multi-angle light scattering was applied to the size separation and characterization of non-labeled B16-F10 exosomes from an aggressive mouse melanoma cell culture line. Fractions were collected and further analyzed using batch mode dynamic light scattering, transmission electron microscopy and compared with known size standards. Fractogram peak positions and computed radii show good agreement between samples and across fractions. Ultraviolet absorbance fractograms in combination with transmission electron micrographs were able to resolve subtle heterogeneity of vesicle retention times between separate batches of B16-F10 exosomes collected several weeks apart. Further, asymmetrical field flow fractionation also effectively separated B16-F10 exosomes into vesicle subpopulations by size. Overall, the flow field flow fractionation instrument combined with multiple detectors was able to rapidly characterize and separate exosomes to a degree not previously demonstrated. These approaches have the potential to facilitate a greater understanding of exosome function by subtype, as well as ultimately allow for “label-free” isolation of large scale clinical exosomes for the purpose of developing future exosome-based diagnostics and therapeutics. PMID:25084738

Clinical and electrocardiographic characteristics for prediction of new-onset atrial fibrillation in asymptomatic patients with atrial premature complexes.

PubMed

Im, Sung Il; Park, Dong Hyun; Kim, Bong Joon; Cho, Kyoung Im; Kim, Hyun Su; Heo, Jung Ho

2018-06-01

Identification of precursors of atrial fibrillation (AF) may lead to early detection and prevent associated morbidity and mortality. Atrial premature complexes (APCs) are commonly seen in healthy subjects. However, there was limited data about the clinical and electrocardiographic (ECG) characteristics for prediction of new-onset AF in asymptomatic patients with APCs in the long-term follow up. The Kosin University (No. 2014-02-04) 24-h holter monitoring, echocardiography, ECG database were reviewed from 2008 to 2016 to identify new- onset AF in patients with APCs. We analyzed demographic and clinical features and the nature of the APCs by ECG according to new-onset AF in those patients. Among 652 patients who underwent 24-h holter monitoring, 226 (34.4%) patients had new-onset AF. There was no difference of the baseline characteristics between new-onset AF group and non-AF group. In univariate analysis, hypertension (HTN), renal failure (CRF), high APC burdens, fastest APC running heart rate (HR), minimal HR, left ventricular ejection fraction (LVEF), left atrial volume index, peak mitral flow velocity of the early rapid filling wave and tricuspid regurgitation grade were significantly associated with new-onset AF. In multivariate analysis, higher APCs burden ( P  = 0.047), higher fastest APCs running HR ( P  = 0.034) and lower minimal HR ( P  = 0.025) were independent risk factors for new-onset AF in asymptomatic patients with APCs. Higher APCs burden, higher fastest APCs running HR and lower minimal HR were associated with new-onset AF in asymptomatic patients with APCs in the long-term follow up.

Migration of nanoparticles from plastic packaging materials containing carbon black into foodstuffs

PubMed Central

Bott, Johannes; Störmer, Angela; Franz, Roland

2014-01-01

Carbon black was investigated to assess and quantify the possibility that nanoparticles might migrate out of plastic materials used in the food packaging industry. Two types of carbon black were incorporated in low-density polyethylene (LDPE) and polystyrene (PS) at 2.5% and 5.0% loading (w/w), and then subjected to migration studies. The samples were exposed to different food simulants according to European Union Plastics Regulation 10/2011, simulating long-term storage with aqueous and fatty foodstuffs. Asymmetric flow field-flow fractionation (AF4) coupled to a multi-angle laser light-scattering (MALLS) detector was used to separate, characterise and quantify the potential release of nanoparticles. The AF4 method was successful in differentiating carbon black from other matrix components, such as extracted polymer chains, in the migration solution. At a detection limit of 12 µg kg−1, carbon black did not migrate from the packaging material into food simulants. The experimental findings are in agreement with theoretical considerations based on migration modelling. From both the experimental findings and theoretical considerations, it can be concluded that carbon black does not migrate into food once it is incorporated into a plastics food contact material. PMID:25105506

Migration of nanoparticles from plastic packaging materials containing carbon black into foodstuffs.

PubMed

Bott, Johannes; Störmer, Angela; Franz, Roland

2014-01-01

Carbon black was investigated to assess and quantify the possibility that nanoparticles might migrate out of plastic materials used in the food packaging industry. Two types of carbon black were incorporated in low-density polyethylene (LDPE) and polystyrene (PS) at 2.5% and 5.0% loading (w/w), and then subjected to migration studies. The samples were exposed to different food simulants according to European Union Plastics Regulation 10/2011, simulating long-term storage with aqueous and fatty foodstuffs. Asymmetric flow field-flow fractionation (AF4) coupled to a multi-angle laser light-scattering (MALLS) detector was used to separate, characterise and quantify the potential release of nanoparticles. The AF4 method was successful in differentiating carbon black from other matrix components, such as extracted polymer chains, in the migration solution. At a detection limit of 12 µg kg⁻¹, carbon black did not migrate from the packaging material into food simulants. The experimental findings are in agreement with theoretical considerations based on migration modelling. From both the experimental findings and theoretical considerations, it can be concluded that carbon black does not migrate into food once it is incorporated into a plastics food contact material.

The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats.

PubMed

Pushparaj, P N; Tan, B K; Tan, C H

2001-12-21

In the present study, we have examined the possible mechanism of the hypoglycemic action of the semi-purified fractions of an ethanolic extract of Averrhoa bilimbi Linn (Oxalidaceae) leaves (ABe) in streptozotocin-diabetic male Sprague-Dawley (SD) rats. The ABe was partitioned with water and butanol to yield a butanol-soluble fraction (BuF) and a water-soluble fraction (AF). The AF was further partitioned with ethyl acetate and hexane to obtain ethyl acetate (EF) and hexane (HF) soluble fractions. The hypoglycemic property of each fraction was assessed by the oral glucose tolerance test (OGTT) at a dose of 125-mg/kg-body weight in streptozotocin (STZ)-diabetic rats (STZ 60 mg/kg i.p.). Fractions AF, BuF and the reference drug metformin (500 mg/kg body weight), produced significant blood glucose-lowering effect in the diabetic rats when compared to the vehicle (distilled water). In the long-term study, the diabetic rats were randomly divided into 4 groups and treated orally by gavage with vehicle, AF (125 mg/kg body weight), BuF (125 mg/kg body weight), and metformin (500 mg/kg body weight) respectively twice a day for 14 days. On day 7 and day 14, AF and BuF, like the reference drug, metformin, lowered the fasting blood glucose concentration significantly (P < 0.05) when compared with the vehicle. The serum insulin level was significantly increased in the AF-treated rats only on day 14 when compared to that in the vehicle-treated rats on day zero (P < 0.05). The serum insulin level in BuF-treated rats was also significantly higher (P < 0.05) on both day 7 and day 14 compared to that on day zero. Hepatic glucose-6-phosphatase activity was significantly lower (P<0.05) in AF- and metformin-treated groups, but not in BuF-treated groups, compared to that in vehicle-treated group. However, there was no change in hepatic glycogen content in AF-, BuF- and metformin-treated group compared to the vehicle-treated group. These results indicate that AF is more potent than BuF in the amelioration of hyperglycemia in STZ-diabetic rats and is a potential source for the isolation of new orally active agent(s) for anti-diabetic therapy.

Effects of Heat Treatment on the Microstructure and Mechanical Properties of Low-Carbon Steel with Magnesium-Based Inclusions

NASA Astrophysics Data System (ADS)

Zhang, Jian; Feng, Pei-Hsien; Pan, Yan-Chi; Hwang, Weng-Sing; Su, Yen-Hao; Lu, Muh-Jung

2016-10-01

The effects of heat treatment on the microstructure and mechanical properties of Mg-containing (7 ppm), low-carbon commercial steel (SS400) were investigated. Twenty different heat treatment paths were performed using a Gleeble 1500 thermomechanical simulator. It was observed by using an optical microscope that as the cooling rate increased and holding temperature decreased, the volume fractions of pearlite, Widmanstätten ferrite, and grain boundary allotriomorphs ferrite fell, whereas that of acicular ferrite (AF) increased. Quantifying the fractions of AF and other phases by using electron backscatter diffraction shows that the heat treatment path with a cooling rate of 20 K/s and holding temperature of 723 K (450 °C) induced the highest volume fraction (44 pct) of AF. As such, the toughness of the sample was increased 12.4 times compared with that observed in the sample containing 4 pct AF. Typical inclusions were analyzed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy. The results showed that the magnesium-based complex inclusions could act as nucleation sites of AF. Inclusions with a size of about 5 μm can serve as heterogeneous nucleation sites for AF. Mg-containing SS400 steel also has excellent hot-ductility in the temperature range of 973 K to 1273 K (700 °C to 1000 °C), and the minimum percentage reduction in area (R.A pct) value of around 63 pct at 1073 K (800 °C).

Clinical impact of quantitative left atrial vortex flow analysis in patients with atrial fibrillation: a comparison with invasive left atrial voltage mapping.

PubMed

Lee, Jung Myung; Hong, Geu-Ru; Pak, Hui-Nam; Shim, Chi Young; Houle, Helene; Vannan, Mani A; Kim, Minji; Chung, Namsik

2015-08-01

Recently, left atrial (LA) vortex flow analysis using contrast transesophageal echocardiography (TEE) has been shown to be feasible and has demonstrated significant differences in vortex flow morphology and pulsatility between normal subjects and patients with atrial fibrillation (AF). However, the relationship between LA vortex flow and electrophysiological properties and the clinical significance of LA vortex flow are unknown. The aims of this study were (1) to compare LA vortex flow parameters with LA voltage and (2) to assess the predictive value of LA vortex flow parameters for the recurrence of AF after radiofrequency catheter ablation (RFCA). Thirty-nine patients with symptomatic non-valvular AF underwent contrast TEE before undergoing RFCA for AF. Quantitative LA vortex flow parameters were analyzed by Omega flow (Siemens Medical Solution, Mountain View, CA, USA). The morphology and pulsatility of LA vortex flow were compared with electrophysiologic parameters that were measured invasively. Hemodynamic, electrophysiological, and vortex flow parameters were compared between patients with and without early recurrence of AF after RFCA. Morphologic parameters, including LA vortex depth, length, width, and sphericity index were not associated with LA voltage or hemodynamic parameters. The relative strength (RS), which represents the pulsatility power of LA, was positively correlated with LA voltage (R = 0.53, p = 0.01) and LA appendage flow velocity (R = 0.73, p < 0.001) and negatively correlated with LA volume index (R = -0.56, p < 0.001). Patients with recurrent AF after RFCA showed significantly lower RS (1.7 ± 0.2 vs 1.9 ± 0.4, p = 0.048) and LA voltage (0.9 ± 0.7 vs 1.7 ± 0.8, p = 0.004) than patients without AF recurrence. In the relatively small LA dimension group (LA volume index ≤ 33 ml/m(2)), RS was significantly lower (2.1 ± 0.3 vs 1.7 ± 0.1, p = 0.029) in patients with the recurrent AF. Quantitative LA vortex flow analysis, especially RS, correlated well with LA voltage. Decreased pulsatility strength in the LA was associated with recurrent AF. LA vortex may have incremental value in predicting the recurrence of AF.

Colloidal Mechanisms of Gold Nanoparticle Loss in Asymmetric Flow Field-Flow Fractionation.

PubMed

Jochem, Aljosha-Rakim; Ankah, Genesis Ngwa; Meyer, Lars-Arne; Elsenberg, Stephan; Johann, Christoph; Kraus, Tobias

2016-10-07

Flow field-flow fractionation is a powerful method for the analysis of nanoparticle size distributions, but its widespread use has been hampered by large analyte losses, especially of metal nanoparticles. Here, we report on the colloidal mechanisms underlying the losses. We systematically studied gold nanoparticles (AuNPs) during asymmetrical flow field-flow fractionation (AF4) by systematic variation of the particle properties and the eluent composition. Recoveries of AuNPs (core diameter 12 nm) stabilized by citrate or polyethylene glycol (PEG) at different ionic strengths were determined. We used online UV-vis detection and off-line elementary analysis to follow particle losses during full analysis runs, runs without cross-flow, and runs with parts of the instrument bypassed. The combination allowed us to calculate relative and absolute analyte losses at different stages of the analytic protocol. We found different loss mechanisms depending on the ligand. Citrate-stabilized particles degraded during analysis and suffered large losses (up to 74%). PEG-stabilized particles had smaller relative losses at moderate ionic strengths (1-20%) that depended on PEG length. Long PEGs at higher ionic strengths (≥5 mM) caused particle loss due to bridging adsorption at the membrane. Bulk agglomeration was not a relevant loss mechanism at low ionic strengths ≤5 mM for any of the studied particles. An unexpectedly large fraction of particles was lost at tubing and other internal surfaces. We propose that the colloidal mechanisms observed here are relevant loss mechanisms in many particle analysis protocols and discuss strategies to avoid them.

Reservoir Cannulas for Pediatric Oxygen Therapy: A Proof-of-Concept Study

PubMed Central

Wu, Grace; DiBlasi, Robert M.; Saxon, Eugene; Austin, Glenn; Ginsburg, Amy Sarah

2016-01-01

Hypoxemia is a complication of pneumonia—the leading infectious cause of death in children worldwide. Treatment generally requires oxygen-enriched air, but access in low-resource settings is expensive and unreliable. We explored use of reservoir cannulas (RCs), which yield oxygen savings in adults but have not been examined in children. Toddler, small child, and adolescent breathing profiles were simulated with artificial lung and airway models. An oxygen concentrator provided flow rates of 0 to 5 L/min via a standard nasal cannula (NC) or RC, and delivered oxygen fraction (FdO2) was measured. The oxygen savings ratio (SR) and absolute flow savings (AFS) were calculated, comparing NC and RC. We demonstrated proof-of-concept that pendant RCs could conserve oxygen during pediatric therapy. SR mean and standard deviation were 1.1 ± 0.2 to 1.4 ± 0.4, 1.1 ± 0.1 to 1.7 ± 0.3, and 1.3 ± 0.1 to 2.4 ± 0.3 for toddler, small child, and adolescent models, respectively. Maximum AFS observed were 0.3 ± 0.3, 0.2 ± 0.1, and 1.4 ± 0.3 L/min for the same models. RCs have the potential to reduce oxygen consumption during treatment of hypoxemia in children; however, further evaluation of products is needed, followed by clinical analysis in patients. PMID:27999601

The Electrophysiologic Effects of Acute Mitral Regurgitation in a Canine Model.

PubMed

Lawrance, Christopher P; Henn, Matthew C; Miller, Jacob R; Kopek, Michael A; Zhang, Andrew J; Schuessler, Richard B; Damiano, Ralph J

2017-04-01

Atrial fibrillation (AF) occurs in 30% of patients with mitral regurgitation referred for surgical intervention. However, the underlying mechanisms in this population are poorly understood. This study examined the effects of acute left atrial volume overload on atrial electrophysiology and the inducibility of AF. Ten canines underwent insertion of an atrioventricular shunt between the left ventricle and left atrium. Shunt and aortic flows were calculated, and the shunt was titrated to a shunt fraction to 40% to 50% of cardiac output. An epicardial plaque with 250 bipolar electrodes was used to determine activation and refractory periods. Biatrial pressures and volumes, conduction times, and atrial fibrillation inducibility were recorded. Data were collected at baseline and 20 minutes after shunt opening and closure. Mean shunt flow was 1.3 ± 0.5 L/min with a shunt fraction of 43% ± 6% simulating moderate to severe mitral regurgitation. Compared with baseline, left atrial volumes and maximum pressures increased by 27% and 29%, respectively, after shunt opening. Biatrial effective refractory periods did not change significantly after shunt opening or closure. Conduction times increased by 9% with shunt opening and returned to baseline after closure. AF duration or inducibility did not change with shunt opening. This canine model of mitral regurgitation demonstrated that acute left atrial volume overload did not increase the inducibility of atrial arrhythmias in contrast with experimental and clinical findings of chronic left atrial volume overload. This suggests that the substrates for AF in patients with mitral regurgitation are a result of chronic remodeling. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Milrinone Use is Associated With Postoperative Atrial Fibrillation Following Cardiac Surgery

PubMed Central

Fleming, Gregory A.; Murray, Katherine T.; Yu, Chang; Byrne, John G.; Greelish, James P.; Petracek, Michael R.; Hoff, Steven J.; Ball, Stephen K.; Brown, Nancy J.; Pretorius, Mias

2009-01-01

Background Postoperative atrial fibrillation (AF), a frequent complication following cardiac surgery, causes morbidity and prolongs hospitalization. Inotropic drugs are commonly used perioperatively to support ventricular function. This study tested the hypothesis that the use of inotropic drugs is associated with postoperative AF. Methods and Results We evaluated perioperative risk factors in 232 patients who underwent elective cardiac surgery. All patients were in sinus rhythm at surgery. Sixty-seven (28.9%) patients developed AF a mean of 2.9±2.1 days after surgery. Patients who developed AF stayed in the hospital longer (P<0.001) and were more likely to die (P=0.02). Milrinone use was associated with an increased risk of postoperative AF (58.2% versus 26.1% in non-users, P<0.001). Older age (63.4±10.7 versus 56.7±12.3 years, P<0.001), hypertension (P=0.04), lower preoperative ejection fraction (P=0.03), mitral valve surgery (P=0.02), right ventricular dysfunction (P=0.03), and higher mean pulmonary artery pressure (PAP) (27.1±9.3 versus 21.8±7.5 mmHg, P=0.001) were also associated with postoperative AF. In multivariable logistic regression, age (P<0.001), ejection fraction (P=0.02), and milrinone use (odds ratio 4.86, 95% CI 2.31-10.25, P<0.001) independently predicted postoperative AF. When data only from patients with pulmonary artery catheters were analyzed and PAP was included in the model, age, milrinone use (odds ratio 4.45, 95% CI 2.01-9.84, P<0.001), and higher PAP (P=0.02) were associated with an increased risk of postoperative AF. Adding other potential confounders or stratifying analysis by mitral valve surgery did not change the association of milrinone use with postoperative AF. Conclusion Milrinone use is an independent risk factor for postoperative AF following elective cardiac surgery. PMID:18824641

Application of different analytical methods for the characterization of non-spherical micro- and nanoparticles.

PubMed

Mathaes, Roman; Winter, Gerhard; Engert, Julia; Besheer, Ahmed

2013-09-10

Non-spherical micro- and nanoparticles have recently gained considerable attention due to their surprisingly different interaction with biological systems compared to their spherical counterparts, opening new opportunities for drug delivery and vaccination. Up till now, electron microscopy is the only method to quantitatively identify the critical quality attributes (CQAs) of non-spherical particles produced by film-stretching; namely size, morphology and the quality of non-spherical particles (degree of contamination with spherical ones). However, electron microscopy requires expensive instrumentation, demanding sample preparation and non-trivial image analysis. To circumvent these drawbacks, the ability of different particle analysis methods to quantitatively identify the CQA of spherical and non-spherical poly(1-phenylethene-1,2-diyl (polystyrene) particles over a wide size range (40 nm, 2 μm and 10 μm) was investigated. To this end, light obscuration, image-based analysis methods (Microflow imaging, MFI, and Vi-Cell XR Coulter Counter) and flow cytometry were used to study particles in the micron range, while asymmetric flow field fractionation (AF4) coupled to multi-angle laser scattering (MALS) and quasi elastic light scattering (QELS) was used for particles in the nanometer range, and all measurements were benchmarked against electron microscopy. Results show that MFI can reliably identify particle size and aspect ratios of the 10 μm particles, but not the 2 μm ones. Meanwhile, flow cytometry was able to differentiate between spherical and non-spherical 10 or 2 μm particles, and determine the amount of impurities in the sample. As for the nanoparticles, AF4 coupled to MALS and QELS allowed the measurement of the geometric (rg) and hydrodynamic (rh) radii of the particles, as well as their shape factors (rg/rh), confirming their morphology. While this study shows the utility of MFI, flow cytometry and AF4 for quantitative evaluation of the CQA of non-spherical particles over a wide size range, the limitations of the methods are discussed. The use of orthogonal characterization methods can provide a complete picture about the CQA of non-spherical particles over a wide size range. Copyright © 2013 Elsevier B.V. All rights reserved.

Catheter ablation of atrial fibrillation in patients with heart failure and preserved ejection fraction.

PubMed

Black-Maier, Eric; Ren, Xinru; Steinberg, Benjamin A; Green, Cynthia L; Barnett, Adam S; Rosa, Normita Sta; Al-Khatib, Sana M; Atwater, Brett D; Daubert, James P; Frazier-Mills, Camille; Grant, Augustus O; Hegland, Donald D; Jackson, Kevin P; Jackson, Larry R; Koontz, Jason I; Lewis, Robert K; Sun, Albert Y; Thomas, Kevin L; Bahnson, Tristam D; Piccini, Jonathan P

2018-05-01

Few studies have examined outcomes of catheter ablation for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The purpose of this study was to compare outcomes of AF ablation in patients with HFpEF vs HF with reduced ejection fraction (HFrEF). We performed a retrospective study of 230 patients with HF who underwent AF ablation, including 97 (42.2%) with HFrEF and 133 (57.8%) with HFpEF. Outcomes included adverse events, symptoms (Mayo AF Symptom Inventory [MAFSI]), New York Heart Association (NYHA) functional class, and freedom from recurrent atrial arrhythmia at 12 months. Overall, 150 of 230 patients had nonparoxysmal AF (62.8% HFpEF vs 63.0% HFrEF). Patients with HFpEF had a smaller mean left atrial diameter (4.4 ± 0.8 cm vs 4.7 ± 0.7 cm; P = .013) and were less likely to be taking a beta-blocker at baseline (72.9% vs 85.6%; P = .022). Median (Q1, Q3) procedure times (233 minutes [192, 290] vs 233.5 minutes [193.0, 297.5]; P = .780) and adverse events such as acute HF (3.8% vs 6.2%; P = .395) were similar between HFpEF and HFrEF patients. Freedom from recurrent atrial arrhythmia was not significantly different in HFpEF vs HFrEF patients (33.9% vs 32.6%; adjusted hazard ratio 1.47; 95% confidence interval 0.72-3.01), with similar improvements in NYHA functional class (-0.32 vs -0.19; P = .135) and MAFSI symptom severity (-0.23 vs -0.09; P = .116) after ablation. Catheter ablation of AF seems to have similar effectiveness in patients with HF, regardless of presence of systolic dysfunction. There were no significant differences in procedural characteristics, arrhythmia-free recurrence, or functional improvements between patients with HFpEF and those with HFrEF. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Biatrial Electrical and Structural Atrial Changes in Heart Failure: Electroanatomic Mapping in Persistent Atrial Fibrillation in Humans.

PubMed

Prabhu, Sandeep; Voskoboinik, Aleksandr; McLellan, Alex J A; Peck, Kah Y; Pathik, Bhupesh; Nalliah, Chrishan J; Wong, Geoff R; Azzopardi, Sonia M; Lee, Geoffrey; Mariani, Justin; Ling, Liang-Han; Taylor, Andrew J; Kalman, Jonathan M; Kistler, Peter M

2018-01-01

This study sought to characterize the biatrial substrate in heart failure (HF) and persistent atrial fibrillation (PeAF). Atrial fibrillation (AF) and HF frequently coexist; however, the contribution of HF to the biatrial substrate in PeAF is unclear. Consecutive patients with PeAF and normal left ventricular (NLV) systolic function (left ventricular ejection fraction [LVEF] >55%) or idiopathic cardiomyopathy (LVEF ≤45%) undergoing AF ablation were enrolled. In AF, pulmonary vein (PV) cycle length (PVCL) was recorded via a multipolar catheter in each PV and in the left atrial appendage for 100 consecutive cycles. After electrical cardioversion, biatrial electroanatomic mapping was performed. Complex electrograms, voltage, scarring, and conduction velocity were assessed. Forty patients, 20 patients with HF (mean age: 62 ± 8.9 years; AF duration: 15 ± 11 months; LVEF: 33 ± 8.4%) and 20 with NLV (mean age: 59 ± 6.7 years; AF duration: 14 ± 9.1 months; p = 0.69; mean LVEF: 61 ± 3.6%; p < 0.001), were enrolled. HF reduced biatrial tissue voltage (p < 0.001) with greater voltage heterogeneity (p < 0.001). HF was associated with significantly more biatrial fractionation (left atrium [LA]: 30% vs. 9%; p < 0.001; right atrium [RA]: 28% vs. 11%; p < 0.001), low voltage (<0.5 mV) (LA: 23% vs. 6%; p = 0.002; RA: 20% vs 11%; p = 0.006), and scarring (<0.05 mV) in the LA (p = 0.005). HF was associated with a slower average PVCL (185 vs. 164 ms; p = 0.016), which correlated significantly with PV antral bipolar voltage (R = -0.62; p < 0.001) and fractionation (R = 0.46; p = 0.001). HF is associated with significantly reduced biatrial tissue voltage, fractionation, and prolongation of PVCL. Advanced biatrial remodeling may have implications for invasive and noninvasive rhythm control strategies in patients with AF and HF. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cardiac Magnetic Resonance-Measured Left Atrial Volume and Function and Incident Atrial Fibrillation: Results From MESA (Multi-Ethnic Study of Atherosclerosis).

PubMed

Habibi, Mohammadali; Samiei, Sanaz; Ambale Venkatesh, Bharath; Opdahl, Anders; Helle-Valle, Thomas M; Zareian, Mytra; Almeida, Andre L C; Choi, Eui-Young; Wu, Colin; Alonso, Alvaro; Heckbert, Susan R; Bluemke, David A; Lima, João A C

2016-08-01

Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases. In a case-cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01-1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48-0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40-0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52-0.95), but not active LA emptying fraction, were associated with incident AF. Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development. © 2016 American Heart Association, Inc.

A Prospective Survey of Atrial Fibrillation Management for Real-world Guideline Adherence: COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) Registry.

PubMed

Kim, Hyeongsoo; Kim, Tae Hoon; Cha, Myung Jin; Lee, Jung Myung; Park, Junbeom; Park, Jin Kyu; Kang, Ki Woon; Shim, Jaemin; Uhm, Jae Sun; Kim, Jun; Park, Hyung Wook; Choi, Eue Keun; Kim, Jin Bae; Kim, Changsoo; Lee, Young Soo; Joung, Boyoung

2017-11-01

The aging population is rapidly increasing, and atrial fibrillation (AF) is becoming a significant public health burden in Asia, including Korea. This study evaluated current treatment patterns and guideline adherence of AF treatment. In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 6,275 patients with nonvalvular AF were consecutively enrolled between June 2016 and April 2017 from 10 tertiary hospitals in Korea. The AF type was paroxysmal, persistent, and permanent in 65.3%, 30.0%, and 2.9% of patients, respectively. Underlying structural heart disease was present in 11.9%. Mean CHA₂DS₂-VASc was 2.7±1.7. Oral anticoagulation (OAC), rate control, and rhythm control were used in 70.1%, 53.9%, and 54.4% of patients, respectively. OAC was performed in 82.7% of patients with a high stroke risk. However, antithrombotic therapy was inadequately used in 53.4% of patients with a low stroke risk. For rate control in 192 patients with low ejection fraction (<40%), β-blocker (65.6%), digoxin (5.2%), or both (19.3%) were adequately used in 90.1% of patients; however, a calcium channel blocker was inadequately used in 9.9%. A rhythm control strategy was chosen in 54.4% of patients. The prescribing rate of class Ic antiarrythmics, dronedarone, and sotalol was 16.9% of patients with low ejection fraction. This study shows how successfully guidelines can be applied in the real world. The nonadherence rate was 17.2%, 9.9%, and 22.4% for stroke prevention, rate control, and rhythm control, respectively. Copyright © 2017. The Korean Society of Cardiology

Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction

PubMed Central

Operario, Darwin J; Platts-Mills, James A; Nadan, Sandrama; Page, Nicola; Seheri, Mapaseka; Mphahlele, Jeffrey; Praharaj, Ira; Kang, Gagandeep; Araujo, Irene T; Leite, Jose Paulo G; Cowley, Daniel; Thomas, Sarah; Kirkwood, Carl D; Dennis, Francis; Armah, George; Mwenda, Jason M; Wijesinghe, Pushpa Ranjan; Rey, Gloria; Grabovac, Varja; Berejena, Chipo; Simwaka, Chibumbya J; Uwimana, Jeannine; Sherchand, Jeevan B; Thu, Hlaing Myat; Galagoda, Geethani; Bonkoungou, Isidore J O; Jagne, Sheriffo; Tsolenyanu, Enyonam; Diop, Amadou; Enweronu-Laryea, Christabel; Borbor, Sam-Aliyah; Liu, Jie; McMurry, Timothy; Lopman, Benjamin; Parashar, Umesh; Gentsch, John; Steele, A Duncan; Cohen, Adam; Serhan, Fatima; Houpt, Eric R

2017-01-01

Abstract Background The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013–2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%–44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9–15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8–9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0–7.6]), Shigella (AF, 4.7 [95% CI, 2.8–6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0–6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9–5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%–61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%–30.4%) in age-eligible children. Conclusions Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea. PMID:28838152

Investigation of zinc oxide particles in cosmetic products by means of centrifugal and asymmetrical flow field-flow fractionation.

PubMed

Sogne, Vanessa; Meier, Florian; Klein, Thorsten; Contado, Catia

2017-09-15

The dimensional characterization of insoluble, inorganic particles, such as zinc oxide ZnO, dispersed in cosmetic or pharmaceutical formulations, is of great interest considering the current need of declaring the possible presence of nanomaterials on the label of commercial products. This work compares the separation abilities of Centrifugal- and Asymmetrical Flow Field-Flow Fractionation techniques (CF3 and AF4, respectively), equipped with UV-vis, MALS and DLS detectors, in size sorting ZnO particles, both as pristine powders and after their extraction from cosmetic matrices. ZnO particles, bare and superficially modified with triethoxycaprylyl silane, were used as test materials. To identify the most suitable procedure necessary to isolate the ZnO particles from the cosmetic matrix, two O/W and two W/O emulsions were formulated on purpose. The suspensions, containing the extracted particles ZnO, were separated by both Field-Flow Fractionation (FFF) techniques to establish a common analysis protocol, applicable for the analysis of ZnO particles extracted from three commercial products, sold in Europe for the baby skin care. Key aspects of this study were the selection of an appropriate dispersing agent enabling the particles to stay in stable suspensions (>24h)and the use of multiple detectors (UV-vis, MALS and DLS) coupled on-line with the FFF channels, to determine the particle dimensions without using the retention parameters. Between the two FFF techniques, CF3 revealed to be the most robust one, able to sort all suspensions created in this work. Copyright © 2017 Elsevier B.V. All rights reserved.

Bile Salt Micelles and Phospholipid Vesicles Present in Simulated and Human Intestinal Fluids: Structural Analysis by Flow Field-Flow Fractionation/Multiangle Laser Light Scattering.

PubMed

Elvang, Philipp A; Hinna, Askell H; Brouwers, Joachim; Hens, Bart; Augustijns, Patrick; Brandl, Martin

2016-09-01

Knowledge about colloidal assemblies present in human intestinal fluids (HIFs), such as bile salt micelles and phospholipid vesicles, is regarded of importance for a better understanding of the in vivo dissolution and absorption behavior of poorly soluble drugs (Biopharmaceutics Classification System class II/IV drugs) because of their drug-solubilizing ability. The characterization of these potential drug-solubilizing compartments is a prerequisite for further studies of the mechanistic interplays between drug molecules and colloidal structures within HIFs. The aim of the present study was to apply asymmetrical flow field-flow fractionation (AF4) in combination with multiangle laser light scattering in an attempt to reveal coexistence of colloidal particles in both artificial and aspirated HIFs and to determine their sizes. Asymmetrical flow field-flow fractionation/multiangle laser light scattering analysis of the colloidal phase of intestinal fluids allowed for a detailed insight into the whole spectrum of submicron- to micrometer-sized particles. With respect to the simulated intestinal fluids mimicking fasted and fed state (FaSSIF-V1 and FeSSIF-V1, respectively), FaSSIF contained one distinct size fraction of colloidal assemblies, whereas FeSSIF contained 2 fractions of colloidal species with significantly different sizes. These size fractions likely represent (1) mixed taurocholate-phospholipid-micelles, as indicated by a size range up to 70 nm (in diameter) and a strong UV absorption and (2) small phospholipid vesicles of 90-210 nm diameter. In contrast, within the colloidal phase of the fasted state aspirate of a human volunteer, 4 different size fractions were separated from each other in a consistent and reproducible manner. The 2 fractions containing large particles showed mean sizes of approximately 50 and 200 nm, respectively (intensity-weighted mean diameter, Dz), likely representing mixed cholate/phospholipid micelles and phospholipid vesicles, respectively. The sizes of the smaller 2 fractions being below the size range of multiangle laser light scattering analysis (<20 nm) and their strong UV absorption indicates that they represent either pure cholate micelles or small mixed micelles. Within the colloidal fraction of the fed-state human aspirate, similar colloidal assemblies were detected as in the fasted state human aspirates. The observed differences between SIF and HIF indicate that the simulated intestinal fluids (FaSSIF-V1 and FeSSIF-V1) represent rather simplified models of the real human intestinal environment in terms of coexisting colloidal particles. It is hypothesized that the different supramolecular assemblies detected differ in their lipid composition, which may affect their affinity toward drug compounds and thus the drug-solubilizing capabilities. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation.

PubMed

Kristensen, Søren Lund; Jhund, Pardeep S; Mogensen, Ulrik M; Rørth, Rasmus; Abraham, William T; Desai, Akshay; Dickstein, Kenneth; Rouleau, Jean L; Zile, Michael R; Swedberg, Karl; Packer, Milton; Solomon, Scott D; Køber, Lars; McMurray, John J V

2017-10-01

Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without ( P <0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all P <0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and ≥3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400-999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; ≥3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found similar results for the components of the composite outcome and all-cause mortality. HF and reduced ejection fraction patients with AF had higher NT-proBNP than those without AF. However, above a concentration of 400 pg/mL (representing most patients in each group), NT-proBNP had similar predictive value for adverse cardiovascular outcomes, irrespective of AF status. URL: https://www.clinicaltrials.gov. Unique identifier NCT00853658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF). © 2017 American Heart Association, Inc.

Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography.

PubMed

Abidov, Aiden; Hachamovitch, Rory; Rozanski, Alan; Hayes, Sean W; Santos, Marcia M; Sciammarella, Maria G; Cohen, Ishac; Gerlach, James; Friedman, John D; Germano, Guido; Berman, Daniel S

2004-09-01

The aim of this research was to determine whether presence of atrial fibrillation (AF) provides incremental prognostic information relative to myocardial perfusion single-photon emission computed tomography (MPS) with respect to risk of cardiac death (CD). The prognostic significance of AF in patients undergoing MPS is not known. A total of 16,048 consecutive patients undergoing MPS were followed-up for a mean of 2.21 +/- 1.15 years for the development of CD. Of those, 384 patients (2.4%) had AF. Cox proportional hazards method was used to compare clinical and perfusion data for the prediction of CD in patients with and without AF. Atrial fibrillation was a significant predictor of CD in patients with normal (1.6% per year vs. 0.4% per year in non-AF patients), mildly abnormal (6.3% per year vs. 1.2% per year), and severely abnormal MPS (6.4% per year vs. 3.7% per year) (p < 0.001 for all). By multivariable analysis, AF patients had worse survival (p = 0.001) even after adjustment for the variables most predictive of CD: age, diabetes, shortness of breath, use of vasodilator stress, rest heart rate, and the nuclear variables. In the 4,239 patients with left ventricular ejection fraction evaluated by gated MPS, AF demonstrated incremental prognostic value not only over clinical and nuclear variables, but also over left ventricular ejection in predicting CD (p = 0.014). The presence of AF independently increases the risk of cardiac events over perfusion and function variables in patients undergoing MPS. Patients with AF have a high risk of CD, even when MPS is only mildly abnormal. Whether patients with AF and mildly abnormal MPS constitute a group more deserving of early referral to cardiac catheterization is a question warranting further study.

Rotor meandering contributes to irregularity in electrograms during atrial fibrillation.

PubMed

Zlochiver, Sharon; Yamazaki, Masatoshi; Kalifa, Jérôme; Berenfeld, Omer

2008-06-01

Radiofrequency ablation therapy of atrial fibrillation (AF) recently incorporated the analysis of dominant frequency (DF) and/or electrogram fractionation for guidance. However, the relationships between DF, fractionation, and spatiotemporal characteristics of the AF source remain unclear. We hypothesize that a meandering reentrant AF source contributes to the wave fractionation and is reflected in the power spectrum of local electrograms elsewhere in the rotor's surroundings. Meandering rotors as AF sources were simulated in 2-dimensional models of human atrial tissue and recorded in isolated sheep hearts. Nondominant elements of the signals were differentiated from the dominant elements using singular value decomposition, whereby the purely periodic constituent (PC) relating to the rotor's DF was eliminated rendering a residual constituent (RC) that consisted of all other activity. Spectral analysis of the decomposed constituents revealed peaks corresponding to the meandering frequency of the rotor tip, the magnitudes of which were proportional to the size of and the distance to the rotor core. Similar analyses on epicardial optical signals and electrograms from isolated sheep hearts, as well as human complex fractionated atrial electrograms, showed applicability of the approach. Increased meandering of the rotor driving AF reduces activation periodicity and increases fractionation. The spectral manifestation of the rotor activity beyond the meandering region makes it possible to characterize AF source stability, as well as DF in humans using electrode mapping.

Rotor Meandering Contributes to Irregularity in Electrograms during Atrial Fibrillation

PubMed Central

Zlochiver, Sharon; Yamazaki, Masatoshi; Kalifa, Jerome; Berenfeld, Omer

2010-01-01

Radiofrequency ablation therapy of atrial fibrillation (AF) recently incorporated the analysis of dominant frequency (DF) and/or electrogram fractionation for guidance. However, the relationships between DF, fractionation and spatio-temporal characteristics of the AF source remain unclear. We hypothesize that meandering reentrant AF source contributes to the wave fractionation and is reflected in the power spectrum of local electrograms elsewhere in the rotor’s surroundings. Methods Meandering rotors as AF sources were simulated in 2D models of human atrial tissue and recorded in isolated sheep hearts. Non-dominant elements of the signals were differentiated from the dominant elements using singular value decomposition, whereby the purely periodic constituent (PC) relating to the rotor’s DF was eliminated rendering a residual constituent (RC) that consisted of all other activity. Results Spectral analysis of the decomposed constituents revealed peaks corresponding to the meandering frequency of the rotor tip, the magnitudes of which were proportional to the size of, and the distance to the rotor core. Similar analyses on epicardial optical signals and electrograms from isolated sheep hearts, as well as human complex fractionated atrial electrograms demonstrated applicability of the approach. Conclusion Increased meandering of the rotor driving AF reduces activation periodicity and increases fractionation. The spectral manifestation of the rotor activity beyond the meandering region makes it possible to characterize AF source stability, as well as DF in humans using electrode mapping. PMID:18534369

Predictors of arrhythmia recurrence after balloon cryoablation of atrial fibrillation: the value of CAAP-AF risk scoring system.

PubMed

Sanhoury, Mohamed; Moltrasio, Massimo; Tundo, Fabrizio; Riva, Stefania; Dello Russo, Antonio; Casella, Michela; Tondo, Claudio; Fassini, Gaetano

2017-08-01

In the present study, we aimed to test the value of CAAP-AF score for prediction of atrial fibrillation (AF) recurrence at follow-up in a group of our patients treated by balloon cryoablation. A total of 283 symptomatic drug-refractory AF patients [261 (92%) with paroxysmal AF] who underwent pulmonary vein isolation (PVI) with second-generation cryoballoon between April 2012 and October 2016 were included. The CAAP-AF score was calculated for every patient. A total of 283 patients [68 female (20%), mean age 59.8 ± 11.4 years] were included in the present analysis. Eighty-nine patients (31%) had hypertension and 13 (4%) had coronary artery disease. The mean left atrial diameter and left ventricular ejection fraction were 40.6 ± 7.0 mm and 60.0 ± 9.1%, respectively. The mean CHA 2 DS 2 -VASc score was 1.2 ± 1.1, and mean number of prior failed antiarrhythmic drugs was 1.4 ± 0.8. At 18 ± 6 months follow-up, 25 patients (8.87%) developed AF recurrence. The recurrence rate was as follows: 3.17% (score 0-3), 8.47% (score 4), 16.28% (score 5), 6.67% (score 6), 23.08% (score 7), and 36.36% (score ≥8). The recurrence rate was 4.86% at a score <5 and 16.49% at a value ≥5; a score cutoff ≥5 predicted AF recurrence with a sensitivity 64% and specificity 68%. The present analysis suggests the usefulness of CAAP-AF scoring system, with its simple and easily obtained six clinical variables, to predict AF recurrence after PVI by means of second-generation cryoballoon. A score value ≥5 predicted AF recurrence with a sensitivity 64% and specificity 68%.

Anti-Inflammatory, Anti-Osteoclastogenic and Antioxidant Effects of Malva sylvestris Extract and Fractions: In Vitro and In Vivo Studies

PubMed Central

Franchin, Marcelo; Massarioli, Adna Prado; Paschoal, Jonas Augusto Rizzato; Alencar, Severino Matias; Franco, Gilson Cesar Nobre; Rosalen, Pedro Luiz

2016-01-01

Given their medical importance, natural products represent a tremendous source of drug discovery. The aim of this study was to investigate Malva sylvestris L. extract and fractions and their pharmacological activities followed by chemical identification. The aqueous fraction (AF) was identified as the bioactive fraction in the in vitro and in vivo assays. The AF controlled the neutrophil migration to the peritoneal cavity by 66%, inhibited the antiedematogenic activity by 58.8%, and controlled IL-1β cytokine expression by 54%. The in vitro viability tests showed a concentration-dependent effect, where the MSE and fractions at concentrations under 10 μg/mL were non-toxic to cells. Transcriptional factors of carbonic anhydrase II (CAII), cathepsin K (Ctsk) and tartrate-resistant acid phosphatase (TRAP) were analyzed by qPCR in RAW 264.7 cell lines. The gene expression analysis showed that the AF was the only treatment that could downregulate all the study genes: CAII, Ctsk and TRAP (p<0.05). TRAP staining was used to evaluate osteoclast formation. AF treatments reduced the number of osteoclastogenesis 2.6-fold compared to the vehicle control group. Matrix metalloproteinase 9 (MMP-9) activity decreased 75% with the AF treatment. Moreover, the bioactive fraction had the ability to regulate the oxidation pathway in the ABTS (2,2-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) assay with an activity equivalent to 1.30 μmol Trolox/g and DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals 1.01 g/L. Positive ion ESI-mass spectrometry for molecular ions at m/z 611 and 633 confirmed rutin as the major compound in the AF. The AF of M. sylvestris presented anti-inflammatory, controlled osteoclastogenic mechanisms and antioxidant abilities in different in vitro and in vivo methods. In addition, we suggest that given its multi-target activity the bioactive fraction may be a good candidate in the therapy of chronic inflammatory diseases. PMID:27643502

Validation of a classification system to grade fractionation in atrial fibrillation and correlation with automated detection systems.

PubMed

Hunter, Ross J; Diab, Ihab; Thomas, Glyn; Duncan, Edward; Abrams, Dominic; Dhinoja, Mehul; Sporton, Simon; Earley, Mark J; Schilling, Richard J

2009-12-01

We tested application of a grading system describing complex fractionated electrograms (CFE) in atrial fibrillation (AF) and used it to validate automated CFE detection (AUTO). Ten seconds bipolar electrograms were classified by visual inspection (VI) during ablation of persistent AF and the result compared with offline manual measurement (MM) by a second blinded operator: Grade 1 uninterrupted fractionated activity (defined as segments > or =70 ms) for > or =70% of recording and uninterrupted > or =1 s; Grade 2 interrupted fractionated activity > or =70% of recording; Grade 3 intermittent fractionated activity 30-70%; Grade 4 discrete (<70 ms) complex electrogram (> or =5 direction changes); Grade 5 discrete simple electrograms (< or =4 direction changes); Grade 6 scar. Grade by VI and MM for 100 electrograms agreed in 89%. Five hundred electrograms were graded on Carto and NavX by VI to validate AUTO in (i) detection of CFE (grades 1-4 considered CFE), and (ii) assessing degree of fractionation by correlating grade and score by AUTO (data shown as sensitivity, specificity, r): NavX 'CFE mean' 92%, 91%, 0.56; Carto 'interval confidence level' using factory settings 89%, 62%, -0.72, and other published settings 80%, 74%, -0.65; Carto 'shortest confidence interval' 74%, 70%, 0.43; Carto 'average confidence interval' 86%, 66%, 0.53. Grading CFE by VI is accurate and correlates with AUTO.

Multifractal analysis for grading complex fractionated electrograms in atrial fibrillation.

PubMed

Orozco-Duque, A; Novak, D; Kremen, V; Bustamante, J

2015-11-01

Complex fractionated atrial electrograms provide an important tool for identifying arrhythmogenic substrates that can be used to guide catheter ablation for atrial fibrillation (AF). However, fractionation is a phenomenon that remains unclear. This paper aims to evaluate the multifractal properties of electrograms in AF in order to propose a method based on multifractal analysis able to discriminate between different levels of fractionation. We introduce a new method, the h-fluctuation index (hFI), where h is the generalised Hurst exponent, to extract information from the shape of the multifractal spectrum. Two multifractal frameworks are evaluated: multifractal detrended fluctuation analysis and wavelet transform modulus maxima. hFI is exemplified through its application in synthetic signals, and it is evaluated in a database of electrograms labeled on the basis of four degrees of fractionation. We compare the performance of hFI with other indexes, and find that hFI outperforms them. The results of the study provide evidence that multifractal analysis is useful for studying fractionation phenomena in AF electrograms, and indicate that hFI can be proposed as a tool for grade fractionation associated with the detection of target sites for ablation in AF.

The effect of baking and enzymatic treatment on the structural properties of wheat starch.

PubMed

Fuentes, Catalina; Zielke, Claudia; Prakash, Manish; Kumar, Puneeth; Peñarrieta, J Mauricio; Eliasson, Ann-Charlotte; Nilsson, Lars

2016-12-15

In this study, bread was baked with and without the addition of α-amylase. Starch was extracted from the baked bread and its molecular properties were characterized using (1)H NMR and asymmetric flow field-flow fractionation (AF4) connected to multi-angle light scattering (MALS) and other detectors. The approach allows determination of molar mass, root- mean-square radius and apparent density as well as the average degree of branching of amylopectin. The results show that starch size and structure is affected as a result of the baking process. The effect is larger when α-amylase is added. The changes include both a decrease molar mass and size as well as an increase in apparent density. Moreover, an increase in average degree of branching and the number of reducing ends H-1(β-r) and H-1(α-r) can be observed. Copyright © 2016. Published by Elsevier Ltd.

Asymmetrical flow field-flow fractionation for the analysis of PEG-asparaginase.

PubMed

John, C; Herz, T; Boos, J; Langer, K; Hempel, G

2016-01-01

Monomethoxypolyethylene glycol L-asparaginase (PEG-ASNASE) is the PEGylated version of the enzyme L-asparaginase (ASNASE). Both are used for remission induction in acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The treatment control is generally carried out by performing activity assays, though methods to determine the actual enzyme rather than its activity are rare. Using asymmetrical flow field-flow fractionation (AF4) offered the chance to develop a method capable of simultaneously measuring PEG-ASNASE and PEG. A method validation was performed in accordance with FDA guidelines for PEG-ASNASE from non-biological solutions. The method unfolded a linearity of 15-750 U/mL with coefficients of correlation of r(2)>0.99. The coefficients of variation (CV) for within-run and between-run variability were 1.18-10.15% and 2.43-8.73%, respectively. Furthermore, the method was used to perform stability tests of the product Oncaspar® (PEG-ASNASE) and estimation of the molecular weight by multi-angle light scattering (MALS) of stressed samples to correlate them with the corresponding activity. The findings indicate that Oncaspar® stock solution should not be stored any longer than 24 h at room temperature and cannot be frozen in pure aqueous media. The validated method might be useful for the pharmaceutical industry and its quality control of PEG-ASNASE production. Copyright © 2015 Elsevier B.V. All rights reserved.

Determination of Hamaker constants of polymeric nanoparticles in organic solvents by asymmetrical flow field-flow fractionation.

PubMed

Noskov, Sergey; Scherer, Christian; Maskos, Michael

2013-01-25

Interaction forces between all objects are either of repulsive or attractive nature. Concerning attractive interactions, the determination of dispersion forces are of special interest since they appear in all colloidal systems and have a crucial influence on the properties and processes in these systems. One possibility to link theory and experiment is the description of the London-Van der Waals forces in terms of the Hamaker constant, which leads to the challenging problem of calculating the van der Waals interaction energies between colloidal particles. Hence, the determination of a Hamaker constant for a given material is needed when interfacial phenomena such as adhesion are discussed in terms of the total potential energy between particles and substrates. In this work, the asymmetrical flow field-flow fractionation (AF-FFF) in combination with a Newton algorithm based iteration process was used for the determination of Hamaker constants of different nanoparticles in toluene. Copyright © 2012 Elsevier B.V. All rights reserved.

Noninvasive evaluation of reverse atrial remodeling after catheter ablation of atrial fibrillation by P wave dispersion.

PubMed

Fujimoto, Yuhi; Yodogawa, Kenji; Takahashi, Kenta; Tsuboi, Ippei; Hayashi, Hiroshi; Uetake, Shunsuke; Iwasaki, Yu-Ki; Hayashi, Meiso; Miyauchi, Yasushi; Shimizu, Wataru

2017-11-01

Atrial fibrillation (AF) itself creates structural and electrophysiological changes such as atrial enlargement, shortening of refractory period and decrease in conduction velocity, called "atrial remodeling", promoting its persistence. Although the remodeling process is considered to be reversible, it has not been elucidated in detail. The aim of this study was to assess the feasibility of P wave dispersion in the assessment of reverse atrial remodeling following catheter ablation of AF. Consecutive 126 patients (88 males, age 63.0 ± 10.4 years) who underwent catheter ablation for paroxysmal AF were investigated. P wave dispersion was calculated from the 12 lead ECG before, 1 day, 1 month, 3 months and 6 months after the procedure. Left atrial diameter (LAD), left atrial volume index (LAVI), left ventricular ejection fraction (LVEF), transmitral flow velocity waveform (E/A), and tissue Doppler (E/e') on echocardiography, plasma B-type natriuretic peptide (BNP) concentrations, serum creatinine, and estimated glomerular filtration rate (eGFR) were also measured. Of all patients, 103 subjects remained free of AF for 1 year follow-up. In these patients, P wave dispersion was not changed 1 day and 1 month after the procedure. However, it was significantly decreased at 3 and 6 months (50.1 ± 14.8 to 45.4 ± 14.4 ms, p < 0.05, 45.2 ± 9.9 ms, p < 0.05, respectively). Plasma BNP concentrations, LAD and LAVI were decreased (81.1 ± 103.8 to 44.8 ± 38.3 pg/mL, p < 0.05, 38.2 ± 5.7 to 35.9 ± 5.6 mm, p < 0.05, 33.3 ± 14.2 to 29.3 ± 12.3 mL/m 2 , p < 0.05) at 6 months after the procedure. There were no significant changes in LVEF, E/A, E/e', serum creatinine, and eGFR during the follow up period. P wave dispersion was decreased at 3 and 6 months after catheter ablation in patients without recurrence of AF. P wave dispersion is useful for assessment of reverse remodeling after catheter ablation of AF.

Mobility of engineered inorganic nanoparticles in porous media

NASA Astrophysics Data System (ADS)

Metreveli, George; Heidmann, Ilona; Schaumann, Gabriele Ellen

2013-04-01

Besides the excellent properties and great potential for various industrial, medical, pharmaceutical, cosmetic, and life science applications, engineered inorganic nanoparticles (EINP) can show also disadvantages concerning increasing risk potential with increasing application, if they are released in the environmental systems. EINP can influence microbial activity and can show toxic effects (Fabrega et al., 2009). Similar to the inorganic natural colloids, EINP can be transported in soil and groundwater systems (Metreveli et al., 2005). Furthermore, due to the large surface area and high sorption and complex formation capacity, EINP can facilitate transport of different contaminants. In this study the mobility behaviour of EINP and their effect on the transport of different metal(loid) species in water saturated porous media was investigated. For these experiments laboratory column system was used. The column was filled with quartz sand. The interactions between EINP and metal(loid)s were characterised by coupling of asymmetrical flow field flow fractionation (AF4) with inductively coupled plasma mass spectrometer (ICP-MS). As EINP laponite (synthetic three layer clay mineral), and as metal(loid)s Cu, Pb, Zn, Pt and As were used. In AF4 experiments sorption of metal(loid)s on the surface of EINP could be observed. The extent of interactions was influenced by pH value and was different for different metal(loid)s. Laboratory column experiments showed high mobility of EINP, which facilitated transport of most of metal(loid)s in water saturated porous media. Furthermore the migration of synthetic silver nanoparticles in natural soil columns was determined in leaching experiments. Acknowledgement Financial support by German Research Council (DFG) and Max-Buchner-Research Foundation (MBFSt) is gratefully acknowledged. We thank Karlsruhe Institute of Technology (KIT) for the opportunity to perform the column and AF4 experiments. References: Fabrega, J., Fawcett, S. R., Renshaw, J. C. Lead, J. R. 2009. Silver nanoparticle impact on bacterial growth: Effect of pH, concentration, and organic matter. Environ. Sci. Technol. 43 (19): 7285-7290 Metreveli, G., Kaulisch, E.-M., Frimmel, F. H. 2005. Coupling of a column system with ICP-MS for the characterisation of colloid mediated metal(loid) transport in porous media. Acta Hydrochim. Hydrobiol. 33 (4): 337-345

Arterial viscoelasticity: role in the dependency of pulse wave velocity on heart rate in conduit arteries.

PubMed

Xiao, Hanguang; Tan, Isabella; Butlin, Mark; Li, Decai; Avolio, Alberto P

2017-06-01

Experimental investigations have established that the stiffness of large arteries has a dependency on acute heart rate (HR) changes. However, the possible underlying mechanisms inherent in this HR dependency have not been well established. This study aimed to explore a plausible viscoelastic mechanism by which HR exerts an influence on arterial stiffness. A multisegment transmission line model of the human arterial tree incorporating fractional viscoelastic components in each segment was used to investigate the effect of varying fractional order parameter (α) of viscoelasticity on the dependence of aortic arch to femoral artery pulse wave velocity (afPWV) on HR. HR was varied from 60 to 100 beats/min at a fixed mean flow of 100 ml/s. PWV was calculated by intersecting tangent method (afPWV Tan ) and by phase velocity from the transfer function (afPWV TF ) in the time and frequency domain, respectively. PWV was significantly and positively associated with HR for α ≥ 0.6; for α = 0.6, 0.8, and 1, HR-dependent changes in afPWV Tan were 0.01 ± 0.02, 0.07 ± 0.04, and 0.22 ± 0.09 m/s per 5 beats/min; HR-dependent changes in afPWV TF were 0.02 ± 0.01, 0.12 ± 0.00, and 0.34 ± 0.01 m/s per 5 beats/min, respectively. This crosses the range of previous physiological studies where the dependence of PWV on HR was found to be between 0.08 and 0.10 m/s per 5 beats/min. Therefore, viscoelasticity of the arterial wall could contribute to mechanisms through which large artery stiffness changes with changing HR. Physiological studies are required to confirm this mechanism. NEW & NOTEWORTHY This study used a transmission line model to elucidate the role of arterial viscoelasticity in the dependency of pulse wave velocity on heart rate. The model uses fractional viscoelasticity concepts, which provided novel insights into arterial hemodynamics. This study also provides a means of assessing the clinical manifestation of the association of pulse wave velocity and heart rate. Copyright © 2017 the American Physiological Society.

Anti-diabetic activity of the semi-purified fractions of Averrhoa bilimbi in high fat diet fed-streptozotocin-induced diabetic rats.

PubMed

Tan, Benny Kwong Huat; Tan, Chee Hong; Pushparaj, Peter Natesan

2005-04-29

The present study was designed to investigate the hypoglycemic and hypolipidemic activities of the semi-purified fractions of an ethanolic leaf extract of Averrhoa bilimbi (ABe) in high fat diet (HFD)-streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats aged 10 weeks (200-250 g) were fed with a high fat diet obtained from Glen Forrest stock feeders (Western Australia) for 2 weeks prior to intraperitoneal injection with streptozotocin (STZ, 50 mg/kg). The leaves of A.bilimbi were exhaustively extracted with 80% ethanol, concentrated at 40 degrees C using a rotavapor and partitioned successively with butanol, ethylacetate and hexane to get aqueous (AF), butanol (BuF), ethylacetate (EF), and hexane fractions (HF). The fractions were freeze-dried to obtain powders of each. To investigate the effect of long term administration of the hypoglycemic fractions, diabetic animals were treated with vehicle (distilled water), AF (125 mg/kg), or BuF (125 mg/kg), twice a day for 14 days. The long term administration of AF and BuF at a dose of 125 mg/kg significantly (P < 0.05) lowered blood glucose and triglyceride concentrations when compared to the vehicle. The hepatic glycogen content was significantly higher (P < 0.05) in AF-treated rats when compared to diabetic control, however no change was found in the BuF-treated rats. Moreover, AF as well as BuF did not cause any significant change in the total cholesterol and HDL-cholesterol. There was also no difference in liver thiobarbituric acid reactive substances (TBARS) and cytochrome P450 values between AF, BuF and vehicle-treated control rats. In conclusion, the results indicate that AF is more potent than BuF in the amelioration of hyperglycemia and hyperlipidemia in HFD fed-STZ diabetic rats. Hence, AF is a potential source for the isolation of active principle(s) for oral anti-diabetic therapy.

Usefulness of Doppler assessment of pulmonary vein and left atrial appendage flow following pulmonary vein isolation of chronic atrial fibrillation in predicting recovery of left atrial function.

PubMed

Donal, Erwan; Grimm, Richard A; Yamada, Hirotsugu; Kim, Yong Jin; Marrouche, Nassir; Natale, Andrea; Thomas, James D

2005-04-15

Atrial fibrillation (AF) is a widespread condition that causes significant morbidity and mortality. Recently, pulmonary venous (PV) isolation using radiofrequency ablation has been used successfully to exclude the pulmonary venous ostia, resulting in correction of AF. Further, miniaturized high-frequency ultrasound phased-array transducers currently provide Doppler and 2-dimensional imaging during the ablation procedure. We examined atrial function and its determinants using intracardiac echocardiography before and after PV isolation in 45 patients who had chronic AF (56 +/- 11 years old). PV, left atrial (LA) appendage, and mitral and tricuspid flows were recorded. Recovery of booster pump function (defined by the presence of mitral inflow A wave, LA appendage a-wave, and PV A-reversal wave velocities >10 cm/s) was observed in 39 of 45 patients (86.6%). PV flow systolic wave before and after ablation correlated with the degree of LA booster pump function after PV isolation. An early systolic PV flow peak velocity >57.47 cm/s predicted "good" LA booster pump function recovery with 96% specificity. Diastolic LA appendage emptying in AF correlated (p <0.001) and predicted good LA booster pump function with 92% specificity for velocities >46.4 cm/s. Thus, monitoring LA function during PV isolation for chronic AF is feasible. Most patients recovered LA booster pump function immediately after PV isolation, and the degree of recovery correlated with LA reservoir function. Preserved reservoir function during AF is predictive of satisfactory recovery of booster pump function after PV isolation.

Atrial fibrillation in heart failure with preserved ejection fraction: Insights into mechanisms and therapeutics.

PubMed

Patel, Ravi B; Vaduganathan, Muthiah; Shah, Sanjiv J; Butler, Javed

2017-08-01

Atrial fibrillation (AF) and heart failure (HF) often coexist, and the outcomes of patients who have both AF and HF are considerably worse than those with either condition in isolation. Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical entity and accounts for approximately one-half of current HF. At least one-third of patients with HFpEF are burdened by comorbid AF. The current understanding of the relationship between AF and HFpEF is limited, but the clinical implications are potentially important. In this review, we explore 1) the pathogenesis that drives AF and HFpEF to coexist; 2) pharmacologic therapies that may attenuate the impact of AF in HFpEF; and 3) future directions in the management of this complex syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of pre-existing or new-onset atrial fibrillation on 30-day clinical outcomes following transcatheter aortic valve replacement: Results from the BRAVO 3 randomized trial.

PubMed

Hengstenberg, Christian; Chandrasekhar, Jaya; Sartori, Samantha; Lefevre, Thierry; Mikhail, Ghada; Meneveau, Nicolas; Tron, Christophe; Jeger, Raban; Kupatt, Christian; Vogel, Birgit; Farhan, Serdar; Sorrentino, Sabato; Sharma, Madhav; Snyder, Clayton; Husser, Oliver; Boekstegers, Peter; Hambrecht, Rainer; Widder, Julian; Hildick-Smith, David; De Carlo, Marco; Wijngaard, Peter; Deliargyris, Efthymios; Bernstein, Debra; Baber, Usman; Mehran, Roxana; Anthopoulos, Prodromos; Dangas, George

2017-11-15

Prior studies have suggested that patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR) are at higher risk for adverse cardiovascular events. Whether procedural bivalirudin compared with unfractionated heparin (UFH) has a beneficial effect on early outcomes in these patients is unknown. We examined for the effect of baseline or new-onset AF within 30 days of TAVR and explored for the effect of bivalirudin versus UFH by AF status, on 30-day outcomes from the BRAVO 3 trial. The BRAVO-3 trial multicenter randomized trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin or UFH. We compared AF and no-AF groups and examined for 30-day Bleeding Academic Research Consortium type ≥3b bleeding, major vascular complications and all ischemic endpoints. Adjusted outcomes were analyzed using logistic regression methods. Of the study population, 41.4% (n = 332) patients had baseline or new-onset AF within 30 days of TAVR, whereas 58.6% (n = 470) had no AF. Patients with AF had greater prevalence of renal dysfunction, lower left ventricular ejection fraction, and higher euroSCORE I compared with their counterparts without AF. Among AF and no-AF patients, there were no significant baseline differences between bivalirudin and UFH groups. At 30 days the incidence of death (6.0 vs. 4.5%, P = 0.324) and stroke (3.9 vs. 2.6%, P = 0.274) was similar in AF vs. no-AF patients. However, new-onset AF (n = 38) was associated with significantly greater crude risk of 30-day stroke compared with no AF (HR 4.49, 95% CI 1.37-14.67). Regardless of AF status, there were no differences in 30-day death (P-int = 0.652) or stroke (P-int = 0.066) by anticoagulation type. Prior or new-onset AF is noted in more than one-third of patients undergoing transfemoral TAVR. Despite greater baseline comorbidities than non-AF patients, AF was not associated with significantly higher risk of adjusted 30-day outcomes. In the BRAVO 3 trial, early outcomes were similar regardless of anticoagulant strategy in each group. © 2017 Wiley Periodicals, Inc.

Quantitative In Vitro Assessment of Liposome Stability and Drug Transfer Employing Asymmetrical Flow Field-Flow Fractionation (AF4).

PubMed

Holzschuh, Stephan; Kaeß, Kathrin; Fahr, Alfred; Decker, Christiane

2016-04-01

In the present study we introduce an efficient approach for a size-based separation of liposomes from plasma proteins employing AF4. We investigated vesicle stability and release behavior of the strongly lipophilic drug temoporfin from liposomes in human plasma for various incubation times at 37°C. We used the radioactive tracer cholesteryl oleyl ether (COE) or dipalmitoyl-phosphocholine (DPPC) as lipid markers and (14)C-labeled temoporfin. First, both lipid labels were examined for their suitability as liposome markers. Furthermore, the influence of plasma origin on liposome stability and drug transfer was investigated. The effect of membrane fluidity and PEGylation on vesicle stability and drug release characteristics was also analyzed. Surprisingly, we observed an enzymatic transfer of (3)H-COE to lipoproteins due to the cholesterol ester transfer protein (CETP) in human plasma in dependence on membrane rigidity and were able to inhibit this transfer by plasma preincubation with the CETP inhibitor torcetrapib. This effect was not seen when liposomes were incubated in rat plasma. DPPC labels suffered from hydrolysis effects during preparation and/or storage. Fluid liposomes were less stable in human plasma than their PEGylated analogues or a rigid formulation. In contrast, the transfer of the incorporated drug to lipoproteins was higher for the rigid formulations. The observed effects render COE-labels questionable for in vivo studies using CEPT-rich species. Here, choline labelled (14)C-DPPC was found to be the most promising alternative. Bilayer composition has a high influence on stability and drug release of a liposomal formulation in human plasma.

Characterisation and Antioxidant Activity of Crude Extract and Polyphenolic Rich Fractions from C. incanus Leaves

PubMed Central

Gori, Antonella; Ferrini, Francesco; Marzano, Maria Cristina; Tattini, Massimiliano; Centritto, Mauro; Baratto, Maria Camilla; Pogni, Rebecca; Brunetti, Cecilia

2016-01-01

Cistus incanus (Cistaceae) is a Mediterranean evergreen shrub. Cistus incanus herbal teas have been used as a general remedy in traditional medicine since ancient times. Recent studies on the antioxidant properties of its aqueous extracts have indicated polyphenols to be the most active compounds. However, a whole chemical characterisation of polyphenolic compounds in leaves of Cistus incanus (C. incanus) is still lacking. Moreover, limited data is available on the contribution of different polyphenolic compounds towards the total antioxidant capacity of its extracts. The purpose of this study was to characterise the major polyphenolic compounds present in a crude ethanolic leaf extract (CEE) of C. incanus and develop a method for their fractionation. Superoxide anion, hydroxyl and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assays were also performed to evaluate the antioxidant properties of the obtained fractions. Three different polyphenolic enriched extracts, namely EAC (Ethyl Acetate Fraction), AF1 and AF2 (Aqueos Fractions), were obtained from CEE. Our results indicated that the EAC, enriched in flavonols, exhibited a higher antiradical activity compared to the tannin enriched fractions (AF1 and AF2). These findings provide new perspectives for the use of the EAC as a source of antioxidant compounds with potential uses in pharmaceutical preparations. PMID:27548139

Asymmetrical flow field-flow fractionation coupled with multi-angle laser light scattering for stability comparison of virus-like particles in different solution environments.

PubMed

Chen, Yi; Zhang, Yan; Zhou, Yuefang; Luo, Jian; Su, Zhiguo

2016-06-08

The stabilities of two commercially available virus like particles, CHO-HBsAg expressed by Chinese hamster ovary (CHO) cells and Hans-HBsAg expressed by Hansenula polymorpha (Hans), were compared using AF4-MALLS under different treatment processes. The initial molecular weight and hydrodynamic diameter of CHO-HBsAg measured with AF4-MALLS were 4727kDa and 29.4nm, while those of Hans-HBsAg were 3039kDa and 22.8nm respectively. In salt solution of 2M ammonium sulfate, the molecular weight and size of CHO-HBsAg had little change, and its antigenicity remained 95%, while those of Hans-HBsAg changed greatly, resulting in aggregation and 75% antigenicity loss. In freeze-thaw operations, Hans-HBsAg aggregated heavily. Most of the aggregates precipitated and the rest soluble aggregates reached 10(5)-10(6)kDa in molecular weight. The antigenicity of Hans-HBsAg decreased to 26.9% after five freeze-thaw cycles. For CHO-HBsAg, there was no obvious aggregation in freeze-thaw, and the antigenicity retained above 98%. In heating process, Hans-HBsAg gradually aggregated to large particles with temperature and the antigenicity decreased to 10% when the temperature reached 80°C. In contrast, CHO-HBsAg would not aggregate with temperature, remained 92% antigenicity at 80°C. The study demonstrated that CHO-HBsAg appeared to be a superior vaccine antigen in term of particle stability and constant antigenicity, which are important in production, transportation and storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aggregation behavior of fullerenes in aqueous solutions: a capillary electrophoresis and asymmetric flow field-flow fractionation study.

PubMed

Astefanei, Alina; Núñez, Oscar; Galceran, Maria Teresa; Kok, Wim Th; Schoenmakers, Peter J

2015-10-01

In this work, the electrophoretic behavior of hydrophobic fullerenes [buckminsterfullerene (C60), C70, and N-methyl-fulleropyrrolidine (C60-pyrr)] and water-soluble fullerenes [fullerol (C60(OH)24); polyhydroxy small gap fullerene, hydrated (C120(OH)30); C60 pyrrolidine tris acid (C60-pyrr tris acid); and (1,2-methanofullerene C60)-61-carboxylic acid (C60CHCOOH)] in micellar electrokinetic capillary chromatography (MECC) was evaluated. The aggregation behavior of the water-soluble compounds in MECC at different buffer and sodium dodecyl sulfate (SDS) concentrations and pH values of the background electrolyte (BGE) was studied by monitoring the changes observed in the electrophoretic pattern of the peaks. Broad and distorted peaks that can be attributed to fullerene aggregation were obtained in MECC which became narrower and more symmetric by working at low buffer and SDS concentrations (below the critical micelle concentration, capillary zone electrophoresis (CZE) conditions). For the characterization of the suspected aggregates formed (size and shape), asymmetrical flow field-flow fractionation (AF4) and transmission electron microscopy (TEM) were used. The results showed that the increase in the buffer concentration promoted the aggregation of the particles, while the presence of SDS micelles revealed multiple peaks corresponding to particles of different aggregation degrees. Furthermore, MECC has been applied for the first time for the analysis of C60 in two different cosmetic products (i.e., anti-aging serum and facial mask).

Combining gas-phase electrophoretic mobility molecular analysis (GEMMA), light scattering, field flow fractionation and cryo electron microscopy in a multidimensional approach to characterize liposomal carrier vesicles

PubMed Central

Gondikas, Andreas; von der Kammer, Frank; Hofmann, Thilo; Marchetti-Deschmann, Martina; Allmaier, Günter; Marko-Varga, György; Andersson, Roland

2017-01-01

For drug delivery, characterization of liposomes regarding size, particle number concentrations, occurrence of low-sized liposome artefacts and drug encapsulation are of importance to understand their pharmacodynamic properties. In our study, we aimed to demonstrate the applicability of nano Electrospray Gas-Phase Electrophoretic Mobility Molecular Analyser (nES GEMMA) as a suitable technique for analyzing these parameters. We measured number-based particle concentrations, identified differences in size between nominally identical liposomal samples, and detected the presence of low-diameter material which yielded bimodal particle size distributions. Subsequently, we compared these findings to dynamic light scattering (DLS) data and results from light scattering experiments coupled to Asymmetric Flow-Field Flow Fractionation (AF4), the latter improving the detectability of smaller particles in polydisperse samples due to a size separation step prior detection. However, the bimodal size distribution could not be detected due to method inherent limitations. In contrast, cryo transmission electron microscopy corroborated nES GEMMA results. Hence, gas-phase electrophoresis proved to be a versatile tool for liposome characterization as it could analyze both vesicle size and size distribution. Finally, a correlation of nES GEMMA results with cell viability experiments was carried out to demonstrate the importance of liposome batch-to-batch control as low-sized sample components possibly impact cell viability. PMID:27639623

Left atrial appendage segmentation and quantitative assisted diagnosis of atrial fibrillation based on fusion of temporal-spatial information.

PubMed

Jin, Cheng; Feng, Jianjiang; Wang, Lei; Yu, Heng; Liu, Jiang; Lu, Jiwen; Zhou, Jie

2018-05-01

In this paper, we present an approach for left atrial appendage (LAA) multi-phase fast segmentation and quantitative assisted diagnosis of atrial fibrillation (AF) based on 4D-CT data. We take full advantage of the temporal dimension information to segment the living, flailed LAA based on a parametric max-flow method and graph-cut approach to build 3-D model of each phase. To assist the diagnosis of AF, we calculate the volumes of 3-D models, and then generate a "volume-phase" curve to calculate the important dynamic metrics: ejection fraction, filling flux, and emptying flux of the LAA's blood by volume. This approach demonstrates more precise results than the conventional approaches that calculate metrics by area, and allows for the quick analysis of LAA-volume pattern changes of in a cardiac cycle. It may also provide insight into the individual differences in the lesions of the LAA. Furthermore, we apply support vector machines (SVMs) to achieve a quantitative auto-diagnosis of the AF by exploiting seven features from volume change ratios of the LAA, and perform multivariate logistic regression analysis for the risk of LAA thrombosis. The 100 cases utilized in this research were taken from the Philips 256-iCT. The experimental results demonstrate that our approach can construct the 3-D LAA geometries robustly compared to manual annotations, and reasonably infer that the LAA undergoes filling, emptying and re-filling, re-emptying in a cardiac cycle. This research provides a potential for exploring various physiological functions of the LAA and quantitatively estimating the risk of stroke in patients with AF. Copyright © 2018 Elsevier Ltd. All rights reserved.

Right Ventricular Structure and Function Are Associated With Incident Atrial Fibrillation: MESA-RV Study (Multi-Ethnic Study of Atherosclerosis-Right Ventricle).

PubMed

Chatterjee, Neal A; Shah, Ravi V; Murthy, Venkatesh L; Praestgaard, Amy; Shah, Sanjiv J; Ventetuolo, Corey E; Barr, R Graham; Kronmal, Richard; Lima, Joao A C; Bluemke, David A; Jerosch-Herold, Michael; Alonso, Alvaro; Kawut, Steven M

2017-01-01

Right ventricular (RV) morphology has been associated with drivers of atrial fibrillation (AF) risk, including left ventricular and pulmonary pathology, systemic inflammation, and neurohormonal activation. The aim of this study was to investigate the association between RV morphology and risk of incident AF. We interpreted cardiac magnetic resonance imaging in 4204 participants free of clinical cardiovascular disease in the MESA (Multi-Ethnic Study of Atherosclerosis). Incident AF was determined using hospital discharge records, study electrocardiograms, and Medicare claims data. The study sample (n=3819) was 61±10 years old and 47% male with 47.2% current/former smokers. After adjustment for demographics and clinical factors, including incident heart failure, higher RV ejection fraction (hazard ratio, 1.16 per SD; 95% confidence interval, 1.03-1.32; P=0.02) and greater RV mass (hazard ratio, 1.25 per SD; 95% confidence interval, 1.08-1.44; P=0.002) were significantly associated with incident AF. After additional adjustment for the respective left ventricular parameter, higher RV ejection fraction remained significantly associated with incident AF (hazard ratio, 1.15 per SD; 95% confidence interval, 1.01-1.32; P=0.04), whereas the association was attenuated for RV mass (hazard ratio, 1.16 per SD; 95% confidence interval, 0.99-1.35; P=0.07). In a subset of patients with available spirometry (n=2540), higher RV ejection fraction and mass remained significantly associated with incident AF after additional adjustment for lung function (P=0.02 for both). Higher RV ejection fraction and greater RV mass were associated with an increased risk of AF in a multiethnic population free of clinical cardiovascular disease at baseline. © 2017 American Heart Association, Inc.

A Specific Antibody to Neuropeptide AF1 (KNEFIRFamide) Recognizes a Small Subset of Neurons in Ascaris suum: Differences from Caenorhabditis elegans

PubMed Central

Sithigorngul, Paisarn; Jarecki, Jessica L.; Stretton, Antony O.W.

2016-01-01

A monoclonal antibody, AF1-003, highly specific to the Ascaris suum neuropeptide AF1 (KNEFIRFamide), was generated. This antibody binds strongly to AF1 and extremely weakly to other peptides with C-terminal FIR-Famide: AF5 (SGKPTFIRFamide), AF6 (FIRFamide), and AF7 (AGPRFIRFamide). It does not recognize 35 other AF (A. suum FMRFamide-like) peptides at the highest concentration tested, nor does it recognize FMRFamide. When crude peptide extracts of A. suum are fractionated by two-step HPLC, the only fractions recognized by AF1-003 are those comigrating with synthetic AF1. By immunocytochemistry, antibody AF1-003 recognizes a small subset of the 298 neurons of A. suum: these include the paired URX and RIP neurons, two pairs of lateral ganglion neurons in the head, and the unpaired PQR and PDA or -B tail neurons that send processes to the head along the dorsal and ventral nerve cords, respectively. AF1 immunoreactivity is also seen in three pairs of pharyngeal neurons. Mass spectroscopy (MS) shows the presence of AF1 in the head, pharynx, and dorsal and ventral nerve cords. In A. suum, the neurons that contain AF1 show little overlap with neurons that express green fluorescent protein constructs targeting the flp-8 gene, which encodes AF1 in Caenorhabditis elegans (Kim and Li [2004] J. Comp. Neurol. 475:540– 550); the URX neurons express AF1 in both species, but, in C. elegans, flp-8 expression was not detected in RIP, PQR, and PDA or -B or in the pharynx. Other, less specific monoclonal antibodies recognize AF1, as well as other peptides to differing degrees; these antibodies are useful reagents for determination of neuronal morphology. PMID:21452223

KRAS, NRAS and BRAF mutations detected by next generation sequencing, and differential clinical outcome in metastatic colorectal cancer (MCRC) patients treated with first line FIr-B/FOx adding bevacizumab (BEV) to triplet chemotherapy.

PubMed

Bruera, Gemma; Pepe, Francesco; Malapelle, Umberto; Pisapia, Pasquale; Mas, Antonella Dal; Di Giacomo, Daniela; Calvisi, Giuseppe; Troncone, Giancarlo; Ricevuto, Enrico

2018-05-29

First line triplet chemotherapy/BEV significantly improved clinical outcome of MCRC. KRAS/NRAS/BRAF mutations were evaluated by next generation sequencing (NGS) in MCRC patients treated with first line FIr-B/FOx. KRAS exons 2-4 ( KRAS 2-4 ), NRAS 2-4 , BRAF 15 were evaluated in 67 tumours by ION Torrent platform. Mutation detection criteria: >500×sequence coverage (cov); >1% mutant allelic fraction (AF). Clinical outcomes were compared by log-rank. In 63 samples, KRAS 2-4 / NRAS 2-4 / BRAF 15 wild-type (wt) were 14 (22.2%), mutant (mut) 49 (77.8%): KRAS 2-4 42 (66.7%); NRAS 2-4 11 (16.4%); BRAF 15 5 (7.5%). Sixty mutations were detected, range 1-3 mut: 43 (71.7%) >1000×cov/>5% AF; 9 (15%) >500×cov/>5% AF; 8 (13.3%) >1000×cov/<5% AF. Mut distribution in KRAS 2-4 / NRAS 2-4 / BRAF 15 : 40 (63.5%) >1000×cov/>5% AF, 8 (12.7%) >500×cov/>5% AF, 1 (1.6%) >1000×cov/<5% AF; BRAF 15 1 (1.5%) >500×cov/>5% AF, 4 (6%) >1000×cov/<5% AF. Prevalence of ≥2 mut samples: KRAS 2-4 / NRAS 2-4 / BRAF 15 8 (12.7%); KRAS 2-4 7 (11.1%); NRAS 2-4 5 (7.5%). BRAF 15 mutant were all ≥2 mut (7.5%), atypical and associated to KRAS and/or NRAS mut: c.1405 G>A; c.1406 G>C; c.1756 G>A, 2 samples; c.1796 C>T. At 21 months (m) follow-up, clinical outcome wt compared to mut was not significantly different: in KRAS 2-4 / NRAS 2-4 / BRAF 15 , progression-free survival (PFS) 18/12 m, overall survival (OS) 28/22 m; 1/≥2 mutations, PFS 14/11, OS 37/22. PFS was trendy worse in RAS / BRAF wt vs ≥2 mut genes ( P 0.059). Most MCRC harboured KRAS 2-4 / NRAS 2-4 / BRAF 15 mutations by NGS, often multiple and affecting few tumoral clones; 22% were triple wt. Clinical outcome is not significantly affected by KRAS 2-4 / NRAS 2-4 / BRAF 15 genotype, trendy different in triple wt, compared with KRAS 2-4 / NRAS 2-4 / BRAF 15 ≥2 mut.

Stroke etiology and collaterals: atheroembolic strokes have greater collateral recruitment than cardioembolic strokes.

PubMed

Rebello, L C; Bouslama, M; Haussen, D C; Grossberg, J A; Dehkharghani, S; Anderson, A; Belagaje, S R; Bianchi, N A; Grigoryan, M; Frankel, M R; Nogueira, R G

2017-06-01

Chronic hypoperfusion from athero-stenotic lesions is thought to lead to better collateral recruitment compared to cardioembolic strokes. It was sought to compare collateral flow in stroke patients with atrial fibrillation (AF) versus stroke patients with cervical atherosclerotic steno-occlusive disease (CASOD). This was a retrospective review of a prospectively collected endovascular database. Patients with (i) anterior circulation large vessel occlusion stroke, (ii) pre-treatment computed tomography angiography (CTA) and (iii) intracranial embolism from AF or CASOD were included. CTA collateral patterns were evaluated and categorized into two groups: absent/poor collaterals (CTA collateral score 0-1) versus moderate/good collaterals (CTA collateral score 2-4). CT perfusion was also utilized for baseline core volume and evaluation of infarct growth. A total of 122 patients fitted the inclusion criteria, of whom 88 (72%) had AF and 34 (27%) CASOD. Patients with AF were older (P < 0.01) and less often males or smokers (P = 0.04 and P < 0.01 respectively). Baseline National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were comparable between groups. Collateral scores were lower in the AF group (P = 0.01) with patients having poor collaterals in 28% of cases versus 9% in the CASOD group (P = 0.03). Mortality rates (20% vs. 0%; P = 0.02) were higher in the AF patients whilst rates of any parenchymal hemorrhage (6% vs. 26%; P < 0.01) were higher in the CASOD group. On multivariable analysis, CASOD was an independent predictor of moderate/good collaterals (odds ratio 4.70; 95% confidence interval 1.17-18.79; P = 0.03). Atheroembolic strokes seem to be associated with better collateral flow compared to cardioembolic strokes. This may in part explain the worse outcomes of AF-related stroke. © 2017 EAN.

Formation of polyelectrolyte complexes with diethylaminoethyl dextran: charge ratio and molar mass effect.

PubMed

Le Cerf, Didier; Pepin, Anne Sophie; Niang, Pape Momar; Cristea, Mariana; Karakasyan-Dia, Carole; Picton, Luc

2014-11-26

The formation of polyelectrolyte complexes (PECs) between carboxymethyl pullulan and DEAE Dextran, was investigated, in dilute solution, with emphasis on the effect of charge density (molar ratio or pH) and molar masses. Electrophoretic mobility measurements have evidenced that insoluble PECs (neutral electrophoretic mobility) occurs for charge ratio between 0.6 (excess of polycation) and 1 (stoichiometry usual value) according to the pH. This atypical result is explained by the inaccessibility of some permanent cationic charge when screened by pH dependant cationic ones (due to the Hoffman alkylation). Isothermal titration calorimetry (ITC) indicates an endothermic formation of PEC with a binding constant around 10(5) L mol(-1). Finally asymmetrical flow field flow fractionation coupled on line with static multi angle light scattering (AF4/MALS) evidences soluble PECs with very large average molar masses and size around 100 nm, in agreement with scrambled eggs multi-association between various polyelectrolyte chains. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pulmonary vein activity does not predict the outcome of catheter ablation for persistent atrial fibrillation: A long-term multicenter prospective study.

PubMed

Prabhu, Sandeep; Kalla, Manish; Peck, Kah Y; Voskoboinik, Aleksandr; McLellan, Alex J A; Pathik, Bupesh; Nalliah, Chrishan J; Wong, Geoff R; Sugumar, Hariharan; Azzopardi, Sonia M; Lee, Geoffrey; Ling, Liang-Han; Kalman, Jonathan M; Kistler, Peter M

2018-03-02

Pulmonary vein (PV) isolation (PVI) remains the cornerstone of catheter ablation (CA) in persistent atrial fibrillation (AF) (PeAF), although less successful than for paroxysmal AF. Whether rapid or fibrillatory (PV AF) PV firing may identify patients with PeAF more likely to benefit from a PV-based ablation approach is unclear. The purpose of this study was to determine the relationship between the PV cycle length (PVCL) and the PV AF outcome after CA. Before ablation, the multipolar catheter was placed in each PV and the left atrial appendage (LAA) for 100 consecutive cycles. The presence of PV AF, the average PVCL of all 4 veins (PV 4VAverage ), the fastest vein average (PV FVAverage ), the fastest cycle length (PV Fast ) both individually and relative to the average LAA cycle length were calculated. The ablation strategy included PVI and posterior wall isolation with a minimum of 12 months follow-up. A total of 123 patients underwent CA (age 62 ± 9.1 years; CHA 2 DS 2 -VASC score 1.6 ± 1.1; left ventricular ejection fraction 48% ± 13%; left atrial area 31 ± 8.7 cm 2 ; AF duration 16 ± 17 months). PVI was achieved in 100% of patients. Multiprocedure success (MPS; freedom from AF/atrial tachycardia episodes lasting >30 seconds) was achieved in 76% of patients at 24 ± 8.1 months of follow-up after 1.2 ± 0.4 procedures. PV activity was not associated with MPS either absolutely (PV 4VAverage [MPS no vs yes: 178 ± 27 ms vs 177 ± 24 ms; P = .92], PV FVAverage [P = .69], or PV Fast [P = .82]) or as a ratio relative to the LAA cycle length (PV 4VAverage /LAA 1.05 ± 0.11 vs 1.06 ± 0.21; P = .87). The presence of PV AF (31% vs 47%; P = .13) did not predict MPS. The rapidity of PV firing or presence of fibrillation within the PV was not predictive of outcome of CA for PeAF. PV activity does not identify patients most likely to benefit from a PV-based ablation strategy. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Prospective study of atrial fibrillation termination during ablation guided by automated detection of fractionated electrograms.

PubMed

Porter, Michael; Spear, William; Akar, Joseph G; Helms, Ray; Brysiewicz, Neil; Santucci, Peter; Wilber, David J

2008-06-01

Complex fractionated atrial electrograms (CFAE) may identify critical sites for perpetuation of atrial fibrillation (AF) and provide useful targets for ablation. Current assessment of CFAE is subjective; automated detection algorithms may improve reproducibility, but their utility in guiding ablation has not been tested. In 67 patients presenting for initial AF ablation (42 paroxysmal, 25 persistent), LA and CS mapping were performed during induced or spontaneous AF. CFAE were identified by an online automated computer algorithm and displayed on electroanatomical maps. A mean of 28 +/- 18 sites/patient were identified (20 +/- 13% of mapped sites), and were more frequent during persistent AF. CFAE occurred most commonly within the CS, on the atrial septum, and around the pulmonary veins. Ablation initially targeting CFAE terminated AF in 88% of paroxysmal AF, but only 20% of persistent AF (P < 0.001). Subsequently, additional ablation was performed in all patients (PV isolation for paroxysmal AF, PV isolation + mitral and roof lines for persistent AF). Minimum follow-up was 1 year. One-year freedom from recurrent atrial arrhythmias without antiarrhythmic drug therapy after a single procedure was 90% for paroxysmal AF, and 68% for persistent AF. Ablation guided by automated detection of CFAE proved feasible, and was associated with a high AF termination rate in paroxysmal, but not persistent AF. As an adjunct to conventional techniques, it was associated with excellent long-term single procedure outcomes in both groups. Criteria for identifying optimal CFAE sites for ablation, and selection of patients most likely to benefit, require additional study.

The lateralized arcuate fasciculus in developmental pitch disorders among mandarin amusics: left for speech and right for music.

PubMed

Chen, Xizhuo; Zhao, Yanxin; Zhong, Suyu; Cui, Zaixu; Li, Jiaqi; Gong, Gaolang; Dong, Qi; Nan, Yun

2018-05-01

The arcuate fasciculus (AF) is a neural fiber tract that is critical to speech and music development. Although the predominant role of the left AF in speech development is relatively clear, how the AF engages in music development is not understood. Congenital amusia is a special neurodevelopmental condition, which not only affects musical pitch but also speech tone processing. Using diffusion tensor tractography, we aimed at understanding the role of AF in music and speech processing by examining the neural connectivity characteristics of the bilateral AF among thirty Mandarin amusics. Compared to age- and intelligence quotient (IQ)-matched controls, amusics demonstrated increased connectivity as reflected by the increased fractional anisotropy in the right posterior AF but decreased connectivity as reflected by the decreased volume in the right anterior AF. Moreover, greater fractional anisotropy in the left direct AF was correlated with worse performance in speech tone perception among amusics. This study is the first to examine the neural connectivity of AF in the neurodevelopmental condition of amusia as a result of disrupted music pitch and speech tone processing. We found abnormal white matter structural connectivity in the right AF for the amusic individuals. Moreover, we demonstrated that the white matter microstructural properties of the left direct AF is modulated by lexical tone deficits among the amusic individuals. These data support the notion of distinctive pitch processing systems between music and speech.

Influence of atrial fibrillation on the mortality of patients with heart failure with preserved ejection fraction.

PubMed

Franco, Jonathan; Formiga, Francesc; Cepeda, Jose; Llacer, Pau; Arévalo-Lorido, Juan; Cerqueiro, Jose; González-Franco, Alvaro; Epelde, Francesc; Manzano, Luis; Montero Pérez-Barquero, Manuel

2018-05-23

The impact of atrial fibrillation (AF) on the prognosis of heart failure with preserved ejection fraction (HFpEF) is still the subject of debate. We analysed the influence of AF on the prognosis on mortality and readmission in patients with HFpEF. Prospective observational study in 1,971 patients with HFpEF, who were admitted for acute heart failure. Patients were divided into 2 groups according to the presence or absence of AF. We analysed mortality, readmissions and combined mortality/readmissions at one year follow-up. A total of 1,177 (59%) patients had AF, mean age 80.3 (7.8) years and 1,233 (63%) were women. Patients with HFpEF and AF were older, female, greater valvular aetiology and lower comorbidity measured by the Charlson index. At the one year follow-up, 430 (22%) patients had died and 840 (43%) had been readmitted. In the 2 groups analysed, there was no difference in all-cause mortality (22 vs. 21%; P=.739, AF vs. no-AF, respectively) or cardiovascular causes (9.6 vs. 8.2%; P=.739, AF vs. no-AF, respectively). In the multivariable analysis, factors associated with higher mortality were: age, male, valvular aetiology, uric acid, and comorbidity. In the analysis of the subgroup with HFpEF with AF, the presence of chronic AF compared to de novo AF was associated with higher mortality (HR 1,716; 95% CI 1,099-2,681; P=.018). In patients with HFpEF, the presence of AF is frequent. During the one-year follow-up, the presence of AF does not influence mortality or readmissions in patients with HFpEF. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation

PubMed Central

Gasparini, Maurizio; Auricchio, Angelo; Metra, Marco; Regoli, François; Fantoni, Cecilia; Lamp, Barbara; Curnis, Antonio; Vogt, Juergen; Klersy, Catherine

2008-01-01

Aims To investigate the effects of cardiac resynchronization therapy (CRT) on survival in heart failure (HF) patients with permanent atrial fibrillation (AF) and the role of atrio-ventricular junction (AVJ) ablation in these patients. Methods and results Data from 1285 consecutive patients implanted with CRT devices are presented: 1042 patients were in sinus rhythm (SR) and 243 (19%) in AF. Rate control in AF was achieved by either ablating the AVJ in 118 patients (AVJ-abl) or prescribing negative chronotropic drugs (AF-Drugs). Compared with SR, patients with AF were significantly older, more likely to be non-ischaemic, with higher ejection fraction, shorter QRS duration, and less often received ICD back-up. During a median follow-up of 34 months, 170/1042 patients in SR and 39/243 in AF died (mortality: 8.4 and 8.9 per 100 person-year, respectively). Adjusted hazard ratios were similar for all-cause and cardiac mortality [0.9 (0.57–1.42), P = 0.64 and 1.00 (0.60–1.66) P = 0.99, respectively]. Among AF patients, only 11/118 AVJ-abl patients died vs. 28/125 AF-Drugs patients (mortality: 4.3 and 15.2 per 100 person-year, respectively, P < 0.001). Adjusted hazard ratios of AVJ-abl vs. AF-Drugs was 0.26 [95% confidence interval (CI) 0.09–0.73, P = 0.010] for all-cause mortality, 0.31 (95% CI 0.10–0.99, P = 0.048) for cardiac mortality, and 0.15 (95% CI 0.03–0.70, P = 0.016) for HF mortality. Conclusion Patients with HF and AF treated with CRT have similar mortality compared with patients in SR. In AF, AVJ ablation in addition to CRT significantly improves overall survival compared with CRT alone, primarily by reducing HF death. PMID:18390869

The combined use of analytical tools for exploring tetanus toxin and tetanus toxoid structures.

PubMed

Bayart, Caroline; Peronin, Sébastien; Jean, Elisa; Paladino, Joseph; Talaga, Philippe; Borgne, Marc Le

2017-06-01

Aldehyde detoxification is a process used to convert toxin into toxoid for vaccine applications. In the case of tetanus toxin (TT), formaldehyde is used to obtain the tetanus toxoid (TTd), which is used either for the tetanus vaccine or as carrier protein in conjugate vaccines. Several studies have already been conducted to better understand the exact mechanism of this detoxification. Those studies led to the identification of a number of formaldehyde-induced modifications on lab scale TTd samples. To obtain greater insights of the changes induced by formaldehyde, we used three industrial TTd batches to identify repeatable modifications in the detoxification process. Our strategy was to combine seven analytical tools to map these changes. Mass spectrometry (MS), colorimetric test and amino acid analysis (AAA) were used to study modifications on amino acids. SDS-PAGE, asymmetric flow field flow fractionation (AF4), fluorescence spectroscopy and circular dichroism (CD) were used to study formaldehyde modifications on the whole protein structure. We identified 41 formaldehyde-induced modifications across the 1315 amino acid primary sequence of TT. Of these, five modifications on lysine residues were repeatable across TTd batches. Changes in protein conformation were also observed using SDS-PAGE, AF4 and CD techniques. Each analytical tool brought a piece of information regarding formaldehyde induced-modifications, and all together, these methods provided a comprehensive overview of the structural changes that occurred with detoxification. These results could be the first step leading to site-directed TT mutagenesis studies that may enable the production of a non-toxic equivalent protein without using formaldehyde. Copyright © 2017 Elsevier B.V. All rights reserved.

Vitamin D and new-onset atrial fibrillation: A meta-analysis of randomized controlled trials.

PubMed

Huang, Wei-Ling; Yang, Jun; Yang, Jian; Wang, Hui-Bo; Yang, Chao-Jun; Yang, Ying

2017-11-14

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which affects 1.5% to 2% of the general population. More than six million Europeans suffer from AF. To research vitamin D levels in the prevention of new-onset atrial fibrillation (AF), we conducted a systematic review of randomized controlled trials (RCTs). We focused on the vitamin D levels in the prevention of new-onset AF. The outcomes assessed were vitamin D levels, left ventricular ejection fraction (LVEF), and left atrium diameter. Six RCTs ultimately met the inclusion criteria in the meta-analysis. The outcomes of Vitamin D levels (MD = -4.27, 95% CI = -5.20 to-3.34, P = 0.30) in the new-onset AF showed no significant difference. The left atrium diameter (MD = 1.96, 95% CI = 1.48 to 2.60, P < 0.01) between new-onset AF and LVEF (MD = -0.92, 95% CI = -1.59 to -0.26, P < 0.01) showed significant difference. Our study shows that circulating vitamin D levels may not play a major role in the development of new-onset AF. Copyright © 2017 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Efficient protocol for isolation and purification of different soyasaponins from soy hypocotyls.

PubMed

Zhao, Dayun; Yan, Mingxia; Huang, Yuai; Sun, Xiangjun

2012-12-01

Soyasaponins are naturally occurring triterpenoid glycosides associated with many biological activities. The aim of the present study was to develop an effective method for isolation and purification of differently glycosylated, acetylated, and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP)-conjugated soyasaponins from soy hypocotyls. Both gel filtration using Sephadex LH-20 chromatography (Amersham Pharmacia Biotech AB; elution phase: methanol, flow rate: 3.0 mL/min, sample loading: 60 mg) and high-speed countercurrent chromatography (stationary phase: n-butanol-acetic acid (5.0%, v/v), mobile phase: water flow rate: 3.0 mL/min, sample loading: 100 mg) could effectively fractionate isoflavones and soyasaponins from the crude extract with yield of soyasaponin complexes 20.5 mg and 22.3 mg, respectively. After fractionation, the soyasaponin complexes could be purified further using preparative HPLC to separate individuals. A total of nine soyasaponins, triacetyl soyasaponin Ab (yield 1.55%, HPLC purity >98%), Aa (2.68%, >99%), Ab (18.53%, >98%), Ae (0.85%, >98%), Ba (0.63%, >91%), Af (1.12%, >85%), Bb (3.45%, >98%) and Be (0.59%, >76.8%) were obtained. DDMP-conjugated groups, αg (2.06%, >85%), βg (7.59%, >85%), and γg (0.29%, >85%) that were very labile even in mild conditions, were also collected. The method described here can be used as an effective protocol to separate different soyasaponins occurring in the original sample. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combining gas-phase electrophoretic mobility molecular analysis (GEMMA), light scattering, field flow fractionation and cryo electron microscopy in a multidimensional approach to characterize liposomal carrier vesicles.

PubMed

Urey, Carlos; Weiss, Victor U; Gondikas, Andreas; von der Kammer, Frank; Hofmann, Thilo; Marchetti-Deschmann, Martina; Allmaier, Günter; Marko-Varga, György; Andersson, Roland

2016-11-20

For drug delivery, characterization of liposomes regarding size, particle number concentrations, occurrence of low-sized liposome artefacts and drug encapsulation are of importance to understand their pharmacodynamic properties. In our study, we aimed to demonstrate the applicability of nano Electrospray Gas-Phase Electrophoretic Mobility Molecular Analyser (nES GEMMA) as a suitable technique for analyzing these parameters. We measured number-based particle concentrations, identified differences in size between nominally identical liposomal samples, and detected the presence of low-diameter material which yielded bimodal particle size distributions. Subsequently, we compared these findings to dynamic light scattering (DLS) data and results from light scattering experiments coupled to Asymmetric Flow-Field Flow Fractionation (AF4), the latter improving the detectability of smaller particles in polydisperse samples due to a size separation step prior detection. However, the bimodal size distribution could not be detected due to method inherent limitations. In contrast, cryo transmission electron microscopy corroborated nES GEMMA results. Hence, gas-phase electrophoresis proved to be a versatile tool for liposome characterization as it could analyze both vesicle size and size distribution. Finally, a correlation of nES GEMMA results with cell viability experiments was carried out to demonstrate the importance of liposome batch-to-batch control as low-sized sample components possibly impact cell viability. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

F 16915 prevents heart failure-induced atrial fibrillation: a promising new drug as upstream therapy.

PubMed

Le Grand, Bruno; Letienne, Robert; Dupont-Passelaigue, Elisabeth; Lantoine-Adam, Frédérique; Longo, Frédéric; David-Dufilho, Monique; Michael, Georghia; Nishida, Kunihiro; Catheline, Daniel; Legrand, Philippe; Hatem, Stéphane; Nattel, Stanley

2014-07-01

Atrial fibrillation (AF) is a common complication of heart failure. The aim of the present study was to investigate the effects of a new pure docosahexaenoic acid derivative called F 16915 in experimental models of heart failure-induced atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a dog model of tachypacing-induced congestive heart failure and (2) in a rat model of heart failure induced by occlusion of left descending coronary artery and 2 months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean duration of AF induced by burst pacing in the dog model (989 ± 111 s in the vehicle group to 79 ± 59 s with F 16915, P < 0.01). This dose of F 16915 also significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle group versus 1/5 with F 16915, P < 0.05). In the rat model, the percentage of shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly restored after 2 months (32.6 ± 7.4 %, n = 9 vs 17.6 ± 3.4 %, n = 9 in the vehicle group, P < 0.01). F 16915 also reduced the de-phosphorylation of connexin43 from atria tissue. The present results show that treatment with F 16915 reduced the heart dilation, resynchronized the gap junction activity, and reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a promising new drug as upstream therapy for the treatment of AF in patients with heart failure.

Implication of left ventricular diastolic dysfunction in cryptogenic ischemic stroke.

PubMed

Seo, Jae-Young; Lee, Kyung Bok; Lee, Jung-Gon; Kim, Ji-Sun; Roh, Hakjae; Ahn, Moo-Young; Park, Byoung Won; Hyon, Min Su

2014-09-01

Left ventricular diastolic dysfunction (LVDD) is a predictor for atrial fibrillation (AF). This study was aimed to investigate whether LVDD in cryptogenic ischemic stroke (CS) could be a clue to stroke mechanism. The clinical and echocardiographic findings of 1589 consecutive patients with acute ischemic stroke or transient ischemic attack between 2004 and 2013 were reviewed. LVDDs among stroke subtypes were graded by transthoracic echocardiography into 4 groups by severity: normal, abnormal relaxation (grade I), pseudonormal (grade II), and restrictive diastolic filling (grade III), whereas severe LVDD was defined as grade III. We classified the lesion pattern of CS into cardioembolism-mimic or non-cardioembolism-mimic and determined whether cardioembolism-mimic lesions were associated with severe LVDD. The fraction of severe LVDD in CS was not different from that of stroke with AF (27.3% versus 37.1%; P=0.173) but was significantly higher than that of stroke without AF (27.3% versus 13.4%; P=0.008). Cardioembolism-mimic CS had more severe LVDD than non-cardioembolism-mimic CS (41.4% versus 11.5%; P=0.013). LVDD of grade II (odds ratio, 4.37; 95% confidence interval, 2.99-6.41) and grade III (odds ratio, 5.60; 95% confidence interval, 3.42-9.17) were independently related to stroke with AF after adjusting covariates. The severe LVDD could be a predictor of stroke with AF, and its frequency was similar between CS and stroke with AF. Cardioembolism-mimic CS had significantly more severe LVDD than non-cardioembolism-mimic CS. LVDD could be helpful to discriminate the stroke mechanism in the patients with acute CS. © 2014 American Heart Association, Inc.

Electrophysiological characteristics of the Marshall bundle in humans

PubMed Central

Han, Seongwook; Joung, Boyoung; Scanavacca, Mauricio; Sosa, Eduardo; Chen, Peng-Sheng; Hwang, Chun

2010-01-01

BACKGROUND Marshall bundles (MBs) are the muscle bundles within the ligament of Marshall. OBJECTIVE This trial sought to the electrophysiological characteristics of the MB and the anatomical connections between MB and left atrium (LA) in patients with persistent atrial fibrillation (AF). METHODS We enrolled 72 patients (male:female 59:13, age 59.9 ± 9.4 years) who underwent MB mapping and ablation for AF. MB mapping was done via an endocardial or epicardial approach during sinus rhythm and AF. RESULTS Recordings were successful in 64 of 72 patients (89%). A single connection was noted in 11 of 64 patients between the MB and the coronary sinus (CS) muscle sleeves. The MB recordings showed distinct MB potentials with a proximal-to-distal activation pattern during sinus rhythm. During AF, organized passive activations and dissociated slow MB ectopic activities were commonly observed in this type of connection. Double connections to both CS and LA around left pulmonary veins were noted in 23 of 64 patients (36%). After the ablation of the distal connection, MB recording showed typical double potentials as in single connection. Multiple connections were noted in 30 of 64 patients (47%). During sinus rhythm, the earliest activation was in the middle of the MB. The activation patterns were irregular and variable in each patient. During AF, rapid and fractionated complex activations were noted in all patients of this group. CONCLUSION We documented 3 different types of MB–LA connections. Rapid and fractionated activations were most commonly observed in the MB that had multiple LA connections. PMID:20188860

Characterization of extractable soil organic matter pools from African Dark Earths (AfDE): A case study in historical biochar and organic waste amendments

NASA Astrophysics Data System (ADS)

Fujiu, Manna; Plante, Alain; Ohno, Tsutomu; Solomon, Dawit; Lehmann, Johannes; Fraser, James; Leach, Melissa; Fairhead, James

2014-05-01

Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils that were formed from the original highly-weathered infertile yellowish to red Oxisols and Ultisols through an extant but hitherto overlooked climate-smart sustainable soil management system that has long been an important feature of the indigenous West African agricultural repertoire. Studies have demonstrated that ADE soils in general have significantly different organic matter properties compared to adjacent non-DE soils, largely attributable to the presence of high concentrations of ash-derived carbon. Quantification and characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) confirmed substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant or relatively stable, but the goal of the current study was to characterize the presumably labile, more rapidly cycling, pools of C in AfDEs through the characterization of hot water- and pyrophosphate-extractable fractions, referred to as HWEOC and PyroC respectively. Extracts were analyzed for carbon content, as well as composition using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FTICR-MS). The amount of extractable C as a proportion of total soil C was relatively low: less than ~0.8% for HWEOC and 2.8% for PyroC. The proportion of HWEOC did not differ (P = 0.18, paired t-test) between the AfDE and the non-AfDE soils, while the proportions of PyroC were significantly larger (P = 0.001) in the AfDE soils compared to the non-AfDE soils. Preliminary analysis of the EEM/PARAFAC data suggests that AfDE samples had a greater fraction of their DOM that was more humic-like than the paired non-AfDE samples, though differences were small. Similarly, FTICR-MS analysis of hot water extracts suggests that differences among the three sites analyzed were larger than between the paired AfDE and non-AfDE extracts. Overall, in spite of substantial differences in the composition of bulk SOM, the extractable fractions appear to be relatively similar between the AfDE and non-AfDE soils.

The prognostic significance of atrial fibrillation in heart failure with preserved ejection function: insights from KaRen, a prospective and multicenter study.

PubMed

Bosseau, Christian; Donal, Erwan; Lund, Lars H; Oger, Emmanuel; Hage, Camilla; Mulak, Geneviève; Daubert, Jean-Claude; Linde, Cecilia

2017-06-01

The prognostic value of atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFPEF) remains controversial. We sought to study the prognostic value of AF in a prospective cohort and to characterize the HFPEF patients with AF. KaRen was a prospective, multicenter, international, observational study intended to characterize HFPEF; 538 patients presenting with an acute decompensated cardiac failure and a left ventricular EF > 45% were included. EKG and echocardiogram performed 4-8 week following the index hospitalization were analyzed in core centers. Clinical and echocardiographic characteristics of patients in sinus rhythm vs. with documented AF at enrolment (decompensated HF), upon their 4-8-week visit (in presumed stable clinical condition) and according to patients' cardiac history, were compared. The primary study endpoint was death from any cause or first hospitalization for decompensated heart failure (HF). A total of 413 patients (32% in AF) were analyzed, with a mean follow-up period of 28 months. The patients were primarily elderly individuals (mean age: 76.2 years), with a slight female predominance and a high prevalence of non-cardiovascular comorbidities. The baseline echocardiographic characteristics and the natriuretic peptide levels were indicative of a more severe heart condition among the patients with AF. However, the patients with AF exhibited a similar survival-free interval compared with the patients in sinus rhythm. In this elderly HFPEF population with a high prevalence of non-cardiovascular comorbidities, the presence of AF was not associated with a worse prognosis despite impaired clinical and echocardiographic features.ClinicalTrials.gov: NCT00774709.

[Determination of cadmium by HG-aFS in soil of virescent zone in Chengdu city].

PubMed

Chen, Yuan; Zeng, Ying; Wu, Hong-ji; Wang, Qin-er

2008-12-01

The different speciations of cadmium in soil samples from Chengdu greenbelt were extracted by Tessier sequential extraction method. The contents of total cadmium and different speciation cadmium were determined using HG-AFS. Under optimization condition of HG-AFS and using 2% HCl as medium, and 30 g x L(-1) KBH4 as reductive reagent, 1 mg x L(-1) Co2+ acting together with 10 g x L(-1) CH4N2S can advance the generating efficiency of cadmium compound. The effects of the coexisting elements in soil on the determination of cadmium can be reduced if certain amount of Na4P2O7, K2SO4 and BaCl2 are added. The linear range is 0-10 mg x L(-1) with r=0.9991 and the detection limit is 0.016 mg x L(-1). The recovery is 97.80%-100.2% with RSD of 1.93%. The analytical method is very sensitive and accurate. The distribution of average percentage of five speciations of cadmium in experimental soil samples is: residual fraction (62.1%) > exchangeable fraction (11.7%) > Fe-Mn oxide-bound (9.71%) > carbonate-bound (4.17%) > organic-bound (3.47%). Although residual fraction is the main speciation of cadmium in soil, the content of exchangeable fraction is relatively high. Thus the bioactivity of cadmium in the research area should be recognized. The concentration of cadmium exceeds the country standard in 19 soil sample, accounting for 86. 4% of all soil samples. The soil from Chengdu greenbelt located in 1st ring road, 2nd ring road and 3rd ring road was polluted to different degree. The relative pollution magnitude of them is: 2nd ring road > 1st ring road > 3rd ring road.

Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

PubMed

Shaikh, Amir Y; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Vasan, Ramachandran S; Hamburg, Naomi M; Magnani, Jared W; Ellinor, Patrick T; Lubitz, Steven A; Mitchell, Gary F; Benjamin, Emelia J; McManus, David D

2016-09-01

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF. © 2016 American Heart Association, Inc.

Patient-specific analysis of blood stasis in the left atrium

NASA Astrophysics Data System (ADS)

Flores, Oscar; Gonzalo, Alejandro; Garcia-Villalba, Manuel; Rossini, Lorenzo; Hsiao, Albert; McVeigh, Elliot; Kahn, Andrew M.; Del Alamo, Juan C.

2016-11-01

Atrial fibrillation (AF) is a common arrhythmia in which the left atrium (LA) beats rapidly and irregularly. Patients with AF are at increased risk of thromboembolic events (TE), particularly stroke. Anticoagulant therapy can reduce the risk of TE in AF, but it can also increase the risks of adverse events such as internal bleeding. The current lack of tools to predict each patient's risk of LA thrombogenesis makes it difficult to decide whether to anticoagulate patients with AF. The aim of this work is to evaluate blood stasis in patient-specific models of the LA, because stasis is a known thrombogenesis risk factor. To achieve our aim, we performed direct numerical simulations of left atrial flow using an immersed boundary solver developed at the UC3M, coupled to a 0D model for the pulmonary circulation. The LA geometry is obtained from time-resolved CT scans and the parameters of the 0D model are found by fitting pulmonary vein flow data obtained by 4D phase contrast MRI. Blood stasis is evaluated from the flow data by computing blood residence time together with other kinematic indices of the velocity field (e.g. strain and kinetic energy). We focus on the flow in the left atrial appendage, including a sensitivity analysis of the effect of the parameters of the 0D model. Funded by the Spanish MECD, the Clinical and Translational Research Institute at UCSD and the American Heart Association.

Size distribution of absorbing and fluorescing DOM in Beaufort Sea, Canada Basin

NASA Astrophysics Data System (ADS)

Gao, Zhiyuan; Guéguen, Céline

2017-03-01

The molecular weight (MW) of dissolved organic matter (DOM) is considered as an important factor affecting the bioavailability of organic matter and associated chemical species. Colored DOM (CDOM) MW distribution was determined, for the first time, in the Beaufort Sea (Canada Basin) by asymmetrical flow field-flow fractionation (AF4) coupled with online diode array ultra violet-visible photometer and offline fluorescence detectors. The apparent MW ranged from 1.07 to 1.45 kDa, congruent with previous studies using high performance size exclusion chromatography and tangential flow filtration. Interestingly, a minimum in MW was associated with the Pacific Summer Waters (PSW), while higher MW was associated with the Pacific Winter Waters (PWW). The Arctic Intermediate Waters (AIW) did not show any significant change in MW and fluorescence intensities distribution between stations, suggesting homogeneous DOM composition in deep waters. Three fluorescence components including two humic-like components and one protein-like component were PARAFAC-validated. With the increase of MW, protein-like fluorescence component became more dominant while the majority remained as marine/microbially derived humic-like components. Overall, it is concluded that water mass origin influenced DOM MW distribution in the Arctic Ocean.

Left atrial ejection force predicts the outcome after catheter ablation for paroxysmal atrial fibrillation.

PubMed

Kishima, Hideyuki; Mine, Takanao; Takahashi, Satoshi; Ashida, Kenki; Ishihara, Masaharu; Masuyama, Tohru

2018-02-01

Left atrium (LA) systolic dysfunction is observed in the early stages of atrial fibrillation (AF) prior to LA anatomical change. We investigated whether LA systolic dysfunction predicts recurrent AF after catheter ablation (CA) in patients with paroxysmal AF. We studied 106 patients who underwent CA for paroxysmal AF. LA systolic function was assessed with the LA emptying volume = Maximum LA volume (LAV max ) - Minimum LA volume (LAV min ), LA emptying fraction = [(LAV max - LAV min )/LAV max ] × 100, and LA ejection force calculated with Manning's method [LA ejection force = (0.5 × ρ × mitral valve area × A 2 )], where ρ is the blood density and A is the late-diastolic mitral inflow velocity. Recurrent AF was detected in 35/106 (33%) during 14.6 ± 9.1 months. Univariate analysis revealed reduced LA ejection force, decreased LA emptying fraction, larger LA diameter, and elevated brain natriuretic peptide as significant variables. On multivariate analysis, reduced LA ejection force and larger LA diameter were independently associated with recurrent AF. Moreover, patients with reduced LA ejection force and larger LA diameter had a higher risk of recurrent AF than preserved LA ejection force (log-rank P = 0.0004). Reduced LA ejection force and larger LA diameter were associated with poor outcome after CA for paroxysmal AF, and could be a new index to predict recurrent AF. © 2017 Wiley Periodicals, Inc.

Impacts of ambient temperature on the burden of bacillary dysentery in urban and rural Hefei, China.

PubMed

Cheng, J; Xie, M Y; Zhao, K F; Wu, J J; Xu, Z W; Song, J; Zhao, D S; Li, K S; Wang, X; Yang, H H; Wen, L Y; Su, H; Tong, S L

2017-06-01

Bacillary dysentery continues to be a major health issue in developing countries and ambient temperature is a possible environmental determinant. However, evidence about the risk of bacillary dysentery attributable to ambient temperature under climate change scenarios is scarce. We examined the attributable fraction (AF) of temperature-related bacillary dysentery in urban and rural Hefei, China during 2006-2012 and projected its shifting pattern under climate change scenarios using a distributed lag non-linear model. The risk of bacillary dysentery increased with the temperature rise above a threshold (18·4 °C), and the temperature effects appeared to be acute. The proportion of bacillary dysentery attributable to hot temperatures was 18·74% (95 empirical confidence interval (eCI): 8·36-27·44%). Apparent difference of AF was observed between urban and rural areas, with AF varying from 26·87% (95% eCI 16·21-36·68%) in urban area to -1·90% (95 eCI -25·03 to 16·05%) in rural area. Under the climate change scenarios alone (1-4 °C rise), the AF from extreme hot temperatures (>31·2 °C) would rise greatly accompanied by the relatively stable AF from moderate hot temperatures (18·4-31·2 °C). If climate change proceeds, urban area may be more likely to suffer from rapidly increasing burden of disease from extreme hot temperatures in the absence of effective mitigation and adaptation strategies.

Are left ventricular ejection fraction and left atrial diameter related to atrial fibrillation recurrence after catheter ablation?

PubMed Central

Jin, Xiao; Pan, Jianke; Wu, Huanlin; Xu, Danping

2018-01-01

Abstract Atrial fibrillation (AF), the most common form of arrhythmia, is associated with the prevalence of many common cardiovascular and cerebrovascular diseases. Catheter ablation is considered the first-line therapy for AF; however, AF recurrence is very common after catheter ablation. Studies have been performed to analyze the factors associated with AF recurrence, but none have reached a consistent conclusion on whether left ventricular ejection fraction (LVEF) and left atrial diameter (LA diameter) affect AF recurrence after catheter ablation. The databases PubMed, Embase, and the Cochrane Library were used to search for relevant studies up to September 2017. RevMan 5.3.5 software provided by the Cochrane Collaboration Network was used to conduct this meta-analysis. Thirteen studies involving 2825 patients were included in this meta-analysis. Overall, the results revealed that elevated LA diameter values were significantly associated with AF recurrence in patients after catheter ablation (MD = 2.19, 95% CI: 1.63–2.75, P < .001), while baseline LVEF levels were not significantly positively associated with AF recurrence in patients after catheter ablation (MD = −0.91, 95% CI: −1.18 to 1.67, P = .14). Overall, elevated LA diameter may be associated with AF recurrence after catheter ablation; however, there was no direct relationship between LVEF values and AF recurrence after catheter ablation when baseline LVEF values are normal or mildly decreased. Besides, because of publication bias, further studies should be performed to explore the mechanisms underlying AF recurrence. PMID:29768386

Association of Left Atrial Function and Left Atrial Enhancement in Patients with Atrial Fibrillation: A Cardiac Magnetic Resonance Study

PubMed Central

Habibi, Mohammadali; Lima, Joao A.C.; Khurram, Irfan M.; Zimmerman, Stefan L.; Zipunnikov, Vadim; Fukumoto, Kotaro; Spragg, David; Ashikaga, Hiroshi; Rickard, John; Marine, Joseph E.; Calkins, Hugh; Nazarian, Saman

2015-01-01

Background Atrial fibrillation (AF) is associated with left atrial (LA) structural and functional changes. Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) and feature-tracking are capable of noninvasive quantification of LA fibrosis and myocardial motion, respectively. We sought to examine the association of phasic LA function with LA enhancement in patients with AF. Methods and Results LA structure and function was measured in 90 AF patients (age 61 ± 10 years, 76% male) referred for ablation and 14 healthy volunteers. Peak global longitudinal LA strain (PLAS), LA systolic strain rate (SR-s), and early (SR-ed) and late diastolic (SR-ld) strain rates were measured using cine-CMR images acquired during sinus rhythm. The degree of LGE was quantified. Compared to patients with paroxysmal AF (60% of cohort), those with persistent AF had larger maximum LA volume index (LAVImax, 56 ± 17ml/m2 versus 49 ± 13ml/m2 p=0.036), and increased LGE (27.1± 11.7% versus 36.8 ± 14.8% p<0.001). Aside from LA active emptying fraction, all LA parameters (passive emptying fraction, PLAS, SR-s, SR-ed and SR-ld) were lower in patients with persistent AF (p< 0.05 for all). Healthy volunteers had less LGE and higher LA functional parameters compared to AF patients (p<0.05 for all). In multivariable analysis, increased LGE was associated with lower LA passive emptying fraction, PLAS, SR-s, SR-ed, and SR-ld (p<0.05 for all). Conclusions Increased LA enhancement is associated with decreased LA reservoir, conduit, and booster pump functions. Phasic measurement of LA function using feature-tracking CMR may add important information regarding the physiological importance of LA fibrosis. PMID:25652181

Recharging California's Groundwater: Crop Suitability and Surface Water Availability for Agricultural Groundwater Banking

NASA Astrophysics Data System (ADS)

Dahlke, H. E.; Kocis, T. N.; Brown, A.

2016-12-01

Groundwater banking, the intentional recharge of groundwater from surface water for storage and recovery, is an important conjunctive use strategy for water management in California (CA). A largely unexplored approach to groundwater banking, agricultural groundwater banking (ag-GB), utilizes flood flows and agricultural lands (alfalfa/pasture) for recharging groundwater. Understanding soil suitability for ag-GB, crop health and flooding tolerance, leaching of soil nitrate and salts, the availability of surface water for recharge, and the economic costs and benefits of ag-GB is fundamental to assessing the feasibility of local-scale implementation of ag-GB. The study presented here considers both the availability of excess streamflow (e.g., the magnitude, frequency, timing, and duration of winter flood flow) for ag-GB and the risks and benefits associated with using alfalfa fields as spreading grounds for ag-GB. The availability of surface water for winter (Nov to Apr) ag-GB were estimated based on daily streamflow records for 93 stream gauges within the Central Valley, CA. Analysis focused on high-magnitude (>90thpercentile) flows because most lower flows are likely legally allocated in CA. Results based >50 years of data indicate that an average winter/spring (Nov. - Apr.) in the Sacramento River Basin could provide 7 million acre-feet (AF) (8.6 km3) of water for ag-GB from flows above the 90th percentile. These flows originate from few storm events (5-7 events) and occur on average for 25-30 days between November and April. Wintertime on-farm recharge experiments were conducted on a 9-yr old, 15-acre alfalfa field in the Scott Valley, CA, where 135 AF and 107 AF of water were recharged during the winters of 2015 and 2016, respectively. Biomass data collected indicates that pulsed application of 6-10 ft of water on dormant alfalfa results in minimal yield loss (0.5 ton/acre reduction), short-duration saturated conditions in the root-zone, and high recharge fractions (70-95%) of applied water. Together these results highlight the opportunity and potential benefits for growers and water districts to implement ag-GB as part of the sustainable groundwater management plans.

[Influence of sinus rhythm restoration and maintenance on left ventricle diameter and function in patients with persistent atrial fibrillation--one year follow-up].

PubMed

Kosior, Dariusz A; Szulc, Marcin; Stawicki, Sławomir; Roik, Marek; Rabczenko, Daniel; Opolski, Grzegorz

2005-01-01

Aim of our study was to determine the dynamics of selected echocardiographic parameters after sinus rhythm (SR) restoration and maintenance in pts with persistent nonvalvular atrial fibrillation (AF) during one year follow-up period. Our study population comprised 104 pts (F/M 33/71; mean age 60.4 +/- 7.4) assigned to SR restoration and maintenance with serial antiarrhythmic drug usage, for whom transthoracic echocardiographic (TTE) variables were recorded prior to, 2 and 12 months after cardioversion (CD). Left ventricle diastolic diameter and fractional shortening were variables of interest. SR was presented in 66 (63.5%) pts at one year. There was no significant differences in left ventricle diastolic diameter during the follow up. A significant increase in left ventricular fractional shortening (29.9 +/- 6.9% vs 34.5 +/- 8.9%; p < 0.001) was found in pts assigned to the sinus rhythm restoration according to intention-to-treat analysis. Such trend was noted only in pts who maintained SR during the follow up (29.9 +/- 7.6% vs 35.6 +/- 9.3%; p < 0.001). Among all considered variables only value of left ventricular fractional shortening increased after successful CV of persistent AF in one year follow-up.

Efficacy of catheter ablation of atrial fibrillation beyond HATCH score.

PubMed

Tang, Ri-Bo; Dong, Jian-Zeng; Long, De-Yong; Yu, Rong-Hui; Ning, Man; Jiang, Chen-Xi; Sang, Cai-Hua; Liu, Xiao-Hui; Ma, Chang-Sheng

2012-10-01

HATCH score is an established predictor of progression from paroxysmal to persistent atrial fibrillation (AF). The purpose of this study was to determine if HATCH score could predict recurrence after catheter ablation of AF. The data of 488 consecutive paroxysmal AF patients who underwent an index circumferential pulmonary veins (PV) ablation were retrospectively analyzed. Of these patients, 250 (51.2%) patients had HATCH score = 0, 185 (37.9%) patients had HATCH score = 1, and 53 (10.9%) patients had HATCH score ≥ 2 (28 patients had HATCH score = 2, 23 patients had HATCH score = 3, and 2 patients had HATCH score = 4). The patients with HATCH score ≥ 2 had significantly larger left atrium size, the largest left ventricular end systolic diameter, and the lowest ejection fraction. After a mean follow-up of (823 ± 532) days, the recurrence rates were 36.4%, 37.8% and 28.3% from the HATCH score = 0, HATCH score = 1 to HATCH score ≥ 2 categories (P = 0.498). Univariate analysis revealed that left atrium size, body mass index, and failure of PV isolation were predictors of AF recurrence. After adjustment for body mass index, left atrial size and PV isolation, the HATCH score was not an independent predictor of recurrence (HR = 0.92, 95% confidence interval = 0.76 - 1.12, P = 0.406) in multivariate analysis. HATCH score has no value in prediction of AF recurrence after catheter ablation.

Challenges in the size analysis of a silica nanoparticle mixture as candidate certified reference material

NASA Astrophysics Data System (ADS)

Kestens, Vikram; Roebben, Gert; Herrmann, Jan; Jämting, Åsa; Coleman, Victoria; Minelli, Caterina; Clifford, Charles; De Temmerman, Pieter-Jan; Mast, Jan; Junjie, Liu; Babick, Frank; Cölfen, Helmut; Emons, Hendrik

2016-06-01

A new certified reference material for quality control of nanoparticle size analysis methods has been developed and produced by the Institute for Reference Materials and Measurements of the European Commission's Joint Research Centre. The material, ERM-FD102, consists of an aqueous suspension of a mixture of silica nanoparticle populations of distinct particle size and origin. The characterisation relied on an interlaboratory comparison study in which 30 laboratories of demonstrated competence participated with a variety of techniques for particle size analysis. After scrutinising the received datasets, certified and indicative values for different method-defined equivalent diameters that are specific for dynamic light scattering (DLS), centrifugal liquid sedimentation (CLS), scanning and transmission electron microscopy (SEM and TEM), atomic force microscopy (AFM), particle tracking analysis (PTA) and asymmetrical-flow field-flow fractionation (AF4) were assigned. The value assignment was a particular challenge because metrological concepts were not always interpreted uniformly across all participating laboratories. This paper presents the main elements and results of the ERM-FD102 characterisation study and discusses in particular the key issues of measurand definition and the estimation of measurement uncertainty.

Inverse supercritical fluid extraction as a sample preparation method for the analysis of the nanoparticle content in sunscreen agents.

PubMed

Müller, David; Cattaneo, Stefano; Meier, Florian; Welz, Roland; de Vries, Tjerk; Portugal-Cohen, Meital; Antonio, Diana C; Cascio, Claudia; Calzolai, Luigi; Gilliland, Douglas; de Mello, Andrew

2016-04-01

We demonstrate the use of inverse supercritical carbon dioxide (scCO2) extraction as a novel method of sample preparation for the analysis of complex nanoparticle-containing samples, in our case a model sunscreen agent with titanium dioxide nanoparticles. The sample was prepared for analysis in a simplified process using a lab scale supercritical fluid extraction system. The residual material was easily dispersed in an aqueous solution and analyzed by Asymmetrical Flow Field-Flow Fractionation (AF4) hyphenated with UV- and Multi-Angle Light Scattering detection. The obtained results allowed an unambiguous determination of the presence of nanoparticles within the sample, with almost no background from the matrix itself, and showed that the size distribution of the nanoparticles is essentially maintained. These results are especially relevant in view of recently introduced regulatory requirements concerning the labeling of nanoparticle-containing products. The novel sample preparation method is potentially applicable to commercial sunscreens or other emulsion-based cosmetic products and has important ecological advantages over currently used sample preparation techniques involving organic solvents. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Newcastle Disease Virus Strains AF2240 and V4-UPM on Cytolysis and Apoptosis of Leukemia Cell Lines

PubMed Central

Alabsi, Aied M.; Bakar, Siti Aishah Abu; Ali, Rola; Omar, Abdul Rahman; Bejo, Mohd Hair; Ideris, Aini; Ali, Abdul Manaf

2011-01-01

Newcastle disease virus (NDV) is used as an antineoplastic agent in clinical tumor therapy. It has prompted much interest as an anticancer agent because it can replicate up to 10,000 times better in human cancer cells than in most normal cells. This study was carried out to determine the oncolytic potential of NDV strain AF2240 and V4-UPM on WEHI-3B leukemia cell line. Results from MTT cytotoxicity assay showed that the CD50 values for both strains were 2 and 8 HAU for AF2240 and V4-UPM, respectively. In addition, bromodeoxyuridine (BrdU) and trypan blue dye exclusion assays showed inhibition in cell proliferation after different periods. Increase in the cellular level of caspase-3 and detection of DNA laddering using agarose gel electrophoresis on treated cells with NDV confirmed that the mode of cell death was apoptosis. In addition, flow-cytometry analysis of cellular DNA content showed that the virus caused an increase in the sub-G1 region (apoptosis peaks). In conclusion, NDV strains AF2240 and V4-UPM caused cytolytic effects against WEHI-3B leukemic cell line. PMID:22272097

Lifestyle Therapy for the Management of Atrial Fibrillation.

PubMed

Abdul-Aziz, Ahmad A; Altawil, Mahmoud; Lyon, Amanda; MacEachern, Mark; Richardson, Caroline R; Rubenfire, Melvyn; Pelosi, Frank; Jackson, Elizabeth A

2018-05-01

Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of morbidity and mortality. There is evidence that lifestyle interventions may serve as complementary treatments to reduce AF burden. The objective of this review was to summarize the efficacy of lifestyle interventions for the management of AF. Studies which included patients with systolic heart failure (ejection fraction ≤40%), and those limited to an examination of vigorous physical activity were excluded from our search. Studies were identified through a search of the following databases: MEDLINE, EMBASE, CINAHIL, and PubMed, run from inception through August 2016. All studies were graded for quality using the Oxford Centre for Evidence-based Medicine recommendations. Meta-analyses of the studies were not performed due to the heterogeneity of the studies. From a total of 1,811 publications, 10 articles were identified and included. Selected publications included 1 study on yoga, 2 studies on acupuncture, 3 studies that examined weight loss programs, and 4 studies that evaluated the impact of moderate physical activity. Yoga was associated with less symptomatic AF episodes and improved quality of life. Acupuncture was associated with reduced AF occurrence in patients with persistent and paroxysmal AF. Weight loss was associated with a significant reduction AF burden and symptoms. Moderate exercise resulted in greater arrhythmia free survival and a mean reduction in AF burden. In conclusion, evidence exists to suggest that yoga, weight loss, and moderate exercise are associated with reductions in AF burden and symptoms. Evidence is greatest for weight loss and moderate exercise. Copyright © 2018 Elsevier Inc. All rights reserved.

Wholly Patient-tailored Ablation of Atrial Fibrillation Guided by Spatio-Temporal Dispersion of Electrograms in the Absence of Pulmonary Veins Isolation

PubMed Central

Seitz, Julien; Bars, Clément; Théodore, Guillaume; Beurtheret, Sylvain; Lellouche, Nicolas; Bremondy, Michel; Ferracci, Ange; Faure, Jacques; Penaranda, Guillaume; Yamazaki, Masatoshi; Avula, Uma Mahesh R.; Curel, Laurence; Siame, Sabrina; Berenfeld, Omer; Pisapia, André; Kalifa, Jérôme

2017-01-01

Background The use of intra-cardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results. We evaluated an electrogram marker of AF drivers: the clustering of electrograms exhibiting spatio-temporal dispersion — regardless of whether such electrograms were fractionated or not. Objective To evaluate the usefulness of spatio-temporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF. Methods We prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. We tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatio-temporal dispersion of AF electrograms, we conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF. Results Ablation at dispersion areas terminated AF in 95%. After ablation of 17±10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4±0.5 procedure/patient vs 41% in the validation set after 1.5±0.5 procedure/patient (arrhythmia free-survival rates: 85% vs 59%, log rank P<0.001). In comparison with the validation set, radiofrequency times (49 ± 21 minutes vs 85 ± 34.5 minutes, p=0.001) and procedure times (168 ± 42 minutes vs. 230 ± 67 minutes, p<.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver. Conclusions The clustering of intra-cardiac electrograms exhibiting spatio-temporal dispersion is indicative of AF drivers. Their ablation allows for a non-extensive and patient-tailored approach to AF ablation. Clinical trial.gov number: NCT02093949 PMID:28104073

Reduced Toxicity High Performance Monopropellant

DTIC Science & Technology

2011-09-01

M315E Distribution A: Approved for public release; distribution unlimited AF - M315E Desirable Properties Characteristic Objective D it *I 3450 N /L...required AF M315E d- excee s SOTA monopropellant (45%) and bipropellant (8%) Next generation exceeds SOTA monopropellant (66%) and bipropellant (23...inert mass fraction Distribution A: Approved for public release; distribution unlimited Toxicity Assessment of AF - M315E Toxicity Testing Results

Modulatory effects of Cassia fistula fruits against free radicals and genotoxicity of mutagens.

PubMed

Kaur, Sandeep; Kumar, Manish; Kaur, Paramjeet; Kaur, Varinder; Kaur, Satwinderjeet

2016-12-01

Cassia fistula L. (Fabaceae) fruits are highly recommended in folklore medicine for curing various ailments. In the current study, methanol (CaFM), hexane (CaFH), chloroform (CaFCl), ethyl acetate (CaFE), butanol (CaFB) and aqueous (CaFA) fractions of C. fistula fruits were investigated for their potential to inhibit the genotoxicity of mutagens and free radicals. The antimutagenicity of fractions was evaluated against the reactive carcinogenic ester generating mutagen, 2-aminofluorene (2-AF) and frame-shift mutation inducing mutagen, 4-nitro-o-phenylenediamine (NPD) in Ames Salmonella typhimurium TA98 tester strain. Among the fractions, CaFE showed strongest protective effect against the mutagenicity of both S9-dependent and direct-acting mutagen with an inhibitory percentage of 81% and 64% at the concentration of 1 × 10 3 and 2.5 × 10 3 respectively. All the fractions were analyzed for free radical scavenging activity using DPPH, nitric oxide, lipid peroxidation and superoxide anion assays. CaFE fraction showed maximum antioxidant activity in comparison to other fractions with an IC 50 of 97.01, 172.36, 144 and 264.79 μg/ml respectively. High performance liquid chromatography showed the presence of catechin, epicatechin and umbelliferone in appreciable amount which may account for its efficacy in combating free radicals and also showed protective effect against the mutagenicity of S9-dependent mutagen, 2-AF. Copyright © 2016 Elsevier Ltd. All rights reserved.

β-Blockers on Discharge From Acute Atrial Fibrillation Are Associated With Decreased Mortality and Lower Cerebrovascular Accidents in Patients With Heart Failure and Reduced Ejection Fraction.

PubMed

Abi Khalil, Charbel; Zubaid, Mohammad; Asaad, Nidal; Rashed, Wafa A; Hamad, Adel Khalifa; Singh, Rajvir; Al Suwaidi, Jassim

2018-04-01

The benefits of β-blockers in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and atrial fibrillation (AF) are controversial. The Gulf Survey of Atrial Fibrillation Events was a prospective, multinational, observational registry of consecutive patients with AF recruited from the emergency department (ED). We studied the incidence of 6- and 12-month mortality, hospitalization for HF or AF, and stroke/transient ischemic attacks (TIAs) in patients with HFrEF, in relation to β-blockers on discharge from the ED or the subsequent hospital stay. Of the 344 patients with HFrEF and AF in the GULF-SAFE, 177 patients (53%) were discharged on β-blockers. Mortality was lower in those patients compared with the non-β-blockers group at 6 and 12 months (odds ratios [ORs] 0.31, 95% CI [0.16-0.61]; OR 0.30, 95% CI [0.16-0.55]; P = .001 for both, respectively), so was the risk of stroke/TIAs. However, hospitalizations for AF increased in the β-blockers group. Even after adjustment for several risk variables in 2 different models, the beneficial effect of β-blockers on mortality persisted, at the cost of more hospitalization for AF.

Determinants of plasma NT-pro-BNP levels in patients with atrial fibrillation and preserved left ventricular ejection fraction.

PubMed

Letsas, Konstantinos P; Filippatos, Gerasimos S; Pappas, Loukas K; Mihas, Constantinos C; Markou, Virginia; Alexanian, Ioannis P; Efremidis, Michalis; Sideris, Antonios; Maisel, Alan S; Kardaras, Fotios

2009-02-01

The present study aimed to investigate the clinical and echocardiographic determinants of plasma NT-pro-BNP levels in patients with atrial fibrillation (AF) and preserved left ventricular ejection fraction (LVEF). NT-pro-BNP levels were measured in 45 patients with paroxysmal AF, 41 patients with permanent AF and 48 controls. NT-pro-BNP levels were found significantly elevated in patients with paroxysmal (215+/-815 pg/ml) and permanent AF (1,086+/-835 pg/ml) in relation to control population (86.3+/-77.9 pg/ml) (P<0.001). According to the univariate linear regression analysis, age, hypertension, beta-blocker use, left atrial diameter (LAD), LVEF and AF status (paroxysmal or permanent or both) were significantly associated with NT-pro-BNP levels (P<0.05). In multiple linear regression analysis, LVEF (B coefficient: -53.030; CI: -95.738 to -10.322; P: 0.015) and LAD (B coefficient: 285.858; CI: 23.731-547.986; P: 0.033) were significant and independent determinants of NT-pro-BNP levels. Plasma NT-pro-BNP levels were significantly higher in patients with paroxysmal and permanent AF compared to those with sinus rhythm in the setting of preserved left ventricular systolic function. LVEF and LAD were independent predictors of NT-pro-BNP levels.

Inhibition of Carrageenan-Induced Acute Inflammation in Mice by Oral Administration of Anthocyanin Mixture from Wild Mulberry and Cyanidin-3-Glucoside

PubMed Central

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements. PMID:23484081

Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside.

PubMed

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements.

Effect of mitral regurgitation on cerebrovascular accidents in patients with atrial fibrillation and left atrial thrombus.

PubMed

Nair, Chandra K; Aronow, Wilbert S; Shen, Xuedong; Anand, Kishlay; Holmberg, Mark J; Esterbrooks, Dennis J

2009-11-01

The effect of mitral regurgitation (MR) on the incidence of new cerebrovascular accidents (CVA) and mortality in patients with atrial fibrillation (AF) and left atrial thrombus (LAT) is unknown. To investigate the effect of MR in patients with AF and LAT on new CVA and mortality. Eighty nine consecutive patients, mean age 71 years, with AF and LAT documented by transesophageal echocardiography were investigated to determine the prevalence and severity of MR and the association of the severity of MR with new cerebrovascular accidents (CVA) and mortality at 34-mo follow-up. Of 89 patients, 1 + MR was present in 23 patients (26%), 2 + MR in 44 patients (50%), 3 + MR in 17 patients (19%), and 4 + MR in 3 patients (4%). Mean follow-up was 34 +/- 28 mo. The Cox proportional hazards model showed that the severity of increased MR did not significantly increase new CVA or mortality at 34-mo follow-up. The only variable predictive of mortality was left ventricular ejection fraction (LVEF), and with every unit increase in LVEF, the risk decreased by 3%. MR occurred in 87 of 89 patients (98%) with AF and LAT. There was no association between the severity of MR and the incidence of CVA or mortality.

The importance of integrated left atrial evaluation: From hypertension to heart failure with preserved ejection fraction.

PubMed

Beltrami, Matteo; Palazzuoli, Alberto; Padeletti, Luigi; Cerbai, Elisabetta; Coiro, Stefano; Emdin, Michele; Marcucci, Rossella; Morrone, Doralisa; Cameli, Matteo; Savino, Ketty; Pedrinelli, Roberto; Ambrosio, Giuseppe

2018-02-01

Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. The most important studies published in the literature on LA size, function and diastolic dysfunction in patients with HFpEF, HT and/or atrial fibrillation (AF) are considered and discussed. In HFpEF and HT, pulsed and tissue Doppler assessments are useful tools to estimate LV filling pressure, atrio-ventricular coupling and LV relaxation but they need to be enriched with LA evaluation in terms of morphology and function. An integrated evaluation should be also applied to patients with a high arrhythmic risk, in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk. Evaluation of LA size, volume, function and structure are mandatory in the management of patients with HT, HFpEF and AF. A multi-modality approach could provide additional information, identifying subjects with more severe LA remodelling. Left atrium assessment deserves an accurate study inside the cardiac imaging approach and optimised measurement with established cut-offs need to be better recognised through multicenter studies. © 2017 John Wiley & Sons Ltd.

Correlation of right atrial appendage velocity with left atrial appendage velocity and brain natriuretic Peptide.

PubMed

Kim, Bu-Kyung; Heo, Jung-Ho; Lee, Jae-Woo; Kim, Hyun-Soo; Choi, Byung-Joo; Cha, Tae-Joon

2012-03-01

Left atrial appendage (LAA) anatomy and function have been well characterized both in healthy and diseased people, whereas relatively little attention has been focused on the right atrial appendage (RAA). We sought to evaluate RAA flow velocity and to compare these parameters with LAA indices and with a study of biomarkers, such as brain natriuretic peptide, among patients with sinus rhythm (SR) and atrial fibrillation (AF). In a series of 79 consecutive patients referred for transesophageal echocardiography, 43 patients (23 with AF and 20 controls) were evaluated. AF was associated with a decrease in flow velocity for both LAA and RAA [LAA velocity-SR vs. AF: 61 ± 22 vs. 29 ± 18 m/sec (p < 0.01), RAA velocity-SR vs. AF: 46 ± 20 vs. 19 ± 8 m/sec (p < 0.01)]. Based on simple linear regression analysis, LAA velocity and RAA velocity were positively correlated, and RAA velocity was inversely correlated with brain natriuretic peptide (BNP). AF was associated with decreased RAA and LAA flow velocities. RAA velocity was found to be positively correlated with LAA velocity and negatively correlated with BNP. The plasma BNP concentration may serve as a determinant of LAA and RAA functions.

Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: I. Reduced flow velocity in the left atrial appendage (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study).

PubMed

Goldman, M E; Pearce, L A; Hart, R G; Zabalgoitia, M; Asinger, R W; Safford, R; Halperin, J L

1999-12-01

Stroke associated with atrial fibrillation (AF) is mainly due to embolism of thrombus formed during stasis of blood in the left atrial appendage (LAA). Pathophysiologic correlates of appendage flow velocity as assessed by transesophageal echocardiography (TEE) in patients with AF have not been defined. To evaluate the hypothesis that reduced velocity is associated with spontaneous echocardiographic contrast and thrombus in the LAA and with clinical embolic events, we measured LAA flow velocity by TEE in 721 patients with nonvalvular AF entering the Stroke Prevention in Atrial Fibrillation (SPAF-III) study. Patient features, TEE findings, and subsequent cardioembolic events were correlated with velocity by multivariate analysis. Patients in AF during TEE displayed lower peak antegrade (emptying) flow velocity (Anu(p)) than those with intermittent AF in sinus rhythm during TEE (33 cm/s vs 61 cm/s, respectively, P <.0001). Anu(p) < 20 cm/s was associated with dense spontaneous echocardiographic contrast (P <.001), appendage thrombus (P <.01), and subsequent cardioembolic events (P <.01). Independent predictors of Anu(p) < 20 cm/s included age (P =.009), systolic blood pressure (P <.001), sustained AF (P =.01), ischemic heart disease (P =.01), and left atrial area (P =.04). Multivariate analysis found both Anu(p) <20 cm/s (relative risk 2.6, P =.02) and clinical risk factors (relative risk 3.3, P =.002) independently associated with LAA thrombus. LAA Anu(p) is reduced in AF and associated with spontaneous echocardiographic contrast, appendage thrombus, and cardioembolic stroke. Systolic hypertension and aortic atherosclerosis, independent clinical predictors of stroke in patients with AF, also correlated with LAA Anu(p). Our results support the role of reduced LAA Anu(p) in the generation of stasis, thrombus formation, and embolism in patients with AF, although other mechanisms also contribute to stroke.

Measurement of subcutaneous adipose tissue blood flow in the morbidly obese using a laser Doppler velocimeter

NASA Astrophysics Data System (ADS)

Klassen, Gerald A.; Paton, Barry E.; Maksym, Geoff; Janigan, David; Perey, Bernard

1992-08-01

Using a laser Doppler velocimeter (LDV) subcutaneous adipose tissue blood flow (AF) was recorded in the upright and supine positions in the upper and lower abdomen in 22 morbidly obese patients before gastroplasty. Age was 42 +/- 3 (mean +/- SEM), weight 135 +/- 7 kg, and body mass index (BMI) 51 +/- 3. Adipose flow expressed as mV was: supine, upper abdomen 647 +/- 23, lower abdomen 604 +/- 24; upright, upper abdomen 621 +/- 27, lower abdomen 607 +/- 29. AF was significantly more in the upper than lower abdomen (supine position) and AF was significantly lower in the lower abdomen upright than the upper abdomen supine. Regression analysis of age indicates that blood flow decreases in the lower abdomen so that in the supine position the difference between upper and lower abdomen AF increases. Similar analysis of BMI did not indicate significant trends. These data indicate that with morbid obesity there is lower tissue blood flow to the lower abdomen. This may explain why such patients may develop areas of painful ischemic necrosis in the dependent region of their anterior abdominal pannus.

Is the Preoperative Administration of Amiodarone or Metoprolol More Effective in Reducing Atrial Fibrillation: After Coronary Bypass Surgery?

PubMed

Onk, Oruc Alper; Erkut, Bilgehan

2015-10-01

This study examined the influence of preoperative administration of amiodarone and metoprolol in preventing postoperative atrial fibrillation (AF) after coronary artery bypass grafting (CABG) surgery.The study comprised 251 patients who underwent CABG surgery at our hospital between January 2012 and May 2014. The patients were randomly divided into 2 groups: amiodarone therapy group (n = 122 patients) and metoprolol therapy group (n = 129 patients).In the amiodarone group, the patients received amiodarone tablet orally 1 week before coronary bypass surgery and during the postoperative period. In the metoprolol group, the patients received metoprolol tablet orally 1 week before surgery and during the postoperative period. The AF development rate was retrospectively evaluated between the first 3 days and 4 weeks after surgery.AF developed in 14 patients in the amiodarone group and 16 patients in the metoprolol group 4 weeks after the operation (P = 0.612).No significant difference was observed between the groups in terms of intensive care unit and hospital stay. Furthermore, hospital charges were similar in both groups (P = 0.741).The results of the logistic regression analysis showed age, left ventricular ejection fraction, left atrial diameter, and aortic cross-clamping time to be predictors for postoperative AF.This study demonstrates that amiodarone and metoprolol have similar effects in prevention of AF after cardiac surgery. However, larger-scale studies need to be conducted to substantiate these findings.

Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation.

PubMed

Greiser, Maura; Neuberger, Hans-Ruprecht; Harks, Erik; El-Armouche, Ali; Boknik, Peter; de Haan, Sunniva; Verheyen, Fons; Verheule, Sander; Schmitz, Wilhelm; Ravens, Ursula; Nattel, Stanley; Allessie, Maurits A; Dobrev, Dobromir; Schotten, Ulrich

2009-03-01

Atrial dilatation is an independent risk factor for thromboembolism in patients with and without atrial fibrillation (AF). In many patients, atrial dilatation goes along with depressed contractile function of the dilated atria. While some mechanisms causing atrial contractile dysfunction in fibrillating atria have been addressed previously, the cellular and molecular mechanisms of atrial contractile remodeling in dilated atria are unknown. This study characterized in vivo atrial contractile function in a goat model of atrial dilatation and compared it to a goat model of AF. Differences in the underlying mechanisms were elucidated by studying contractile function, electrophysiology and sarcoplasmic reticulum (SR) Ca2+ load in atrial muscle bundles and by analyzing expression and phosphorylation levels of key Ca2+-handling proteins, myofilaments and the expression and activity of their upstream regulators. In 7 chronically instrumented, awake goats atrial contractile dysfunction was monitored during 3 weeks of progressive atrial dilatation after AV-node ablation (AV block goats (AVB)). In open chest experiments atrial work index (AWI) and refractoriness were measured (10 goats with AVB, 5 goats with ten days of AF induced by repetitive atrial burst pacing (AF), 10 controls). Isometric force of contraction (FC), transmembrane action potentials (APs) and rapid cooling contractures (RCC, a measure of SR Ca2+ load) were studied in right atrial muscle bundles. Total and phosphorylated Ca2+-handling and myofilament protein levels were quantified by Western blot. In AVB goats, atrial size increased by 18% (from 26.6+/-4.4 to 31.6+/-5.5 mm, n=7 p<0.01) while atrial fractional shortening (AFS) decreased (from 18.4+/-1.7 to 12.8+/-4.0% at 400 ms, n=7, p<0.01). In open chest experiments, AWI was reduced in AVB and in AF goats compared to controls (at 400 ms: 8.4+/-0.9, n=7, and 3.2+/-1.8, n=5, vs 18.9+/-5.3 mmxmmHg, n=7, respectively, p<0.05 vs control). FC of isolated right atrial muscle bundles was reduced in AVB (n=8) and in AF (n=5) goats compared to controls (n=9) (at 2 Hz: 2.3+/-0.5 and 0.7+/-0.2 vs 5.5+/-1.0 mN/mm2, respectively, p<0.05). APs were shorter in AF, but unchanged in AVB goats. RCCs were reduced in AVB and AF versus control (AVB, 3.4+/-0.5 and AF, 4.1+/-1.4 vs 12.2+/-3.2 mN/mm2, p<0.05). Protein levels of protein kinase A (PKA) phosphorylated phospholamban (PLB) were reduced in AVB (n=8) and AF (n=8) vs control (n=7) by 37.9+/-12.4% and 29.7+/-10.1%, respectively (p<0.01), whereas calmodulin-dependent protein kinase II (CaMKII) phosphorylated ryanodine channels (RyR2) were increased by 166+/-55% in AVB (n=8) and by 146+/-56% in AF (n=8) goats (p<0.01). PKA-phosphorylated myosin-binding protein-C and troponin-I were reduced exclusively in AVB goat atria (by 75+/-10% and 55+/-15%, respectively, n=8, p<0.05). Atrial dilatation developing during slow ventricular rhythm after complete AV block as well as AF-induced remodeling are associated with atrial contractile dysfunction. Both AVB and AF goat atria show decreased SR Ca2+ load, likely caused by PLB dephosphorylation and RYR2 hyperphosphorylation. While shorter APs further compromise contractility in AF goat atria, reduced myofilament phosphorylation may impair contractility in AVB goat atria. Thus, atrial hypocontractility appears to have distinct molecular contributors in different types of atrial remodeling.

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

PubMed

Castellsagué, Xavier; Alemany, Laia; Quer, Miquel; Halec, Gordana; Quirós, Beatriz; Tous, Sara; Clavero, Omar; Alòs, Llúcia; Biegner, Thorsten; Szafarowski, Tomasz; Alejo, Maria; Holzinger, Dana; Cadena, Enrique; Claros, Edith; Hall, Gillian; Laco, Jan; Poljak, Mario; Benevolo, Maria; Kasamatsu, Elena; Mehanna, Hisham; Ndiaye, Cathy; Guimerà, Núria; Lloveras, Belen; León, Xavier; Ruiz-Cabezas, Juan C; Alvarado-Cabrero, Isabel; Kang, Chang-Suk; Oh, Jin-Kyoung; Garcia-Rojo, Marcial; Iljazovic, Ermina; Ajayi, Oluseyi F; Duarte, Flora; Nessa, Ashrafun; Tinoco, Leopoldo; Duran-Padilla, Marco A; Pirog, Edyta C; Viarheichyk, Halina; Morales, Hesler; Costes, Valérie; Félix, Ana; Germar, Maria Julieta V; Mena, Marisa; Ruacan, Arzu; Jain, Asha; Mehrotra, Ravi; Goodman, Marc T; Lombardi, Luis Estuardo; Ferrera, Annabelle; Malami, Sani; Albanesi, Estela I; Dabed, Pablo; Molina, Carla; López-Revilla, Rubén; Mandys, Václav; González, Manuel E; Velasco, Julio; Bravo, Ignacio G; Quint, Wim; Pawlita, Michael; Muñoz, Nubia; de Sanjosé, Silvia; Xavier Bosch, F

2016-06-01

We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of C and Si on strain aging of strain-based API X60 pipeline steels

NASA Astrophysics Data System (ADS)

Sung, Hyo Kyung; Lee, Dong Ho; Lee, Sunghak; Lee, Byeong-Joo; Hong, Seung-Pyo; Kim, Young-Woon; Yoo, Jang Yong; Hwang, Byoungchul; Shin, Sang Yong

2017-05-01

Four types of strain-based API X60 pipeline steels were fabricated by varying the C and Si contents, and the effects of C and Si on strain aging were investigated. The 0.05 wt% C steels consisted mainly of polygonal ferrite (PF), whereas the 0.08 wt% C steels consisted of acicular ferrite (AF). The volume fraction of AF increased with increasing C content because C is an austenite stabilizer element. The volume fractions of bainitic ferrite (BF) of the 0.15 wt% Si steels were higher than those of the 0.25 wt% Si steels, whereas the volume fractions of the secondary phases were lower. From the tensile properties before and after the aging process of the strainbased API X60 pipeline steels, the yield strength increased and the uniform and total elongation decreased, which is the strain aging effect. The strain aging effect in the strain-based API X60 pipeline steels was minimized when the volume fraction of AF was increased and secondary phases were distributed uniformly. On the other hand, an excessively high C content formed fine precipitates, and the strain aging effect occurred because of the interactions among dislocations and fine precipitates.

Clinical predictors of cardiac magnetic resonance late gadolinium enhancement in patients with atrial fibrillation.

PubMed

Chrispin, Jonathan; Ipek, Esra Gucuk; Habibi, Mohammadali; Yang, Eunice; Spragg, David; Marine, Joseph E; Ashikaga, Hiroshi; Rickard, John; Berger, Ronald D; Zimmerman, Stefan L; Calkins, Hugh; Nazarian, Saman

2017-03-01

This study aims to examine the association of clinical co-morbidities with the presence of left atrial (LA) late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). Previous studies have established the severity of LA LGE to be associated with atrial fibrillation (AF) recurrence following AF ablation. We sought to determine whether baseline clinical characteristics were associated with LGE extent among patients presenting for an initial AF ablation. The cohort consisted of 179 consecutive patients with no prior cardiac ablation procedures who underwent pre-procedure LGE-CMR. The extent of LA LGE for each patient was calculated using the image intensity ratio, normalized to the mean blood pool intensity, corresponding to a bipolar voltage ≤0.3 mV. The association of LGE extent with baseline clinical characteristics was examined using non-parametric and multivariable models. The mean age of the cohort was 60.9 ± 9.6 years and 128 (72%) were male. In total, 56 (31%) patients had persistent AF. The mean LA volume was 118.4 ± 41.6 mL, and the mean LA LGE extent was 14.1 ± 10.4%. There was no association with any clinical variables with LGE extent by quartiles in the multivariable model. Extent of LGE as a continuous variable was positively, but weakly associated with LA volume in a multivariable model adjusting for age, body mass index, AF persistence, and left ventricular ejection fraction (1.5% scar/mL, P = 0.038). In a cohort of patients presenting for initial AF ablation, the presence of pre-ablation LA LGE extent was weakly, but positively associated with increasing LA volume. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Preservation of the soft protein corona in distinct flow allows identification of weakly bound proteins.

PubMed

Weber, C; Simon, J; Mailänder, V; Morsbach, S; Landfester, K

2018-06-08

Nanocarriers that are used for targeted drug delivery come in contact with biological liquids and subsequently proteins will adsorb to the nanocarriers' surface to form the so called 'protein corona'. The protein corona defines the biological identity and determines the biological response towards the nanocarriers in the body. To make nanomedicine safe and reliable it is required to get a better insight into this protein corona and, therefore, the adsorbed proteins have to be characterized. Currently, centrifugation is the common method to isolate the protein corona for further investigations. However, with this method it is only possible to investigate the strongly bound proteins, also referred to as 'hard protein corona'. Therefore, we want to introduce a new separation technique to separate nanoparticles including the soft protein corona containing also loosely bound proteins for further characterization. The used separation technique is the asymmetric flow field-flow fractionation (AF4). We were able to separate the nanoparticles with proteins forming the soft protein corona and were able to show that in our system only the hard protein corona directly influenced the cell uptake behavior. Currently, there is an ongoing debate whether only strongly bound proteins (hard corona) or also loosely bound proteins (soft corona) contribute to the biological identity of nanocarriers, because up to now isolation of the soft corona was not possible. Here, asymmetric flow field-flow fractionation was used to isolate nanoparticles with a preserved soft corona from the biological medium. This enabled the characterization of the soft corona composition and to evaluate its influence on cellular uptake. For our system we found that only the strongly bound proteins (hard corona) determined cell internalization. This method can now be used to evaluate the impact of the soft corona further and to characterize nanomaterials that cannot be separated from blood plasma by other means. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Transient cerebral hypoperfusion and hypertensive events during atrial fibrillation: a plausible mechanism for cognitive impairment

NASA Astrophysics Data System (ADS)

Anselmino, Matteo; Scarsoglio, Stefania; Saglietto, Andrea; Gaita, Fiorenzo; Ridolfi, Luca

2016-06-01

Atrial fibrillation (AF) is associated with an increased risk of dementia and cognitive decline, independent of strokes. Several mechanisms have been proposed to explain this association, but altered cerebral blood flow dynamics during AF has been poorly investigated: in particular, it is unknown how AF influences hemodynamic parameters of the distal cerebral circulation, at the arteriolar and capillary level. Two coupled lumped-parameter models (systemic and cerebrovascular circulations, respectively) were here used to simulate sinus rhythm (SR) and AF. For each simulation 5000 cardiac cycles were analyzed and cerebral hemodynamic parameters were calculated. With respect to SR, AF triggered a higher variability of the cerebral hemodynamic variables which increases proceeding towards the distal circulation, reaching the maximum extent at the arteriolar and capillary levels. This variability led to critical cerebral hemodynamic events of excessive pressure or reduced blood flow: 303 hypoperfusions occurred at the arteriolar level, while 387 hypertensive events occurred at the capillary level during AF. By contrast, neither hypoperfusions nor hypertensive events occurred during SR. Thus, the impact of AF per se on cerebral hemodynamics candidates as a relevant mechanism into the genesis of AF-related cognitive impairment/dementia.

Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials.

PubMed

Hughey, Andrew B; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Besley, Dennis; Krol, Gregory D; Ahsan, Syed; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2018-06-14

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2 ), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI 2 registry taking warfarin, approximately 40-60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI 2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI 2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

Prevalence and mechanism of rotor activation identified during atrial fibrillation by noncontact mapping: Lack of evidence for a role in the maintenance of atrial fibrillation.

PubMed

Yamabe, Hiroshige; Kanazawa, Hisanori; Ito, Miwa; Kaneko, Shozo; Ogawa, Hisao

2016-12-01

It remains unclear whether atrial fibrillation (AF) is maintained by the rotor. We evaluated the role of the rotor and examined its mechanism. Among 75 patients with AF (60 paroxysmal, 15 persistent AF) who underwent 3-dimensional noncontact left atrial mapping during AF, we examined the prevalence and location of rotor activation and elucidated its mechanism. Catheter ablation was performed in a stepwise fashion (linear roof lesion and complex fractionated atrial electrogram ablation after pulmonary vein [PV) isolation) until AF termination. Rotor activation was observed in 11 patients (14.7%; 10 paroxysmal and 1 persistent AF) (tachycardia cycle length 160.0 ± 19.8 ms). Rotors were observed transiently (duration 6128 ± 9094 ms) during AF at the roof (n = 5), septum (n = 3), and ostium of the left superior PV (n = 3). Five rotors circulated in clockwise and 6 in counterclockwise directions. The length of the block line at the center of the rotor was 15.2 ± 6.9 mm. The electrograms at the block line showed low-amplitude multiple deflections (n = 7) or double potentials (n = 4), and the amplitudes during rotor activation were significantly lower than those during sinus rhythm (0.27 ± 0.18 mV vs 1.22 ± 0.92 mV; P < .01). No conduction disturbances were found during sinus rhythm, suggesting that the central line of block was formed functionally. AF was terminated by PV isolation alone without additional lesions in patients with rotors. Functionally formed rotor activation was observed during AF in a limited number of patients. These rotor activations may not be related to AF maintenance, but rather may reflect a transient organization of random propagation. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

From time-series to complex networks: Application to the cerebrovascular flow patterns in atrial fibrillation

NASA Astrophysics Data System (ADS)

Scarsoglio, Stefania; Cazzato, Fabio; Ridolfi, Luca

2017-09-01

A network-based approach is presented to investigate the cerebrovascular flow patterns during atrial fibrillation (AF) with respect to normal sinus rhythm (NSR). AF, the most common cardiac arrhythmia with faster and irregular beating, has been recently and independently associated with the increased risk of dementia. However, the underlying hemodynamic mechanisms relating the two pathologies remain mainly undetermined so far; thus, the contribution of modeling and refined statistical tools is valuable. Pressure and flow rate temporal series in NSR and AF are here evaluated along representative cerebral sites (from carotid arteries to capillary brain circulation), exploiting reliable artificially built signals recently obtained from an in silico approach. The complex network analysis evidences, in a synthetic and original way, a dramatic signal variation towards the distal/capillary cerebral regions during AF, which has no counterpart in NSR conditions. At the large artery level, networks obtained from both AF and NSR hemodynamic signals exhibit elongated and chained features, which are typical of pseudo-periodic series. These aspects are almost completely lost towards the microcirculation during AF, where the networks are topologically more circular and present random-like characteristics. As a consequence, all the physiological phenomena at the microcerebral level ruled by periodicity—such as regular perfusion, mean pressure per beat, and average nutrient supply at the cellular level—can be strongly compromised, since the AF hemodynamic signals assume irregular behaviour and random-like features. Through a powerful approach which is complementary to the classical statistical tools, the present findings further strengthen the potential link between AF hemodynamic and cognitive decline.

Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: Association With Exercise Capacity, Left Ventricular Filling Pressures, Natriuretic Peptides, and Left Atrial Volume.

PubMed

Lam, Carolyn S P; Rienstra, Michiel; Tay, Wan Ting; Liu, Licette C Y; Hummel, Yoran M; van der Meer, Peter; de Boer, Rudolf A; Van Gelder, Isabelle C; van Veldhuisen, Dirk J; Voors, Adriaan A; Hoendermis, Elke S

2017-02-01

This study sought to study the association of atrial fibrillation (AF) with exercise capacity, left ventricular filling pressure, natriuretic peptides, and left atrial size in heart failure with preserved ejection fraction (HFpEF). The diagnosis of HFpEF in patients with AF remains a challenge because both contribute to impaired exercise capacity, and increased natriuretic peptides and left atrial volume. We studied 94 patients with symptomatic heart failure and left ventricular ejection fractions ≥45% using treadmill cardiopulmonary exercise testing and right- and/or left-sided cardiac catheterization with simultaneous echocardiography. During catheterization, 62 patients were in sinus rhythm, and 32 patients had AF. There were no significant differences in age, sex, body size, comorbidities, or medications between groups; however, patients with AF had lower peak oxygen consumption (VO 2 ) compared with those with sinus rhythm (10.8 ± 3.1 ml/min/kg vs. 13.5 ± 3.8 ml/min/kg; p = 0.002). Median (25th to 75th percentile) N-terminal pro-B-type natriuretic peptide (NT-proBNP) was higher in AF versus sinus rhythm (1,689; 851 to 2,637 pg/ml vs. 490; 272 to 1,019 pg/ml; p < 0.0001). Left atrial volume index (LAVI) was higher in AF than sinus rhythm (57.8 ± 17.0 ml/m 2 vs. 42.5 ± 15.1 ml/m 2 ; p = 0.001). Invasive hemodynamics showed higher mean pulmonary capillary wedge pressure (PCWP) (19.9 ± 3.7 vs. 15.2 ± 6.8) in AF versus sinus rhythm (all p < 0.001), with a trend toward higher left ventricular end-diastolic pressure (17.7 ± 3.0 mm Hg vs. 15.7 ± 6.9 mm Hg; p = 0.06). After adjusting for clinical covariates and mean PCWP, AF remained associated with reduced peak VO 2 increased log NT-proBNP, and enlarged LAVI (all p ≤0.005). AF is independently associated with greater exertional intolerance, natriuretic peptide elevation, and left atrial remodeling in HFpEF. These data support the application of different thresholds of NT-proBNP and LAVI for the diagnosis of HFpEF in the presence of AF versus the absence of AF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effects of radiofrequency catheter ablation on left ventricular structure and function in patients with atrial fibrillation: a meta-analysis.

PubMed

Zhu, Pengju; Zhang, Yong; Jiang, Peiqing; Wang, Zhongsu; Wang, Jiangrong; Yin, Xiangcui; Hou, Yinglong

2014-08-01

Radiofrequency catheter ablation (RFCA) is an effective therapy for atrial fibrillation (AF). This study was designed to investigate the effects of RFCA on left ventricular (LV) structure and function in AF patients. A systematic literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed to identify trials involving changes of LV structure and function in AF patients undergoing RFCA. Effect size was expressed as weighted mean difference (WMD) with 95% confidence interval (CI). LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were estimated. A total of 21 trials including 1,135 participants were qualified for this meta-analysis. Compared to the baseline values, there were significant decreases in LVEDV (WMD, -6.39 ml; 95%CI, -12.46 to -0.33) and LVESV (WMD, -6.39 ml; 95%CI, -11.35 to -1.42) and a significant improvement in LVEF (WMD, 6.23%; 95%CI, 3.70 to 8.75), but no significant changes were observed in LVEDD (WMD, -0.64 mm; 95%CI, -2.40 to 1.13) and LVESD (WMD, -0.38 mm; 95%CI, -1.32 to 0.56) after RFCA. Subgroup analysis demonstrated that patients with low LVEF (WMD, 11.90%; 95%CI, 9.16 to 14.64) gained more benefits than those with normal LVEF (WMD, 1.56%; 95%CI, 0.38 to 2.74). Besides, patients with chronic AF (WMD, 10.96%; 95%CI, 4.92 to 17.01) improved more than those with paroxysmal AF (WMD, 1.93%; 95%CI, -0.27 to 4.12). RFCA in AF patients could reverse LV structural remodeling and improve LV systolic function, especially in patients with low LVEF and chronic AF.

Regulation of amniotic fluid volume: mathematical model based on intramembranous transport mechanisms

PubMed Central

Anderson, Debra F.; Cheung, Cecilia Y.

2014-01-01

Experimentation in late-gestation fetal sheep has suggested that regulation of amniotic fluid (AF) volume occurs primarily by modulating the rate of intramembranous transport of water and solutes across the amnion into underlying fetal blood vessels. In order to gain insight into intramembranous transport mechanisms, we developed a computer model that allows simulation of experimentally measured changes in AF volume and composition over time. The model included fetal urine excretion and lung liquid secretion as inflows into the amniotic compartment plus fetal swallowing and intramembranous absorption as outflows. By using experimental flows and solute concentrations for urine, lung liquid, and swallowed fluid in combination with the passive and active transport mechanisms of the intramembranous pathway, we simulated AF responses to basal conditions, intra-amniotic fluid infusions, fetal intravascular infusions, urine replacement, and tracheoesophageal occlusion. The experimental data are consistent with four intramembranous transport mechanisms acting in concert: 1) an active unidirectional bulk transport of AF with all dissolved solutes out of AF into fetal blood presumably by vesicles; 2) passive bidirectional diffusion of solutes, such as sodium and chloride, between fetal blood and AF; 3) passive bidirectional water movement between AF and fetal blood; and 4) unidirectional transport of lactate into the AF. Further, only unidirectional bulk transport is dynamically regulated. The simulations also identified areas for future study: 1) identifying intramembranous stimulators and inhibitors, 2) determining the semipermeability characteristics of the intramembranous pathway, and 3) characterizing the vesicles that are the primary mediators of intramembranous transport. PMID:25186112

The United States Military Entrance Processing Command (USMEPCOM) Uses Six Sigma Process to Develop and Improve Data Quality

DTIC Science & Technology

2007-06-01

MEPS - MIRS Applicant Accession Data Services Applicants Service - MIRS (AF, Navy, CG) Applicant Information (15K DMDC MEPS MCRISS / ARISS QuICR...A000V Army / Marine Corps ARISS / MCRISS Send 4K transmission to MIRS Personal Record Created in MIRS A000V SSN Process Flow 18 Determine SSN...All Clear SSN Process Flow Result Codes M CIAD 20 USMIRS Data Flow Testing 2000 Accession Partners ARISS MCRISS OPM DMDC NDSL ViroMed WinCAT/ (DOS

Microbial Electrosynthesis and Anaerobic Fermentation: An Economic Evaluation for Acetic Acid Production from CO2 and CO.

PubMed

Christodoulou, Xenia; Velasquez-Orta, Sharon B

2016-10-18

Microbial electrosynthesis (MES) and anaerobic fermentation (AF) are two biological processes capable of reducing CO 2 , CO, and water into acetic acid, an essential industrial reagent. In this study, we evaluated investment and production costs of acetic acid via MES and AF, and compared them to industrial chemical processes: methanol carbonylation and ethane direct oxidation. Production and investment costs were found high-priced for MES (1.44 £/kg, 1770 £/t) and AF (4.14 £/kg, 1598 £/t) because of variable and fixed costs and low production yields (100 t/y) compared to methanol carbonylation (0.26 £/kg, 261 £/t) and ethane direct oxidation (0.11 £/kg, 258 £/t). However, integrating AF with MES would reduce the release of CO 2 , double production rates (200 t/y), and decrease investment costs by 9% (1366 £/t). This resulted into setting the production costs at 0.24 £/kg which is currently market competitive (0.48 £/kg). This economically feasible bioprocess produced molar flow rates of 4550 mol per day from MES and AF independently. Our findings offer a bright opportunity toward the use and scale-up of MES and AF for an economically viable acetic acid production process.

Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling.

PubMed

Walters, Tomos E; Kalman, Jonathan M; Patel, Sheila K; Mearns, Megan; Velkoska, Elena; Burrell, Louise M

2017-08-01

Angiotensin converting enzyme 2 (ACE2) is an integral membrane protein whose main action is to degrade angiotensin II. Plasma ACE2 activity is increased in various cardiovascular diseases. We aimed to determine the relationship between plasma ACE2 activity and human atrial fibrillation (AF), and in particular its relationship to left atrial (LA) structural remodelling. One hundred and three participants from a tertiary arrhythmia centre, including 58 with paroxysmal AF (PAF), 20 with persistent AF (PersAF), and 25 controls, underwent clinical evaluation, echocardiographic analysis, and measurement of plasma ACE2 activity. A subgroup of 20 participants underwent invasive LA electroanatomic mapping. Plasma ACE2 activity levels were increased in AF [control 13.3 (9.5-22.3) pmol/min/mL; PAF 16.9 (9.7-27.3) pmol/min/mL; PersAF 22.8 (13.7-33.4) pmol/min/mL, P = 0.006]. Elevated plasma ACE2 was associated with older age, male gender, hypertension and vascular disease, elevated left ventricular (LV) mass, impaired LV diastolic function and advanced atrial disease (P < 0.05 for all). Independent predictors of elevated plasma ACE2 activity were AF (P = 0.04) and vascular disease (P < 0.01). There was a significant relationship between elevated ACE2 activity and low mean LA bipolar voltage (adjusted R2 = 0.22, P = 0.03), a high proportion of complex fractionated electrograms (R2 = 0.32, P = 0.009) and a long LA activation time (R2 = 0.20, P = 0.04). Plasma ACE2 activity is elevated in human AF. Both AF and vascular disease predict elevated plasma ACE2 activity, and elevated plasma ACE2 is significantly associated with more advanced LA structural remodelling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Mechanistic Comparison of "Nearly Missed" Versus "On-Target" Rotor Ablation.

PubMed

Yamazaki, Masatoshi; Avula, Uma Mahesh R; Berenfeld, Omer; Kalifa, Jérôme

2015-08-01

This study used advanced optical mapping techniques to examine atrial fibrillation (AF) dynamics before and after 2 distinct electrogram-based ablation strategies: complex fractionated atrial electrograms (CFAEs) and DFmax/rotor ablation. Among the electrogram analytical features proposed to unravel the atrial regions that perpetuate AF, CFAEs, highest dominant frequency sites (DFmax), and, more recently, phase analysis-enabled rotor mapping have received the largest attention. Still, the mechanisms by which these approaches modulate AF dynamics and lead to AF termination are unknown. In Langendorff-perfused sheep hearts, AF was maintained by the continuous perfusion of acetylcholine and high-resolution endocardial-epicardial optical videos were recorded from the left atrial free wall and the posterior left atrium. Then, DFmax/rotor regions (n = 7), or CFAE regions harboring the highest wavebreak density (HWD) (n = 5), were targeted with a 4F ablation catheter (5 to 15 W, 30 to 60 s/point). Thereafter, we examined the changes in AF dynamics and whether AF terminated. DFmax/rotor point ablation resulted in a significant decrease in DFmax values. In 2 animals AF terminated, whereas in the remaining 5 animals the post-ablation DFmax domain remained in the vicinity of its pre-ablation location. However, after HWD/CFAEs density ablation, DFmax values did not change, AF did not terminate, and post-ablation DFmax domains relocated from the left atrial free wall to the pulmonary vein-posterior left atrium region. In another group of hearts (n = 12), we observed that upon a progressive increase in acetylcholine concentration-mimicking the acute electrophysiological changes occurring after ablation-3-dimensional rotors drifted from one atrial region to another along large gradients of myocardial thickness. "On-target" DFmax/rotor ablation leads to the annihilation of the fibrillation-driving rotor. This translates into large decreases in AF frequency or AF termination. In contrast, "nearly missed" HWD/CFAEs ablation spares the fibrillation-driving rotor, and set the stage for rotor drift along large myocardial thickness gradients. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Heart rate and outcome in heart failure with reduced ejection fraction: Differences between atrial fibrillation and sinus rhythm-A CIBIS II analysis.

PubMed

Mulder, Bart A; Damman, Kevin; Van Veldhuisen, Dirk J; Van Gelder, Isabelle C; Rienstra, Michiel

2017-09-01

Heart rate has been associated with prognosis in patients with heart failure with reduced ejection fraction (HFREF) and sinus rhythm; whether this also holds true in patients with atrial fibrillation (AF) is unknown. To evaluate cardiac rhythm and baseline heart rate and the influence of outcome in patients with HFREF enrolled in the Cardiac Insufficiency Bisoprolol Study II. In total, 2539 patients were stratified according to their baseline heart rhythm (AF or sinus rhythm) and into quartiles of heart rate (≤70 bpm, 71-78 bpm, 79-90 bpm, and >90 bpm). The primary outcome was all-cause mortality. Mean follow-up was 1.3 years. Mean age was 61 years, mean left ventricular ejection fraction was 28%, and 80% were male. A total of 521 (21%) patients had AF at baseline. The risk associated with all-cause mortality for each 5 bpm increase in heart rate in patients with sinus rhythm (hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.01-1.11, P = 0.012) was significantly different from those with AF (HR: 1.00, 95% CI: 0.94-1.07, P = 0.90, P for interaction = 0.041). The risk associated with higher heart rate in sinus rhythm was primarily attributable to excess risk in the highest quartile (HR: 1.64, 95% CI: 1.18-2.30, P = 0.003). Allocation to bisoprolol did not modify the interaction between heart rate, rhythm and outcome. In HFREF patients with AF, a higher heart rate is not associated with increased event rates in contrast to HFREF patients with sinus rhythm. © 2017 Wiley Periodicals, Inc.

Impaired left atrial function predicts inappropriate shocks in primary prevention implantable cardioverter-defibrillator candidates.

PubMed

Tao, Susumu; Ashikaga, Hiroshi; Ciuffo, Luisa A; Yoneyama, Kihei; Lima, Joao A C; Frank, Terry F; Weiss, Robert G; Tomaselli, Gordon F; Wu, Katherine C

2017-07-01

Inappropriate implantable cardioverter-defibrillator (ICD) shocks, commonly caused by atrial fibrillation (AF), are associated with an increased mortality. Because impaired left atrial (LA) function predicts development of AF, we hypothesized that impaired LA function predicts inappropriate shocks beyond a history of AF. We prospectively analyzed the association between LA function and incident inappropriate shocks in primary prevention ICD candidates. In the Prospective Observational Study of ICD (PROSE-ICD), we assessed LA function using tissue-tracking cardiac magnetic resonance (CMR) prior to ICD implantation. A total of 162 patients (113 males, age 56 ± 15 years) were included. During the mean follow-up of 4.0 ± 2.9 years, 26 patients (16%) experienced inappropriate shocks due to AF (n = 19; 73%), supraventricular tachycardia (n = 5; 19%), and abnormal sensing (n = 2; 8%). In univariable analyses, inappropriate shocks were associated with AF history prior to ICD implantation, age below 70 years, QRS duration less than 120 milliseconds, larger LA minimum volume, lower LA stroke volume, lower LA emptying fraction, impaired LA maximum and preatrial contraction strains (S max and S preA ), and impaired LA strain rate during left ventricular systole and atrial contraction (SR s and SR a ). In multivariable analysis, impaired S max (hazard ratio [HR]: 0.96, P = 0.044), S preA (HR: 0.94, P = 0.030), and SR a (HR: 0.25, P < 0.001) were independently associated with inappropriate shocks. The receiver-operating characteristics curve showed that SR a improved the predictive value beyond the patient demographics including AF history (P = 0.033). Impaired LA function assessed by tissue-tracking CMR is an independent predictor of inappropriate shocks in primary prevention ICD candidates beyond AF history. © 2017 Wiley Periodicals, Inc.

Atrial Electrogram Fractionation Distribution before and after Pulmonary Vein Isolation in Human Persistent Atrial Fibrillation-A Retrospective Multivariate Statistical Analysis.

PubMed

Almeida, Tiago P; Chu, Gavin S; Li, Xin; Dastagir, Nawshin; Tuan, Jiun H; Stafford, Peter J; Schlindwein, Fernando S; Ng, G André

2017-01-01

Purpose: Complex fractionated atrial electrograms (CFAE)-guided ablation after pulmonary vein isolation (PVI) has been used for persistent atrial fibrillation (persAF) therapy. This strategy has shown suboptimal outcomes due to, among other factors, undetected changes in the atrial tissue following PVI. In the present work, we investigate CFAE distribution before and after PVI in patients with persAF using a multivariate statistical model. Methods: 207 pairs of atrial electrograms (AEGs) were collected before and after PVI respectively, from corresponding LA regions in 18 persAF patients. Twelve attributes were measured from the AEGs, before and after PVI. Statistical models based on multivariate analysis of variance (MANOVA) and linear discriminant analysis (LDA) have been used to characterize the atrial regions and AEGs. Results: PVI significantly reduced CFAEs in the LA (70 vs. 40%; P < 0.0001). Four types of LA regions were identified, based on the AEGs characteristics: (i) fractionated before PVI that remained fractionated after PVI (31% of the collected points); (ii) fractionated that converted to normal (39%); (iii) normal prior to PVI that became fractionated (9%) and; (iv) normal that remained normal (21%). Individually, the attributes failed to distinguish these LA regions, but multivariate statistical models were effective in their discrimination ( P < 0.0001). Conclusion: Our results have unveiled that there are LA regions resistant to PVI, while others are affected by it. Although, traditional methods were unable to identify these different regions, the proposed multivariate statistical model discriminated LA regions resistant to PVI from those affected by it without prior ablation information.

40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2012 CFR

2012-07-01

... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover, when...

40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover, when...

40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover, when...

Non-selective His bundle pacing with a biphasic waveform: enhancing septal resynchronization.

PubMed

Ortega, Daniel F; Barja, Luis D; Logarzo, Emilio; Mangani, Nicolas; Paolucci, Analia; Bonomini, Maria P

2018-05-01

His bundle pacing has shown to prevent detrimental effects from right ventricular apical pacing (RVA) and proved to resynchronize many conduction disturbances cases. However, the extent of His bundle pacing resynchronization is limited. An optimized stimulation waveform could expand this limit when implemented in His bundle pacing sets. In this work, we temporarily implemented RVA and Non-selective His bundle pacing with a biphasic anodal-first waveform (AF-nHB) and compared their effects against sinus rhythm (SR). Fifteen patients referred for electrophysiologic study with conduction disturbances, cardiomyopathy and ejection fraction below 35% were enrolled for the study. The following acute parameters were measured: QRS duration, left ventricular activation (RLVT), time of isovolumic contraction (IVCT), ejection fraction (EF), and dP/dtmax. QRS duration and RLVT decreased markedly under AF-nHB (SR: 169 ± 34 ms vs. nHB: 116 ± 31 ms, P < 0.0005) while RVA significantly increased QRS duration (SR: 169 ms vs. RVA: 198 ms, P < 0.05) and did not change RLVT (P = NS). Consistently, IVCT moderately decreased under AF-nHB (SR: 238 ms vs. RVA: 184 ms, P < 0.05 vs. SR) and dP/dtmax showed a 93.35 [mmHg] average increase under AF-nHB against SR. Also, T-wave inversions were observed during AF-nHB immediately after SR and RVA pacing suggesting the occurrence of cardiac memory. AF-nHB corrected bundle branch blocks in patients with severe conduction disturbances, even in those with dilated cardiomiopathy, outstanding from RVA. Also, the occurrence of cardiac memory during AF-nHB turned up as an observational finding of this study.

Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant) in CCl4 challenged rats.

PubMed

Joshi, Bhuwan Chandra; Prakash, Atish; Kalia, Ajudhia N

2015-01-01

The aim of the present study was to isolate hepatoprotective component from Urtica dioica Linn. (whole plant) against CCl 4 -induced hepatotoxicity in-vitro (HepG2 cells) and in-vivo (rats) model. Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF), ethyl acetate fraction (EAF), n -butanol fraction (NBF) and aqueous fraction (AF) were determined by DPPH and NO radicals scavenging assay. Fractions were subjected to in-vitro HepG2 cell line study. Further, the most potent fraction (EAF) was subjected to in-vivo hepatoprotective potential against CCl 4 challenged rats. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s). Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1 H NMR, 13 C NMR and MS spectroscopy. Ethyl acetate fraction (EAF) of hydro-alcoholic extract of U. dioica possessed the potent antioxidant activity viz. DPPH (IC 50 78.99 ± 0.17 μg/ml) and NO (IC 50 101.39 ± 0.30 μg/ml). The in-vitro HepG2 cell line study showed that the EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and oxidative parameters in tissue of CCl 4 -induced rats, suggesting hepatoprotective and anti-oxidant action respectively. Column chromatography of most potent antioxidant fraction (EAF) lead to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid) which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF of hydro-alcoholic extract has significant antioxidant and hepatoprotective potential on CCl 4 induced hepatotoxicity in-vitro and in-vivo .

Diminished forearm vasomotor response to central hypervolemic loading in aerobically fit individuals

NASA Technical Reports Server (NTRS)

Shi, X.; Gallagher, K. M.; SMith, S. A.; Bryant, K. H.; Raven, P. B.; Blomqvist, C. G. (Principal Investigator)

1996-01-01

The aim of this study was to test the hypothesis that cardiopulmonary baroreflex control of forearm vascular resistance (FVR) during central hypervolemic loading was less sensitive in exercise trained high fit individuals (HF) compared to untrained average fit individuals (AF). Eight AF (age: 24 +/- 1 yr and weight: 78.9 +/- 1.7 kg) and eight HF (22 +/- 1 yr 79.5 +/- 2.4 kg) voluntarily participated in the investigation. Maximal aerobic power (determined on a treadmill), plasma volume and blood volume (Evans blue dilution method) were significantly greater in the HF than AF (60.8 +/- 0.7 vs. 41.2 +/- 1.9 ml.kg-1.min-1, 3.96 +/- 0.17 vs 3.36 +/- 0.08 1, and 6.33 +/- 0.23 vs 5.28 +/- 0.13 1). Baseline heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP, measured by an intraradial catheter or a Finapres finger cuff), forearm blood flow (FBF, plethysmography), and FVR, calculated from the ratio (MAP-CVP)/FBF, were not different between the HF and the AF. Lower body negative pressure (LBNP, -5, -10, -15, and -20 torr) and passive leg elevation (LE, 50 cm) combined with lower body positive pressure (LBPP, +5, +10, and +20 torr) were utilized to elicit central hypovolemia and hypervolemia, respectively. Range of CVP (from LBNP to LE+LBPP) was similar in the AF (from -3.9 to +1.9 mm Hg) and HF (from -4.0 to +2.2 mm Hg). However, FVR/CVP was significantly less in the HF (-1.8 +/- 0.1 unit.mm Hg-1) than AF (-34 +/- 0.1 unit.mm Hg-1). The FVR decrease in response to increase in CVP was significantly diminished in the HF (-1.46 +/- 0.45 unit.mm Hg-1) compared to the AF (-4.40 +/- 0.97 unit.mm Hg-1), and during LBNP induced unloading the FVR/CVP of the HF (-2.01 +/- 0.49 unit.mm Hg-1) was less (P < 0.08) than the AF (-3.28 +/- 0.69 unit.mm Hg-1). We concluded that the cardiopulmonary baroreceptor mediated FVR reflex response was significantly less sensitive to changes in CVP in individuals who practice exercise training.

Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study.

PubMed

Prabhu, Sandeep; Taylor, Andrew J; Costello, Ben T; Kaye, David M; McLellan, Alex J A; Voskoboinik, Aleksandr; Sugumar, Hariharan; Lockwood, Siobhan M; Stokes, Michael B; Pathik, Bhupesh; Nalliah, Chrishan J; Wong, Geoff R; Azzopardi, Sonia M; Gutman, Sarah J; Lee, Geoffrey; Layland, Jamie; Mariani, Justin A; Ling, Liang-Han; Kalman, Jonathan M; Kistler, Peter M

2017-10-17

Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy. The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF. This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months. A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093). AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effects of molecular weight on the diffusion coefficient of aquatic dissolved organic matter and humic substances.

PubMed

Balch, J; Guéguen, C

2015-01-01

In situ measurements of labile metal species using diffusive gradients in thin films (DGT) passive samplers are based on the diffusion rates of individual species. Although most studies have dealt with chemically isolated humic substances, the diffusion of dissolved organic matter (DOM) across the hydrogel is not well understood. In this study, the diffusion coefficient (D) and molecular weight (MW) of 11 aquatic DOM and 4 humic substances (HS) were determined. Natural, unaltered aquatic DOM was capable of diffusing across the diffusive gel membrane with D values ranging from 2.48×10(-6) to 5.31×10(-6) cm(2) s(-1). Humic substances had diffusion coefficient values ranging from 3.48×10(-6) to 6.05×10(-6) cm(2) s(-1), congruent with previous studies. Molecular weight of aquatic DOM and HS samples (∼500-1750 Da) measured using asymmetrical flow field-flow fractionation (AF4) strongly influenced D, with larger molecular weight DOM having lower D values. No noticeable changes in DOM size properties were observed during the diffusion process, suggesting that DOM remains intact following diffusion across the diffusive gel. The influence of molecular weight on DOM mobility will assist in further understanding and development of the DGT technique and the uptake and mobility of contaminants associated with DOM in aquatic environments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification of (E,E)-2,4-undecadienal from coriander (Coriandrum sativum L.) as a highly effective deodorant compound against the offensive odor of porcine large intestine.

PubMed

Ikeura, Hiromi; Kohara, Kaori; Li, Xin-Xian; Kobayashi, Fumiyuki; Hayata, Yasuyoshi

2010-10-27

The leaves of coriander ( Coriandrum sativum L.) exhibited a strong deodorizing effect against porcine internal organs (large intestine). The effective deodorizing compounds of coriander were identified by separating the volatile component of coriander, testing the effectiveness of each fraction against the offensive odor of porcine large intestine, and then identifying the compounds by GC-MS. The volatile component of coriander was first separated into six fractions (A-F) by preparative gas chromatography, and the deodorizing activity of each of these fractions against the offensive odor was measured. Fraction D, which showed the strongest deodorizing effect, was then separated into 12 subfractions by preparative GC. The deodorant activity of each subfraction was evaluated, and the deodorant compounds were identified by GC-MS. It was discovered that (E,E)-2,4-undecadienal was the most effective deodorizing compound. The deodorizing activity of (E,E)-2,4-undecadienal on the porcine large intestine increased as with concentration, reaching almost complete deodorizing ability at 10 ppb.

The role of influenza, RSV and other common respiratory viruses in severe acute respiratory infections and influenza-like illness in a population with a high HIV sero-prevalence, South Africa 2012-2015.

PubMed

Pretorius, Marthi A; Tempia, Stefano; Walaza, Sibongile; Cohen, Adam L; Moyes, Jocelyn; Variava, Ebrahim; Dawood, Halima; Seleka, Mpho; Hellferscee, Orienka; Treurnicht, Florette; Cohen, Cheryl; Venter, Marietjie

2016-02-01

Viruses detected in patients with acute respiratory infections may be the cause of illness or asymptomatic shedding. To estimate the attributable fraction (AF) and the detection rate attributable to illness for each of the different respiratory viruses We compared the prevalence of 10 common respiratory viruses (influenza A and B viruses, parainfluenza virus 1-3; respiratory syncytial virus (RSV); adenovirus, rhinovirus, human metapneumovirus (hMPV) and enterovirus) in both HIV positive and negative patients hospitalized with severe acute respiratory illness (SARI), outpatients with influenza-like illness (ILI), and control subjects who did not report any febrile, respiratory or gastrointestinal illness during 2012-2015 in South Africa. We enrolled 1959 SARI, 3784 ILI and 1793 controls with a HIV sero-prevalence of 26%, 30% and 43%, respectively. Influenza virus (AF: 86.3%; 95%CI: 77.7-91.6%), hMPV (AF: 85.6%; 95%CI: 72.0-92.6%), and RSV (AF: 83.7%; 95%CI: 77.5-88.2%) infections were associated with severe disease., while rhinovirus (AF: 46.9%; 95%CI: 37.6-56.5%) and adenovirus (AF: 36.4%; 95%CI: 20.6-49.0%) were only moderately associated. Influenza, RSV and hMPV can be considered pathogens if detected in ILI and SARI while rhinovirus and adenovirus were commonly identified in controls suggesting that they may cause only a proportion of clinical disease observed in positive patients. Nonetheless, they may be important contributors to disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Decrease in B-Type Natriuretic Peptide Levels and Successful Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure.

PubMed

Yanagisawa, Satoshi; Inden, Yasuya; Kato, Hiroyuki; Fujii, Aya; Mizutani, Yoshiaki; Ito, Tadahiro; Kamikubo, Yosuke; Kanzaki, Yasunori; Hirai, Makoto; Murohara, Toyoaki

2016-03-01

Little is known about the association between B-type natriuretic peptide (BNP) levels and catheter ablation of atrial fibrillation (AF) in patients with heart failure. This study aimed to examine the impact of elimination of AF by catheter ablation on BNP levels in patients with left ventricular systolic dysfunction. Fifty-four AF patients with left ventricular ejection fraction (LVEF) ≤ 50%, who underwent radiofrequency catheter ablation therapy of AF, were included. BNP sampling was performed at baseline, 3 days, and 1 month after ablation. After a follow-up period of 6 months, the BNP levels decreased significantly in the nonrecurrence group (n = 35; median 126.3 [interquartile 57.2-206.5] pg/mL, 63.5 [23.9-180.2] pg/mL, and 45.9 [21.9-160.3] pg/mL, P < 0.001, respectively), but not in the recurrence group (n = 19; 144.7 [87.1-217.3] pg/mL, 88.8 [12.9-213.2] pg/mL, and 118.5 [51.6-298.2] pg/mL, P = 0.368, respectively). The patients in the nonrecurrence group had a higher percentage relative reduction in BNP levels from baseline to 1 month after ablation than those in the recurrence group (56.5 [-9.0-77.4]% vs -2.4 [-47.1-60.9]%, P = 0.027). Additionally, a relative reduction in BNP levels significantly correlated with an increase in LVEF after ablation (r = 0.486, P < 0.001). Plasma BNP levels decreased significantly with successful catheter ablation of AF in patients with impaired LVEF. The decrease in BNP levels might be associated with early recovery of cardiac function and subsequent maintenance of sinus rhythm at follow-up. ©2015 Wiley Periodicals, Inc.

Regulation of amniotic fluid volume: mathematical model based on intramembranous transport mechanisms.

PubMed

Brace, Robert A; Anderson, Debra F; Cheung, Cecilia Y

2014-11-15

Experimentation in late-gestation fetal sheep has suggested that regulation of amniotic fluid (AF) volume occurs primarily by modulating the rate of intramembranous transport of water and solutes across the amnion into underlying fetal blood vessels. In order to gain insight into intramembranous transport mechanisms, we developed a computer model that allows simulation of experimentally measured changes in AF volume and composition over time. The model included fetal urine excretion and lung liquid secretion as inflows into the amniotic compartment plus fetal swallowing and intramembranous absorption as outflows. By using experimental flows and solute concentrations for urine, lung liquid, and swallowed fluid in combination with the passive and active transport mechanisms of the intramembranous pathway, we simulated AF responses to basal conditions, intra-amniotic fluid infusions, fetal intravascular infusions, urine replacement, and tracheoesophageal occlusion. The experimental data are consistent with four intramembranous transport mechanisms acting in concert: 1) an active unidirectional bulk transport of AF with all dissolved solutes out of AF into fetal blood presumably by vesicles; 2) passive bidirectional diffusion of solutes, such as sodium and chloride, between fetal blood and AF; 3) passive bidirectional water movement between AF and fetal blood; and 4) unidirectional transport of lactate into the AF. Further, only unidirectional bulk transport is dynamically regulated. The simulations also identified areas for future study: 1) identifying intramembranous stimulators and inhibitors, 2) determining the semipermeability characteristics of the intramembranous pathway, and 3) characterizing the vesicles that are the primary mediators of intramembranous transport. Copyright © 2014 the American Physiological Society.

A silk peptide fraction restores cognitive function in AF64A-induced Alzheimer disease model rats by increasing expression of choline acetyltransferase gene.

PubMed

Cha, Yeseul; Lee, Sang Hoon; Jang, Su Kil; Guo, Haiyu; Ban, Young-Hwan; Park, Dongsun; Jang, Gwi Yeong; Yeon, Sungho; Lee, Jeong-Yong; Choi, Ehn-Kyoung; Joo, Seong Soo; Jeong, Heon-Sang; Kim, Yun-Bae

2017-01-01

This study investigated the effects of a silk peptide fraction obtained by incubating silk proteins with Protease N and Neutrase (SP-NN) on cognitive dysfunction of Alzheimer disease model rats. In order to elucidate underlying mechanisms, the effect of SP-NN on the expression of choline acetyltransferase (ChAT) mRNA was assessed in F3.ChAT neural stem cells and Neuro2a neuroblastoma cells; active amino acid sequence was identified using HPLC-MS. The expression of ChAT mRNA in F3.ChAT cells increased by 3.79-fold of the control level by treatment with SP-NN fraction. The active peptide in SP-NN was identified as tyrosine-glycine with 238.1 of molecular weight. Male rats were orally administered with SP-NN (50 or 300mg/kg) and challenged with a cholinotoxin AF64A. As a result of brain injury and decreased brain acetylcholine level, AF64A induced astrocytic activation, resulting in impairment of learning and memory function. Treatment with SP-NN exerted recovering activities on acetylcholine depletion and brain injury, as well as cognitive deficit induced by AF64A. The results indicate that, in addition to a neuroprotective activity, the SP-NN preparation restores cognitive function of Alzheimer disease model rats by increasing the release of acetylcholine. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene

PubMed Central

Catalina, Purificación; Rodríguez, René; Melen, Gustavo J.; Bueno, Clara; Arriero, Mar; García-Sánchez, Félix; Lassaletta, Alvaro; García-Sanz, Ramón

2009-01-01

MLL-AF4 fusion is a hallmark genetic abnormality in infant B-acute lymphoblastic leukemia (B-ALL) known to arise in utero. The cellular origin of leukemic fusion genes during human development is difficult to ascertain. The bone marrow (BM) microenvironment plays an important role in the pathogenesis of several hematological malignances. BM mesenchymal stem cells (BM-MSC) from 38 children diagnosed with cytogenetically different acute leukemias were screened for leukemic fusion genes. Fusion genes were absent in BM-MSCs of childhood leukemias carrying TEL-AML1, BCR-ABL, AML1-ETO, MLL-AF9, MLL-AF10, MLL-ENL or hyperdiploidy. However, MLL-AF4 was detected and expressed in BM-MSCs from all cases of MLL-AF4+ B-ALL. Unlike leukemic blasts, MLL-AF4+ BM-MSCs did not display monoclonal Ig gene rearrangements. Endogenous or ectopic expression of MLL-AF4 exerted no effect on MSC culture homeostasis. These findings suggest that MSCs may be in part tumor-related, highlighting an unrecognized role of the BM milieu on the pathogenesis of MLL-AF4+ B-ALL. MLL-AF4 itself is not sufficient for MSC transformation and the expression of MLL-AF4 in MSCs is compatible with a mesenchymal phenotype, suggesting a differential impact in the hematopoietic system and mesenchyme. The absence of monoclonal rearrangements in MLL-AF4+ BM-MSCs precludes the possibility of cellular plasticity or de-differentiation of B-ALL blasts and suggests that MLL-AF4 might arise in a population of prehematopoietic precursors. PMID:19995953

Ablation of Persistent Atrial Fibrillation Targeting Low-Voltage Areas With Selective Activation Characteristics.

PubMed

Jadidi, Amir S; Lehrmann, Heiko; Keyl, Cornelius; Sorrel, Jérémie; Markstein, Viktor; Minners, Jan; Park, Chan-Il; Denis, Arnaud; Jaïs, Pierre; Hocini, Mélèze; Potocnik, Clemens; Allgeier, Juergen; Hochholzer, Willibald; Herrera-Sidloky, Claudia; Kim, Steve; Omri, Youssef El; Neumann, Franz-Josef; Weber, Reinhold; Haïssaguerre, Michel; Arentz, Thomas

2016-03-01

Complex-fractionated atrial electrograms and atrial fibrosis are associated with maintenance of persistent atrial fibrillation (AF). We hypothesized that pulmonary vein isolation (PVI) plus ablation of selective atrial low-voltage sites may be more successful than PVI only. A total of 85 consecutive patients with persistent AF underwent high-density atrial voltage mapping, PVI, and ablation at low-voltage areas (LVA < 0.5 mV in AF) associated with electric activity lasting > 70% of AF cycle length on a single electrode (fractionated activity) or multiple electrodes around the circumferential mapping catheter (rotational activity) or discrete rapid local activity (group I). The procedural end point was AF termination. Arrhythmia freedom was compared with a control group (66 patients) undergoing PVI only (group II). PVI alone was performed in 23 of 85 (27%) patients of group I with low amount (< 10% of left atrial surface area) of atrial low voltage. Selective atrial ablation in addition to PVI was performed in 62 patients with termination of AF in 45 (73%) after 11 ± 9 minutes radiofrequency delivery. AF-termination sites colocalized within LVA in 80% and at border zones in 20%. Single-procedural arrhythmia freedom at 13 months median follow-up was achieved in 59 of 85 (69%) patients in group I, which was significantly higher than the matched control group (31/66 [47%], P < 0.001). There was no significant difference in the success rate of patients in group I with a low amount of low voltage undergoing PVI only and patients requiring PVI+selective low-voltage ablation (P = 0.42). Ablation of sites with distinct activation characteristics within/at borderzones of LVA in addition to PVI is more effective than conventional PVI-only strategy for persistent AF. PVI only seems to be sufficient to treat patients with left atrial low voltage < 10%. © 2016 American Heart Association, Inc.

Diastolic Function in Normal Sinus Rhythm vs. Chronic Atrial Fibrillation: Comparison by Fractionation of E-wave Deceleration Time into Stiffness and Relaxation Components.

PubMed

Mossahebi, Sina; Kovács, Sándor J

2014-01-01

Although the electrophysiologic derangement responsible for atrial fibrillation (AF) has been elucidated, how AF remodels the ventricular chamber and affects diastolic function (DF) has not been fully characterized. The previously validated Parametrized Diastolic Filling (PDF) formalism models suction-initiated filling kinematically and generates error-minimized fits to E-wave contours using unique load (x o ), relaxation (c), and stiffness (k) parameters. It predicts that E-wave deceleration time (DT) is a function of both stiffness and relaxation. Ascribing DT s to stiffness and DTr to relaxation such that DT=DT s +DT r is legitimate because of causality and their predicted and observed high correlation (r=0.82 and r=0.94) with simultaneous (diastatic) chamber stiffness (dP/dV) and isovolumic relaxation (tau), respectively. We analyzed simultaneous echocardiography-cardiac catheterization data and compared 16 age matched, chronic AF subjects to 16, normal sinus rhythm (NSR) subjects (650 beats). All subjects had diastatic intervals. Conventional DF parameters (DT, AT, E peak , E dur , E-VTI, E/E') and E-wave derived PDF parameters (c, k, DT s , DT r ) were compared. Total DT and DT s , DT r in AF were shorter than in NSR (p<0.005), chamber stiffness, (k) in AF was higher than in NSR (p<0.001). For NSR, 75% of DT was due to stiffness and 25% was due to relaxation whereas for AF 81% of DT was due to stiffness and 19% was due to relaxation (p<0.005). We conclude that compared to NSR, increased chamber stiffness is one measurable consequence of chamber remodeling in chronic, rate controlled AF. A larger fraction of E-wave DT in AF is due to stiffness compared to NSR. By trending individual subjects, this method can elucidate and characterize the beneficial or adverse long-term effects on chamber remodeling due to alternative therapies in terms of chamber stiffness and relaxation.

Chemistry of 1,1,2,2,9,9,10,10-octafluoro-[2,2]-paracyclophane: Its synthesis and reactions

NASA Astrophysics Data System (ADS)

Duan, Jian-Xin

This dissertation describes the first example of the synthesis of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane (AF4) under non-high-dilution conditions. Under very mild reaction conditions, bis-p-(chlorodifluoromethyl)benzene (TFPX dichloride) and its derivatives reacted with Zn dust in N,N-dimethyl acetamide (DMA) (Zinc method) affording the corresponding AF4 and its derivatives in moderate to good yields. Purification of products was also studied and an efficient purification process was developed. A new and very cheap method for preparation of TFPX dichloride is also disclosed. Using the very cheap fluorinating reagent, anhydrous hydrogen fluoride (AHF), 1,4-bis(trichloromethyl)benezene or its derivatives were converted to TFPX and its derivatives in high yields (F/Cl exchange reaction). With the success of the Zinc method and F/Cl exchange reaction, highly pure AF4 thus can be provided to the semiconductor industry and academy research scientists in large quantity and at a very low price. Starting from AF4, numerous AF4 derivatives were synthesized using convenient reaction conditions. Reaction of AF4 with fuming nitric acid at room temperature gave mono-nitroAF4 in almost quantitative yield. Reduction of the mono-nitroAF4 with iron powder in the presence of HCl in alcoholic solvent gave the aminoAF4 in 90% yield. Via the diazonium salt intermediate, iodoAF4 was also obtained in good yield. Under similar reaction conditions, disubstituted AF4 derivatives were also prepared in good yields. Heating a mixture of AF4, trifluoroacetyl peroxide and dichloromethane gave the trifluoromethylated dimeric AF4 as a mixture of diastereomers. When these products were heated to 170--180°C in the presence of I 2, 4-trifluoromethyl-AF4 was obtained in almost 87% yield. X-ray structural analysis showed that the C-C bond connecting the two cyclophane moieties to be longer than the normal C-C bond. Kinetic studies, conducted in the presence of excess amount of hydrogen donor, showed this bond to be quite weak. Oxidation of AF4 with HIO3 in the presence of catalytic amount of H2SO4 in trifluoroacetic acid gave AF4 quinone in one step. AF4 quinone can be easily reduced to the hydroquinone by Na 2S2O4 aqueous solution.

Effect of Obesity on the Prognostic Impact of Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

PubMed

Yagawa, Mayuko; Nagatomo, Yuji; Izumi, Yuki; Mahara, Keitaro; Tomoike, Hitonobu; Shiraishi, Yasuyuki; Kohno, Takashi; Mizuno, Atsushi; Goda, Ayumi; Kohsaka, Shun; Yoshikawa, Tsutomu

2017-06-23

Although obesity is associated with left ventricular hypertrophy, diastolic dysfunction, and occurrence of atrial fibrillation (AF), obese heart failure (HF) patients have a more favorable clinical outcome (obesity paradox). The clinical impact of AF on obese or lean HF patients has not been fully elucidated.Methods and Results:We analyzed 1,681 patients who were enrolled in the West Tokyo Heart Failure Registry (WET-HF Registry), a multicenter, prospective cohort registry from 2005 through 2014. We assigned them to 3 categories based on body mass index (BMI): low, BMI <18.5; medium, BMI ≥18.5 and <25; and high, BMI ≥25 (n=182/915/400). The clinical endpoint was all-cause death or readmission for acute decompensated HF. During 406 days of follow-up (IQR, 116-739 days), AF was associated with a higher risk of the endpoint in the HF with preserved ejection fraction (HFpEF) group (P<0.001, log-rank test), but not in the HF with reduced EF (HFrEF) group. AF was associated with a higher risk of the endpoint in low and medium BMI patients with HFpEF (P=0.016 and 0.009, respectively). On Multivariate Cox proportional hazards analysis, AF was an independent predictor of the endpoint in patients with BMI <25 from the HFpEF group (hazard ratio, 1.74; 95% CI: 1.21-2.54, P=0.003), but not in the other subgroups. AF had a negative impact on clinical outcome in non-obese patients with HFpEF.

Finding binaries from phase modulation of pulsating stars with Kepler: V. Orbital parameters, with eccentricity and mass-ratio distributions of 341 new binaries

NASA Astrophysics Data System (ADS)

Murphy, Simon J.; Moe, Maxwell; Kurtz, Donald W.; Bedding, Timothy R.; Shibahashi, Hiromoto; Boffin, Henri M. J.

2018-03-01

The orbital parameters of binaries at intermediate periods (102-103 d) are difficult to measure with conventional methods and are very incomplete. We have undertaken a new survey, applying our pulsation timing method to Kepler light curves of 2224 main-sequence A/F stars and found 341 non-eclipsing binaries. We calculate the orbital parameters for 317 PB1 systems (single-pulsator binaries) and 24 PB2s (double-pulsators), tripling the number of intermediate-mass binaries with full orbital solutions. The method reaches down to small mass ratios q ≈ 0.02 and yields a highly homogeneous sample. We parametrize the mass-ratio distribution using both inversion and Markov-Chain Monte Carlo forward-modelling techniques, and find it to be skewed towards low-mass companions, peaking at q ≈ 0.2. While solar-type primaries exhibit a brown dwarf desert across short and intermediate periods, we find a small but statistically significant (2.6σ) population of extreme-mass-ratio companions (q < 0.1) to our intermediate-mass primaries. Across periods of 100-1500 d and at q > 0.1, we measure the binary fraction of current A/F primaries to be 15.4 per cent ± 1.4 per cent, though we find that a large fraction of the companions (21 per cent ± 6 per cent) are white dwarfs in post-mass-transfer systems with primaries that are now blue stragglers, some of which are the progenitors of Type Ia supernovae, barium stars, symbiotics, and related phenomena. Excluding these white dwarfs, we determine the binary fraction of original A/F primaries to be 13.9 per cent ± 2.1 per cent over the same parameter space. Combining our measurements with those in the literature, we find the binary fraction across these periods is a constant 5 per cent for primaries M1 < 0.8 M⊙, but then increases linearly with log M1, demonstrating that natal discs around more massive protostars M1 ≳ 1 M⊙ become increasingly more prone to fragmentation. Finally, we find the eccentricity distribution of the main-sequence pairs to be much less eccentric than the thermal distribution.

[Establishment of the retrovirus-mediated murine model with MLL-AF9 leukemia].

PubMed

Xu, Si-Miao; Yang, Yang; Zhou, Mi; Zhao, Xue-Jiao; Qin, Yu; Zhang, Pei-Ling; Yuan, Rui-Feng; Zhou, Jian-Feng; Fang, Yong

2013-10-01

This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.

Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48

PubMed Central

Gupta, Deepak K.; Shah, Amil M.; Giugliano, Robert P.; Ruff, Christian T.; Antman, Elliott M.; Grip, Laura T.; Deenadayalu, Naveen; Hoffman, Elaine; Patel, Indravadan; Shi, Minggao; Mercuri, Michele; Mitrovic, Veselin; Braunwald, Eugene; Solomon, Scott D.

2014-01-01

Aims The complex relationship between left atrial (LA) structure and function, electrical burden of atrial fibrillation (AF) and stroke risk is not well understood. We aimed to describe LA structure and function in AF. Methods and results Left atrial structure and function was assessed in 971 subjects enrolled in the echocardiographic substudy of ENGAGE AF-TIMI 48. Left atrial size, emptying fraction (LAEF), and contractile function were compared across AF types (paroxysmal, persistent, or permanent) and CHADS2 scores as an estimate of stroke risk. The majority of AF patients (55%) had both LA enlargement and reduced LAEF, with an inverse relationship between LA size and LAEF (R = −0.57, P < 0.001). With an increasing electrical burden of AF and higher CHADS2 scores, LA size increased and LAEF declined. Moreover, 19% of AF subjects had impaired LAEF despite normal LA size, and LA contractile dysfunction was present even among the subset of AF subjects in sinus rhythm at the time of echocardiography. Conclusions In a contemporary AF population, LA structure and function were increasingly abnormal with a greater electrical burden of AF and higher stroke risk estimated by the CHADS2 score. Moreover, LA dysfunction was present despite normal LA size and sinus rhythm, suggesting that the assessment of LA function may add important incremental information in the evaluation of AF patients. Clinical Trial Registration: http://www.clinicaltrials.gov; ID = NCT00781391. PMID:24302269

An Experimental Investigation of Sewage Sludge Gasification in a Fluidized Bed Reactor

PubMed Central

Calvo, L. F.; García, A. I.; Otero, M.

2013-01-01

The gasification of sewage sludge was carried out in a simple atmospheric fluidized bed gasifier. Flow and fuel feed rate were adjusted for experimentally obtaining an air mass : fuel mass ratio (A/F) of 0.2 < A/F < 0.4. Fuel characterization, mass and power balances, produced gas composition, gas phase alkali and ammonia, tar concentration, agglomeration tendencies, and gas efficiencies were assessed. Although accumulation of material inside the reactor was a main problem, this was avoided by removing and adding bed media along gasification. This allowed improving the process heat transfer and, therefore, gasification efficiency. The heating value of the produced gas was 8.4 MJ/Nm, attaining a hot gas efficiency of 70% and a cold gas efficiency of 57%. PMID:24453863

Colloidal mobilization of arsenic from mining-affected soils by surface runoff.

PubMed

Gomez-Gonzalez, Miguel Angel; Voegelin, Andreas; Garcia-Guinea, Javier; Bolea, Eduardo; Laborda, Francisco; Garrido, Fernando

2016-02-01

Scorodite-rich wastes left as a legacy of mining and smelting operations pose a threat to environmental health. Colloids formed by the weathering of processing wastes may control the release of arsenic (As) into surface waters. At a former mine site in Madrid (Spain), we investigated the mobilization of colloidal As by surface runoff from weathered processing wastes and from sediments in the bed of a draining creek and a downstream sedimentation-pond. Colloids mobilized by surface runoff during simulated rain events were characterized for their composition, structure and mode of As uptake using asymmetric flow field-flow fractionation coupled to inductively plasma mass spectrometry (AF4-ICP-MS) and X-ray absorption spectroscopy (XAS) at the As and Fe K-edges. Colloidal scorodite mobilized in surface runoff from the waste pile is acting as a mobile As carrier. In surface runoff from the river bed and the sedimentation pond, ferrihydrite was identified as the dominant As-bearing colloidal phase. The results from this study suggest that mobilization of As-bearing colloids by surface runoff may play an important role in the dispersion of As from metallurgical wastes deposited above ground and needs to be considered in risk assessment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Does fluorescence diagnosis have a role in follow up of response to therapy in mycosis fungoides?

PubMed

Bosseila, Manal; Mahgoub, Doaa; El-Sayed, Abeer; Salama, Dina; Abd El-Moneim, Marwa; Al-Helf, Fatma

2014-12-01

Monitoring of tumor burden during mycosis fungoides (MF) treatment, is crucial to adjust therapy accordingly. This is usually achieved through combined by clinical assessment with histopathological and immunohistochemical evaluation. To assess the validity of fluorescence diagnosis (FD) in the measurement of response to therapy in early MF, using in comparison flow cytometric technique of skin biopsies for CD4+/CD7- malignant T-cell count before and after therapy. Twenty-two patients of histologically proven early MF (stages Ia, Ib, IIa) were subjected to fluorescence diagnosis of their most affected skin lesion before and after 12 weeks of phototherapy with or without combination therapy. In comparison flow cytometric assessment of skin biopsies for CD4+/CD7- malignant T-cell count was evaluated before and after therapy from skin biopsy of the same lesion. All tested MF lesions showed varying degrees of fluorescence by FD at week zero, with a mean accumulation factor (AF), which is the fluorescence ratio between the tumor tissue and normal skin, of 2.2. After 12 weeks of therapy, the mean AF showed significant reduction to 1.94 (p=0.009). The percent of CD4+/CD7- cells dropped significantly after treatment (p=0.029). No correlation between CD4+/CD7- cell counts and the mean AF could be deduced. In cases of mycosis fungoides, fluorescence diagnosis can represent an effective tool for evaluating the response to therapy. Changes in accumulation factor values can be used for follow-up of therapy in the same patient, but it should not be used as an absolute value. Copyright © 2014 Elsevier B.V. All rights reserved.

Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverter-defibrillator. For the Worldwide Jewel AF Investigators.

PubMed

Swerdlow, C D; Schsls, W; Dijkman, B; Jung, W; Sheth, N V; Olson, W H; Gunderson, B D

2000-02-29

To distinguish prolonged episodes of atrial fibrillation (AF) that require cardioversion from self-terminating episodes that do not, an atrial implantable cardioverter-defibrillator (ICD) must be able to detect AF continuously for extended periods. The ICD should discriminate between atrial tachycardia/flutter (AT), which may be terminated by antitachycardia pacing, and AF, which requires cardioversion. We studied 80 patients with AT/AF and ventricular arrhythmias who were treated with a new atrial/dual-chamber ICD. During a follow-up period lasting 6+/-2 months, we validated spontaneous, device-defined AT/AF episodes by stored electrograms in all patients. In 58 patients, we performed 80 Holter recordings with telemetered atrial electrograms, both to validate the continuous detection of AT/AF and to determine the sensitivity of the detection of AT/AF. Detection was appropriate in 98% of 132 AF episodes and 88% of 190 AT episodes (98% of 128 AT episodes with an atrial cycle length <300 ms). Intermittent sensing of far-field R waves during sinus tachycardia caused 27 inappropriate AT/AF detections; these detections lasted 2.6+/-2.0 minutes. AT/AF was detected continuously in 27 of 28 patients who had spontaneous episodes of AT/AF (96%). The device memory recorded 90 appropriate AT/AF episodes lasting >1 hour, for a total of 2697 hours of continuous detection of AT/AF. During Holter monitoring, the sensitivity of the detection of AT/AF (116 hours) was 100%; the specificity of the detection of non-AT/AF rhythms (1290 hours) was 99.99%. Of 166 appropriate episodes detected as AT, 45% were terminated by antitachycardia pacing. A new ICD detects AT/AF accurately and continuously. Therapy may be programmed for long-duration AT/AF, with a low risk of underdetection. Discrimination of AT from AF permits successful pacing therapy for a significant fraction of AT.

Gastrointestinal infections and diarrheal disease in Ghanaian infants and children: an outpatient case-control study.

PubMed

Krumkamp, Ralf; Sarpong, Nimako; Schwarz, Norbert Georg; Adlkofer, Julia; Adelkofer, Julia; Loag, Wibke; Eibach, Daniel; Hagen, Ralf Matthias; Adu-Sarkodie, Yaw; Tannich, Egbert; May, Jürgen

2015-03-01

Diarrheal diseases are among the most frequent causes of morbidity and mortality in children worldwide, especially in resource-poor areas. This case-control study assessed the associations between gastrointestinal infections and diarrhea in children from rural Ghana. Stool samples were collected from 548 children with diarrhea and from 686 without gastrointestinal symptoms visiting a hospital from 2007-2008. Samples were analyzed by microscopy and molecular methods. The organisms most frequently detected in symptomatic cases were Giardia lamblia, Shigella spp./ enteroinvasive Escherichia coli (EIEC), and Campylobacter jejuni. Infections with rotavirus (adjusted odds ratio [aOR] = 8.4; 95% confidence interval [CI]: 4.3-16.6), C. parvum/hominis (aOR = 2.7; 95% CI: 1.4-5.2) and norovirus (aOR = 2.0; 95%CI: 1.3-3.0) showed the strongest association with diarrhea. The highest attributable fractions (AF) for diarrhea were estimated for rotavirus (AF = 14.3%; 95% CI: 10.9-17.5%), Shigella spp./EIEC (AF = 10.5%; 95% CI: 3.5-17.1%), and norovirus (AF = 8.2%; 95% CI 3.2-12.9%). Co-infections occurred frequently and most infections presented themselves independently of other infections. However, infections with E. dispar, C. jejuni, and norovirus were observed more often in the presence of G. lamblia. Diarrheal diseases in children from a rural area in sub-Saharan Africa are mainly due to infections with rotavirus, Shigella spp./EIEC, and norovirus. These associations are strongly age-dependent, which should be considered when diagnosing causes of diarrhea. The presented results are informative for both clinicians treating gastrointestinal infections as well as public health experts designing control programs against diarrheal diseases.

Mutations in GPR143/OA1 and ABCA4 Inform Interpretations of Short-Wavelength and Near-Infrared Fundus Autofluorescence

PubMed Central

Paavo, Maarjaliis; Zhao, Jin; Kim, Hye Jin; Lee, Winston; Zernant, Jana; Cai, Carolyn; Allikmets, Rando; Tsang, Stephen H.; Sparrow, Janet R.

2018-01-01

Purpose We sought to advance interpretations and quantification of short-wavelength fundus autofluorescence (SW-AF) emitted from bisretinoid lipofuscin and near-infrared autofluoresence (NIR-AF) originating from melanin. Methods Carriers of mutations in X-linked GPR143/OA1, a common form of ocular albinism; patients with confirmed mutations in ABCA4 conferring increased SW-AF; and subjects with healthy eyes were studied. SW-AF (488 nm excitation, 500–680 nm emission) and NIR-AF (excitation 787 nm, emission >830 nm) images were acquired with a confocal scanning laser ophthalmoscope. SW-AF images were analyzed for quantitative autofluoresence (qAF). Analogous methods of image acquisition and analysis were performed in albino and pigmented Abca4−/− mice and wild-type mice. Results Quantitation of SW-AF (qAF), construction of qAF color-coded maps, and examination of NIR-AF images from GPR143/OA1 carriers revealed mosaics in which patches of fundus exhibiting NIR-AF signal had qAF levels within normal limits whereas the hypopigmented areas in the NIR-AF image corresponded to foci of elevated qAF. qAF also was increased in albino versus pigmented mice. Although melanin contributes to fundus infrared reflectance, the latter appeared to be uniform in en face reflectance images of GPR143/OA1-carriers. In patients diagnosed with ABCA4-associated disease, NIR-AF increased in tandem with increased qAF originating in bisretinoid lipofuscin. Similarly in Abca4−/− mice having increased SW-AF, NIR-AF was more pronounced than in wild-type mice. Conclusions These studies corroborate RPE melanin as the major source of NIR-AF but also indicate that bisretinoid lipofuscin, when present at sufficient concentrations, contributes to the NIR-AF signal. Ocular melanin attenuates the SW-AF signal.

Aldosterone and renin in cardiac patients referred for catheterization.

PubMed

Erne, Paul; Müller, Andrea; Rossi, Gian Paolo; Seifert, Burkhardt; Stehlin, Fabrice; Redondo, Maurice; Bauer, Peter T; Kobza, Richard; Resink, Therese J; Radovanovic, Dragana

2017-06-01

Little is known regarding alterations of the renin-angiotensin system in patients referred for cardiac catheterization. Here, we measured plasma levels of active renin and aldosterone in patients referred for cardiac catheterization in order to determine the prevalence of elevated renin, aldosterone, and the aldosterone-renin ratio.A chemiluminescence assay was used to measure plasma aldosterone concentration (PAC) and active renin levels in 833 consecutive patients, after an overnight fasting and without any medication for least 12 hours. We evaluated associations of the hormonal elevations in relation to hypertension, atrial fibrillation (AF), hypertensive cardiomyopathy, coronary artery disease (CAD), valvular disease, impaired left ventricular ejection fraction (LVEF < 35%), and pulmonary hypertension (arterial pulmonary mean pressure >25 mm Hg).Hyperaldosteronism occurred in around one-third of all examined patients, without significant differences between patients with or without the named cardiac diseases. In a comparison between patients with or without any given cardiac disease condition, renin was significantly elevated in patients with either hypertension (36.4% vs 15.9%), CAD (33.9% vs 22.1%), or impaired LVEF (47.3% vs 24.8%). The angiotensin-renin ratio was elevated in AF patients and in patients with hypertensive cardiomyopathy. Patients with AF and coexisting hypertension had elevated renin more frequently than AF patients without coexisting hypertension (35.3% vs 16.5%; P  =  .005). Patients with persistent/permanent AF more frequently had elevated renin than patients with paroxysmal AF (34.1% vs 15.8%; P  =  .007).This prospective study of consecutive cardiac disease patients referred for cardiac catheterization has revealed distinct cardiac disease condition-associated differences in the frequencies of elevations in plasma renin, PAC, and the aldosterone-renin ratio.

Association of cardiac cachexia and atrial fibrillation in heart failure patients.

PubMed

Arámbula-Garza, Estefanía; Castillo-Martínez, Lilia; González-Islas, Dulce; Orea-Tejeda, Arturo; Santellano-Juárez, Brenda; Keirns-Davies, Candace; Peláez-Hernández, Viridiana; Sánchez-Santillán, Rocío; Pineda-Juárez, Juan; Cintora-Martínez, Carlos; Pablo-Santiago, Ruth

2016-11-15

Cachexia is a common complication in patients with advanced heart failure (HF) associated with inflammatory response activation. Atrial fibrillation (AF) is the most frequent arrhythmia (26%), probably both exacerbate the cardiac cachexia (CC). Evaluate the association of cardiac cachexia and atrial fibrillation in heart failure patients. In a case control study, CC was diagnosed by electrical bioimpedance with vectorial analysis (BIVA). Subjects with congenital heart disease, cancer, HIV, drug use and other causes than HF were excluded. Of the 359 subjects analyzed (men: 52.9%) median age 65years (55-74). Those with CC were older [72 (61-67)] vs. without [62 (52-70) years old, p<0.01]. During follow-up 47.8% of subjects developed CC and 17.27% AF, this was significantly more frequent in cachectic patients CC (23% vs 12.11%, OR: 2.17, 95% CI: 1.19-4.01, p=0.006). Subjects, with AF had lower left ventricular ejection fraction (25.49±12.96 vs. 32.01±15.02, p=0.08), lower posterior wall thickness (10.03±2.12 vs. 11.00±2.47, p=0.007), larger diameter of the left atrium (49.87±9.84 vs. 42.66±7.56, p<0.001), and a higher prevalence of CC (85.42% vs. 69.77%, p=0.028). The 50.58% of was in NYHA class I. In NYHA III, 22.95% were in AF vs. 12.10% with not AF (p=0.027). The frequent coexistence of CC and AF as HF complications indicate greater severity of HF, regardless of its type of HF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Aldosterone and renin in cardiac patients referred for catheterization

PubMed Central

Erne, Paul; Müller, Andrea; Rossi, Gian Paolo; Seifert, Burkhardt; Stehlin, Fabrice; Redondo, Maurice; Bauer, Peter T.; Kobza, Richard; Resink, Therese J.; Radovanovic, Dragana

2017-01-01

Abstract Little is known regarding alterations of the renin-angiotensin system in patients referred for cardiac catheterization. Here, we measured plasma levels of active renin and aldosterone in patients referred for cardiac catheterization in order to determine the prevalence of elevated renin, aldosterone, and the aldosterone-renin ratio. A chemiluminescence assay was used to measure plasma aldosterone concentration (PAC) and active renin levels in 833 consecutive patients, after an overnight fasting and without any medication for least 12 hours. We evaluated associations of the hormonal elevations in relation to hypertension, atrial fibrillation (AF), hypertensive cardiomyopathy, coronary artery disease (CAD), valvular disease, impaired left ventricular ejection fraction (LVEF < 35%), and pulmonary hypertension (arterial pulmonary mean pressure >25 mm Hg). Hyperaldosteronism occurred in around one-third of all examined patients, without significant differences between patients with or without the named cardiac diseases. In a comparison between patients with or without any given cardiac disease condition, renin was significantly elevated in patients with either hypertension (36.4% vs 15.9%), CAD (33.9% vs 22.1%), or impaired LVEF (47.3% vs 24.8%). The angiotensin-renin ratio was elevated in AF patients and in patients with hypertensive cardiomyopathy. Patients with AF and coexisting hypertension had elevated renin more frequently than AF patients without coexisting hypertension (35.3% vs 16.5%; P  =  .005). Patients with persistent/permanent AF more frequently had elevated renin than patients with paroxysmal AF (34.1% vs 15.8%; P  =  .007). This prospective study of consecutive cardiac disease patients referred for cardiac catheterization has revealed distinct cardiac disease condition-associated differences in the frequencies of elevations in plasma renin, PAC, and the aldosterone-renin ratio. PMID:28640140

[Estimates of Attributable Fraction of occupational cancers in the recent epidemiological literature].

PubMed

Merler, Enzo

2009-01-01

The article reviews the estimates of Attributable Fraction (AF) of occupational cancers. Because of their relevance, it starts with a synthesis and a comment on the estimates of avoidable cancers, and among these of cancers due to occupation, as expressed in 1981 by Doll and Peto. The main studies that have brought back into the epidemiological pathway the exercise of producing FA are quoted and the results of the new studies reviewed. The dimension of occupational cancers is of public health importance, because caused by exposures assumed to be avoidable. However, the estimates of AF are prone to uncertainties and limitations. Occupational cancers represent the major killer among deaths due to occupational diseases and injuries and a relevant fraction, especially among males, of total cancers. When related to developed countries, estimates may underestimate the risks, because of the insufficient data on exposures for workers in small firms, the lack of information on exposures in agriculture, the scanty availability of epidemiological studies on cancer risks among women. The trend towards a reduction of employees in industrial activities, the elimination or control of some exposures should suggest, instead, a reduction for occupational cancer. However, the more recent estimates of AF of occupational cancers are still in line with the estimates expressed more that 20 years ago. In developing countries, the estimates of AF are plenty of assumptions. In addition, some characteristics (i.e. the younger age of starting work, the extension of work at older age) suggest the need of better data, whereas information on exposures and events are dramatically lacking.

Fractional flow in fractured chalk; a flow and tracer test revisited.

PubMed

Odling, N E; West, L J; Hartmann, S; Kilpatrick, A

2013-04-01

A multi-borehole pumping and tracer test in fractured chalk is revisited and reinterpreted in the light of fractional flow. Pumping test data analyzed using a fractional flow model gives sub-spherical flow dimensions of 2.2-2.4 which are interpreted as due to the partially penetrating nature of the pumped borehole. The fractional flow model offers greater versatility than classical methods for interpreting pumping tests in fractured aquifers but its use has been hampered because the hydraulic parameters derived are hard to interpret. A method is developed to convert apparent transmissivity and storativity (L(4-n)/T and S(2-n)) to conventional transmissivity and storativity (L2/T and dimensionless) for the case where flow dimension, 2

Prognostic impact of heart rate in elderly with systolic heart failure and concomitant atrial fibrillation.

PubMed

Barywani, Salim; Petzold, Max

2017-08-01

The present study aimed to investigate the impact of resting heart rate (HR) on 5-year all-cause mortality in patients ≥80 years with heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant atrial fibrillation (AF) after optimal up-titration of beta-blockers (BBs). Patients (n = 185) aged ≥80 years with HF and left ventricular ejection fraction ≤40% were included between January 2000 and January 2008 from two university hospitals, Sahlgrenska and Östra and retrospectively studied from January 2 to May 30, 2013. Up-titrations of guideline recommended medications were performed at HF outpatient clinics. Of whole study population, 54% (n= 100) had AF. After optimal up-titration of BBs and angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), mean HR in patients with AF was 73 ± 15 beats/minute (bpm), 36% had resting HR ≤65 bpm. Five-year all-cause mortality among patients with AF was significantly lower in patients with HR ≤65 bpm (63%) compared to HR >65 (80%). Cox proportional-hazard regression analysis adjusted for clinically important baseline variables and doses of ACEIs/ARBs and BBs demonstrated resting HR ≤65 bpm as an independent predictor of improved survival compared to resting HR >65 bpm (HR 0.3, 95%CI 0.1-0.7, P 0.005). In octogenarians with HFrEF and concomitant AF, lowering resting HR to levels as low as HR ≤65 bpm was still associated with improved survival from all-cause mortality. Our data indicate that mortality in AF became comparable to SR when patients were on maximally up-titrated beta-blocker doses with HR as low as 75 bpm.

The modified stepwise ablation guided by low-dose ibutilide in chronic atrial fibrillation trial (The MAGIC-AF Study).

PubMed

Singh, Sheldon M; d'Avila, Andre; Kim, Young-Hoon; Aryana, Arash; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Barrett, Conor D; Heist, E Kevin; Parides, Michael K; Thorpe, Kevin E; Reddy, Vivek Y

2016-05-21

Complex fractionated atrial electrograms (CFAE) are targeted during persistent atrial fibrillation (AF) ablation. However, many CFAE sites are non-specific resulting in extensive ablation. Ibutilide has been shown to reduce left atrial surface area exhibiting CFAE. We hypothesized that ibutilide administration prior to CFAE ablation would identify sites critical for persistent AF maintenance allowing for improved procedural efficacy and long-term freedom from atrial arrhythmias. Two hundred patients undergoing a first-ever persistent AF catheter ablation procedure were randomly assigned to receive either 0.25 mg of intravenous ibutilide or saline placebo upon completion of pulmonary vein isolation. Complex fractionated atrial electrogram sites were then targeted with ablation. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs. Similar procedural characteristics (procedure, fluoroscopy, and ablation times) were observed with both strategies despite a greater reduction in left atrial surface area with CFAE sites (8 vs. 1%, P < 0.0001) and AF termination during CFAE ablation with ibutilide compared with placebo (75 vs. 57%, P = 0.007). The primary efficacy endpoint was achieved in 56% of patients receiving ibutilide and 49% receiving placebo (P = 0.35). No significant differences in peri-procedural complications were observed in both groups. Despite a reduction in CFAE area and greater AF termination during CFAE ablation, procedural characteristics and clinical outcomes were unchanged when CFAE ablation was guided by ibutilide administration. ClinicalTrials.gov number: NCT01014741. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions

PubMed Central

Scholz, Bastian; Kowarz, Eric; Rössler, Tanja; Ahmad, Khalil; Steinhilber, Dieter; Marschalek, Rolf

2015-01-01

AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble “super-elongation complexes” (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system. Here we addressed several questions: how is P-TEFb recruited into SEC, how is the AF4 interactome composed, and what is the function of the naturally occuring AF4N protein variant which exhibits only the first 360 amino acids of the AF4 full-length protein. Noteworthy, shorter protein variants are a specific feature of all AFF protein family members. Here, we demonstrate that full-length AF4 and AF4N are both catalyzing the transition of P-TEFb from 7SK RNP to their N-terminal domain. We have also mapped the protein-protein interaction network within both complexes. In addition, we have first evidence that the AF4N protein also recruits TFIIH and the tumor suppressor MEN1. This indicate that AF4N may have additional functions in transcriptional initiation and in MEN1-dependend transcriptional processes. PMID:26171280

A silk peptide fraction restores cognitive function in AF64A-induced Alzheimer disease model rats by increasing expression of choline acetyltransferase gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cha, Yeseul

This study investigated the effects of a silk peptide fraction obtained by incubating silk proteins with Protease N and Neutrase (SP-NN) on cognitive dysfunction of Alzheimer disease model rats. In order to elucidate underlying mechanisms, the effect of SP-NN on the expression of choline acetyltransferase (ChAT) mRNA was assessed in F3.ChAT neural stem cells and Neuro2a neuroblastoma cells; active amino acid sequence was identified using HPLC-MS. The expression of ChAT mRNA in F3.ChAT cells increased by 3.79-fold of the control level by treatment with SP-NN fraction. The active peptide in SP-NN was identified as tyrosine-glycine with 238.1 of molecular weight.more » Male rats were orally administered with SP-NN (50 or 300 mg/kg) and challenged with a cholinotoxin AF64A. As a result of brain injury and decreased brain acetylcholine level, AF64A induced astrocytic activation, resulting in impairment of learning and memory function. Treatment with SP-NN exerted recovering activities on acetylcholine depletion and brain injury, as well as cognitive deficit induced by AF64A. The results indicate that, in addition to a neuroprotective activity, the SP-NN preparation restores cognitive function of Alzheimer disease model rats by increasing the release of acetylcholine. - Highlights: • Cognition-enhancing effects of SP-NN, a silk peptide preparation, were investigated. • SP-NN enhanced ChAT mRNA expression in F3.ChAT neural stem cells and Neuro-2a neuroblastoma cells. • Active molecule was identified as a dipeptide composed of tyrosine-glycine. • SP-NN reversed cognitive dysfunction elicited by AF64A. • Neuroprotection followed by increased acetylcholine level was achieved with SP-NN.« less

The hypolipidemic effect and antithrombotic activity of Mucuna pruriens protein hydrolysates.

PubMed

Herrera Chalé, Francisco; Ruiz Ruiz, Jorge Carlos; Betancur Ancona, David; Acevedo Fernández, Juan José; Segura Campos, Maira Rubi

2016-01-01

Hydrolysates and peptide fractions (PF) obtained from M. pruriens protein concentrates with commercial and digestive enzymatic systems were studied for their hypolipidemic and antithrombotic activities. Hydrolysates obtained with Pepsin-Pancreatin (PP) and their peptide fractions inhibited cholesterol micellar solubility with a maximum value of 1.83% in PP. Wistar rats were used to evaluate the hypolipidemic effect of hydrolysates and PF. The higher reductions of cholesterol and triglyceride levels were exhibited by PP and both peptide fractions <1 kDa obtained from PP and Alcalase®-Flavourzyme® hydrolysate (AF) at a dose of 15 mg kg(-1) of animal weight. PF > 10 kDa from both hydrolysates showed the maximum antithrombotic activity with values of 33.33% for PF > 10 kDa from AF and 31.72% for PF > 10 kDa from PP. The results suggest that M. pruriens bioactive peptides with the hypolipidemic effect and antithrombotic activity might be utilized as nutraceuticals.

Identification of active atrial fibrillation sources and their discrimination from passive rotors using electrographical flow mapping.

PubMed

Bellmann, Barbara; Lin, Tina; Ruppersberg, Peter; Zettwitz, Marit; Guttmann, Selma; Tscholl, Verena; Nagel, Patrick; Roser, Mattias; Landmesser, Ulf; Rillig, Andreas

2018-05-09

The optimal ablation approach for the treatment of persistent atrial fibrillation (AF) is still under debate; however, the identification and elimination of AF sources is thought to play a key role. Currently available technologies for the identification of AF sources are not able to differentiate between active rotors or focal impulse (FI) and passive circular turbulences as generated by the interaction of a wave front with a functional obstacle such as fibrotic tissue. This study introduces electrographic flow (EGF) mapping as a novel technology for the identification and characterization of AF sources in humans. Twenty-five patients with AF (persistent: n = 24, long-standing persistent: n = 1; mean age 70.0 ± 8.3 years, male: n = 17) were included in this prospective study. Focal impulse and Rotor-Mapping (FIRM) was performed in addition to pulmonary vein isolation using radiofrequency in conjunction with a 3D-mapping-system. One-minute epochs were exported from the EP-recording-system and re-analyzed using EGF mapping after the procedure. 44 potential AF sources (43 rotors and one FI) were identified with FIRM and 39 of these rotors were targeted for ablation. EGF mapping verified 40 of these patterns and identified 24/40 (60%) as active sources while 16/40 (40%) were classified as passive circular turbulences. Four rotors were not identified by EGF mapping. EGF is the first method to identify active AF sources during AF ablation procedures in humans and discriminate them from passive rotational phenomena, which occur if the excitation wavefront passes conduction bariers. EGF mapping may allow improved guidance of AF ablation procedures.

Using Kepler K2 to Measure the Binary Fraction of PN Central Stars

NASA Astrophysics Data System (ADS)

Jacoby, George H.; Hillwig, Todd; De Marco, Orsola; Hurowitz, Jonathan; Jones, David; Kronberger, Matthias; Harmer, Dianne

2018-01-01

During the initial Kepler mission, 5 Planetary Nebula (PN) central stars were observed. The light curves for 4 of these central stars indicated a history of close binary interactions. That large fraction was suggestive that the actual fraction of PN harboring close binaries is much larger than the known lower limit of 20%, but that sample is far too small to be compelling. We have since acquired Kepler K2 data for Campaigns 0, 2, 7, and 11, hosting PN samples of 3, 4, 8, and 185 targets, respectively. We will provide an update on the number of binary candidates found in each field, and in particular, the Galactic Bulge field of Campaign 11. We also will discuss the challenges of working with Kepler observations in the crowded Campaign 11 field and the impact of those challenges on our ability to estimate the fraction of PN central stars that are binaries. This study was supported in part by NASA grants NNX17AE64G and NNX17AF80G.

Left atrial dysfunction in patients with patent foramen ovale and atrial septal aneurysm: an alternative concurrent mechanism for arterial embolism?

PubMed

Rigatelli, Gianluca; Aggio, Silvio; Cardaioli, Paolo; Braggion, Gabriele; Giordan, Massimo; Dell'avvocata, Fabio; Chinaglia, Mauro; Rigatelli, Giorgio; Roncon, Loris; Chen, Jack P

2009-07-01

We postulate that, in patients with large patent foramen ovales (PFO) and atrial septal aneurysms (ASA), left atrial (LA) dysfunction simulating "atrial fibrillation (AF)-like" pathophysiology might represent an alternate mechanism in the promotion of arterial embolism. Despite prior reports concerning paradoxical embolism through a PFO, the magnitude of this phenomenon as a risk factor for stroke remains undefined, because deep venous thrombosis is infrequently detected in such patients. To test our hypothesis, we prospectively enrolled 98 consecutive patients with previous stroke (mean age 37 +/- 12.5 years, 58 women) referred to our center for catheter-based PFO closure. Baseline values of LA passive and active emptying, LA conduit function, LA ejection fraction, and spontaneous echocontrast (SEC) in the LA and LA appendage were compared with those of 50 AF patients as well as a sex/age/cardiac risk-matched population of 70 healthy control subjects. Pre-closure PFO subjects demonstrated significantly greater reservoir function as well as passive and active emptying, with significantly reduced conduit function and LA ejection fraction, when compared with AF and control patients. Furthermore, in PFO patients, 66.3% (65 of 98) had moderate-to-severe ASA and basal shunt; SEC was observed in 52% of PFO plus ASA patients before closure. Multivariate stepwise logistic regression revealed moderate-to-severe ASA (odds ratio: 9.4, 95% confidence interval: 7.0 to 23.2, p < 0.001) as the most powerful predictor of LA dysfunction. After closure, all LA parameters normalized to the levels of control subjects: no SEC, device-related thrombosis, or aortic erosion were observed on follow-up echocardiography. This study suggests that moderate-to-severe ASA might be associated with LA dysfunction in patients with PFO. The resultant similarities to the pathophysiology of AF might represent an additional contributing mechanism for arterial embolism in such patients.

Prognostic indicators for dogs with dilated cardiomyopathy.

PubMed

Borgarelli, Michele; Santilli, Roberto A; Chiavegato, David; D'Agnolo, Gino; Zanatta, Renato; Mannelli, Alessandro; Tarducci, Alberto

2006-01-01

The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic, and Doppler echocardiographic variables in dogs with dilated cardiomyopathy. The relationship to survival of 11 variables was evaluated in 63 dogs. Studied variables were age at time of diagnosis, class of heart failure (HF), dyspnea, ascites, atrial fibrillation (AF), ejection fraction (EF), E-point septal separation, end-diastolic volume index, end-systolic volume index (ESV-I), and restrictive or nonrestrictive transmitral flow (TMF) pattern. Median survival time was 671 days (lower 95% confidence limit, 350 days). Survival curves showed that severity of HF, ascites, ESV-I greater than 140 mL/m2, EF less than 25%, and restrictive TMF pattern had a significant negative relation to survival time. Thirty-nine dogs with both sinus rhythm and AF presented adequate TMF recordings; in these dogs, after stratification by TMF pattern, the restrictive TMF pattern was the most important negative prognostic indicator. We conclude that in dogs with dilated cardiomyopathy the restrictive TMF pattern appears to represent a useful prognostic indicator. Class of HF, ascites, ESV-I, and EF are also useful indexes if an adequate TMF pattern is not recorded.

Isolation of canine mesenchymal stem cells from amniotic fluid and differentiation into hepatocyte-like cells.

PubMed

Choi, Seon-A; Choi, Hoon-Sung; Kim, Keun Jung; Lee, Dong-Soo; Lee, Ji Hey; Park, Jie Yeun; Kim, Eun Young; Li, Xiaoxia; Oh, Hyun-Yang; Lee, Dong-Seok; Kim, Min Kyu

2013-01-01

Recent findings have demonstrated that amniotic fluid cells are an interesting and potential source of mesenchymal stem cells (MSCs). In this study, we isolated MSCs from canine amniotic fluid and then characterized their multilineage differentiation ability. Canine amniotic fluid stem (cAFS) cells at passage 5 had a fibroblast-like morphology instead of forming colonies and were positive for pluripotent stem cell markers such as OCT4, NANOG, and SOX2. Flow cytometry analysis showed the expression of MSC surface markers CD44, CD29, and CD90 on the cAFS cells. In addition, these cells were cultured under conditions favorable for adipogenic, chondrogenic, and osteogenic induction. The results of this experiment confirmed the mesenchymal nature of cAFS cells and their multipotent potential. Interestingly, although the cells exhibited a fibroblast-like morphology after hepatogenic induction, reverse transcription-polymerase chain reaction revealed that the expression of several hepatic genes, such as albumin, tyrosine aminotransferase, and alpha-1 antiproteinase, increased following maturation and differentiation. These findings indicated that cAFS cells have functional properties similar to those of hepatocytes. Taken together, the results of our study demonstrated that cAFS cells with mesenchymal characteristics can be successfully isolated from canine amniotic fluid and possess functional properties characteristic of hepatocytes. The findings of our work suggest that cAFS cells have the potential to be a resource for cell-based therapies in a canine model of hepatic disease.

Common Atrial Fibrillation Risk Alleles at 4q25 Predict Recurrence after Catheter-based Atrial Fibrillation Ablation

PubMed Central

Shoemaker, M. Benjamin; Muhammad, Raafia; Parvez, Babar; White, Brenda W.; Streur, Megan; Song, Yanna; Stubblefield, Tanya; Kucera, Gayle; Blair, Marcia; Rytlewski, Jason; Parvathaneni, Sunthosh; Nagarakanti, Rangadham; Saavedra, Pablo; Ellis, Christopher; Whalen, S. Patrick; Roden, Dan M; Darbar, Dawood

2012-01-01

Background Common single nucleotide polymorphisms (SNPs) at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical AF. Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5–30% of AF cases. Objective To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases. Methods Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years, 71% male, 89% typical AF) between 2004 and 2011. The primary endpoint was time to recurrence of any non-sinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF; [AT/AF]). Results Two-hundred AT/AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76 95% confidence interval [CI] 0.6–0.95, P=0.016) compared with wild-type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio = 0.79, 95% CI 0.62–0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio = 0.61, 95% CI 0.37–1.0) (P=0.037). Conclusion Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of predominately typical AF patients. Our findings suggest the rs2200733 polymorphism may hold promise as an as an objectively measured patient characteristic that can used as a clinical tool for selection of patients for AF ablation. PMID:23178686

ICP-MS based methods to characterize nanoparticles of TiO2 and ZnO in sunscreens with focus on regulatory and safety issues.

PubMed

Bocca, Beatrice; Caimi, Stefano; Senofonte, Oreste; Alimonti, Alessandro; Petrucci, Francesco

2018-07-15

This study sought to develop analytical methods to characterize titanium dioxide (TiO 2 ) and zinc oxide (ZnO) nanoparticles (NPs), including the particle size distribution and concentration, in cream and spray sunscreens with different sun protection factor (SPF). The Single Particle Inductively Coupled Plasma-Mass Spectrometry (SP ICP-MS) was used as screening and fast method to determine particles size and number. The Asymmetric Flow-Field Flow Fractionation (AF4-FFF) as a pre-separation technique was on-line coupled to the Multi-Angle Light Scattering (MALS) and ICP-MS to determine particle size distributions and size dependent multi-elemental concentration. Both methods were optimized in sunscreens in terms of recovery, repeatability, limit of detection and linear dynamic range. Results showed that sunscreens contained TiO 2 particles with an average size of ≤107 nm and also a minor number of ZnO particles sized ≤98 nm. The higher fraction of particles <100 nm was observed in sunscreens with SPF 50+ (ca. 80%); the lower percentage (12-35%) in sunscreens with lower SPF values. Also the higher TiO 2 (up to 24% weight) and ZnO (ca. 0.25% weight) concentrations were found in formulations of SPF 50+. Creamy sunscreens could be considered safe containing TiO 2 and ZnO NPs less than the maximum allowable concentration of 25% weight as set by the European legislation. On the contrary, spray products required additional considerations with regard to the potential inhalation of NPs. The developed methods can contribute to the actual demand for regulatory control and safety assessment of metallic NPs in consumers' products. Copyright © 2018 Elsevier B.V. All rights reserved.

[Impact of CHA2DS2 VASc score on substrate for persistent atrial fibrillation and outcome post catheter ablation of atrial fibrillation].

PubMed

Ribo, Tang; Jianzeng, Dong; Xiaohui, Liu; Meisheng, Shang; Ronghui, Yu; Deyong, Long; Xin, Du; Junping, Kang; Jiahui, Wu; Man, Ning; Caihua, Sang; Chenxi, Jiang; Rong, Bai; Songnan, Li; Yan, Yao; Songnan, Wen; Changsheng, Ma

2015-08-01

To explore if CHA2DS2 VASc score can predict substrate for persistent atrial fibrillation ( AF) and outcome post catheter ablation of AF. From January 2011 to December 2012,116 patients underwent catheter ablation of persistent AF in our department and were enrolled in this study. CHA2DS2VASc score was calculated as follows: two points were assigned for a history of stroke or transient ischemic attack and age ≥ 75 and 1 point each was assigned for age ≥ 65, a history of hypertension, diabetes,recent cardiac failure, vessel disease, female. Left atrial geometry ( LA) was reconstructed with a 3.5 mm tip ablation catheter with fill-in threshold 10 in CARTO system. The mapping catheter was stabled at each endocardial location for at least 3 seconds for recording. The electrogram recordings at each endocardial location were analyzed with a custom software embedded in the CARTO mapping system. Interval confidence level (ICL) was used to characterize complex fractionated atrial electrograms (CFAEs) . As the default setting of the software, ICL more than or equal to 7 was considered sites with a highly repetitive CFAEs complex. CFAEs index was defined as the fraction of area of ICL more than or equal to 7 to the left atrial surface. The CFAEs index and outcome of catheter ablation among different CHA2DS2VASc groups were compared. Of the 116 patients, CHA2DS2VASc was 0 in 33 patients, 1 in 31 patients and ≥ 2 in 52 patients. Left atrial surface ((121.2 ± 18.9) cm2, (133.6 ± 23.8) cm2, (133.9 ± 16.1) cm2, P = 0.008), left atrial volume ((103.6 ± 24.8) ml, (118.3 ± 27.8) ml, (120.9 ± 20.9) ml, P = 0.005) and CFAEs index (44.6% ± 22.4%, 54.2% ± 22.2%, 58.7% ± 23.1%, P = 0.023) increased in proportion with increasing CHA2DS2VASc. ICLmax, ICLmin and CFAEs spatial distribution were similar among the three groups. During the mean follow-up of (13 ± 8) months, the recurrence rate were 36.4%, 35.5%, 55.8% among the three groups (P = 0.025). A high CHA2DS2VASc score is associated with extensive AF substrate and higher recurrence rate post catheter ablation of persistent AF.

Decreased Mortality With Beta-Blockers in Patients With Heart Failure and Coexisting Atrial Fibrillation: An AF-CHF Substudy.

PubMed

Cadrin-Tourigny, Julia; Shohoudi, Azadeh; Roy, Denis; Talajic, Mario; Tadros, Rafik; Mondésert, Blandine; Dyrda, Katia; Rivard, Léna; Andrade, Jason G; Macle, Laurent; Guerra, Peter G; Thibault, Bernard; Dubuc, Marc; Khairy, Paul

2017-02-01

The impact of beta-blockers on mortality and hospitalizations was assessed in the largest randomized trial of patients with both atrial fibrillation (AF) and heart failure with a reduced ejection fraction (HFrEF): the Atrial Fibrillation-Congestive Heart Failure trial. Although beta-blockers are the cornerstone of therapy for HFrEF, a recent patient-level meta-analysis cast doubt on their efficacy in patients with coexisting AF. From a total of 1,376 subjects randomized in the AF-CHF trial, those without beta-blockers at baseline were propensity matched to a maximum of 2 exposed patients. All absolute standardized differences after matching were ≤10%. Primary analyses respected the intention-to-treat principle. In on-treatment sensitivity analyses, beta-blocker status was modeled as a time-dependent covariate. Baseline characteristics were comparable among the matched cohorts (mean age 70 ± 11 years, 81% male, and mean left ventricular ejection fraction 27 ± 6%). During a median follow-up of 37 months, beta-blockers were associated with significantly lower all-cause mortality (hazard ratio [HR]: 0.721, 95% confidence interval [CI]: 0.549 to 0.945; p = 0.0180) but not hospitalizations (HR: 0.886; 95% CI: 0.715 to 1.100; p = 0.2232). Similar results were obtained in sensitivity analyses that modeled beta-blockers as a time-dependent variable (HR: 0.668 for all-cause mortality; 95% CI: 0.511 to 0.874; p = 0.0032; HR: 0.814 for hospitalizations; 95% CI: 0.653 to 1.014; p = 0.0658). There were no significant interactions between beta-blockers and patterns (i.e., persistent vs. paroxysmal) or burden of AF with respect to mortality or hospitalizations. In propensity-matched analyses, beta-blockers were associated with significantly lower mortality but not hospitalizations in patients with HFrEF and AF, irrespective of the pattern or burden of AF. These results support current evidence-based recommendations for beta-blockers in patients with HFrEF, whether or not they have associated AF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium.

PubMed

Toporcov, Tatiana Natasha; Znaor, Ariana; Zhang, Zuo-Feng; Yu, Guo-Pei; Winn, Deborah M; Wei, Qingyi; Vilensky, Marta; Vaughan, Thomas; Thomson, Peter; Talamini, Renato; Szeszenia-Dabrowska, Neonila; Sturgis, Erich M; Smith, Elaine; Shangina, Oxana; Schwartz, Stephen M; Schantz, Stimson; Rudnai, Peter; Richiardi, Lorenzo; Ramroth, Heribert; Purdue, Mark P; Olshan, Andrew F; Eluf-Neto, José; Muscat, Joshua; Moyses, Raquel Ajub; Morgenstern, Hal; Menezes, Ana; McClean, Michael; Matsuo, Keitaro; Mates, Dana; Macfarlane, Tatiana V; Lissowska, Jolanta; Levi, Fabio; Lazarus, Philip; La Vecchia, Carlo; Lagiou, Pagona; Koifman, Sergio; Kjaerheim, Kristina; Kelsey, Karl; Holcatova, Ivana; Herrero, Rolando; Healy, Claire; Hayes, Richard B; Franceschi, Silvia; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W; Curioni, Otávio Alberto; Maso, Luigino Dal; Curado, Maria Paula; Conway, David I; Chen, Chu; Castellsague, Xavier; Canova, Cristina; Cadoni, Gabriella; Brennan, Paul; Boccia, Stefania; Antunes, José Leopoldo Ferreira; Ahrens, Wolfgang; Agudo, Antonio; Boffetta, Paolo; Hashibe, Mia; Lee, Yuan-Chin Amy; Filho, Victor Wünsch

2015-02-01

Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. We pooled data from 25 case-control studies and conducted separate analyses for adults ≤ 45 years old ('young adults', 2010 cases and 4042 controls) and >45 years old ('older adults', 17700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI=9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking=5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR=2.27 (95% CI=1.26, 4.10)], but not in the older adults [OR=1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium

PubMed Central

Toporcov, Tatiana Natasha; Znaor, Ariana; Zhang, Zuo-Feng; Yu, Guo-Pei; Winn, Deborah M; Wei, Qingyi; Vilensky, Marta; Vaughan, Thomas; Thomson, Peter; Talamini, Renato; Szeszenia-Dabrowska, Neonila; Sturgis, Erich M; Smith, Elaine; Shangina, Oxana; Schwartz, Stephen M; Schantz, Stimson; Rudnai, Peter; Richiardi, Lorenzo; Ramroth, Heribert; Purdue, Mark P; Olshan, Andrew F; Eluf-Neto, José; Muscat, Joshua; Moyses, Raquel Ajub; Morgenstern, Hal; Menezes, Ana; McClean, Michael; Matsuo, Keitaro; Mates, Dana; Macfarlane, Tatiana V; Lissowska, Jolanta; Levi, Fabio; Lazarus, Philip; Vecchia, Carlo La; Lagiou, Pagona; Koifman, Sergio; Kjaerheim, Kristina; Kelsey, Karl; Holcatova, Ivana; Herrero, Rolando; Healy, Claire; Hayes, Richard B; Franceschi, Silvia; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W; Curioni, Otávio Alberto; Maso, Luigino Dal; Curado, Maria Paula; Conway, David I; Chen, Chu; Castellsague, Xavier; Canova, Cristina; Cadoni, Gabriella; Brennan, Paul; Boccia, Stefania; Antunes, José Leopoldo Ferreira; Ahrens, Wolfgang; Agudo, Antonio; Boffetta, Paolo; Hashibe, Mia; Lee, Yuan-Chin Amy; Filho, Victor Wünsch

2015-01-01

Background: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. Methods: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤45 years old (‘young adults’, 2010 cases and 4042 controls) and >45 years old (‘older adults’, 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (−11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (−2.41%, 5.80%) in older adults. Conclusions: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults. PMID:25613428

Impaired endothelial function in lone atrial fibrillation.

PubMed

Polovina, Marija; Potpara, Tatjana; Giga, Vojislav; Stepanović, Jelena; Ostojić, Miodrag

2013-10-01

Impaired endothelial function has been previously documented in patients with atrial fibrillation (AF) and underlying comorbidities or older patients with idiopathic AF. The aim of this study was to evaluate systemic endothelial function in younger AF patients (less than < 60 years old) with lone AF (that is, without associated cardiopulmonary comorbidities, including arterial hypertension), by comparing brachial artery flow-mediated dilation (FMD) in lone AF patients with FMD of healthy subjects in sinus rhythm. Two groups of participants were prospectively enrolled. The first group comprised of 38 AF patients (the mean age 45 +/- 11 years, 68% male) with persistent (> 7 days) lone AF. The second group comprised of 28 healthy controls in sinus rhythm (the mean age 43 +/- 13, 53% male), matched by age, gender and atherosclerotic risk factors. All the participants underwent physical examination, laboratory analysis [including determination of C-reactive protein (CRP)], standard echocardiography and exercise-stress testing. Brachial artery FMD and endothelium independent dilation (NMD) were assessed with a high-resolution ultrasound probe and arterial diameters taken from 5 consecutive cardiac cycles were averaged for each measurement to accommodate to beat-to-beat flow variations in AF. There were no differences between the 2 groups regarding age, gender and most clinical, laboratory and echocardiographic characteristics (all p > 0.05), apart from the increased heart rate (p = 0.018), body mass index (p = 0.027), CRP levels (p = 0.007) and left atrial anteroposterior dimension (p < 0.001) in AF patients. FMD of AF patients [median value 5.0%, interquartile range (IQR) 2.87%-7.50%] was significantly lower (p < 0.001) than FMD of healthy controls (median value 8.85%, IQR 5.80%-12.50%), whereas there were no differences in median NMD values (p > 0.05). In the multivariate analysis, the independent FMD determinants in our study population were the presence of AF, smoking and total cholesterol levels (all p < 0.001). In patients with AF, the strongest independent FMD determinant was arrhythmia duration (p < 0.001), followed by smoking (p = 0.013) and total cholesterol levels (p = 0.045). Our findings confirm that sustained AF is associated with systemic endothelial dysfunction even in relatively young patients with no cardiovascular disorders or risk factors. AF is an independent contributor to lower FMD and a prolonged arrhythmia duration may confer the risk for more profound endothelial damage.

C and N Content in Density Fractions of Whole Soil and Soil Size Fraction Under Cacao Agroforestry Systems and Natural Forest in Bahia, Brazil

NASA Astrophysics Data System (ADS)

Rita, Joice Cleide O.; Gama-Rodrigues, Emanuela Forestieri; Gama-Rodrigues, Antonio Carlos; Polidoro, Jose Carlos; Machado, Regina Cele R.; Baligar, Virupax C.

2011-07-01

Agroforestry systems (AFSs) have an important role in capturing above and below ground soil carbon and play a dominant role in mitigation of atmospheric CO2. Attempts has been made here to identify soil organic matter fractions in the cacao-AFSs that have different susceptibility to microbial decomposition and further represent the basis of understanding soil C dynamics. The objective of this study was to characterize the organic matter density fractions and soil size fractions in soils of two types of cacao agroforestry systems and to compare with an adjacent natural forest in Bahia, Brazil. The land-use systems studied were: (1) a 30-year-old stand of natural forest with cacao (cacao cabruca), (2) a 30-year-old stand of cacao with Erythrina glauca as shade trees (cacao + erythrina), and (3) an adjacent natural forest without cacao. Soil samples were collected from 0-10 cm depth layer in reddish-yellow Oxisols. Soil samples was separated by wet sieving into five fraction-size classes (>2000 μm, 1000-2000 μm, 250-1000 μm, 53-250 μm, and <53 μm). C and N accumulated in to the light (free- and intra-aggregate density fractions) and heavy fractions of whole soil and soil size fraction were determined. Soil size fraction obtained in cacao AFS soils consisted mainly (65 %) of mega-aggregates (>2000 μm) mixed with macroaggregates (32-34%), and microaggregates (1-1.3%). Soil organic carbon (SOC) and total N content increased with increasing soil size fraction in all land-use systems. Organic C-to-total N ratio was higher in the macroaggregate than in the microaggregate. In general, in natural forest and cacao cabruca the contribution of C and N in the light and heavy fractions was similar. However, in cacao + erythrina the heavy fraction was the most common and contributed 67% of C and 63% of N. Finding of this study shows that the majority of C and N in all three systems studied are found in macroaggregates, particularly in the 250-1000 μm size aggregate class. The heavy fraction was the most common organic matter fraction in these soils. Thus, in mature cacao AFS on highly weathered soils the main mechanisms of C stabilization could be the physical protection within macroaggregate structures thereby minimizing the impact of conversion of forest to cacao AFS.

C and N content in density fractions of whole soil and soil size fraction under cacao agroforestry systems and natural forest in Bahia, Brazil.

PubMed

Rita, Joice Cleide O; Gama-Rodrigues, Emanuela Forestieri; Gama-Rodrigues, Antonio Carlos; Polidoro, Jose Carlos; Machado, Regina Cele R; Baligar, Virupax C

2011-07-01

Agroforestry systems (AFSs) have an important role in capturing above and below ground soil carbon and play a dominant role in mitigation of atmospheric CO(2). Attempts has been made here to identify soil organic matter fractions in the cacao-AFSs that have different susceptibility to microbial decomposition and further represent the basis of understanding soil C dynamics. The objective of this study was to characterize the organic matter density fractions and soil size fractions in soils of two types of cacao agroforestry systems and to compare with an adjacent natural forest in Bahia, Brazil. The land-use systems studied were: (1) a 30-year-old stand of natural forest with cacao (cacao cabruca), (2) a 30-year-old stand of cacao with Erythrina glauca as shade trees (cacao + erythrina), and (3) an adjacent natural forest without cacao. Soil samples were collected from 0-10 cm depth layer in reddish-yellow Oxisols. Soil samples was separated by wet sieving into five fraction-size classes (>2000 μm, 1000-2000 μm, 250-1000 μm, 53-250 μm, and <53 μm). C and N accumulated in to the light (free- and intra-aggregate density fractions) and heavy fractions of whole soil and soil size fraction were determined. Soil size fraction obtained in cacao AFS soils consisted mainly (65 %) of mega-aggregates (>2000 μm) mixed with macroaggregates (32-34%), and microaggregates (1-1.3%). Soil organic carbon (SOC) and total N content increased with increasing soil size fraction in all land-use systems. Organic C-to-total N ratio was higher in the macroaggregate than in the microaggregate. In general, in natural forest and cacao cabruca the contribution of C and N in the light and heavy fractions was similar. However, in cacao + erythrina the heavy fraction was the most common and contributed 67% of C and 63% of N. Finding of this study shows that the majority of C and N in all three systems studied are found in macroaggregates, particularly in the 250-1000 μm size aggregate class. The heavy fraction was the most common organic matter fraction in these soils. Thus, in mature cacao AFS on highly weathered soils the main mechanisms of C stabilization could be the physical protection within macroaggregate structures thereby minimizing the impact of conversion of forest to cacao AFS.

Estimation of absorbed fraction to the anterior nose from inhaled beta emitters

NASA Astrophysics Data System (ADS)

Moussa, Hanna Moussa

2000-08-01

The main purpose of this research is to introduce a new and more realistic geometry for the anterior nose region (ET1) as an alternative to the one provided in ICRP Publication 66. For a more accurate estimation of electron absorbed fraction (AF) to the nuclei of basal cells in the ET 1 region, the proposed new geometry (frustum of a cone) replaces the cylinder geometry, which was used in ICRP 66. Since the electron absorbed fraction (AF) data in ICRP 66 are calculated based on the nose size for an adult Caucasian male, a second purpose of this research is to investigate how the nose size (different ethnic groups) and nose tissue composition (male, female and adolescent), affects the electron absorbed fraction values. The third aim of this research is to develop a Monte Carlo program to estimate the electron energies that emerge from the surface of spherical dust particles. Given that electrons can be located anywhere between the center and the surface of the sphere, we vary the sphere radius from 0.5 to 50 μm and investigate the effects of self-absorption on the emitted electron energies and absorbed fraction.

Comparison of spectral estimators for characterizing fractionated atrial electrograms

PubMed Central

2013-01-01

Background Complex fractionated atrial electrograms (CFAE) acquired during atrial fibrillation (AF) are commonly assessed using the discrete Fourier transform (DFT), but this can lead to inaccuracy. In this study, spectral estimators derived by averaging the autocorrelation function at lags were compared to the DFT. Method Bipolar CFAE of at least 16 s duration were obtained from pulmonary vein ostia and left atrial free wall sites (9 paroxysmal and 10 persistent AF patients). Power spectra were computed using the DFT and three other methods: 1. a novel spectral estimator based on signal averaging (NSE), 2. the NSE with harmonic removal (NSH), and 3. the autocorrelation function average at lags (AFA). Three spectral parameters were calculated: 1. the largest fundamental spectral peak, known as the dominant frequency (DF), 2. the DF amplitude (DA), and 3. the mean spectral profile (MP), which quantifies noise floor level. For each spectral estimator and parameter, the significance of the difference between paroxysmal and persistent AF was determined. Results For all estimators, mean DA and mean DF values were higher in persistent AF, while the mean MP value was higher in paroxysmal AF. The differences in means between paroxysmals and persistents were highly significant for 3/3 NSE and NSH measurements and for 2/3 DFT and AFA measurements (p<0.001). For all estimators, the standard deviation in DA and MP values were higher in persistent AF, while the standard deviation in DF value was higher in paroxysmal AF. Differences in standard deviations between paroxysmals and persistents were highly significant in 2/3 NSE and NSH measurements, in 1/3 AFA measurements, and in 0/3 DFT measurements. Conclusions Measurements made from all four spectral estimators were in agreement as to whether the means and standard deviations in three spectral parameters were greater in CFAEs acquired from paroxysmal or in persistent AF patients. Since the measurements were consistent, use of two or more of these estimators for power spectral analysis can be assistive to evaluate CFAE more objectively and accurately, which may lead to improved clinical outcome. Since the most significant differences overall were achieved using the NSE and NSH estimators, parameters measured from their spectra will likely be the most useful for detecting and discerning electrophysiologic differences in the AF substrate based upon frequency analysis of CFAE. PMID:23855345

Experimental study on the void fraction of air-water two-phase flow in a horizontal circular minichannel

NASA Astrophysics Data System (ADS)

Sudarja, Indarto, Deendarlianto, Haq, Aqli

2016-06-01

Void fraction is an important parameter in two-phase flow. In the present work, the adiabatic two-phase air-water flow void fraction in a horizontal minichannel has been studied experimentally. A transparent circular channel with 1.6 mm inner diameter was employed as the test section. Superficial gas and liquid velocities were varied in the range of 1.25 - 66.3 m/s and 0.033 - 4.935 m/s, respectively. Void fraction data were obtained by analyzing the flow images being captured by using a high-speed camera. Here, the homogeneous (β) and the measured void fractions (ɛ), respectively, were compared to the existing correlations. It was found that: (1) for the bubbly and slug flows, the void fractions increases with the increase of JG, (2) for churn, slug-annular, and annular flow patterns, there is no specific correlation between JG and void fraction was observed due to effect of the slip between gas and liquid, and (3) whilst for bubbly and slug flows the void fractions are close to homogeneous line, for churn, annular, and slug-annular flows are far below the homogeneous line. It indicates that the slip ratios for the second group of flow patterns are higher than unity.

Can P wave wavelet analysis predict atrial fibrillation after coronary artery bypass grafting?

PubMed

Vassilikos, Vassilios; Dakos, George; Chouvarda, Ioanna; Karagounis, Labros; Karvounis, Haralambos; Maglaveras, Nikolaos; Mochlas, Sotirios; Spanos, Panagiotis; Louridas, George

2003-01-01

The purpose of this study was the evaluation of Morlet wavelet analysis of the P wave as a means of predicting the development of atrial fibrillation (AF) in patients who undergo coronary artery bypass grafting (CABG). The P wave was analyzed using the Morlet wavelet in 50 patients who underwent successful CABG. Group A consisted of 17 patients, 12 men and 5 women, of mean age 66.9 +/- 5.9 years, who developed AF postoperatively. Group B consisted of 33 patients, 29 men and 4 women, mean age 62.4 +/- 7.8 years, who remained arrhythmid-free. Using custom-designed software, P wave duration and wavelet parameters expressing the mean and maximum energy of the P wave were calculated from 3-channel digital recordings derived from orthogonal ECG leads (X, Y, and Z), and the vector magnitude (VM) was determined in each of 3 frequency bands (200-160 Hz, 150-100 Hz and 90-50 Hz). Univariate logistic-regression analysis identified a history of hypertension, the mean and maximum energies in all frequency bands along the Z axis, the mean and maximum energies (expressed by the VM) in the 200-160 Hz frequency band, and the mean energy in the 150-100 Hz frequency band along the Y axis as predictors for post-CABG AF. Multivariate analysis identified hypertension, ejection fraction, and the maximum energies in the 90-50 Hz frequency band along the Z and composite-vector axes as independent predictors. This multivariate model had a sensitivity of 91% and a specificity of 65%. We conclude that the Morlet wavelet analysis of the P wave is a very sensitive method of identifying patients who are likely to develop AF after CABG. The occurrence of post-CABG AF can be explained by a different activation pattern along the Z axis.

The burden of occupationally-related cutaneous malignant melanoma in Britain due to solar radiation.

PubMed

Rushton, Lesley; J Hutchings, Sally

2017-02-14

Increasing evidence highlights the association of occupational exposure and cutaneous malignant melanoma (CMM). We estimated the burden of CMM and total skin cancer burden in Britain due to occupational solar radiation exposure. Attributable fractions (AF) and numbers were estimated for CMM mortality and incidence using risk estimates from the published literature and national data sources for proportions exposed. We extended existing methods to account for the exposed population age structure. The estimated total AF for CMM is 2.0% (95% CI: 1.4-2.7%), giving 48 (95% CI: 33-64) deaths in (2012) and 241 (95% CI: 168-325) registrations (in 2011) attributable to occupational exposure to solar radiation. Higher exposure and larger numbers exposed led to much higher numbers for men than women. Industries of concern are construction, agriculture, public administration and defence, and land transport. These results emphasise the urgent need to develop appropriate strategies to reduce this burden.

Adverse effects of permanent atrial fibrillation on heart failure in patients with preserved left ventricular function and chronic right apical pacing for complete heart block.

PubMed

Lampe, Brigitte; Hammerstingl, Christoph; Schwab, Jörg Otto; Mellert, Fritz; Stoffel-Wagner, Birgit; Grigull, Andreas; Fimmers, Rolf; Maisch, Bernhard; Nickenig, Georg; Lewalter, Thorsten; Yang, Alexander

2012-10-01

The impact of atrial fibrillation (AF) on heart failure (HF) was evaluated in patients with preserved left ventricular (LV) function and long-term right ventricular (RV) pacing for complete heart block. Clinical, echocardiographic, and laboratory parameters of HF were assessed in 35 patients with established AF who had undergone ablation of the atrioventricular node and pacemaker implantation (Group A) and 31 patients who received dual-chamber pacing for spontaneous complete heart block (Group B). During a follow-up period of 12.7 ± 7.5 years, New York Heart Association (NYHA) functional class increased from 1.3 ± 0.5 to 2.1 ± 0.6 (p < 0.0001) in Group A, and from 1.3 ± 0.4 to 1.6 ± 0.7 (p < 0.01) in Group B. Left ventricular ejection fraction (LVEF) decreased from 59.7 ± 5.1 to 53.0 ± 8.2 (p < 0.0001) in Group A, but remained stable (58.6 ± 4.2 vs. 56.9 ± 7.0 %, p = 0,21) in Group B. At the end of follow-up, markers of LV function were moderately depressed in Group A compared with those in Group B: NYHA class 2.1 ± 0.6 versus 1.6 ± 0.7, p = 0.001; LVEF 53.0 ± 8.2 versus 56.9 ± 7.0 %, p < 0.05; LV diastolic diameter 53.6 ± 5.8 mm versus 50.7 ± 4.9 mm, p < 0.05; N-terminal pro-brain natriuretic peptide (NT-proBNP) 1116.8 ± 883.9 versus 622.9 ± 1059.4 pg/ml, p < 0.05. Progression of paroxysmal AF to permanent AF during follow-up was common, while new onset of AF was rare. Permanent AF was an independent predictor of declining LVEF >10 %, increasing NYHA class ≥1, and NT-proBNP levels >1,000 pg/ml. Permanent AF was associated with adverse effects on LV function and symptoms of HF in patients with long-term RV pacing for complete heart block, and appears to play an important role in the development of HF in this specific patient cohort.

Risk factors for persistent atrial fibrillation following successful hyperthyroidism treatment with radioiodine therapy.

PubMed

Zhou, Zhen-Hu; Ma, Long-Le; Wang, Le-Xin

2011-01-01

To investigate the predicting factors for persistent atrial fibrillation (AF) following radioiodine therapy for hyperthyroidism. Standard 12-lead ECG and 24-h Holter monitoring were performed in 94 patients (38 males, mean age 46.1±8.2 years) with persistent AF following radioiodine therapy for hyperthyroidism. Left ventricular (LV) function was assessed with two-dimensional echocardiography. Euthyroidism or hypothyroidism was achieved in 81% and 19% of the patients, respectively, after radioiodine therapy. At the end of follow-up (1.6±1.3 years), LV ejection fraction in the 52 patients with LV dysfunction was increased from 39.3±3.3% to 59.0±5.5% (p<0.01). In the 38 patients with pre-treatment paroxysmal AF, no AF was documented during the follow-up. In the 45 patients with pre-treatment persistent AF, AF was found in 27 (60%) during the follow-up. Multivariate logistic regression analysis showed that more than 55 years old in age (RR 2.76, 95% CI: 1.16-8.79, p<0.01), duration of hyperthyroidism (RR 3.08, 95% CI: 1.22-11.41, p<0.01) and duration of pre-treatment atrial fibrillation (RR 2.96, 95% CI: 1.31-7.68, p<0.01) were independent predictors for persistent AF following radioiodine therapy. Older age, duration of hyperthyroidism and pre-treatment duration of AF are risk factors for persistent AF following radioiodine therapy.

Flow Regime Based Climatologies of Lightning Probabilities for Spaceports and Airports

NASA Technical Reports Server (NTRS)

Bauman, William H., III; Volmer, Matthew; Sharp, David; Spratt, Scott; Lafosse, Richard A.

2007-01-01

Objective: provide forecasters with a "first guess" climatological lightning probability tool (1) Focus on Space Shuttle landings and NWS T AFs (2) Four circles around sites: 5-, 10-, 20- and 30 n mi (4) Three time intervals: hourly, every 3 hr and every 6 hr It is based on: (1) NLDN gridded data (2) Flow regime (3) Warm season months of May-Sep for years 1989-2004 Gridded data and available code yields squares, not circles Over 850 spread sheets converted into manageable user-friendly web-based GUI

Global-scale high-resolution ( 1 km) modelling of mean, maximum and minimum annual streamflow

NASA Astrophysics Data System (ADS)

Barbarossa, Valerio; Huijbregts, Mark; Hendriks, Jan; Beusen, Arthur; Clavreul, Julie; King, Henry; Schipper, Aafke

2017-04-01

Quantifying mean, maximum and minimum annual flow (AF) of rivers at ungauged sites is essential for a number of applications, including assessments of global water supply, ecosystem integrity and water footprints. AF metrics can be quantified with spatially explicit process-based models, which might be overly time-consuming and data-intensive for this purpose, or with empirical regression models that predict AF metrics based on climate and catchment characteristics. Yet, so far, regression models have mostly been developed at a regional scale and the extent to which they can be extrapolated to other regions is not known. We developed global-scale regression models that quantify mean, maximum and minimum AF as function of catchment area and catchment-averaged slope, elevation, and mean, maximum and minimum annual precipitation and air temperature. We then used these models to obtain global 30 arc-seconds (˜ 1 km) maps of mean, maximum and minimum AF for each year from 1960 through 2015, based on a newly developed hydrologically conditioned digital elevation model. We calibrated our regression models based on observations of discharge and catchment characteristics from about 4,000 catchments worldwide, ranging from 100 to 106 km2 in size, and validated them against independent measurements as well as the output of a number of process-based global hydrological models (GHMs). The variance explained by our regression models ranged up to 90% and the performance of the models compared well with the performance of existing GHMs. Yet, our AF maps provide a level of spatial detail that cannot yet be achieved by current GHMs.

Conventional versus 3-D Echocardiography to Predict Arrhythmia Recurrence After Atrial Fibrillation Ablation.

PubMed

Bossard, Matthias; Knecht, Sven; Aeschbacher, Stefanie; Buechel, Ronny R; Hochgruber, Thomas; Zimmermann, Andreas J; Kessel-Schaefer, Arnheid; Stephan, Frank-Peter; Völlmin, Gian; Pradella, Maurice; Sticherling, Christian; Osswald, Stefan; Kaufmann, Beat A; Conen, David; Kühne, Michael

2017-06-01

Arrhythmia recurrence after atrial fibrillation (AF) ablation remains high and requires repeat interventions in a substantial number of patients. We assessed the value of conventional and 3-D echocardiography to predict AF recurrence. Consecutive patients undergoing AF ablation by means of pulmonary vein isolation were included in a prospective registry. Echocardiograms were obtained prior to the ablation procedure, and analyzed offline in a standardized manner, including 3-D left atrial (LA) volumetry and determination of LA function and sphericity. The primary endpoint, AF recurrence (>30 seconds) between 3 to 12 months after AF ablation, was independently adjudicated. We included 276 patients (73% male, mean age 59.9 ± 9.9 years). Paroxysmal and persistent AF were present in 178 (64%) and 98 (36%) patients, respectively. Mean left ventricular ejection fraction and indexed LA volume in 3-D (LAVI) were 52 ± 12% and 42 ± 13 mL/m 2 , respectively. AF recurrence was observed in 110 (40%) patients after a single procedure. Median (interquartile range) time to AF recurrence was 123 (92; 236) days. In multivariable Cox regression models, the only predictors for AF recurrence were the minimal, maximal, and indexed 3-D LA volumes, P = 0.024, P = 0.016, and P = 0.014, respectively. Quartile specific analysis of 3-D LAVI showed an HR of 1.885 (95%CI 1.066-3.334; P for trend = 0.015) for the highest compared to the lowest quartile. Our results show the important role of LA volume for the long-term freedom from arrhythmia after AF ablation. These data also highlight the potential of 3-D echocardiography in this context and may facilitate patient selection for AF ablation. © 2017 Wiley Periodicals, Inc.

Panoramic Electrophysiological Mapping but not Electrogram Morphology Identifies Stable Sources for Human Atrial Fibrillation

PubMed Central

Narayan, Sanjiv M.; Shivkumar, Kalyanam; Krummen, David E.; Miller, John M.; Rappel, Wouter-Jan

2013-01-01

Background The foundation for successful arrhythmia ablation is the mapping of electric propagation to identify underlying mechanisms. In atrial fibrillation (AF), however, mapping is difficult so that ablation has often targeted electrogram features, with mixed results. We hypothesized that wide field-of-view (panoramic) mapping of both atria would identify causal mechanisms for AF and allow interpretation of local electrogram features, including complex fractionated atrial electrograms (CFAE). Methods and Results Contact mapping was performed using biatrial multipolar catheters in 36 AF subjects (29 persistent). Stable AF rotors (spiral waves) or focal sources were seen in 35 of 36 cases and targeted for ablation (focal impulse and rotor modulation) before pulmonary vein isolation. In 31 of 36 subjects (86.1%), AF acutely terminated (n=20; 16 to sinus rhythm) or organized (n=11; 19±8% slowing) with 2.5 minutes focal impulse and rotor modulation (interquartile range, 1.0–3.1) at one source, defined as the primary source. Subjects exhibited 2.1±1.0 concurrent AF sources of which the primary, by phase mapping, precessed in limited areas (persistent 2.5±1.7 versus paroxysmal 1.7±0.5 cm2; P=0.30). Notably, source regions showed mixed electrogram amplitudes and CFAE grades that did not differ from surrounding atrium (P=NS). AF sources were not consistently surrounded by CFAE (P=0.67). Conclusions Stable rotors and focal sources for human AF were revealed by contact panoramic mapping (focal impulse and rotor modulation mapping), but not by electrogram footprints. AF sources precessed within areas of ≈2 cm2, with diverse voltage characteristics poorly correlated with CFAE. Most CFAE sites lie remote from AF sources and are not suitable targets for catheter ablation of AF. PMID:23392583

Experimental and numerical studies of a microfluidic device with compliant chambers for flow stabilization

NASA Astrophysics Data System (ADS)

Iyer, V.; Raj, A.; Annabattula, R. K.; Sen, A. K.

2015-07-01

This paper reports experimental and numerical studies of a passive microfluidic device that stabilizes a pulsating incoming flow and delivers a steady flow at the outlet. The device employs a series of chambers along the flow direction with a thin polymeric membrane (of thickness 75-250 µm) serving as the compliant boundary. The deformation of the membrane allows accumulation of fluid during an overflow and discharge of fluid during an underflow for flow stabilization. Coupled fluid-structure simulations are performed using Mooney-Rivlin formulations to account for a thin hyperelastic membrane material undergoing large deformations to accurately predict the device performance. The device was fabricated with PDMS as the substrate material and thin PDMS membrane as the compliant boundary. The performance of the device is defined in terms of a parameter called ‘Attenuation Factor (AF)’. The effect of various design parameters including membrane thickness, elastic modulus, chamber size and number of chambers in series as well as operating conditions including the outlet pressure, mean input flow rate, fluctuation amplitude and frequency on the device performance were studied using experiments and simulations. The simulation results successfully confront the experimental data (within 10%) which validates the numerical simulations. The device was used at the exit of a PZT actuated valveless micropump to take pulsating flow at the upstream and deliver steady flow downstream. The amplitude of the pulsating flow delivered by the micropump was significantly reduced (AF = 0.05 for a device with three 4 mm chambers) but at the expense of a reduction in the pressure capability (<20%). The proposed device could potentially be used for reducing flow pulsations in practical microfluidic circuits.

NanoRelease: Pilot interlaboratory comparison of a ...

EPA Pesticide Factsheets

A major use of multi-walled carbon nanotubes (MWCNTs) is as functional fillers embedded in a solid matrix, such as plastics or coatings. Weathering and abrasion of the solid matrix during use can lead to environmental releases of the MWCNTs. Here we focus on a protocol to identify and quantify the primary release induced by weathering, and assess reproducibility, transferability, and sensitivity towards different materials and uses. We prepared 132 specimens of two polymer-MWCNT composites containing the same grade of MWCNTs used in earlier OECD hazard assessments but without UV stabilizer. We report on a pilot inter-laboratory comparison (ILC) with four labs (two US and two EU) aging by UV and rain, then shipping for analysis. Two labs (one US and one EU) conducted the release sampling and analysis by Transmission Electron Microscopy (TEM), Inductively Coupled Plasma- Mass Spectrometry (ICP-MS), Ultraviolet–Visible Spectroscopy (UV–Vis), Analytical Ultracentrifugation (AUC), and Asymmetric Flow Field Flow Fractionation (AF4). We compare results between aging labs, between analysis labs and between materials. Surprisingly, we found quantitative agreement between analysis labs for TEM, ICP-MS, UV–Vis; low variation between aging labs by all methods; and consistent rankings of release between TEM, ICP-MS, UV–Vis, AUC. Significant disagreement was related primarily to differences in aging, but even these cases remained within a factor of two. Published in t

Dy-V magnetic interaction and local structure bias on the complex spin and orbital ordering in Dy₁₋ xTb xVO₃ (x=0 and 0.2)

DOE PAGES

Yan, J.-Q.; Cao, H. B.; McGuire, M. A.; ...

2013-06-10

The spin and orbital ordering in Dy₁₋ xTb xVO₃ (x=0 and 0.2) was studied by measuring x-ray powder diffraction, magnetization, specific heat, and neutron single-crystal diffraction. The results show that G-OO/C-AF and C-OO/G-AF phases coexist in Dy 0.8Tb 0.20VO 3 in the temperature range 2–60 K, and the volume fraction of each phase is temperature and field dependent. The ordering of Dy moments at T* = 12 K induces a transition from G-OO/C-AF to a C-OO/G-AF phase. Magnetic fields suppress the long-range order of Dy moments and thus the C-OO/G-AF phase below T*. The polarized moments induced at the Dymore » sublattice by external magnetic fields couple to the V 3d moments, and this coupling favors the G-OO/C-AF state. Also discussed is the effect of the Dy-V magnetic interaction and local structure distortion on the spin and orbital ordering in Dy₁₋ xTb xVO₃.« less

Is CHA2DS2-VASc appropriate for hyperthyroid patients with atrial fibrillation? Implications of adding a transesophageal echocardiography evaluation.

PubMed

de Souza, Marcus Vinicius Leitão; de Fátima Dos Santos Teixeira, Patricia; Vaisman, Mario; Xavier, Sergio Salles

2017-02-01

Anticoagulation remains a controversial issue among hyperthyroid patients with atrial fibrillation (AF). We aimed to evaluate the prevalence of the thrombogenic milieu (TM), detected using transesophageal echocardiography (TEE), among patients with AF related to hyperthyroidism, and to correlate these findings with the clinical embolic risk classification (CHA 2 DS 2 -VASc). CHA 2 DS 2 -VASc score, thyroid hormonal status, time since hyperthyroidism diagnosis, transthoracic echocardiography (TTE) and TEE were assessed in 47 consecutive patients aged between 18 and 65years with AF related to hyperthyroidism. The following TEE parameters defined TM: dense spontaneous echo contrast, thrombi, or left atrial appendage (LAA) blood flow velocities <0.20m/s. Non-classic TM was defined as non-dense SEC plus LAA flow velocity 0.20-0.40m/s. Pulmonary hypertension was present in 39/47 (81.4%) and TM in 22/47 (46.8%) patients. Despite a low CHA 2 DS 2 -VASc score of 0/1, 10 of 19 (52.6%) patients had a TM, whereas 16 of 28 (57.1%) patients with score ≥2 had none. The probability of having a TM did not correlate with CHA 2 DS 2 -VASc scores. On regression binary analysis, hyperthyroidism diagnosed more than 12months previous was independently associated with non-classic TM (p=0.031). Among patients younger than 65years of age with AF related to hyperthyroidism, pulmonary hypertension and TM on TEE were highly prevalent. There was no association between CHA 2 DS 2 -VASc with TEE markers of TM. Thyroid status, especially longer duration of hyperthyroidism might influence thrombogenic abnormalities. TEE adds useful information that may change antithrombotic therapy if otherwise guided solely by clinical risk classification. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Performance and age of African and non-African runners in half- and full marathons held in Switzerland, 2000–2010

PubMed Central

Aschmann, André; Knechtle, Beat; Cribari, Marco; Rüst, Christoph Alexander; Onywera, Vincent; Rosemann, Thomas; Lepers, Romuald

2013-01-01

Background Endurance running performance of African (AF) and non-African (NAF) athletes is investigated, with better performances seen for Africans. To date, no study has compared the age of peak performance between AF and NAF runners. The present research is an analysis of the age and running performance of top AF and NAF athletes, using the hypothesis that AF athletes were younger and faster than NAF athletes. Methods Age and performance of male and female AF and NAF athletes in half-marathons and marathons held in Switzerland in 2000–2010 were investigated using single and multilevel hierarchical regression analyses. Results For half-marathons, male NAF runners were older than male AF runners (P = 0.02; NAF, 31.1 years ± 6.4 years versus AF, 26.2 years ± 4.9 years), and their running time was longer (P = 0.02; NAF, 65.3 minutes ± 1.7 minutes versus AF, 64.1 minutes ± 0.9 minutes). In marathons, differences between NAF and AF male runners in age (NAF, 33.0 years ± 4.8 years versus AF, 28.6 years ± 3.8 years; P < 0.01) and running time (NAF, 139.5 minutes ± 5.6 minutes versus AF, 133.3 minutes ± 2.7 minutes; P < 0.01) were more pronounced. There was no difference in age (NAF, 31.0 years ± 7.0 years versus AF, 26.7 years ± 6.0 years; P > 0.05) or running time (NAF, 75.0 minutes ± 3.7 minutes versus AF, 75.6 minutes ± 5.3 minutes; P > 0.05) between NAF and AF female half-marathoners. For marathoners, NAF women were older than AF female runners (P = 0.03; NAF, 31.6 years ± 4.8 years versus AF, 27.8 years ± 5.3 years), but their running times were similar (NAF, 162.4 minutes ± 7.2 minutes versus AF, 163.0 minutes ± 7.0 minutes; P > 0.05). Conclusion In Switzerland, the best AF male half-marathoners and marathoners were younger and faster than the NAF counterpart runners. In contrast to the results seen in men, AF and NAF female runners had similar performances. Future studies need to investigate performance and age of AF and NAF marathoners in the World Marathon Majors Series. PMID:24379724

Water-soluble ions species of size-resolved aerosols: Implications for the atmospheric acidity in São Paulo megacity, Brazil

NASA Astrophysics Data System (ADS)

Vieira-Filho, Marcelo; Pedrotti, Jairo J.; Fornaro, Adalgiza

2016-11-01

Over the last decade, an increase of ammonium salts in atmospheric deposition has been reported worldwide, especially in megacities. The present study aims to give a better comprehension analysis about particulate matter acidity in São Paulo megacity (MASP), Brazil. Size-resolved aerosols were sampled in MASP, during 2012 winter, showing a bimodal mass concentration distribution, with sulfate concentration exceeding 3.40 μg m- 3, which accounted for over 25% of PM0.56 mass. Regarding the relative distribution of ionic species, 90% of NH4+ levels, were restricted to smaller than 1 μm diameter range. The average neutralization index for PM < 1 μm was 0.62, which indicated an ammonia-limiting atmosphere due to partial neutralization of atmospheric acids. Particles of the accumulation mode presented more acid behavior than other aerosol fractions, with pH value as low as 4.15 in PM0.56. The total neutralization index registered the lowest value for PM0.56, but it did not respond promptly to aerosol variations as the E-AIM model predictions. The highest discrepancies between the acidity proxies occurred in the smaller fractions of particulate matter, especially in the after-filter (AF) stage (diameter < 0.020 μm). In addition, AF stage had the highest contribution to PM total mass, about 14% for all the stages analyzed. Such contribution indicates that acidity in ultrafine particles are still mixed for the MASP and need further investigation.

Supersonic nonlinear potential analysis

NASA Technical Reports Server (NTRS)

Siclari, M. J.

1984-01-01

The NCOREL computer code was established to compute supersonic flow fields of wings and bodies. The method encompasses an implicit finite difference transonic relaxation method to solve the full potential equation in a spherical coordinate system. Two basic topic to broaden the applicability and usefulness of the present method which is encompassed within the computer code NCOREL for the treatment of supersonic flow problems were studied. The first topic is that of computing efficiency. Accelerated schemes are in use for transonic flow problems. One such scheme is the approximate factorization (AF) method and an AF scheme to the supersonic flow problem is developed. The second topic is the computation of wake flows. The proper modeling of wake flows is important for multicomponent configurations such as wing-body and multiple lifting surfaces where the wake of one lifting surface has a pronounced effect on a downstream body or other lifting surfaces.

Global longitudinal strain corrected by RR interval is a superior predictor of all-cause mortality in patients with systolic heart failure and atrial fibrillation.

PubMed

Modin, Daniel; Sengeløv, Morten; Jørgensen, Peter Godsk; Bruun, Niels Eske; Olsen, Flemming Javier; Dons, Maria; Fritz Hansen, Thomas; Jensen, Jan Skov; Biering-Sørensen, Tor

2018-04-01

Quantification of systolic function in patients with atrial fibrillation (AF) is challenging. A novel approach, based on RR interval correction, to counteract the varying heart cycle lengths in AF has recently been proposed. Whether this method is superior in patients with systolic heart failure (HFrEF) with AF remains unknown. This study investigates the prognostic value of RR interval-corrected peak global longitudinal strain {GLSc = GLS/[RR^(1/2)]} in relation to all-cause mortality in HFrEF patients displaying AF during echocardiographic examination. Echocardiograms from 151 patients with HFrEF and AF during examination were analysed offline. Peak global longitudinal strain (GLS) was averaged from 18 myocardial segments obtained from three apical views. GLS was indexed with the square root of the RR interval {GLSc = GLS/[RR^(1/2)]}. Endpoint was all-cause mortality. During a median follow-up of 2.7 years, 40 patients (26.5%) died. Neither uncorrected GLS (P = 0.056) nor left ventricular ejection fraction (P = 0.053) was significantly associated with all-cause mortality. After RR^(1/2) indexation, GLSc became a significant predictor of all-cause mortality (hazard ratio 1.16, 95% confidence interval 1.02-1.22, P = 0.014, per %/s^(1/2) decrease). GLSc remained an independent predictor of mortality after multivariable adjustment (age, sex, mean heart rate, mean arterial blood pressure, left atrial volume index, and E/e') (hazard ratio 1.17, 95% confidence interval 1.05-1.31, P = 0.005 per %/s^(1/2) decrease). Decreasing {GLSc = GLS/[RR^(1/2)]}, but not uncorrected GLS nor left ventricular ejection fraction, was significantly associated with increased risk of all-cause mortality in HFrEF patients with AF and remained an independent predictor after multivariable adjustment. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

The solid-state fermentation of Artemisia capillaris leaves with Ganoderma lucidum enhances the anti-inflammatory effects in a model of atopic dermatitis

PubMed Central

Son, Hyeong-U; Lee, Seul; Heo, Jin-Chul; Lee, Sang-Han

2017-01-01

Artemisia capillaris, which belongs to the Asteraceae family and the genus Artemisia, has been reported to exert inhibitory effects on diabetes, cancer and inflammation. In this study, in order to enhance the bioactivity potential of the leaves of Artemisia by Ganoderma lucidum mycelium, we prepared aqueous samples of Artemisia capillaris (Ac) leaves, Ganoderma lucidum (Gl) and aqueous fractions produced by the solid fermentation of Ganoderma lucidum on Artemisia capillaris leaves (afAc/Gl). Thereafter, we evaluated whether these samples have potential to attenuate inflammation-related symptoms in an amimal model of 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis. We found that afAc/Gl exhibited enhanced anti-inflamamatory activity following the solid fermentation process when compared with Ac or Gl on ear thickness, ear epidermal thickness and eosinophil infiltration in the skin tissues. The expression of nitric oxide (NO) synthases (NOSs) was measured by immunohistochemical staining. The results revealed that afAc/Gl decreased endothelial NOS and inducible NOS expression compared with the DNFB group, while neuronal NOS expression was not altered. By comparing NO production, we found that as opposed to Ac, afAc/Gl has potential to inhibit atopic dermatitis-related symptoms during the inflammatory event. As regards matrix metalloproteinase (MMP) expression patterns, afAc/Gl exerted potent inhibitory activity on the mRNA expression of MMP-2, -7, -9, -12, -14 and -19. Taken together, these results suggest that the solid state fermentation of Ac by Gl is an effective strategy to obtaining useful ingredients which are converted into valuable compounds during an atopic inflammatory insult. PMID:28393198

The solid-state fermentation of Artemisia capillaris leaves with Ganoderma lucidum enhances the anti-inflammatory effects in a model of atopic dermatitis.

PubMed

Son, Hyeong-U; Lee, Seul; Heo, Jin-Chul; Lee, Sang-Han

2017-05-01

Artemisia capillaris, which belongs to the Asteraceae family and the genus Artemisia, has been reported to exert inhibitory effects on diabetes, cancer and inflammation. In this study, in order to enhance the bioactivity potential of the leaves of Artemisia by Ganoderma lucidum mycelium, we prepared aqueous samples of Artemisia capillaris (Ac) leaves, Ganoderma lucidum (Gl) and aqueous fractions produced by the solid fermentation of Ganoderma lucidum on Artemisia capillaris leaves (afAc/Gl). Thereafter, we evaluated whether these samples have potential to attenuate inflammation-related symptoms in an amimal model of 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis. We found that afAc/Gl exhibited enhanced anti-inflamamatory activity following the solid fermentation process when compared with Ac or Gl on ear thickness, ear epidermal thickness and eosinophil infiltration in the skin tissues. The expression of nitric oxide (NO) synthases (NOSs) was measured by immunohistochemical staining. The results revealed that afAc/Gl decreased endothelial NOS and inducible NOS expression compared with the DNFB group, while neuronal NOS expression was not altered. By comparing NO production, we found that as opposed to Ac, afAc/Gl has potential to inhibit atopic dermatitis-related symptoms during the inflammatory event. As regards matrix metalloproteinase (MMP) expression patterns, afAc/Gl exerted potent inhibitory activity on the mRNA expression of MMP-2, -7, -9, -12, -14 and -19. Taken together, these results suggest that the solid state fermentation of Ac by Gl is an effective strategy to obtaining useful ingredients which are converted into valuable compounds during an atopic inflammatory insult.

In permanent atrial fibrillation, PDE3 reduces force responses to 5‐HT, but PDE3 and PDE4 do not cause the blunting of atrial arrhythmias

PubMed Central

Schwarz, Simon; Ravens, Ursula; Knaut, Michael

2016-01-01

Abstract Background and Purpose 5‐HT increases force and L‐type Ca2 + current (ICa,L) and causes arrhythmias through 5‐HT4 receptors in human atrium. In permanent atrial fibrillation (peAF), atrial force responses to 5‐HT are blunted, arrhythmias abolished but ICa,L responses only moderately attenuated. We investigated whether, in peAF, this could be due to an increased function of PDE3 and/or PDE4, using the inhibitors cilostamide (300 nM) and rolipram (1 μM) respectively. Experimental Approach Contractile force, arrhythmic contractions and ICa,L were assessed in right atrial trabeculae and myocytes, obtained from patients with sinus rhythm (SR), paroxysmal atrial fibrillation (pAF) and peAF. Key Results Maximum force responses to 5‐HT were reduced to 15% in peAF, but not in pAF. Cilostamide, but not rolipram, increased both the blunted force responses to 5‐HT in peAF and the inotropic potency of 5‐HT fourfold to sevenfold in trabeculae of patients with SR, pAF and peAF. Lusitropic responses to 5‐HT were not decreased in peAF. Responses of ICa,L to 5‐HT did not differ and were unaffected by cilostamide or rolipram in myocytes from patients with SR or peAF. Concurrent cilostamide and rolipram increased 5‐HT's propensity to elicit arrhythmias in trabeculae from patients with SR, but not with peAF. Conclusions and Implications PDE3, but not PDE4, reduced inotropic responses to 5‐HT in peAF, independently of lusitropy and ICa,L, but PDE3 activity was the same as that in patients with SR and pAF. Atrial remodelling in peAF abolished the facilitation of 5‐HT to induce arrhythmias by inhibition of PDE3 plus PDE4. PMID:27238373

Catheter ablation versus medical therapy for patients with persistent atrial fibrillation: a systematic review and meta-analysis of evidence from randomized controlled trials.

PubMed

Chen, Chen; Zhou, Xinbin; Zhu, Min; Chen, Shenjie; Chen, Jie; Cai, Hongwen; Dai, Jin; Xu, Xiaoming; Mao, Wei

2018-06-01

The superiority of catheter ablation (CA) for persistent (and long-standing persistent) atrial fibrillation (AF) is currently not well defined. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the clinical outcomes of CA compared with medical therapy in persistent AF patients. We systematically searched PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov for RCTs comparing CA with medical therapy in patients with persistent AF. For CA vs medical rhythm control, the primary outcome was freedom from atrial arrhythmia. For CA vs medical rate control, the primary outcome was the change in the left ventricular ejection fraction (LVEF). Eight studies with a total of 809 patients were included in the final analysis. Compared with medical rhythm control, CA was superior in achieving freedom from atrial arrhythmia (RR 2.08, 95% CI [1.67, 2.58]; P < 0.00001). Similar result was found in CA arm without antiarrhythmic drug use after operation (RR 1.82, 95%CI [1.33, 2.49]; P = 0.0002). CA was also superior in reducing the probability of cardioversion (RR 0.59, 95%CI [0.46, 0.76]; P < 0.0001) and hospitalization (RR 0.54, 95%CI [0.39, 0.74]; P = 0.0002). Compared with the medical rate control in persistent AF patients with heart failure (HF), CA significantly improved the LVEF (MD 7.72, 95%CI [4.78, 10.67]; P < 0.00001) and reduced Minnesota Living with Heart Failure Questionnaire scores (MD 11.1395% CI [2.52-19.75]; P = 0.01). CA appeared to be superior to medical therapy in persistent AF patients and might be considered as a first-line therapy for some persistent AF patients especially for those with HF.

Randomized ablation strategies for the treatment of persistent atrial fibrillation: RASTA study.

PubMed

Dixit, Sanjay; Marchlinski, Francis E; Lin, David; Callans, David J; Bala, Rupa; Riley, Michael P; Garcia, Fermin C; Hutchinson, Mathew D; Ratcliffe, Sarah J; Cooper, Joshua M; Verdino, Ralph J; Patel, Vickas V; Zado, Erica S; Cash, Nancy R; Killian, Tony; Tomson, Todd T; Gerstenfeld, Edward P

2012-04-01

The single-procedure efficacy of pulmonary vein isolation (PVI) is less than optimal in patients with persistent atrial fibrillation (AF). Adjunctive techniques have been developed to enhance single-procedure efficacy in these patients. We conducted a study to compare 3 ablation strategies in patients with persistent AF. Subjects were randomized as follows: arm 1, PVI + ablation of non-PV triggers identified using a stimulation protocol (standard approach); arm 2, standard approach + empirical ablation at common non-PV AF trigger sites (mitral annulus, fossa ovalis, eustachian ridge, crista terminalis, and superior vena cava); or arm 3, standard approach + ablation of left atrial complex fractionated electrogram sites. Patients were seen at 6 weeks, 6 months, and 1 year; transtelephonic monitoring was performed at each visit. Antiarrhythmic drugs were discontinued at 3 to 6 months. The primary study end point was freedom from atrial arrhythmias off antiarrhythmic drugs at 1 year after a single-ablation procedure. A total of 156 patients (aged 59±9 years; 136 males; AF duration, 47±50 months) participated (arm 1, 55 patients; arm 2, 50 patients; arm 3, 51 patients). Procedural outcomes (procedure, fluoroscopy, and PVI times) were comparable between the 3 arms. More lesions were required to target non-PV trigger sites than a complex fractionated electrogram (33±9 versus 22±9; P<0.001). The primary end point was achieved in 71 patients and was worse in arm 3 (29%) compared with arm 1 (49%; P=0.04) and arm 2 (58%; P=0.004). These data suggest that additional substrate modification beyond PVI does not improve single-procedure efficacy in patients with persistent AF. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00379301.

Catheter ablation of asymptomatic longstanding persistent atrial fibrillation: impact on quality of life, exercise performance, arrhythmia perception, and arrhythmia-free survival.

PubMed

Mohanty, Sanghamitra; Santangeli, Pasquale; Mohanty, Prasant; Di Biase, Luigi; Holcomb, Shawna; Trivedi, Chintan; Bai, Rong; Burkhardt, David; Hongo, Richard; Hao, Steven; Beheiry, Salwa; Santoro, Francesco; Forleo, Giovanni; Gallinghouse, Joseph G; Horton, Rodney; Sanchez, Javier E; Bailey, Shane; Hranitzky, Patrick M; Zagrodzky, Jason; Natale, Andrea

2014-10-01

Impact of catheter ablation on exercise performance, quality of life (QoL) and symptom perception in asymptomatic longstanding persistent AF (LSP-AF) patients has not been reported yet. Sixty-one consecutive patients (mean age 62 ±13 years, 71% males) with asymptomatic LSP-AF undergoing first catheter ablation were enrolled. Extended pulmonary vein antrum isolation plus ablation of complex fractionated atrial electrograms and nonpulmonary vein triggers was performed in all. QoL survey was taken at baseline and 12-months postablation, using Short Form-36 (SF-36). Information on arrhythmia perception was obtained using a standard questionnaire and corroborating symptoms with documented evidence of arrhythmia. Exercise tests were performed on 38 patients at baseline and 5 months after procedure. Recurrence was assessed using event recorder, cardiology evaluation, electrocardiogram, and 7-day holter monitoring. After 20 ± 5 months follow-up, 36 (57%) patients remained recurrence-free off-AAD. Of the 25 patients experiencing recurrence, 21 (84%) were symptomatic. Compared to baseline, follow-up SF-36 scores improved significantly in many measures. For patients with successful ablation, physical component summary (PCS) and mental component summary (MCS) demonstrated substantial improvement ( 64.2 ± 22.3 to 70.1 ± 18.6 [P = 0.041]; PCS: 62.6 ± 18.4 to 70.0 ± 14.4 [P = 0.032]). Postablation exercise study in recurrence-free patients showed significant reduction in resting and peak heart rate (75 ± 11 vs. 90 ± 17 and 132 ± 20 vs. 154.5 ± 36, respectively, P < 0.001), increase in peak oxygen pulse (13.4 ± 3 vs. 18.9 ± 16 mL/beat, Δ5.5 ± 15, P = 0.001), peak VO2 /kg (19.7 ± 5 to 23.4 ± 13 mL/kg/min [Δ 3.7 ± 10, P = 0.043]), and corresponding MET (5.6 ± 1 to 6.7 ± 4 [Δ1.1 ± 3, P = 0.03]). No improvement was observed in patients with failed procedures. Successful ablation improves exercise performance and QoL in asymptomatic LSP-AF patients. © 2014 Wiley Periodicals, Inc.

Determination of size and mass-and number-based concentration of biogenic SeNPs synthesized by lactic acid bacteria by using a multimethod approach.

PubMed

Moreno-Martin, Gustavo; Pescuma, Micaela; Pérez-Corona, Teresa; Mozzi, Fernanda; Madrid, Yolanda

2017-11-01

Selenium nanoparticles (SeNPs) were synthesized by a green technology using lactic acid bacteria (LAB, Lactobacillus acidophilus, L. delbrueckii subsp. bulgaricus and L. reuteri). The exposure of aqueous sodium selenite to LAB led to the synthesis of SeNPs. Characterization of SeNPs by transmission electron microscopy with energy dispersive X-ray spectrum (EDXS) analysis revealed the presence of stable, predominantly monodispersed and spherical SeNPs of an average size of 146 ± 71 nm. Additionally, SeNPs hydrodynamic size was determined by dispersive light scattering (DLS) and nanoparticle tracking analysis (NTA). For this purpose, a methodology based on the use of surfactants in basic medium was developed for isolating SeNPs from the bacterial pellet. The hydrodynamic size values provided by DLS and NTA were 258 ± 4 and 187 ± 56 nm, respectively. NTA measurements of number-based concentration reported values of (4.67±0.30)x10 9 SeNPs mL -1 with a relative standard deviation lower than 5% (n = 3). The quantitative results obtained by NTA were supported by theoretical calculations. Asymmetrical flow field flow fractionation (AF 4 ) on line coupled to the inductively couple plasma mass spectrometry (ICP-MS) and off-line coupled to DLS was further employed to characterize biogenic SeNPs. The distribution of the particle size for the Se-containing peak provide an average size of (247 ± 14) nm. The data obtained by independent techniques were in good agreement and the developed methodology could be implemented for characterizing NPs in complex matrices such as biogenic nanoparticles embedded inside microbial material. Copyright © 2017. Published by Elsevier B.V.

Analysis of a six-component, flow-through, strain-gage, force balance used for hypersonic wind tunnel models with scramjet exhaust flow simulation. M.S. Thesis Final Report

NASA Technical Reports Server (NTRS)

Kniskern, Marc W.

1990-01-01

The thermal effects of simulant gas injection and aerodynamic heating at the model's surface on the measurements of a non-watercooled, flow through balance were investigated. A stainless steel model of a hypersonic air breathing propulsion cruise missile concept (HAPCM-50) was used to evaluate this balance. The tests were conducted in the 20-inch Mach 6 wind tunnel at NASA-Langley. The balance thermal effects were evaluated at freestream Reynolds numbers ranging from .5 to 7 x 10(exp 6) ft and angles of attack between -3.5 to 5 deg at Mach 6. The injection gases considered included cold air, hot air, and a mixture of 50 percent Argon and 50 percent Freon-12. The stagnation temperatures of the cold air, hot air, and Ar-Fr(12) reached 111, 214, and 283 F, respectively within the balance. A bakelite sleeve was inserted into the inner tube of the balance to minimize the thermal effects of these injection gases. Throughout the tests, the normal force, side force, yaw moment, roll moment, and pitching moment balance measurements were unaffected by the balance thermal effects of the injection gases and the wind tunnel flow. However, the axial force (AF) measurement was significantly affected by balance heating. The average zero shifts in the AF measurements were 1.9, 3.8, and 5.9 percent for cold air, hot air, and Ar-Fr(12) injection, respectively. The AF measurements decreased throughout these tests which lasted from 70 to 110 seconds. During the cold air injection tests, the AF measurements were accurate up to at least ten seconds after the model was injected into the wind tunnel test section. For the hot air and Ar-Fr(12) tests, the AF measurements were accurate up to at least five seconds after model injection.

Fundus Autofluorescence and Photoreceptor Cell Rosettes in Mouse Models

PubMed Central

Flynn, Erin; Ueda, Keiko; Auran, Emily; Sullivan, Jack M.; Sparrow, Janet R.

2014-01-01

Purpose. This study was conducted to study correlations among fundus autofluorescence (AF), RPE lipofuscin accumulation, and photoreceptor cell degeneration and to investigate the structural basis of fundus AF spots. Methods. Fundus AF images (55° lens; 488-nm excitation) and spectral-domain optical coherence tomography (SD-OCT) scans were acquired in pigmented Rdh8−/−/Abca4−/− mice (ages 1–9 months) with a confocal scanning laser ophthalmoscope (cSLO). For quantitative fundus AF (qAF), gray levels (GLs) were calibrated to an internal fluorescence reference. Retinal bisretinoids were measured by quantitative HPLC. Histometric analysis of outer nuclear layer (ONL) thicknesses was performed, and cryostat sections of retina were examined by fluorescence microscopy. Results. Quantified A2E and qAF intensities increased until age 4 months in the Rdh8−/−/Abca4−/− mice. The A2E levels declined after 4 months of age, but qAF intensity values continued to rise. The decline in A2E levels in the Rdh8−/−/Abca4−/− mice paralleled reduced photoreceptor cell viability as reflected in ONL thinning. Hyperautofluorescent puncta in fundus AF images corresponded to photoreceptor cell rosettes in SD-OCT images and histological sections stained with hematoxylin and eosin. The inner segment/outer segment–containing core of the rosette emitted an autofluorescence detected by fluorescence microscopy. Conclusions. When neural retina is disordered, AF from photoreceptor cells can contribute to noninvasive fundus AF images. Hyperautofluorescent puncta in fundus AF images are attributable, in at least some cases, to photoreceptor cell rosettes. PMID:25015357

Aligning Forces for Quality multi-stakeholder healthcare alliances: do they have a sustainable future?

PubMed

Alexander, Jeffrey A; Hearld, Larry R; Wolf, Laura J; Vanderbrink, Jocelyn M

2016-08-01

Multi-stakeholder healthcare alliances in the Robert Wood Johnson Foundation's Aligning Forces for Quality (AF4Q) program brought together diverse stakeholders to work collaboratively to improve healthcare in their local communities. This article evaluates how well the AF4Q alliances were collectively positioned to sustain themselves as AF4Q program support ended. This analysis relied on a mixed-methods design using data from a survey of more than 700 participants in 15 of the 16 AF4Q alliances (1 alliance was unable to participate because it was in the process of closing down operations at the time of survey implementation), qualitative interviews with leaders in all 16 of the alliances, and secondary sources. Qualitative analysis of interview data and secondary sources were used to develop a classification of alliance strategic directions after the AF4Q program relative to their strategies during the AF4Q initiative. Descriptive analyses of survey data were conducted in the following areas: (1) alliance priorities for sustainability, (2) alliance positioning for sustainability, and (3) alliance challenges to sustainability. The likelihood of sustainability and the strategic direction of the former AF4Q alliances are both decidedly mixed. A substantial number of alliances are at risk because of an unclear strategic direction following the AF4Q program, poor financial support, and a lack of relevant community leadership. Some have a clear plan to continue on the path they set during the program. Others appear likely to continue to operate, but they plan to do so in a form that differs from the neutral convener multi-stakeholder model emphasized during the AF4Q program as they specialize, make a major shift in focus, develop fee-for-service products, or focus on particular stakeholder groups (ie, employers and providers). In most cases, preserving the organization itself, rather than its programmatic activities from the AF4Q program era, appeared to receive the greatest emphasis in sustainability efforts. As their core strategy, most alliances will not perpetuate the original AF4Q program vision of diverse local stakeholders coming together to implement a prescribed set of aligned interventions centered on healthcare improvement.

Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents.

PubMed

Wu, J; Liu, P; Zhu, J L; Maddukuri, S; Zern, M A

1998-03-01

To improve liposome-directed therapy of liver disease and gene delivery, it would be beneficial to selectively target hepatocytes. For this purpose, conventional liposomes (CL) were labeled with asialofetuin (AF), an asialoglycoprotein. The biodistribution of AF-labeled liposomes (AF-L) in mice and their incorporation into rat hepatocytes, and their potential use in acute liver injury, were investigated. AF-L displayed a quicker plasma clearance than CL, and 25.4%, 2.7%, and 1.2% of the injected dose remained in the plasma versus 47.0%, 26.1%, and 9.5% of CL, respectively at 2, 4, and 20 hours after the injection. Total liver uptake of AF-L (73%+/-3.9%) was markedly higher (P < .005) than CL (16.5%+/-1.8%) 4 hours after the injection. Liposomal radioactivity (cpm/mg) was greatly enhanced in the liver (11-fold) during the first 4 hours after the administration of 14C-AF-L, and was much higher than in 14C-CL-injected mice (1.5-fold). In vitro incubation of isolated rat hepatocytes with 14C-AF-L or intravenous injection of 14C-AF-L in rats resulted in higher hepatocyte-bound radioactivity compared with 14C-CL (P < .01-.005). AF-L-associated 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) fluorescent signals were not only located in Kupffer cells, but also in hepatocytes, in which bile canaliculus networks were imaged. Intravenous administration of vitamin E (VE)-associated CL (VE-CL, 1 mg/mouse) significantly lowered alanine transaminase (ALT) levels in CCl4-treated mice (196+/-79 vs. 2,107+/-235 U/mL; P < .01). The ALT level in CCl4 + VE-AF-L group was decreased to 38+/-16 units/mL, which was significantly lower than the CC14 + VE-CL group (P < .05). In conclusion, labeling liposomes with AF led to a shortened liposome plasma half-life and greatly enhanced uptake of AF-L liposome by the liver. The enhanced uptake resulted from an increased incorporation of hepatocytes with AF-L liposomes. VE-associated AF liposomes further improved the protective effect of VE liposomes on CC14-induced acute liver injury in mice. Preferential hepatocyte incorporation of AF-L liposomes suggests a useful hepatocyte-targeting approach for drug delivery and gene transfection.

Educational inequalities in mortality of patients with atrial fibrillation in Norway.

PubMed

Akerkar, Rupali; Ebbing, Marta; Sulo, Gerhard; Ariansen, Inger; Igland, Jannicke; Tell, Grethe S; Egeland, Grace M

2017-04-01

We explored the educational gradient in mortality in atrial fibrillation (AF) patients. We prospectively followed patients hospitalized with AF as primary discharge diagnosis in the Cardiovascular Disease in Norway 2008-2012 project. The average length of follow-up was 2.4 years. Mortality by educational level was assessed by Cox proportional hazard models. Population attributable fractions (PAF) were calculated. Analyses stratified by age (≤75 and >75 years of age), and adjusted for age, gender, medical intervention, and Charlson Comorbidity Index. Of 42,138 AF patients, 16% died by end of 2012. Among younger patients, those with low education (≤10 years) had a HR of 2.3 (95% confidence interval 2.0, 2.6) for all-cause mortality relative to those with any college or university education. Similar results were observed for cardiovascular mortality. Disparities in mortality were greater among younger than older patients. A PAF of 35.9% (95% confidence interval 27.9, 43.1) was observed for an educational level of high school/vocational school or less versus higher education in younger patients. Increasing educational level associated with better prognosis suggesting underlying education-related behavioral and medical determinants of mortality. A considerable proportion of mortality within 5 years following hospital discharge could be prevented.

Dual throat thruster cold flow analysis

NASA Technical Reports Server (NTRS)

Lundgreen, R. B.; Nickerson, G. R.; Obrien, C. J.

1978-01-01

The concept was evaluated with cold flow (nitrogen gas) testing and through analysis for application as a tripropellant engine for single-stage-to-orbit type missions. Three modes of operation were tested and analyzed: (1) Mode 1 Series Burn, (2) Mode 1 Parallel Burn, and (3) Mode 2. Primary emphasis was placed on the Mode 2 plume attachment aerodynamics and performance. The conclusions from the test data analysis are as follows: (1) the concept is aerodynamically feasible, (2) the performance loss is as low as 0.5 percent, (3) the loss is minimized by an optimum nozzle spacing corresponding to an AF-ATS ratio of about 1.5 or an Le/Rtp ratio of 3.0 for the dual throat hardware tested, requiring only 4% bleed flow, (4) the Mode 1 and Mode 2 geometry requirements are compatible and pose no significant design problems.

A First-Order Methodology for Calculating Probability of Mission Success

DTIC Science & Technology

1979-01-31

Af(A)/2 + T- fA1 A2 1/8 R(T) (A) -T Af(A)4,(A) + T Af(A)[Af(A) + 4)(A)1$3 A 11/4. 61~ a 2 T R T 2f2 ()+T4f2 ()7A2 -4-A2]/ R 2 f(A) T 2(1 + T 2(3A 2/2...Library ATTN: W. Wright, Jr. ATTN: P. Haas Management Science Associates ATTN: K. Kaplan Rand Corp. ATTN: A. Laupa Martin Marietta Corp, ATTN: C. Mow ATTN

Electron absorbed fractions of energy and S-values in an adult human skeleton based on µCT images of trabecular bone

NASA Astrophysics Data System (ADS)

Kramer, R.; Richardson, R. B.; Cassola, V. F.; Vieira, J. W.; Khoury, H. J.; Lira, C. A. B. de O.; Robson Brown, K.

2011-03-01

When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at the Department of Nuclear Energy at the Federal University of Pernambuco, a skeletal dosimetry method based on µCT images of trabecular bone introduced into the spongiosa voxels of human phantoms has been developed and applied mainly to external exposure to photons. This study uses the same method to calculate AFs of energy and S-values (absorbed dose per unit activity) for electron-emitting radionuclides known to concentrate in skeletal tissues. The modelling of the skeletal tissue regions follows ICRP110, which defines the BE as a 50 µm thick sub-region of marrow next to the bone surfaces. The paper presents mono-energetic AFs for the AM and the BE for eight different skeletal regions for electron source energies between 1 keV and 10 MeV. The S-values are given for the beta emitters 14C, 59Fe, 131I, 89Sr, 32P and 90Y. Comparisons with results from other investigations showed good agreement provided that differences between methodologies and trabecular bone volume fractions were properly taken into account. Additionally, a comparison was made between specific AFs of energy in the BE calculated for the actual 50 µm endosteum and the previously recommended 10 µm endosteum. The increase in endosteum thickness leads to a decrease of the endosteum absorbed dose by up to 3.7 fold when bone is the source region, while absorbed dose increases by ~20% when the beta emitters are in marrow.

Monitoring the growth of polyoxomolybdate nanoparticles in suspension by flow field-flow fractionation.

PubMed

Chen, Bailin; Jiang, Huijian; Zhu, Yan; Cammers, Arthur; Selegue, John P

2005-03-30

We follow the evolution of polyoxomolybdate nanoparticles in suspensions derived from the keplerate (NH4)42[MoVI72MoV60O372(CH3CO2)30(H2O)72].ca..300H2O.ca..10CH3CO2NH4 ({Mo132}) by flow field-flow fractionation (FlFFF) to monitor the particle-size distribution in situ, atomic force and high-resolution transmission electron microscopy (AFM, SEM, and HRTEM) to confirm particle sizes, inductively coupled plasma-optical emission spectrometry (ICP-OES) to determine the Mo content of the FlFFF-separated fractions, and UV/visible spectroscopy to confirm the identity of the species in suspension. We observe the formation of 3-75-nm polyoxomolybdate particles in suspension and the dynamic growth of {Mo132} crystals.

Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators.

PubMed

Hart, R G; Pearce, L A; Rothbart, R M; McAnulty, J H; Asinger, R W; Halperin, J L

2000-01-01

This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation (AF). Although intermittent AF is common, relatively little is known about the attendant risk of stroke. A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years. Independent risk factors for ischemic stroke were identified by multivariate analysis. Patients with intermittent AF were, on average, younger (66 vs. 70 years, p < 0.001), were more often women (37% vs. 26% p < 0.001) and less often had heart failure (11% vs. 21%, p < 0.001) than those with sustained AF. The annualized rate of ischemic stroke was similar for those with intermittent (3.2%) and sustained AF (3.3%). In patients with intermittent AF, independent predictors of ischemic stroke were advancing age (relative risk [RR] = 2.1 per decade, p < 0.001), hypertension (RR = 3.4, p = 0.003) and prior stroke (RR = 4.1, p = 0.01). Of those with intermittent AF predicted to be high risk (24%), the observed stroke rate was 7.8% per year (95% confidence interval 4.5 to 14). In this large cohort of AF patients given aspirin, those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors. Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation. High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF.

Relation between aphasia and arcuate fasciculus in chronic stroke patients

PubMed Central

2014-01-01

Background The role of the arcuate fasciculus (AF) in the dominant hemisphere in stroke patients with aphasia has not been clearly elucidated. We investigated the relation between language function and diffusion tensor tractography (DTT) findings for the left AF in chronic stroke patients with aphasia. Method Twenty five consecutive right-handed stroke patients with aphasia following lesions in the left hemisphere were recruited for this study. The aphasia quotient (AQ) of Korean-Western Aphasia Battery was used for assessment of language function. We measured values of fractional anisotropy (FA), apparent diffusion coefficient (ADC), voxel number of the left AF. We classified patients into three groups: type A - the left AF was not reconstructed, type B - the left AF was discontinued between Wernicke’s and Broca’s areas, and type C – the left AF was preserved around the stroke lesion. Results Moderate positive correlation was observed between AQ and voxel number of the left AF (r = 0.471, p < 0.05). However, no correlation was observed between AQ and FA (r = 0.275, p > 0.05) and ADC values (r = -0.286, p > 0.05). Significant differences in AQ scores were observed between the three types (p < 0.05); the AQ score of type C was higher than those of type A and B, and that of type B was also higher than that of type A (p < 0.05). Conclusion According to our findings, the remaining volume of the left AF, irrespective of directionality and diffusivity, showed moderate positive correlation with language function in chronic stroke patients with aphasia. Discontinuation or non-construction of the left AF was also an important factor for language function. PMID:24607148

Electrophysiological Rotor Ablation in In-Silico Modeling of Atrial Fibrillation: Comparisons with Dominant Frequency, Shannon Entropy, and Phase Singularity.

PubMed

Hwang, Minki; Song, Jun-Seop; Lee, Young-Seon; Li, Changyong; Shim, Eun Bo; Pak, Hui-Nam

2016-01-01

Although rotors have been considered among the drivers of atrial fibrillation (AF), the rotor definition is inconsistent. We evaluated the nature of rotors in 2D and 3D in- silico models of persistent AF (PeAF) by analyzing phase singularity (PS), dominant frequency (DF), Shannon entropy (ShEn), and complex fractionated atrial electrogram cycle length (CFAE-CL) and their ablation. Mother rotor was spatiotemporally defined as stationary reentries with a meandering tip remaining within half the wavelength and lasting longer than 5 s. We generated 2D- and 3D-maps of the PS, DF, ShEn, and CFAE-CL during AF. The spatial correlations and ablation outcomes targeting each parameter were analyzed. 1. In the 2D PeAF model, we observed a mother rotor that matched relatively well with DF (>9 Hz, 71.0%, p<0.001), ShEn (upper 2.5%, 33.2%, p<0.001), and CFAE-CL (lower 2.5%, 23.7%, p<0.001). 2. The 3D-PeAF model also showed mother rotors that had spatial correlations with DF (>5.5 Hz, 39.7%, p<0.001), ShEn (upper 8.5%, 15.1%, p <0.001), and CFAE (lower 8.5%, 8.0%, p = 0.002). 3. In both the 2D and 3D models, virtual ablation targeting the upper 5% of the DF terminated AF within 20 s, but not the ablations based on long-lasting PS, high ShEn area, or lower CFAE-CL area. Mother rotors were observed in both 2D and 3D human AF models. Rotor locations were well represented by DF, and their virtual ablation altered wave dynamics and terminated AF.

Electrophysiological Rotor Ablation in In-Silico Modeling of Atrial Fibrillation: Comparisons with Dominant Frequency, Shannon Entropy, and Phase Singularity

PubMed Central

Hwang, Minki; Song, Jun-Seop; Lee, Young-Seon; Li, Changyong; Shim, Eun Bo; Pak, Hui-Nam

2016-01-01

Background Although rotors have been considered among the drivers of atrial fibrillation (AF), the rotor definition is inconsistent. We evaluated the nature of rotors in 2D and 3D in- silico models of persistent AF (PeAF) by analyzing phase singularity (PS), dominant frequency (DF), Shannon entropy (ShEn), and complex fractionated atrial electrogram cycle length (CFAE-CL) and their ablation. Methods Mother rotor was spatiotemporally defined as stationary reentries with a meandering tip remaining within half the wavelength and lasting longer than 5 s. We generated 2D- and 3D-maps of the PS, DF, ShEn, and CFAE-CL during AF. The spatial correlations and ablation outcomes targeting each parameter were analyzed. Results 1. In the 2D PeAF model, we observed a mother rotor that matched relatively well with DF (>9 Hz, 71.0%, p<0.001), ShEn (upper 2.5%, 33.2%, p<0.001), and CFAE-CL (lower 2.5%, 23.7%, p<0.001). 2. The 3D-PeAF model also showed mother rotors that had spatial correlations with DF (>5.5 Hz, 39.7%, p<0.001), ShEn (upper 8.5%, 15.1%, p <0.001), and CFAE (lower 8.5%, 8.0%, p = 0.002). 3. In both the 2D and 3D models, virtual ablation targeting the upper 5% of the DF terminated AF within 20 s, but not the ablations based on long-lasting PS, high ShEn area, or lower CFAE-CL area. Conclusion Mother rotors were observed in both 2D and 3D human AF models. Rotor locations were well represented by DF, and their virtual ablation altered wave dynamics and terminated AF. PMID:26909492

Spectroscopic monitoring of bright A-F type candidate hybrid stars discovered by the Kepler mission

NASA Astrophysics Data System (ADS)

Lampens, Patricia; Frémat, Y.; Vermeylen, Lore; De Cat, Peter; Dumortier, Louis; Sódor, Ádám; Sharka, Marek; Bognár, Zsófia

2018-04-01

We report on a study of 250 optical spectra for 50 bright A/F-type candidate hybrid pulsating stars from the Kepler field. Most of the spectra have been collected with the high-resolution spectrograph HERMES attached to the Mercator telescope, La Palma. We determined the radial velocities (RVs), projected rotational velocities, fundamental atmospheric parameters and provide a classification based on the appearance of the cross-correlation profiles and the behaviour of the RVs with time in order to find true hybrid pulsators. Additionally, we also detected new spectroscopic binary and multiple systems in our sample and determined the fraction of spectroscopic systems. In order to be able to extend this investigation to the fainter A-F type candidate hybrid stars, various high-quality spectra collected with 3-4 m sized telescopes suitably equipped with a high-resolution spectrograph and furthermore located in the Northern hemisphere would be ideal. This programme could be done using the new instruments installed at the Devasthal Observatory.

Microtropiosides A-F: ent-Labdane diterpenoid glucosides from the leaves of Microtropis japonica (Celastraceae).

PubMed

Koyama, Yuka; Matsunami, Katsuyoshi; Otsuka, Hideaki; Shinzato, Takakazu; Takeda, Yoshio

2010-04-01

From a 1-BuOH-soluble fraction of a MeOH extract of the leaves of Microtropis japonica, collected in the Okinawa islands, six ent-labdane glucosides, named microtropiosides A-F, were isolated together with one known acyclic sesquiterpene glucoside. Their structures were elucidated by a combination of spectroscopic analyses, and their absolute configurations determined by application of the beta-D-glucopyranosylation-induced shift-trend rule in (13)C NMR spectroscopy and the modified Mosher's method. Copyright 2010 Elsevier Ltd. All rights reserved.

Quantitative fundus autofluorescence in mice: correlation with HPLC quantitation of RPE lipofuscin and measurement of retina outer nuclear layer thickness.

PubMed

Sparrow, Janet R; Blonska, Anna; Flynn, Erin; Duncker, Tobias; Greenberg, Jonathan P; Secondi, Roberta; Ueda, Keiko; Delori, François C

2013-04-17

Our study was conducted to establish procedures and protocols for quantitative autofluorescence (qAF) measurements in mice, and to report changes in qAF, A2E bisretinoid concentration, and outer nuclear layer (ONL) thickness in mice of different genotypes and age. Fundus autofluorescence (AF) images (55° lens, 488 nm excitation) were acquired in albino Abca4(-/-), Abca4(+/-), and Abca4(+/+) mice (ages 2-12 months) with a confocal scanning laser ophthalmoscope (cSLO). Gray levels (GLs) in each image were calibrated to an internal fluorescence reference. The bisretinoid A2E was measured by quantitative high performance liquid chromatography (HPLC). Histometric analysis of ONL thicknesses was performed. The Bland-Altman coefficient of repeatability (95% confidence interval) was ±18% for between-session qAF measurements. Mean qAF values increased with age (2-12 months) in all groups of mice. qAF was approximately 2-fold higher in Abca4(-/-) mice than in Abca4(+/+) mice and approximately 20% higher in heterozygous mice. HPLC measurements of the lipofuscin fluorophore A2E also revealed age-associated increases, and the fold difference between Abca4(-/-) and wild-type mice was more pronounced (approximately 3-4-fold) than measurable by qAF. Moreover, A2E levels declined after 8 months of age, a change not observed with qAF. The decline in A2E levels in the Abca4(-/-) mice corresponded to reduced photoreceptor cell viability as reflected in ONL thinning beginning at 8 months of age. The qAF method enables measurement of in vivo lipofuscin and the detection of genotype and age-associated differences. The use of this approach has the potential to aid in understanding retinal disease processes and will facilitate preclinical studies.

Direct electric current modifies important cellular aspects and ultrastructure features of Candida albicans yeasts: Influence of doses and polarities.

PubMed

Barbosa, Gleyce Moreno; Dos Santos, Eldio Gonçalves; Capella, Francielle Neves Carvalho; Homsani, Fortune; de Pointis Marçal, Carina; Dos Santos Valle, Roberta; de Araújo Abi-Chacra, Érika; Braga-Silva, Lys Adriana; de Oliveira Sales, Marcelo Henrique; da Silva Neto, Inácio Domingos; da Veiga, Venicio Feo; Dos Santos, André Luis Souza; Holandino, Carla

2017-02-01

Available treatments against human fungal pathogens present high levels of resistance, motivating the development of new antifungal therapies. In this context, the present work aimed to analyze direct electric current (DC) antifungal action, using an in vitro apparatus equipped with platinum electrodes. Candida albicans yeast cells were submitted to three distinct conditions of DC treatment (anodic flow-AF; electroionic flow-EIF; and cathodic flow-CF), as well as different charges, ranging from 0.03 to 2.40 C. Our results indicated C. albicans presented distinct sensibility depending on the DC intensity and polarity applied. Both the colony-forming unit assay and the cytometry flow with propidium iodide indicated a drastic reduction on cellular viability after AF treatment with 0.15 C, while CF- and EIF-treated cells stayed alive when DC doses were increased up to 2.40 C. Additionally, transmission electron microscopy revealed important ultrastructural alterations in AF-treated yeasts, including cell structure disorganization, ruptures in plasmatic membrane, and cytoplasmic rarefaction. This work emphasizes the importance of physical parameters (polarity and doses) in cellular damage, and brings new evidence for using electrotherapy to treat C. albicans pathology process. Bioelectromagnetics. 38:95-108, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Conflict in Somalia: impact on child undernutrition

PubMed Central

Kinyoki, Damaris K; Moloney, Grainne M; Uthman, Olalekan A; Kandala, Ngianga-Bakwin; Odundo, Elijah O; Noor, Abdisalan M; Berkley, James A

2017-01-01

Introduction In Somalia, protracted conflict and drought have caused population displacement and livelihood destruction. There is also widespread childhood undernutrition. We aimed to determine the independent effects of conflict on wasting and stunting among children aged 6–59 months nationwide in Somalia. Methods Data were from household surveys during 2007–2010, including 73 778 children in 1066 clusters, the Armed Conflict Location and Event Data project database and remote sensing. We used Bayesian hierarchical spatial-temporal regression to examine the effects of conflict on wasting and stunting. Models included individual, household and environmental covariates and recent (<3 months) or longer term (3–12 months) conflict events. Results 15 355 (21%) and 22 739 (31%) observations were from wasted and stunted children, respectively. The conflict was associated with undernutrition independently of the individual, household and environmental factors, and its inclusion improved model performance. Recent conflict was associated with wasting (OR 1.37, 95% credible interval (CrI): (1.33, 1.42) and attributable fraction (AF) 7.6%)) and stunting (OR 1.21, 95% CrI (1.15, 1.28), AF 6.9%). Longer term conflict had greater effects on wasting (OR 1.76, 95% CrI (1.71, 1.81), AF 6.0%) and stunting (OR 1.88, 95% CrI = (1.83, 1.94), AF 7.4%). After controlling for conflict, the harmful effect of internal displacement and protective effects of rainfall and vegetation cover on undernutrition were enhanced. Conclusion Conflict and internal displacement have large effects on undernutrition in ways not fully captured by simply measuring individual, household and environmental factors or drought. PMID:28966793

A QoS scheme for a congestion core network based on dissimilar QoS structures in smart-phone environments.

PubMed

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones.

A QoS Scheme for a Congestion Core Network Based on Dissimilar QoS Structures in Smart-Phone Environments

PubMed Central

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones. PMID:22163453

Left-to-right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation.

PubMed

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2010-10-01

Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right-dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K(+) currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of I(K1) (Kir2.1 and Kir2.3) and I(K,ACh) (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) I(K,ACh) was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced I(K,ACh) in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches.

Left-to-Right Atrial Inward Rectifier Potassium Current Gradients in Patients With Paroxysmal Versus Chronic Atrial Fibrillation

PubMed Central

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R.; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2018-01-01

Background Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right–dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K+ currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Methods and Results Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of IK1 (Kir2.1 and Kir2.3) and IK,ACh (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) IK,ACh was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced IK,ACh in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Conclusions Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches. PMID:20657029

Development and validation of a high-performance liquid chromatography method with post-column derivatization for the detection of aflatoxins in cereals and grains.

PubMed

Asghar, Muhammad Asif; Iqbal, Javed; Ahmed, Aftab; Khan, Mobeen Ahmed; Shamsuddin, Zuzzer Ali; Jamil, Khalid

2016-06-01

A novel, reliable and rapid high-performance liquid chromatography (HPLC) method with post-column derivatization was developed and validated. The HPLC method was used for the simultaneous determination of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) in various cereals and grains. Samples were extracted with 80:20 (v/v) methanol:water and purified using C18 (40-63 μm) solid-phase extraction cartridges. AFs were separated using a LiChroCART-RP-18 (5 μm, 250 × 4.0 mm(2)) column. The mobile phase consisted of methanol:acetonitrile:buffer (17.5:17.5:65 v/v) (pH 7.4) delivered at the flow rate of 1.0 mL min(-1) The fluorescence of each AF was detected at λex = 365 nm and λem = 435 nm. All four AFs were properly resolved within the total run time of 20 min. The established method was extensively validated as a final verification of the method development by the evaluation of selectivity (AFB1, AFB2, AFG1 and AFG2), linearity (R(2) ≥ 0.9994), precision (average SD ≤ 2.79), accuracy (relative mean error ≤ -5.51), robustness (p < 0.0080), ruggedness (p < 0.0100) and average recoveries (89.2-97.8%). The limits of quantification of AFB1, AFB2, AFG1 and AFG2 were 0.080, 0.073, 0.062 and 0.066 ng g(-1), respectively. Finally, the developed method was applied for the analysis of AFs in 45 samples comprising rice (n = 20), wheat (n = 15) and maize (n = 10). The results showed that 65% of rice, 20% of wheat and 80% of maize samples were found contaminated with AFs. Thus, according to the achieved results, it is suggested that the newly developed HPLC method could be effectively applied for the routine analysis of the AFs in different cereals and grains. © The Author(s) 2014.

Application of Electromagnetic Induction Technique to Measure the Void Fraction in Oil/Gas Two Phase Flow

NASA Astrophysics Data System (ADS)

Wahhab, H. A. Abdul; Aziz, A. R. A.; Al-Kayiem, H. H.; Nasif, M. S.; Reda, M. N.

2018-03-01

In this work, electromagnetic induction technique of measuring void fraction in liquid/gas fuel flow was utilized. In order to improve the electric properties of liquid fuel, an iron oxide Fe3O4 nanoparticles at 3% was blended to enhance the liquid fuel magnetization. Experiments have been conducted for a wide range of liquid and gas superficial velocities. From the experimental results, it was realized that there is an existing linear relationship between the void fraction and the measured electromotive force, when induction coils were connected in series for excitation coils, regardless of increase or decrease CNG bubbles distribution in liquid fuel flow. Therefore, it was revealed that the utilized method yielded quite reasonable account for measuring the void fraction, showing good agreement with the other available measurement techniques in the two-phase flow, and also with the published literature of the bubbly flow pattern. From the results of the present investigation, it has been proven that the electromagnetic induction is a feasible technique for the actual measurement of void fraction in a Diesel/CNG fuel flow.

Echocardiographic predictors of atrial fibrillation recurrence after catheter ablation: A literature review.

PubMed

Liżewska-Springer, Aleksandra; Dąbrowska-Kugacka, Alicja; Lewicka, Ewa; Drelich, Łukasz; Królak, Tomasz; Raczak, Grzegorz

2018-06-20

Catheter ablation (CA) is a well-known treatment option for patients with symptomatic drug-resistant atrial fibrillation (AF). Multiple factors have been identified to determine AF recurrence after CA, however their predictive value is rather small. Identification of novel predictors of CA outcome is therefore of primary importance to reduce health costs and improve long-term results of this intervention. The recurrence of AF following CA is related to the severity of left ventricular (LV) dysfunction, extend of atrial dilatation and fibrosis. The aim of this paper was to present and discuss the latest studies on utility of echocardiographic parameters in terms of CA effectiveness in patients with paroxysmal and persistent AF. PubMed, Google Scholar, EBSCO databases were searched for studies reporting echocardiographic preprocedural predictors of AF recurrence after CA. LV systolic and diastolic function, as well as atrial size, strain and dyssynchrony were taken into consideration. Twenty one full-text articles were analyzed, including three meta-analyses. Several echocardiographic parameters have been reported to determine a risk of AF recurrence after CA. There are conventional methods that measure left atrial (LA) size and volume, LV ejection fraction, parameters assessing LV diastolic dysfunction, and methods using more innovative technologies based on speckle tracking echocardiography (STE) to determine LA synchrony and strain. Each of these parameters has its own predictive value. Regarding CA effectiveness, every patient has to be evaluated individually to estimate the risk of AF recurrence, optimally using a combination of several echocardiographic parameters.

Is There Any Difference in Risk Factors between Male and Female Patients in New-Onset Atrial Fibrillation after Coronary Artery Bypass Grafting?

PubMed

Akça, Barış; Erdil, Nevzat; Colak, Mehmet Cengiz; Disli, Olcay Murat; Battaloglu, Bektas; Colak, Cemil

2018-03-06

 We aimed to investigate the risk factors of post-coronary artery bypass grafting (CABG) atrial fibrillation (AF) in male and female patients without any history of AF, to identify the sex-specific risk factors, and to examine the effect of sex-specific risk factors on the overall population.  This retrospective study was conducted using the hospital database with 4,758 patients who underwent CABG surgery. Among them, 2,836 patients with complete data participated in this study. The female patients were divided into two groups as patients who developed new-onset AF after CABG and those who did not. The relationship between the patients' variables and risk factors of post-CABG AF was examined.  The overall incidence of post CABG AF was 12.9% (386/2,836). Sex-specific incidence of AF was similar: 3.2% (91/690) and 12.9% (277/2146) in female and male patients, respectively ( p  = 0.849). Multiple analysis revealed the independent risk factors for male and female patients, respectively: mean age (odds ratio [OR] = 1.057, OR = 1,076), age over 65 years (OR = 2.156, OR = 2.736), the European System For Cardiac Operative Risk Evaluation Scores (EuroSCORE) (OR = 1.13, OR = 1.218), COPD (OR = 1.589, OR = 1.789), BUN level (OR = 1.026, OR = 1.019), mean cardiopulmonary bypass (CPB) time (OR = 1.007, OR = 1.010), prolonged CPB time (OR = 1.604, OR = 2.309), mean cross-clamp time (OR = 1.009, OR = 1.017), need of inotropic support (OR = 2.249, OR = 2.731), and mean mechanical ventilation time (VT) (OR = 1.026, OR = 1.027).Low left ventricular ejection fraction (LVEF) (OR = 1.419), left ventricular (LV) aneurysm repair (OR = 1.533), carotid artery disease (OR = 1.750), prolonged VT (OR = 1.729), and use of intra-aortic balloon pump (IABP) (OR = 2.436) were found to be the risk factors only for male AF patients.Unstable angina (OR = 1.969), right coronary artery (RCA) disease (OR = 2), prolonged cross-clamp time (OR = 2.152), and the number of grafts per operation (OR = 1.298) were found to be the risk factors only for female AF patients.  This study suggests that predictors of AF in the overall population may be due to isolated patient groups. Multiple regression analysis and artificial intelligence modelling should be performed on large-scale, isolated groups to make strong AF prediction. Georg Thieme Verlag KG Stuttgart · New York.

Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.

PubMed

Baumgartner, Christine; da Costa, Bruno R; Collet, Tinh-Hai; Feller, Martin; Floriani, Carmen; Bauer, Douglas C; Cappola, Anne R; Heckbert, Susan R; Ceresini, Graziano; Gussekloo, Jacobijn; den Elzen, Wendy P J; Peeters, Robin P; Luben, Robert; Völzke, Henry; Dörr, Marcus; Walsh, John P; Bremner, Alexandra; Iacoviello, Massimo; Macfarlane, Peter; Heeringa, Jan; Stott, David J; Westendorp, Rudi G J; Khaw, Kay-Tee; Magnani, Jared W; Aujesky, Drahomir; Rodondi, Nicolas

2017-11-28

Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. © 2017 American Heart Association, Inc.

β-Cyclodextrin-dextran polymers for the solubilization of poorly soluble drugs.

PubMed

di Cagno, Massimiliano; Terndrup Nielsen, Thorbjørn; Lambertsen Larsen, Kim; Kuntsche, Judith; Bauer-Brandl, Annette

2014-07-01

The aim of this study was to assess the potential of novel β-cyclodextrin (βCD)-dextran polymers for drug delivery. The size distribution of βCD-dextrans (for eventual parenteral administration), the influence of the dextran backbones on the stability of the βCD/drug complex, the solubilization efficiency of poorly soluble drugs and drug release properties were investigated. Size analysis of different βCD-dextrans was measured by size exclusion chromatography (SEC) and asymmetrical flow field-flow fractionation (AF4). Stability of drug/βCD-dextrans was assessed by isothermal titration calorimetry (ITC) and molar enthalpies of complexation and equilibrium constants compared to some commercially available βCD derivatives. For evaluation of the solubilization efficiency, phase-solubility diagrams were made employing hydrocortisone (HC) as a model of poorly soluble drugs, whereas reverse dialysis was used to detect potential drug supersaturation (increased molecularly dissolved drug concentration) as well as controlled release effects. Results indicate that all investigated βCD-polymers are of appropriate sizes for parenteral administration. Thermodynamic results demonstrate that the presence of the dextran backbone structure does not affect the stability of the βCD/drug complex, compared to native βCD and commercially available derivatives. Solubility studies evidence higher solubilizing abilities of these new polymers in comparison to commercially available βCDs, but no supersaturation states were induced. Moreover, drug release studies evidenced that diffusion of HC was influenced by the solubilization induced by the βCD-derivatives. Copyright © 2014 Elsevier B.V. All rights reserved.

Use pattern of pesticides and their predicted mobility into shallow groundwater and surface water bodies of paddy lands in Mahaweli river basin in Sri Lanka.

PubMed

Aravinna, Piyal; Priyantha, Namal; Pitawala, Amarasooriya; Yatigammana, Sudharma K

2017-01-02

Pesticides applied on agricultural lands reach groundwater by leaching, and move to offsite water bodies by direct runoff, erosion and spray drift. Therefore, an assessment of the mobility of pesticides in water resources is important to safeguard such resources. Mobility of pesticides on agricultural lands of Mahaweli river basin in Sri Lanka has not been reported to date. In this context, the mobility potential of 32 pesticides on surface water and groundwater was assessed by widely used pesticide risk indicators, such as Attenuation Factor (AF) index and the Pesticide Impact Rating Index (PIRI) with some modifications. Four surface water bodies having greater than 20% land use of the catchment under agriculture, and shallow groundwater table at 3.0 m depth were selected for the risk assessment. According to AF, carbofuran, quinclorac and thiamethoxam are three most leachable pesticides having AF values 1.44 × 10 -2 , 1.87 × 10 -3 and 5.70 × 10 -4 , respectively. Using PIRI, offsite movement of pesticides by direct runoff was found to be greater than with the erosion of soil particles for the study area. Carbofuran and quinclorac are most mobile pesticides by direct runoff with runoff fractions of 0.01 and 0.08, respectively, at the studied area. Thiamethoxam and novaluron are the most mobile pesticides by erosion with erosion factions of 1.02 × 10 -4 and 1.05 × 10 -4 , respectively. Expected pesticide residue levels in both surface and groundwater were predicted to remain below the USEPA health advisory levels, except for carbofuran, indicating that pesticide pollution is unlikely to exceed the available health guidelines in the Mahaweli river basin in Sri Lanka.

Multiphase flowmeter successfully measures three-phase flow at extremely high gas-volume fractions -- Gulf of Suez, Egypt

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leggett, R.B.; Borling, D.C.; Powers, B.S.

1998-02-01

A multiphase flowmeter (MPFM) installed in offshore Egypt has accurately measured three-phase flow in extremely gassy flow conditions. The meter is completely nonintrusive, with no moving parts, requires no flow mixing before measurement, and has no bypass loop to remove gas before multiphase measurement. Flow regimes observed during the field test of this meter ranged from severe slugging to annular flow caused by the dynamics of gas-lift gas in the production stream. Average gas-volume fraction ranged from 93 to 98% during tests conducted on seven wells. The meter was installed in the Gulf of Suez on a well protector platformmore » in the Gulf of Suez Petroleum Co. (Gupco) October field, and was placed in series with a test separator located on a nearby production platform. Wells were individually tested with flow conditions ranging from 1,300 to 4,700 B/D fluid, 2.4 to 3.9 MMscf/D of gas, and water cuts from 1 to 52%. The meter is capable of measuring water cuts up to 100%. Production was routed through both the MPFM and the test separator simultaneously as wells flowed with the assistance of gas-lift gas. The MPFM measured gas and liquid rates to within {+-} 10% of test-separator reference measurement flow rates, and accomplished this at gas-volume fractions from 93 to 96%. At higher gas-volume fractions up to 98%, accuracy deteriorated but the meter continued to provide repeatable results.« less

Characterization of genome-wide association-identified variants for atrial fibrillation in African Americans.

PubMed

Delaney, Jessica T; Jeff, Janina M; Brown, Nancy J; Pretorius, Mias; Okafor, Henry E; Darbar, Dawood; Roden, Dan M; Crawford, Dana C

2012-01-01

Despite a greater burden of risk factors, atrial fibrillation (AF) is less common among African Americans than European-descent populations. Genome-wide association studies (GWAS) for AF in European-descent populations have identified three predominant genomic regions associated with increased risk (1q21, 4q25, and 16q22). The contribution of these loci to AF risk in African American is unknown. We studied 73 African Americans with AF from the Vanderbilt-Meharry AF registry and 71 African American controls, with no history of AF including after cardiac surgery. Tests of association were performed for 148 SNPs across the three regions associated with AF, and 22 SNPs were significantly associated with AF (P<0.05). The SNPs with the strongest associations in African Americans were both different from the index SNPs identified in European-descent populations and independent from the index European-descent population SNPs (r(2)<0.40 in HapMap CEU): 1q21 rs4845396 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.13-0.67, P = 0.003), 4q25 rs4631108 (OR 3.43, 95% CI 1.59-7.42, P = 0.002), and 16q22 rs16971547 (OR 8.1, 95% CI 1.46-45.4, P = 0.016). Estimates of European ancestry were similar among cases (23.6%) and controls (23.8%). Accordingly, the probability of having two copies of the European derived chromosomes at each region did not differ between cases and controls. Variable European admixture at known AF loci does not explain decreased AF susceptibility in African Americans. These data support the role of 1q21, 4q25, and 16q22 variants in AF risk for African Americans, although the index SNPs differ from those identified in European-descent populations.

A Simple Score That Predicts Paroxysmal Atrial Fibrillation on Outpatient Cardiac Monitoring after Embolic Stroke of Unknown Source.

PubMed

Ricci, Brittany; Chang, Andrew D; Hemendinger, Morgan; Dakay, Katarina; Cutting, Shawna; Burton, Tina; Mac Grory, Brian; Narwal, Priya; Song, Christopher; Chu, Antony; Mehanna, Emile; McTaggart, Ryan; Jayaraman, Mahesh; Furie, Karen; Yaghi, Shadi

2018-06-01

Occult paroxysmal atrial fibrillation (AF) is detected in 16%-30% of patients with embolic stroke of unknown source (ESUS). The identification of AF predictors on outpatient cardiac monitoring can help guide clinicians decide on a duration or method of cardiac monitoring after ESUS. We included all patients with ESUS who underwent an inpatient diagnostic evaluation and outpatient cardiac monitoring between January 1, 2013, and December 31, 2016. Patients were divided into 2 groups based on detection of AF or atrial flutter during monitoring. We compared demographic data, clinical risk factors, and cardiac biomarkers between the 2 groups. Multivariable logistic regression was used to determine predictors of AF. We identified 296 consecutive patients during the study period; 38 (12.8%) patients had AF detected on outpatient cardiac monitoring. In a multivariable regression analysis, advanced age (ages 65-74: odds ratio [OR] 2.36, 95% confidence interval [CI] .85-6.52; ages 75 or older: OR 4.08, 95% CI 1.58-10.52) and moderate-to-severe left atrial enlargement (OR 4.66, 95% CI 1.79-12.12) were predictors of AF on outpatient monitoring. We developed the Brown ESUS-AF score: age (65-74 years: 1 point, 75 years or older: 2 points) and left atrial enlargement (moderate or severe: 2 points) with good prediction of AF (area under the curve .725) and was internally validated using bootstrapping. The percentage of patients with AF detected in each score category were as follows: 0: 4.2%; 1: 14.8%; 2: 20.8%; 3: 22.2%; 4: 55.6%. The Brown ESUS-AF score predicts AF on prolonged outpatient monitoring after ESUS. More studies are needed to externally validate our findings. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Occupational risk factors have to be considered in the definition of high-risk lung cancer populations.

PubMed

Wild, P; Gonzalez, M; Bourgkard, E; Courouble, N; Clément-Duchêne, C; Martinet, Y; Févotte, J; Paris, C

2012-03-27

The aim of this study was to compute attributable fractions (AF) to occupational factors in an area in North-Eastern France with high lung cancer rates and a past of mining and steel industry. A population-based case-control study among males aged 40-79 was conducted, including confirmed primary lung cancer cases from all hospitals of the study region. Controls were stratified by broad age-classes, district and socioeconomic classes. Detailed occupational and personal risk factors were obtained in face-to-face interviews. Cumulative occupational exposure indices were obtained from the questionnaires. Attributable fractions were computed from multiple unconditional logistic regression models. A total of 246 cases and 531 controls were included. The odds ratios (ORs) adjusted on cumulative smoking and family history of lung cancer increased significantly with the cumulative exposure indices to asbestos, polycyclic aromatic hydrocarbons and crystalline silica, and with exposure to diesel motor exhaust. The AF for occupational factors exceeded 50%, the most important contributor being crystalline silica and asbestos. These AFs are higher than most published figures. This can be because of the highly industrialised area or methods for exposure assessments. Occupational factors are important risk factors and should not be forgotten when defining high-risk lung cancer populations.

46 CFR 160.047-4 - Construction.

Code of Federal Regulations, 2012 CFR

2012-10-01

... AF-1, CFM-1, and CFS-1. The buoyant pad inserts for Models AF-1, CFM-1, and CFS-1 buoyant vests shall...)—Distribution of Fibrous Glass in Buoyant Pad Inserts Model AF-1 (minimum) Model CFM-1 (minimum) Model CFS-1... and CFM-1 Each Models CKS-1 and CFS-1 Each Front pads 61/4 pounds ±1/4 pound 41/4 pounds ±1/4 pound 23...

46 CFR 160.047-4 - Construction.

Code of Federal Regulations, 2011 CFR

2011-10-01

... AF-1, CFM-1, and CFS-1. The buoyant pad inserts for Models AF-1, CFM-1, and CFS-1 buoyant vests shall...)—Distribution of Fibrous Glass in Buoyant Pad Inserts Model AF-1 (minimum) Model CFM-1 (minimum) Model CFS-1... and CFM-1 Each Models CKS-1 and CFS-1 Each Front pads 61/4 pounds ±1/4 pound 41/4 pounds ±1/4 pound 23...

The antipsychotic-like effects of positive allosteric modulators of metabotropic glutamate mGlu4 receptors in rodents

PubMed Central

Sławińska, Anna; Wierońska, Joanna M; Stachowicz, Katarzyna; Marciniak, Marcin; Łasoń-Tyburkiewicz, Magdalena; Gruca, Piotr; Papp, Mariusz; Kusek, Magdalena; Tokarski, Krzysztof; Doller, Darío; Pilc, Andrzej

2013-01-01

Background and Purpose Because agonists at metabotropic glutamate receptors exert beneficial effects in schizophrenia, we have assessed the actions of Lu AF21934 and Lu AF32615, two chemically distinct, selective and brain-penetrant positive allosteric modulators (PAMs) of the mGlu4 receptor, in several tests reflecting positive, negative and cognitive symptoms of schizophrenia in rodents. Experimental Approach Hyperactivity induced by MK-801 or amphetamine and head twitches induced by 2,5-dimethoxy-4-iodoamphetamine (DOI) in mice were used as models for positive symptoms. Disruption of social interaction and spatial delayed alternation tests induced by MK-801 in rats were used as models for negative and cognitive symptoms of schizophrenia, respectively. Key Results Lu AF21934 (0.1–5 mg·kg−1) and Lu AF32615 (2–10 mg·kg−1) dose-dependently inhibited hyperactivity induced by MK-801 or amphetamine. They also antagonized head twitches and increased frequency of spontaneous excitatory postsynaptic currents (EPSCs) in brain slices, induced by DOI. In mice lacking the mGlu4 receptor (mGlu4−/−) mice, Lu AF21934 did not antagonize DOI-induced head twitches. MK-801-induced disruption in the social interaction test was decreased by Lu AF21934 at 0.5 mg·kg−1 and by Lu AF32615 at 10 mg·kg−1. In the delayed spatial alternation test, Lu AF21934 was active at 1 and 2 mg·kg−1, while Lu AF32615 was active at 10 mg·kg−1. Conclusions and Implications We propose that activation by PAMs of the mGlu4 receptor is a promising approach to the discovery of novel antipsychotic drugs. PMID:23714045

Change in Coronary Blood Flow After Percutaneous Coronary Intervention in Relation to Baseline Lesion Physiology Results of the JUSTIFY-PCI Study

PubMed Central

Nijjer, Sukhjinder S.; Petraco, Ricardo; van de Hoef, Tim P.; Sen, Sayan; van Lavieren, Martijn A.; Foale, Rodney A.; Meuwissen, Martijn; Broyd, Christopher; Echavarria-Pinto, Mauro; Al-Lamee, Rasha; Foin, Nicolas; Sethi, Amarjit; Malik, Iqbal S.; Mikhail, Ghada W.; Hughes, Alun D.; Mayet, Jamil; Francis, Darrel P.; Di Mario, Carlo; Escaned, Javier; Piek, Jan J.; Davies, Justin E.

2016-01-01

Background Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicardial obstruction. However, no study has objectively confirmed this and assessed changes in flow over different phases of the cardiac cycle. We quantified the change in resting and hyperemic flow velocity after PCI in stenoses defined physiologically by fractional flow reserve and other parameters. Methods and Results Seventy-five stenoses (67 patients) underwent paired flow velocity assessment before and after PCI. Flow velocity was measured over the whole cardiac cycle and the wave-free period. Mean fractional flow reserve was 0.68±0.02. Pre-PCI, hyperemic flow velocity is diminished in stenoses classed as physiologically significant compared with those classed nonsignificant (P<0.001). In significant stenoses, flow velocity over the resting wave-free period and hyperemic flow velocity did not differ statistically. After PCI, resting flow velocity over the wave-free period increased little (5.6±1.6 cm/s) and significantly less than hyperemic flow velocity (21.2±3 cm/s; P<0.01). The greatest increase in hyperemic flow velocity was observed when treating stenoses below physiological cut points; treating stenoses with fractional flow reserve ≤0.80 gained Δ28.5±3.8 cm/s, whereas those fractional flow reserve >0.80 had a significantly smaller gain (Δ4.6±2.3 cm/s; P<0.001). The change in pressure-only physiological indices demonstrated a curvilinear relationship to the change in hyperemic flow velocity but was flat for resting flow velocity. Conclusions Pre-PCI physiology is strongly associated with post-PCI increase in hyperemic coronary flow velocity. Hyperemic flow velocity increases 6-fold more when stenoses classed as physiologically significant undergo PCI than when nonsignificant stenoses are treated. Resting flow velocity measured over the wave-free period changes at least 4-fold less than hyperemic flow velocity after PCI. PMID:26025217

Change in coronary blood flow after percutaneous coronary intervention in relation to baseline lesion physiology: results of the JUSTIFY-PCI study.

PubMed

Nijjer, Sukhjinder S; Petraco, Ricardo; van de Hoef, Tim P; Sen, Sayan; van Lavieren, Martijn A; Foale, Rodney A; Meuwissen, Martijn; Broyd, Christopher; Echavarria-Pinto, Mauro; Al-Lamee, Rasha; Foin, Nicolas; Sethi, Amarjit; Malik, Iqbal S; Mikhail, Ghada W; Hughes, Alun D; Mayet, Jamil; Francis, Darrel P; Di Mario, Carlo; Escaned, Javier; Piek, Jan J; Davies, Justin E

2015-06-01

Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicardial obstruction. However, no study has objectively confirmed this and assessed changes in flow over different phases of the cardiac cycle. We quantified the change in resting and hyperemic flow velocity after PCI in stenoses defined physiologically by fractional flow reserve and other parameters. Seventy-five stenoses (67 patients) underwent paired flow velocity assessment before and after PCI. Flow velocity was measured over the whole cardiac cycle and the wave-free period. Mean fractional flow reserve was 0.68±0.02. Pre-PCI, hyperemic flow velocity is diminished in stenoses classed as physiologically significant compared with those classed nonsignificant (P<0.001). In significant stenoses, flow velocity over the resting wave-free period and hyperemic flow velocity did not differ statistically. After PCI, resting flow velocity over the wave-free period increased little (5.6±1.6 cm/s) and significantly less than hyperemic flow velocity (21.2±3 cm/s; P<0.01). The greatest increase in hyperemic flow velocity was observed when treating stenoses below physiological cut points; treating stenoses with fractional flow reserve ≤0.80 gained Δ28.5±3.8 cm/s, whereas those fractional flow reserve >0.80 had a significantly smaller gain (Δ4.6±2.3 cm/s; P<0.001). The change in pressure-only physiological indices demonstrated a curvilinear relationship to the change in hyperemic flow velocity but was flat for resting flow velocity. Pre-PCI physiology is strongly associated with post-PCI increase in hyperemic coronary flow velocity. Hyperemic flow velocity increases 6-fold more when stenoses classed as physiologically significant undergo PCI than when nonsignificant stenoses are treated. Resting flow velocity measured over the wave-free period changes at least 4-fold less than hyperemic flow velocity after PCI. © 2015 American Heart Association, Inc.

Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials.

PubMed

Brown, Jennifer R; Moslehi, Javid; O'Brien, Susan; Ghia, Paolo; Hillmen, Peter; Cymbalista, Florence; Shanafelt, Tait D; Fraser, Graeme; Rule, Simon; Kipps, Thomas J; Coutre, Steven; Dilhuydy, Marie-Sarah; Cramer, Paula; Tedeschi, Alessandra; Jaeger, Ulrich; Dreyling, Martin; Byrd, John C; Howes, Angela; Todd, Michael; Vermeulen, Jessica; James, Danelle F; Clow, Fong; Styles, Lori; Valentino, Rudy; Wildgust, Mark; Mahler, Michelle; Burger, Jan A

2017-10-01

The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize AF with ibrutinib and its management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4% (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence: 13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65 years or over were independent risk factors for AF. Multiple AF events were more common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most (85.7%) patients with AF did not discontinue ibrutinib, and more than half received common anticoagulant/antiplatelet medications on study. Low-grade bleeds were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib, 2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset, these results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation ( clinicaltrials.gov identifier: 01578707, 01722487, 01611090, 01646021 ). Copyright© 2017 Ferrata Storti Foundation.

Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials

PubMed Central

Brown, Jennifer R.; Moslehi, Javid; O’Brien, Susan; Ghia, Paolo; Hillmen, Peter; Cymbalista, Florence; Shanafelt, Tait D.; Fraser, Graeme; Rule, Simon; Kipps, Thomas J.; Coutre, Steven; Dilhuydy, Marie-Sarah; Cramer, Paula; Tedeschi, Alessandra; Jaeger, Ulrich; Dreyling, Martin; Byrd, John C.; Howes, Angela; Todd, Michael; Vermeulen, Jessica; James, Danelle F.; Clow, Fong; Styles, Lori; Valentino, Rudy; Wildgust, Mark; Mahler, Michelle; Burger, Jan A.

2017-01-01

The first-in-class Bruton’s tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has been reported in 6–16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize AF with ibrutinib and its management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4% (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence: 13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65 years or over were independent risk factors for AF. Multiple AF events were more common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most (85.7%) patients with AF did not discontinue ibrutinib, and more than half received common anticoagulant/antiplatelet medications on study. Low-grade bleeds were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib, 2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset, these results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation (clinicaltrials.gov identifier: 01578707, 01722487, 01611090, 01646021). PMID:28751558

Opportunistic screening of atrial fibrillation by automatic blood pressure measurement in the community.

PubMed

Omboni, Stefano; Verberk, Willem J

2016-04-12

Timely detection of atrial fibrillation (AF) may effectively prevent cardiovascular consequences. However, traditional diagnostic tools are either poorly reliable (pulse palpation) or not readily accessible (ECG) in general practice. We tested whether an automatic oscillometric blood pressure (BP) monitor embedded with an algorithm for AF detection might be effective for opportunistic screening of asymptomatic AF in the community. A community-based screening campaign in an unselected population to verify the feasibility of AF screening with a Microlife WatchBP Office BP monitor with a patented AFIB algorithm. When possible AF was detected (≥2 of 3 BP measurements reporting AF), a doctor immediately performed a single-lead ECG in order to confirm or exclude the presence of the arrhythmia. The main demographic and clinical data were also collected. 220 consecutive participants from an unselected sample of individuals in a small Italian community. Number of patients detected with AF and diagnosed risk factors for AF. In 12 of 220 participants, the device detected possible AF during the BP measurement: in 4 of them (1.8%), the arrhythmia was confirmed by the ECG. Patients with AF were more likely to be older (77.0±1.2 vs 57.2±15.2 years, p=0.010), obese (50.0 vs 14.4%, p=0.048) and to suffer from a cardiovascular disease (50.0 vs 10.6%, p=0.014) than patients without AF. Participants with a positive BP AF reading and non-AF arrhythmias (n=8) did not differ in their general characteristics from participants with a negative BP AF reading and were younger than patients with AF (mean age 56.4±14.8, p=0.027; 5 of 8 participants aged <65 years). Opportunistic screening of AF by BP measurement is feasible to diagnose this arrhythmia in unaware participants, particularly in those older than 65 years, who are the target patient group recommended by current AF screening guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Antioxidant Capacities of Fractions of Bamboo Shaving Extract and Their Antioxidant Components.

PubMed

Gong, Jinyan; Huang, Jun; Xiao, Gongnian; Chen, Feng; Lee, Bolim; Ge, Qing; You, Yuru; Liu, Shiwang; Zhang, Ying

2016-07-30

This research was conducted for evaluation of antioxidant activities of four fractions from bamboo shavings extract (BSE) and their antioxidant components. The antioxidant capacities of BSE and four fractions on ABTS, DPPH, FRAP and total antioxidant capacity assays exhibited the following descending order: DF > n-butanol fraction (BF) > BSE ≈ ethyl acetate fraction (AF) > water fraction (WF). Among the identified phenolic compounds, caffeic acid exhibited the highest antioxidant capacities on DPPH, FRAP and total antioxidant capacity assays. An extremely significant positive correlation between the antioxidant activities with the contents of total flavonoids, total phenolic acids, or total phenolics was observed in this study. The result indicated that the bamboo shaving extract and its solvent fractions could act as natural antioxidants in light of their potent antioxidant activities.

[Plasma cardiac natriuretic peptide as a biological marker of recurrence of atrial fibrillation in elderly people].

PubMed

Mabuchi, N; Tsutamoto, T; Maeda, K; Masahiko, K

2000-07-01

We designed this study to evaluate the relationship between plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels and recurrence of atrial fibrillation (AF) after direct current cardioversion (DC) and the differences with aging. Fifty patients with mild congestive heart failure (CHF) undergoing elective DC of AF were included in this study (New York Heart Association (NYHA) functional class II: n = 42, III = 8). Patients who failed to show restoration of sinus rhythm or those with mitral valve stenosis were excluded. Before successful DC, we measured plasma levels of ANP and BNP and evaluated left atrial dimension (LAD), left ventricular end-diastolic dimension (LVDd), and left ventricular ejection fraction (EF) by echocardiography. Twenty-one patients had recurrence of AF within 2 months after DC (average 9.05 days). We followed up the other 29 patients for 580.5 days. By Cox stepwise multivariate analysis, history of AF (p = 0.007), low plasma levels of ANP (p = 0.003), and high plasma levels of BNP (p = 0.0003) were found to be independent predictors of recurrent AF. High plasma BNP levels indicating ventricular dysfunction and low plasma ANP levels may be due to atrial histological change such as fibrosis. In these patients, plasma ratios of ANP and BNP (ANP/BNP) less than 0.43 were predictive factors for AF recurrence (sensitivity 70%, specificity 62%), especially in patients who were older than 70 years (sensitivity 100%, specificity 80%). Relatively low plasma ANP level compared to BNP is an independent risk factor of AF recurrence in patients with CHF, especially in elderly patients, suggesting that plasma cardiac natriuretic peptides are important biochemical markers of AF recurrence in elderly patients with CHF.

Genetic Risk Prediction of Atrial Fibrillation

PubMed Central

Lubitz, Steven A.; Yin, Xiaoyan; Lin, Henry J.; Kolek, Matthew; Smith, J. Gustav; Trompet, Stella; Rienstra, Michiel; Rost, Natalia S.; Teixeira, Pedro L.; Almgren, Peter; Anderson, Christopher D.; Chen, Lin Y.; Engström, Gunnar; Ford, Ian; Furie, Karen L.; Guo, Xiuqing; Larson, Martin G.; Lunetta, Kathryn L.; Macfarlane, Peter W.; Psaty, Bruce M.; Soliman, Elsayed Z.; Sotoodehnia, Nona; Stott, David J.; Taylor, Kent D.; Weng, Lu-Chen; Yao, Jie; Geelhoed, Bastiaan; Verweij, Niek; Siland, Joylene E.; Kathiresan, Sekar; Roselli, Carolina; Roden, Dan; van der Harst, Pim; Darbar, Dawood; Jukema, J. Wouter; Melander, Olle; Rosand, Jonathan; Rotter, Jerome I.; Heckbert, Susan R.; Ellinor, Patrick T.; Alonso, Alvaro; Benjamin, Emelia J.

2017-01-01

Background Atrial fibrillation (AF) is common and has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. Methods To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 controls. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1×10−3 to <1×10−8 in a prior independent genetic association study. Results Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13–1.46; P=1.5×10−4) to 1.67 (25 variants; 95%CI, 1.47–1.90; P=9.3×10−15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629–0.811; maximum ΔC statistic from clinical score alone, 0.009–0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke, versus those in the lowest quartile (95%CI, 1.39–4.58; P=2.7×10−3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20–4.40; P=0.01). Conclusions Comprehensive AF genetic risk scores were associated with incident AF beyond clinical AF risk factors, with magnitudes of risk comparable to other clinical risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts to determine whether AF genetic risk may improve identification of subclinical AF or distinguish stroke mechanisms are warranted. PMID:27793994

Using multi-stakeholder alliances to accelerate the adoption of health information technology by physician practices.

PubMed

McHugh, Megan; Shi, Yunfeng; McClellan, Sean R; Shortell, Stephen M; Fareed, Naleef; Harvey, Jillian; Ramsay, Patricia; Casalino, Lawrence P

2016-06-01

Multi-stakeholder alliances - groups of payers, purchasers, providers, and consumers that work together to address local health goals - are frequently used to improve health care quality within communities. Under the Aligning Forces for Quality (AF4Q) initiative, multi-stakeholder alliances were given funding and technical assistance to encourage the use of health information technology (HIT) to improve quality. We investigated whether HIT adoption was greater in AF4Q communities than in other communities. Drawing upon survey data from 782 small and medium-sized physician practices collected as part of the National Study of Physician Organizations during July 2007 - March 2009 and January 2012-November 2013, we used weighted fixed effects models to detect relative changes in four measures representing three domains: use of electronic health records (EHRs), receipt of electronic information from hospitals, and patients' online access to their medical records. Improvement on a composite EHR adoption measure was 7.6 percentage points greater in AF4Q communities than in non-AF4Q communities, and the increase in the probability of adopting all five EHR capabilities was 23.9 percentage points greater in AF4Q communities. There was no significant difference in improvement in receipt of electronic information from hospitals or patients' online access to medical records between AF4Q and non-AF4Q communities. By linking HIT to quality improvement efforts, AF4Q alliances may have facilitated greater adoption of EHRs in small and medium-sized physician practices, but not receipt of electronic information from hospitals or patients' online access to medical records. Multi-stakeholder alliances charged with promoting HIT to advance quality improvement may accelerate adoption of EHRs. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry.

PubMed

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph Gabriel

2015-01-01

Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. ISRCTN registry of clinical trials: ISRCTN43070564.

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry

PubMed Central

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M.; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph. Gabriel

2015-01-01

Background Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. Methods and Findings CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. Conclusions In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. Trial Registration ISRCTN registry of clinical trials: ISRCTN43070564. PMID:25915904

Stability of rotors and focal sources for human atrial fibrillation: focal impulse and rotor mapping (FIRM) of AF sources and fibrillatory conduction.

PubMed

Swarup, Vijay; Baykaner, Tina; Rostamian, Armand; Daubert, James P; Hummel, John; Krummen, David E; Trikha, Rishi; Miller, John M; Tomassoni, Gery F; Narayan, Sanjiv M

2014-12-01

Several groups report electrical rotors or focal sources that sustain atrial fibrillation (AF) after it has been triggered. However, it is difficult to separate stable from unstable activity in prior studies that examined only seconds of AF. We applied phase-based focal impulse and rotor mapping (FIRM) to study the dynamics of rotors/sources in human AF over prolonged periods of time. We prospectively mapped AF in 260 patients (169 persistent, 61 ± 12 years) at 6 centers in the FIRM registry, using baskets with 64 contact electrodes per atrium. AF was phase mapped (RhythmView, Topera, Menlo Park, CA, USA). AF propagation movies were interpreted by each operator to assess the source stability/dynamics over tens of minutes before ablation. Sources were identified in 258 of 260 of patients (99%), for 2.8 ± 1.4 sources/patient (1.8 ± 1.1 in left, 1.1 ± 0.8 in right atria). While AF sources precessed in stable regions, emanating activity including spiral waves varied from collision/fusion (fibrillatory conduction). Each source lay in stable atrial regions for 4,196 ± 6,360 cycles, with no differences between paroxysmal versus persistent AF (4,290 ± 5,847 vs. 4,150 ± 6,604; P = 0.78), or right versus left atrial sources (P = 0.26). Rotors and focal sources for human AF mapped by FIRM over prolonged time periods precess ("wobble") but remain within stable regions for thousands of cycles. Conversely, emanating activity such as spiral waves disorganize and collide with the fibrillatory milieu, explaining difficulties in using activation mapping or signal processing analyses at fixed electrodes to detect AF rotors. These results provide a rationale for targeted ablation at AF sources rather than fibrillatory spiral waves. © 2014 Wiley Periodicals, Inc.

Stroke as the Initial Manifestation of Atrial Fibrillation: The Framingham Heart Study.

PubMed

Lubitz, Steven A; Yin, Xiaoyan; McManus, David D; Weng, Lu-Chen; Aparicio, Hugo J; Walkey, Allan J; Rafael Romero, Jose; Kase, Carlos S; Ellinor, Patrick T; Wolf, Philip A; Seshadri, Sudha; Benjamin, Emelia J

2017-02-01

To prevent strokes that may occur as the first manifestation of atrial fibrillation (AF), screening programs have been proposed to identify patients with undiagnosed AF who may be eligible for treatment with anticoagulation. However, the frequency with which patients with AF present with stroke as the initial manifestation of the arrhythmia is unknown. We estimated the frequency with which AF may present as a stroke in 1809 community-based Framingham Heart Study participants with first-detected AF and without previous strokes, by tabulating the frequencies of strokes occurring on the same day, within 30 days before, 90 days before, and 365 days before first-detected AF. Using previously reported AF incidence rates, we estimated the incidence of strokes that may represent the initial manifestation of AF. We observed 87 strokes that occurred ≤1 year before AF detection, corresponding to 1.7% on the same day, 3.4% within 30 days before, 3.7% within 90 days before, and 4.8% ≤1 year before AF detection. We estimated that strokes may present as the initial manifestation of AF at a rate of 2 to 5 per 10 000 person-years, in both men and women. We observed that stroke is an uncommon but measureable presenting feature of AF. Our data imply that emphasizing cost-effectiveness of population-wide AF-screening efforts will be important given the relative infrequency with which stroke represents the initial manifestation of AF. © 2017 American Heart Association, Inc.

Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.

PubMed

Kishore, Amit; Vail, Andy; Majid, Arshad; Dawson, Jesse; Lees, Kennedy R; Tyrrell, Pippa J; Smith, Craig J

2014-02-01

Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity even within specified subgroups. Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Evaluating the Atrial Myopathy Underlying Atrial Fibrillation: Identifying the Arrhythmogenic and Thrombogenic Substrate

PubMed Central

Goldberger, Jeffrey J.; Arora, Rishi; Green, David; Greenland, Philip; Lee, Daniel C.; Lloyd-Jones, Donald M.; Markl, Michael; Ng, Jason; Shah, Sanjiv J.

2015-01-01

Atrial disease or myopathy forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. Current diagnostic approaches in patients with AF focus on identifying clinical predictors with evaluation of left atrial size by echocardiography serving as the sole measure specifically evaluating the atrium. Although the atrial substrate underlying AF is likely developing for years prior to the onset of AF, there is no current evaluation to identify the pre-clinical atrial myopathy. Atrial fibrosis is one component of the atrial substrate that has garnered recent attention based on newer MRI techniques that have been applied to visualize atrial fibrosis in humans with prognostic implications regarding success of treatment. Advanced ECG signal processing, echocardiographic techniques, and MRI imaging of fibrosis and flow provide up-to-date approaches to evaluate the atrial myopathy underlying AF. While thromboembolic risk is currently defined by clinical scores, their predictive value is mediocre. Evaluation of stasis via imaging and biomarkers associated with thrombogenesis may provide enhanced approaches to assess risk for stroke in patients with AF. Better delineation of the atrial myopathy that serves as the substrate for AF and thromboembolic complications might improve treatment outcomes. Furthermore, better delineation of the pathophysiologic mechanisms underlying the development of the atrial substrate for AF, particularly in its earlier stages, could help identify blood and imaging biomarkers that could be useful to assess risk for developing new onset AF and suggest specific pathways that could be targeted for prevention. PMID:26216085

Turbulent kinetic energy in the right ventricle: Potential MR marker for risk stratification of adults with repaired Tetralogy of Fallot.

PubMed

Fredriksson, Alexandru; Trzebiatowska-Krzynska, Aleksandra; Dyverfeldt, Petter; Engvall, Jan; Ebbers, Tino; Carlhäll, Carl-Johan

2018-04-01

To assess right ventricular (RV) turbulent kinetic energy (TKE) in patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary regurgitation (PR), as well as to investigate the relationship between these 4D flow markers and RV remodeling. Seventeen patients with rToF and 10 healthy controls were included in the study. Patients were divided into two groups based on PR fraction: one lower PR fraction group (≤11%) and one higher PR fraction group (>11%). Field strength/sequences: 3D cine phase contrast (4D flow), 2D cine phase contrast (2D flow), and balanced steady-state free precession (bSSFP) at 1.5T. The RV volume was segmented in the morphologic short-axis images and TKE parameters were computed inside the segmented RV volume throughout diastole. Statistical tests: One-way analysis of variance with Bonferroni post-hoc test; unpaired t-test; Pearson correlation coefficients; simple and stepwise multiple regression models; intraclass correlation coefficient (ICC). The higher PR fraction group had more remodeled RVs (140 ± 25 vs. 107 ± 22 [lower PR fraction, P < 0.01] and 93 ± 15 ml/m 2 [healthy, P < 0.001] for RV end-diastolic volume index [RVEDVI]) and higher TKE values (5.95 ± 3.15 vs. 2.23 ± 0.81 [lower PR fraction, P < 0.01] and 1.91 ± 0.78 mJ [healthy, P < 0.001] for Peak Total RV TKE). Multiple regression analysis between RVEDVI and 4D/2D flow parameters showed that Peak Total RV TKE was the strongest predictor of RVEDVI (R 2  = 0.47, P = 0.002). The 4D flow-specific TKE markers showed a slightly stronger association with RV remodeling than conventional 2D flow PR parameters. These results suggest novel hemodynamic aspects of PR in the development of late complications after ToF repair. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1043-1053. © 2017 International Society for Magnetic Resonance in Medicine.

Effectiveness of atrial fibrillation rotor ablation is dependent on conduction velocity: An in-silico 3-dimensional modeling study

PubMed Central

Lim, Byounghyun; Hwang, Minki; Song, Jun-Seop; Ryu, Ah-Jin; Joung, Boyoung; Shim, Eun Bo; Ryu, Hyungon

2017-01-01

Background We previously reported that stable rotors are observed in in-silico human atrial fibrillation (AF) models, and are well represented by a dominant frequency (DF). In the current study, we hypothesized that the outcome of DF ablation is affected by conduction velocity (CV) conditions and examined this hypothesis using in-silico 3D-AF modeling. Methods We integrated 3D CT images of left atrium obtained from 10 patients with persistent AF (80% male, 61.8±13.5 years old) into in-silico AF model. We compared AF maintenance durations (max 300s), spatiotemporal stabilities of DF, phase singularity (PS) number, life-span of PS, and AF termination or defragmentation rates after virtual DF ablation with 5 different CV conditions (0.2, 0.3, 0.4, 0.5, and 0.6m/s). Results 1. AF maintenance duration (p<0.001), spatiotemporal mean variance of DF (p<0.001), and the number of PS (p = 0.023) showed CV dependent bimodal patterns (highest at CV0.4m/s and lowest at CV0.6m/s) consistently. 2. After 10% highest DF ablation, AF defragmentation rates were the lowest at CV0.4m/s (37.8%), but highest at CV0.5 and 0.6m/s (all 100%, p<0.001). 3. In the episodes with AF termination or defragmentation followed by 10% highest DF ablation, baseline AF maintenance duration was shorter (p<0.001), spatiotemporal mean variance of DF was lower (p = 0.014), and the number of PS was lower (p = 0.004) than those with failed AF defragmentation after DF ablation. Conclusion Virtual ablation of DF, which may indicate AF driver, was more likely to terminate or defragment AF with spatiotemporally stable DF, but not likely to do so in long-lasting and sustained AF conditions, depending on CV. PMID:29287119

Multiplexed electrokinetic sample fractionation, preconcentration and elution for proteomics.

PubMed

Hua, Yujuan; Jemere, Abebaw B; Dragoljic, Jelena; Harrison, D Jed

2013-07-07

Both 6 and 8-channel integrated microfluidic sample pretreatment devices capable of performing "in space" sample fractionation, collection, preconcentration and elution of captured analytes via sheath flow assisted electrokinetic pumping are described. Coatings and monolithic polymer beds were developed for the glass devices to provide cationic surface charge and anodal electroosmotic flow for delivery to an electrospray emitter tip. A mixed cationic ([2-(methacryloyloxy)ethyl] trimethylammonium chloride) (META) and hydrophobic butyl methacrylate-based monolithic porous polymer, photopolymerized in the 6- or 8-fractionation channels, was used to capture and preconcentrate samples. A 0.45 wt% META loaded bed generated comparable anodic electroosmotic flow to the cationic polymer PolyE-323 coated channel segments in the device. The balanced electroosmotic flow allowed stable electrokinetic sheath flow to prevent cross contamination of separated protein fractions, while reducing protein/peptide adsorption on the channel walls. Sequential elution of analytes trapped in the SPE beds revealed that the monolithic columns could be efficiently used to provide sheath flow during elution of analytes, as demonstrated for neutral carboxy SNARF (residual signal, 0.08% RSD, n = 40) and charged fluorescein (residual signal, 2.5% n = 40). Elution from monolithic columns showed reproducible performance with peak area reproducibility of ~8% (n = 6 columns) in a single sequential elution and the run-to-run reproducibility was 2.4-6.7% RSD (n = 4) for elution from the same bed. The demonstrated ability of this device design and operation to elute from multiple fractionation beds into a single exit channel for sample analysis by fluorescence or electrospray mass spectrometry is a crucial component of an integrated fractionation and assay system for proteomics.

Turbulent Flow over Small Amplitude Solid Waves

DTIC Science & Technology

1984-01-01

are ignored gives good agreement with the measure- ments of the variation of the wall shear stress for large values of a. An equilibrium turbulence...a [ iaUv -aUJe =--7— +R’ 3y yy + a [ v" - a^v - ia ^ U - p’ + f’ + R a^ + iaf yy yy xy a^ R ] e^’^^. ’ (3.7) XX The...U’" + R" = 0 , - (3.12) xy 17 ia [U(F" - a^F) - U"F + a^U^] = F"" - 2a^F" + a^F + 2a^ U" - a^ U + /? , (3.13) /?= ia ^ R +3a^R’ + ia ( r

Association between atrial fibrillation, atrial enlargement, and left ventricular geometric remodeling.

PubMed

Seko, Yuta; Kato, Takao; Haruna, Tetsuya; Izumi, Toshiaki; Miyamoto, Shoichi; Nakane, Eisaku; Inoko, Moriaki

2018-04-23

This study investigated the relationship between atrial fibrillation (AF) and left ventricular (LV) geometric patterns in a hospital-based population in Japan. We retrospectively analyzed 4444 patients who had undergone simultaneous scheduled transthoracic echocardiography (TTE) and electrocardiography during 2013. A total of 430 patients who had findings of previous myocardial infarctions (n = 419) and without the data on body surface area (n = 11) were excluded from the study. We calculated the LV mass index (LVMI) and relative wall (RWT) and categorized 4014 patients into four groups as follows: normal geometry (n = 3046); concentric remodeling (normal LVMI and high RWT, n = 437); concentric hypertrophy (high LVMI and high RWT, n = 149); and eccentric remodeling (high LVMI and normal RWT, n = 382). The mean left atrial volume indices (LAVI) were 22.5, 23.8, 33.3, and 37.0 mm/m 2 in patients with normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy, respectively. The mean LV ejection fractions (LVEF) were 62.7, 62.6, 60.8, and 53.8%, respectively, whereas the prevalence of AF was 10.4%, 10.5%, 14.8%, and 16.8% in patients with normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy, respectively. In conclusion, the prevalence of AF was increasing according to LV geometric remodeling patterns in association with LA size and LVEF.

Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function.

PubMed

Molnar, Amber O; Eddeen, Anan Bader; Ducharme, Robin; Garg, Amit X; Harel, Ziv; McCallum, Megan K; Perl, Jeffrey; Wald, Ron; Zimmerman, Deborah; Sood, Manish M

2017-07-06

Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function. Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF ( P <0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P <0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses. Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Antiferromagnetic Ordering in Organic Conductor λ-(BEDT-TTF)2GaCl4 Probed by 13C NMR

NASA Astrophysics Data System (ADS)

Saito, Yohei; Fukuoka, Shuhei; Kobayashi, Takuya; Kawamoto, Atsushi; Mori, Hatsumi

2018-01-01

The ground state of λ-(BEDT-TTF)2GaCl4, which has the same structure as the organic superconductor λ-(BETS)2GaCl4, was investigated by magnetic susceptibility and 13C NMR measurements. The temperature dependence of the magnetic susceptibility revealed an antiferromagnetic (AF) correlation with J/kB ≃ 98 K. NMR spectrum splitting and the divergence of 1/T1 were observed at approximately 13 K, which is associated with the AF transition. We found that the AF structure is commensurate according to discrete NMR peak splitting, suggesting that the ground state of λ-(BEDT-TTF)2GaCl4 is an AF dimer-Mott insulating state. Our results suggest that the superconducting phase of λ-type salts would be located near the AF insulating phase.

Magnitude of increase in QTc interval after initiation of dofetilide in patients with persistent atrial fibrillation is associated with increased rates of pharmacological cardioversion and long-term freedom from recurrent atrial fibrillation.

PubMed

Huang, Henry D; Waks, Jonathan W; Steinhaus, Daniel A; Zimetbaum, Peter

2016-07-01

Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence. We performed retrospective analyses of a prospective cohort of patients with AF admitted for dofetilide initiation between 2001 and 2014. Clinical characteristics and electrocardiographic variables were assessed. We evaluated outcomes of successful PCV in patients with persistent AF and time to recurrence of AF in patients with paroxysmal and persistent AF. During the study, 243 patients with persistent AF and 176 patients with paroxysmal AF initiated dofetilide. PCV occurred in 93/243 (41.7%) patients with persistent AF. After multivariable adjustment, QTc interval change was associated with PCV (adjusted odds ratio 1.21; P = .003 per 10-ms QTc increase). Inhospital QTc interval change was associated with long-term freedom from AF in patients with persistent AF (adjusted hazard ratio 0.92; P = .011 at 4 years per 10-ms QTc increase), but not in patients with paroxysmal AF. In patients with persistent AF, PCV was also associated with long-term freedom from recurrent AF (adjusted hazard ratio 0.62; P = .009 at 4 years). The magnitude of QTc interval prolongation during dofetilide initiation is an independent predictor of successful PCV and long-term freedom from arrhythmia in patients with persistent AF. QTc interval change had no association with AF recurrence in patients with paroxysmal AF, suggesting that different mechanisms of arrhythmogenesis may be operant in different AF types. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Initial experience of a novel mapping system combined with remote magnetic navigation in the catheter ablation of atrial fibrillation.

PubMed

Lin, Changjian; Pehrson, Steen; Jacobsen, Peter Karl; Chen, Xu

2017-12-01

There have been advancements of sophisticated mapping systems used for ablation procedures over the last decade. Utilization of these novel mapping systems in combination with remote magnetic navigation (RMN) needs to be established. We investigated the new EnSite Precision mapping system (St. Jude Medical, Inc., St. Paul, MN, USA), which collects magnetic data for checking navigation field stability and is built on an open platform, allowing physicians to choose diagnostic and ablation catheters. We address its compatibility with RMN. To assess the clinical utility of a novel 3D mapping system (EnSite Precision mapping system) combined with RMN (Niobe ES, Stereotaxis, Inc., St. Louis, MO, USA) for atrial fibrillation (AF) ablation. In this prospective nonrandomized study, two groups of patients were treated in our center for drug refractory AF. Patients were consecutively enrolled in each group. Group A (n = 35, 14 persistent AF [PsAF]) was treated using the novel 3D mapping system combined with RMN. Group B (n = 38, 16 PsAF) was treated using Carto ® 3 (Biosense Webster, Inc., Diamond Bar, CA, USA) combined with RMN. In Group A, the left atrium (LA) was mapped with a circular magnetic catheter manually and was then replaced by a RMN ablation catheter. At the end of the procedures in Group A, the circular catheter was used for confirming field stability. In Group B, an ablation catheter was controlled by RMN to perform both LA mapping and ablation. All patients underwent pulmonary vein antrum isolation. Additional complex fractionated atrial electrograms (CFAEs) ablation was performed for PsAF. Procedural, ablation, and fluoroscopy times were recorded and complications were assessed. Electrophysiological end points were achieved in all patients. Using the novel mapping system, LA mapping time was fast (308 ± 60 seconds) with detailed anatomy points (178,831 ± 70,897) collected and magnetic points throughout LA. At the end of the procedures in Group A, the LA model was confirmed to be stable and its location was within the distance threshold (1 mm). Procedure time (117.9 ± 29.6 minutes vs. 119.2 ± 29.7 minutes, P = 0.89), fluoroscopy time (6.1 ± 2.4 minutes vs. 4.8 ± 2.2 minutes, P = 0.07), and ablation time (28.0 ± 12.9 minutes vs. 27.9 ± 15.8 minutes, P = 0.98) were similar in Group A versus Group B, respectively. No complications occurred in either group. LA mapped by the novel system is stable and reliable. Combined with RMN, it could be effectively used for AF ablation without impacting overall procedural times. © 2017 Wiley Periodicals, Inc.

Evaluation Lactogenic Activity of Ethyl Acetate Fraction of Torbangun (Coleus amboinicus L.) Leaves

NASA Astrophysics Data System (ADS)

Damanik, R. M.; Kustiyah, L.; Hanafi, M.; Iwansyah, A. C.

2017-12-01

This study aimed to assess the lactogenic property of ethyl acetate fraction of torbangun (Coleus amboinicus L.) leaves and to identify the compounds that responsibility as ‘milk booster’ using LC- MS approach. Lactagogue activity was evaluated in terms of quantity of milk produced from the rats treated with commercial milk booster (AF), ethyl acetate fraction of torbangun leaves (EA), water extraction of torbangun (AQ) and kaempferol (KP). The feed was given orally every two days and starting from Day 2 after giving birth until Day 28. The performance of milk production was measured along the experimental period by weight-suckle-weight method. The level of prolactin serum was determined by ELISA methods. Histopathological analysis of mammary gland, liver, intestines and kidney tissues was carried out. Moreover, in order to profiling and identification of compounds of ethyl acetate fraction, ultra-performance liquid chromatography quadrupole time of flight to electrospray ionization mass spectrometry (UPLC-QTOF-ESI-MS) in the positive-ion mode was performed. The ethyl acetate fraction of torbangun leaves (EA) was induced milk production about 17%, and AF 22% and KP 51% compared to the control group. Meanwhile, the EA was not significantly stimulate the synthesis of serum prolactin at Day 14 and Day 28 (p>0.05). Administration of EA did not cause any signs or symptoms of toxicity. In addition, a total of ten compounds was identified by UPLC-QTOF-ESI/MS in the ethyl acetate fraction of the leaves of C. amboinicus, mostly phenolic compounds, flavonols and some of their glycoside derivatives, such as: digiprolatone, and kaempferol-3-7-O-di-rhamnopyranoside. The present study reveals the ethyl acetate fraction of torbangun leaves and its bioactive compounds has the potency as a remedy for stimulating and improving milk production.

Uranium from Seawater Marine Testing Program at the University of Miami’s Broad Key Island Research Station

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gill, Gary A.; Kuo, Li-Jung; Strivens, Jonathan E.

Marine testing at Broad Key Island (BKI), Florida was conducted to validate adsorption capacity and adsorption kinetics results obtained for several formulations of the ORNL amidoxime-based polymeric adsorbents in Sequim Bay, Washington in another location with different oceanographic and water quality conditions (e.g. temperature, dissolved organic carbon, salinity and trace element content). Broad Key is a small island off the southeast coast of Florida at the southern end of Biscayne Bay. Flow-through column and recirculating flume experiments were conducted at BKI using ambient filtered seawater and identical exposure systems as were used at the Pacific Northwest National Laboratory’s (PNNL) Marinemore » Sciences laboratory (MSL). Testing was conducted in two periods in FY 2015 and FY 2016 with five different amidoxime-based adsorbent materials, four produced by ORNL (AF1, AI8, AF8, and AF1-DMSO) and one by LCW technologies (LCW-10). All exposures were conducted at ambient seawater temperatures, with moderate temperature control on the ambient seawater to mitigate large daily swings in the seawater temperature. The ORNL adsorbents AF1, AI8 and AF1-AO-DMSO all had fairly similar adsorption capacities (6.0 to 6.6 g U/ kg adsorbent) after 56 days of exposure at ambient temperature (26 to 31 °C) and salinity (35.7 to 37.4), but the AF8 adsorbent was considerably lower at 4.4 g U/kg adsorbent. All the adsorbents tested at BKI had higher capacities than was observed at PNNL, with the higher temperatures likely a major factor contributing to this difference. In general, the elemental distribution (expressed as a relative percentage) on all the adsorbents agreed well, including good agreement with the elemental distribution pattern for AF1 adsorbent exposed at PNNL. The most notable exception to a uniform elemental distributional pattern across the various adsorbents occurs with vanadium. The relative mass percentage for vanadium retained by the adsorbents ranged from a minimum of 13% for the AF8 formulation to a maximum of 29% for the AI8 formulation. All the V/U mass ratios at BKI are lower than observed for the AF1 adsorbent at PNNL (3.0). Temperature likely plays a significant role in the V/U mass ratio difference between BKI and PNNL. Because uranium has a higher adsorption capacity at higher temperatures, one would expect that warmer exposures would favor a lower V/U mass ratio, which could explain why the V/U mass ratio for the PNNL exposures are higher than observed for the BKI exposures. Marine Testing at BKI offers the opportunity to test adsorbent performance under warmer ambient and more saline conditions than exist at the marine test site on Sequim Bay. This is particularly important since the amidoxime-based adsorbents respond strongly to temperature. In addition, since salinities are about 15% higher at BKI compared to Sequim Bay (36 vs. 31), uranium adsorption capacities are about 15% higher at the BKI site compared to Sequim Bay.« less

The potential use of stem cells derived from human amniotic fluid in renal diseases.

PubMed

Noronha, Irene L; Cavaglieri, Rita C; Janz, Felipe L; Duarte, Sergio A; Lopes, Marco A B; Zugaib, Marcelo; Bydlowski, Sergio P

2011-09-01

Amniotic fluid (AF) contains a variety of cell types derived from fetal tissues that can easily grow in culture. These cells can be obtained during amniocentesis for prenatal screening of fetal genetic diseases, usually performed during the second trimester of pregnancy. Of particular interest, some expanded sub-populations derived from AF cells are capable of extensive self-renewal and maintain prolonged undifferentiated proliferation, which are defining properties of stem cells. These human AF stem cells (hAFSCs) exhibit multilineage potential and can differentiate into the three germ layers. They have high proliferation rates and express mesenchymal and embryonic markers, but do not induce tumor formation. In this study, hAFSCs derived from amniocentesis performed at 16-20 weeks of pregnancy were isolated, grown in culture, and characterized by flow cytometry and by their potential ability to differentiate into osteogenic, adipogenic, and chondrogenic lineages. After 4-7 passages, 5 × 10 5 hAFSCs were inoculated under the kidney capsule of Wistar rats that were subjected to an experimental model of chronic renal disease, the 5/6 nephrectomy model (Nx). After 30 days, Nx rats treated with hAFSCs displayed significant reductions in blood pressure, proteinuria, macrophages, and α-smooth muscle actin expression compared with Nx animals. These preliminary results suggest that hAFSCs isolated and expanded from AF obtained by routine amniocentesis can promote renoprotection in the Nx model. Considering that the AF cells not used for fetal karyotyping are usually discarded, and that their use does not raise ethical issues, they may represent an alternative source of stem cells for cell therapy and regenerative medicine.

Atrial supply-demand balance in healthy adult pigs: coronary blood flow, oxygen extraction, and lactate production during acute atrial fibrillation.

PubMed

van Bragt, Kelly A; Nasrallah, Hussein M; Kuiper, Marion; Luiken, Joost J; Schotten, Ulrich; Verheule, Sander

2014-01-01

Little is known about how atrial oxygen supply responds to increased demand, and under which conditions it falls short (supply-demand mismatch). Here, we have investigated the vasodilator response, oxygen extraction, and lactate production of the left atrium (LA) and left ventricle (LV) in response to atrial pacing and atrial fibrillation (AF). Series A (n = 9 Dutch landrace pigs) was instrumented to measure LA and LV vascular conductance in branches of the circumflex artery. Coronary conductance reserve (CCR) was calculated as the ratio between conductance during adenosine infusion and baseline. Series B (n = 7) was instrumented with sampling catheters in LA and LV veins for determination of blood gases and lactate levels. LA CCR (1.76 ± 0.14) was significantly lower than LV CCR (3.16 ± 0.27, P = 0.002). However, basal oxygen extraction was lower in LA (27 ± 3%) than that in the LV (58 ± 6%, P = 0.0006), indicating a larger extraction reserve in the LA than that in the LV (4.68 ± 0.84 vs. 1.88 ± 0.26, P = 0.01). Atrial pacing caused an increase in LA conductance (Series A) and oxygen extraction (Series B). AF increased LA vascular conductance to 177 ± 14% at 1 min, 168 ± 14 at 5 min, and 164 ± 31% at 10 min of AF (P < 0.05 vs. baseline). Atrial oxygen extraction also increased from 26 ± 3% at baseline to 63 ± 5% (P < 0.01) at 5 min and 60 ± 11% (P < 0.01) at 10 min of AF. Arterio-venous lactate difference increased significantly (P = 0.02) during AF. In healthy pigs, the LA has a lower CCR, but a higher extraction reserve compared with the LV. Although both reserves were recruited during AF, atrial lactate production increased significantly.

Atrial cellular electrophysiological changes in patients with ventricular dysfunction may predispose to AF

PubMed Central

Workman, Antony J; Pau, Davide; Redpath, Calum J; Marshall, Gillian E; Russell, Julie A; Norrie, John; Kane, Kathleen A; Rankin, Andrew C

2009-01-01

Background Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear. Objective To investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes which could predispose to AF. Methods Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery. Action potentials or ion currents were measured using the whole-cell-patch clamp technique. Results The presence of moderate or severe LVSD was associated with a shortened atrial cellular effective refractory period, ERP (209±8 ms; 52 cells, 18 patients vs 233±7 ms; 134 cells, 49 patients; P<0.05); confirmed by multiple linear regression analysis. The LV ejection fraction (LVEF) was markedly lower in patients with moderate or severe LVSD (36±4%, n=15) than in those without LVSD (62±2%, n=31; P<0.05). In cells from patients with LVEF≤45%, the ERP and action potential duration at 90% repolarisation were shorter than in those from patients with LVEF>45%, by 24 and 18%, respectively. The LVEF and ERP were positively correlated (r=0.65, P<0.05). The L-type calcium ion current, inward rectifier potassium ion current, and sustained outward ion current was unaffected by LVSD. The transient outward potassium ion current was decreased by 34%, with a positive shift in its activation voltage, and no change in its decay kinetics. Conclusion LVSD in patients in SR is independently associated with a shortening of the atrial cellular ERP, which may be expected to contribute to a predisposition to AF. PMID:19324301

Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial mechanical function after reversion of atrial arrhythmias to sinus rhythm: reversal of tachycardia-mediated atrial cardiomyopathy with fish oils.

PubMed

Kumar, Saurabh; Sutherland, Fiona; Wheeler, Miriam; Heck, Patrick M; Lee, Geoffrey; Teh, Andrew W; Garg, Manohar L; Morgan, John G; Sparks, Paul B

2011-05-01

Atrial mechanical stunning is a form of tachycardia-mediated atrial cardiomyopathy that manifests after reversion of persistent atrial arrhythmias to sinus rhythm. This study sought to examine whether chronic omega-3 polyunsaturated fatty acid supplementation with fish oils can reverse atrial mechanical stunning. Patients undergoing reversion of persistent atrial fibrillation (AF) or atrial flutter (AFL) to sinus rhythm were randomized to a control group (n = 26) or an omega-3 group (n = 23). The latter were prescribed 6 g/day of fish oil for ≥1 month prior to the procedure. Parameters of left atrial appendage function were compared immediately before and immediately after reversion. After fish oil intake for a mean of 70 days, the following were noted favoring the omega-3 group among both AF and AFL patients: (1) 2-fold higher serum omega-3 levels (P < .001), (2) less mean decrease in emptying velocity (e.g., AF: 8% vs. 32%, P = .02), (3) less mean decrease in appendage emptying fraction (e.g., AFL: 7% vs. 60%, P = .002), (4) lower incidence of new or increased spontaneous echocardiographic contrast (e.g., AF: 11% vs. 62.5%, P = .003), and (5) lower incidence of atrial mechanical stunning (e.g., AFL: 20% vs. 100%, P = .001). Omega-3 intake conferred protection against stunning in a multivariable analysis (odds ratio 0.18, P = .02). Chronic fish oil ingestion in humans attenuates atrial mechanical stunning after reversion of atrial arrhythmias to sinus rhythm. This suggests that fish oils may target or even reverse underlying cellular and/or structural remodeling that occurs in response to persistent atrial arrhythmias. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.

PubMed

Piccini, Jonathan P; Connolly, Stuart J; Abraham, William T; Healey, Jeff S; Steinberg, Benjamin A; Al-Khalidi, Hussein R; Dignacco, Patricia; van Veldhuisen, Dirk J; Sauer, William H; White, Michel; Wilton, Stephen B; Anand, Inder S; Dufton, Christopher; Marshall, Debra A; Aleong, Ryan G; Davis, Gordon W; Clark, Richard L; Emery, Laura L; Bristow, Michael R

2018-05-01

Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501). Copyright © 2017 Elsevier Inc. All rights reserved.

Does permanent atrial fibrillation modify response to cardiac resynchronization therapy in heart failure patients?

PubMed

Abreu, Ana; Oliveira, Mário; Silva Cunha, Pedro; Santa Clara, Helena; Portugal, Guilherme; Gonçalves Rodrigues, Inês; Santos, Vanessa; Morais, Luís; Selas, Mafalda; Soares, Rui; Branco, Luísa; Ferreira, Rui; Mota Carmo, Miguel

2017-10-01

The benefits of cardiac resynchronization therapy (CRT) documented in heart failure (HF) may be influenced by atrial fibrillation (AF). We aimed to compare CRT response in patients in AF and in sinus rhythm (SR). We prospectively studied 101 HF patients treated by CRT. Rates of clinical, echocardiographic and functional response, baseline NYHA class and variation, left ventricular ejection fraction, volumes and mass, atrial volumes, cardiopulmonary exercise test (CPET) duration (CPET dur), peak oxygen consumption (VO 2 max) and ventilatory efficiency (VE/VCO 2 slope) were compared between AF and SR patients, before and at three and six months after implantation of a CRT device. All patients achieved ≥95% biventricular pacing, and 5.7% underwent atrioventricular junction ablation. Patients were divided into AF (n=35) and SR (n=66) groups; AF patients were older, with larger atrial volumes and lower CPET dur and VO 2 max before CRT. The percentages of clinical and echocardiographic responders were similar in the two groups, but there were more functional responders in the AF group (71% vs. 39% in SR patients; p=0.012). In SR patients, left atrial volume and left ventricular mass were significantly reduced (p=0.015 and p=0.021, respectively), whereas in AF patients, CPET dur (p=0.003) and VO 2 max (p=0.001; 0.083 age-adjusted) showed larger increases. Clinical and echocardiographic response rates were similar in SR and AF patients, with a better functional response in AF. Improvement in left ventricular function and volumes occurred in both groups, but left ventricular mass reduction and left atrial reverse remodeling were seen exclusively in SR patients (ClinicalTrials.gov identifier: NCT02413151; FCT code: PTDC/DES/120249/2010). Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

AT1 receptors mediate angiotensin II-induced release of nitric oxide in afferent arterioles.

PubMed

Patzak, Andreas; Lai, En Y; Mrowka, Ralf; Steege, Andreas; Persson, Pontus B; Persson, A Erik G

2004-11-01

Recent studies have indicated that angiotensin II (Ang II) possibly activates the nitric oxide (NO) system. We investigated the role of AT receptor subtypes (AT-R) in mediating the Ang II-induced NO release in afferent arterioles (Af) of mice. Isolated Af of mice were perfused, and the isotonic contraction measured. Further, NO release was determined using DAF-FM, a fluorescence indicator for NO. Moreover, we qualitatively assessed the expression of AT-R at the mRNA level using reverse transcription-polymerase chain reaction (RT-PCR). Ang II reduced luminal diameters dose dependently (67.3 +/- 6.3% at 10(-6) mol/L). Inhibition of AT2-R with PD123.319 did not change the Ang II contractile response. AT1-R blockade with ZD7155 inhibited contraction. Stimulation of AT2-R during AT1-R inhibition with ZD7155, and preconstriction with norepinephrine (NE) had no influence on the diameter. Drug application via the perfusion pipette changed flow and pressure, and enhanced NO fluorescence by DeltaF = 4.0 +/- 0.4% (N= 14, background). Luminal application of Ang II (10(-7) mol/L) increased the NO fluorescence by DeltaF = 9.9 +/- 1.2% (N= 8). AT1-R blockade blunted the increase to background levels (DeltaF to 4.0 +/- 0.3%, N= 6, P < 0.05), but AT2-R blockade did not (8.1 +/- 0.9%, N= 9). L-NAME nearly abolished the Ang II effect on the NO fluorescence (DeltaF = 1.6 +/- 0.5% (N= 8). NE did not increase NO release beyond the background levels. RT-PCR showed expression of both AT1-R and AT2-R. The results indicate an Ang II-induced NO release in Af of mice, which is mediated by AT1-R. Thus, Ang II balances its own constrictor action in Af. This control mechanism is very important in view of high renin and angiotensin II concentration in the juxtaglomerular apparatus.

Is HATCH score a reliable predictor of atrial fibrillation after cavotricuspid isthmus ablation for typical atrial flutter?

PubMed

García-Seara, Javier; Gude Sampedro, Francisco; Martínez Sande, Jose L; Fernández López, Xesus Alberte; Rodríguez Mañero, Moisés; González Melchor, Laila; Alvarez Alvarez, Belén; Iglesias Alvarez, Diego; González Juanatey, José Ramón

2016-09-01

We determined the effectiveness of the HATCH score in patients with typical atrial flutter (AFl) undergoing cavotricuspid isthmus (CTI) ablation to predict long-term atrial fibrillation (AF). We conducted an observational retrospective single-center cohort study including all patients admitted to our hospital for a CTI ablation between 1998 and 2010. The patients were divided into four categories: 1) new-onset AF (no prior AF and AF during follow-up (FU)); 2) old AF (prior AF and no AF during FU); 3) prior and post AF (AF prior and post CTI ablation); and 4) no AF. Four hundred and eight patients were included. In patients without prior AF, the hazard ratio (HR) for new-onset AF during FU was 0.98 (CI 95%: 0.65-1.50; p = 0.95) and 1.00 (CI 95%: 0.57-1.77; p = 0.98) for HATCH ≥ 2 and HATCH ≥ 3, respectively. In patients with prior AF, the HR for AF was 1.41 (CI 95%: 0.87-2.28; p = 0.17) and 1.79 (CI 95%: 0.96-3.35; p = 0.06), for HATCH ≥ 2 and HATCH ≥ 3, respectively. Left atrial enlargement was positively correlated with the occurrence of AF during FU, especially in the subgroup without prior AF, which had a HR of 2.44 (CI 95%: 1.35-4.40; p = 0.003), a HR of 2.88 (CI 95%: 1.36-6.10; p = 0.006) and a HR of 3.68 (CI 95%: 1.71-7.94; p = 0.001), for slight, moderate and severely dilated left atrial dimension, respectively, compared with a normal value. HATCH score did not predict AF in patients with typical AFl who underwent CTI ablation. Basal left atrium dimension could help predict new-onset AF.

Calculations of absorbed fractions in small water spheres for low-energy monoenergetic electrons and the Auger-emitting radionuclides (123)Ι and (125)Ι.

PubMed

Bousis, Christos; Emfietzoglou, Dimitris; Nikjoo, Hooshang

2012-12-01

To calculate the absorbed fraction (AF) of low energy electrons in small tissue-equivalent spherical volumes by Monte Carlo (MC) track structure simulation and assess the influence of phase (liquid water versus density-scaled water vapor) and of the continuous-slowing-down approximation (CSDA) used in semi-analytic calculations. An event-by-event MC code simulating the transport of electrons in both the vapor and liquid phase of water using appropriate electron-water interaction cross sections was used to quantify the energy deposition of low-energy electrons in spherical volumes. Semi-analytic calculations within the CSDA using a convolution integral of the Howell range-energy expressions are also presented for comparison. The AF for spherical volumes of radii from 10-1000 nm are presented for monoenergetic electrons over the energy range 100-10,000 eV and the two Auger-emitting radionuclides (125)I and (123)I. The MC calculated AF for the liquid phase are found to be smaller than those of the (density scaled) gas phase by up to 10-20% for the monoenergetic electrons and 10% for the two Auger-emitters. Differences between the liquid-phase MC results and the semi-analytic CSDA calculations are up to ∼ 55% for the monoenergetic electrons and up to ∼ 35% for the two Auger-emitters. Condensed-phase effects in the inelastic interaction of low-energy electrons with water have a noticeable but relatively small impact on the AF for the energy range and target sizes examined. Depending on the electron energies, the semi-analytic approach may lead to sizeable errors for target sizes with linear dimensions below 1 micron.

Characterization of Genome-Wide Association-Identified Variants for Atrial Fibrillation in African Americans

PubMed Central

Delaney, Jessica T.; Jeff, Janina M.; Brown, Nancy J.; Pretorius, Mias; Okafor, Henry E.; Darbar, Dawood; Roden, Dan M.; Crawford, Dana C.

2012-01-01

Background Despite a greater burden of risk factors, atrial fibrillation (AF) is less common among African Americans than European-descent populations. Genome-wide association studies (GWAS) for AF in European-descent populations have identified three predominant genomic regions associated with increased risk (1q21, 4q25, and 16q22). The contribution of these loci to AF risk in African American is unknown. Methodology/Principal Findings We studied 73 African Americans with AF from the Vanderbilt-Meharry AF registry and 71 African American controls, with no history of AF including after cardiac surgery. Tests of association were performed for 148 SNPs across the three regions associated with AF, and 22 SNPs were significantly associated with AF (P<0.05). The SNPs with the strongest associations in African Americans were both different from the index SNPs identified in European-descent populations and independent from the index European-descent population SNPs (r2<0.40 in HapMap CEU): 1q21 rs4845396 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.13–0.67, P = 0.003), 4q25 rs4631108 (OR 3.43, 95% CI 1.59–7.42, P = 0.002), and 16q22 rs16971547 (OR 8.1, 95% CI 1.46–45.4, P = 0.016). Estimates of European ancestry were similar among cases (23.6%) and controls (23.8%). Accordingly, the probability of having two copies of the European derived chromosomes at each region did not differ between cases and controls. Conclusions/Significance Variable European admixture at known AF loci does not explain decreased AF susceptibility in African Americans. These data support the role of 1q21, 4q25, and 16q22 variants in AF risk for African Americans, although the index SNPs differ from those identified in European-descent populations. PMID:22384221

Test-retest reproducibility of accommodative facility measures in primary school children.

PubMed

Adler, Paul; Scally, Andrew J; Barrett, Brendan T

2018-05-08

To determine the test-retest reproducibility of accommodative facility (AF) measures in an unselected sample of UK primary school children. Using ±2.00 DS flippers and a viewing distance of 40 cm, AF was measured in 136 children (range 4-12 years, average 8.1 ± 2.1) by five testers on three occasions (average interval between successive tests: eight days, range 1-21 days). On each occasion, AF was measured monocularly and binocularly, for two minutes. Full datasets were obtained in 111 children (81.6 per cent). Intra-individual variation in AF was large (standard deviation [SD] = 3.8 cycles per minute [cpm]) and there was variation due to the identity of the tester (SD = 1.6 cpm). On average, AF was greater: (i) in monocular compared to binocular testing (by 1.4 cpm, p < 0.001); (ii) in the second minute of testing compared to the first (by 1.3 cpm, p < 0.001); (iii) in older compared to younger children (for example, AF for 4/5-year-olds was 3.3 cpm lower than in children ≥ 10 years old, p = 0.009); and (iv) on subsequent testing occasions (for example, visit-2 AF was 2.0 cpm higher than visit-1 AF, p < 0.001). After the first minute of testing at visit-1, only 36.9 per cent of children exceeded published normative values for AF (≥ 11 cpm monocularly and ≥ 8 cpm binocularly), but this rose to 83.8 per cent after the third test. Using less stringent pass criteria (≥ 6 cpm monocularly and ≥ 3 cpm binocularly), the equivalent figures were 82.9 and 96.4 per cent, respectively. Reduced AF did not co-exist with abnormal near point of accommodation or reduced visual acuity. The results reveal considerable intra-individual variability in raw AF measures in children. When the results are considered as pass/fail, children who initially exhibit normal AF continued to do so on repeat testing. Conversely, the vast majority of children with initially reduced AF exhibit normal performance on repeat testing. Using established pass/fail criteria, the prevalence of persistently reduced AF in this sample is 3.6 per cent. © 2018 Optometry Australia.

Amniotic-Fluid Stem Cells: Growth Dynamics and Differentiation Potential after a CD-117-Based Selection Procedure

PubMed Central

Arnhold, S.; Glüer, S.; Hartmann, K.; Raabe, O.; Addicks, K.; Wenisch, S.; Hoopmann, M.

2011-01-01

Amniotic fluid (AF) has become an interesting source of fetal stem cells. However, AF contains heterogeneous and multiple, partially differentiated cell types. After isolation from the amniotic fluid, cells were characterized regarding their morphology and growth dynamics. They were sorted by magnetic associated cell sorting using the surface marker CD 117. In order to show stem cell characteristics such as pluripotency and to evaluate a possible therapeutic application of these cells, AF fluid-derived stem cells were differentiated along the adipogenic, osteogenic, and chondrogenic as well as the neuronal lineage under hypoxic conditions. Our findings reveal that magnetic associated cell sorting (MACS) does not markedly influence growth characteristics as demonstrated by the generation doubling time. There was, however, an effect regarding an altered adipogenic, osteogenic, and chondrogenic differentiation capacity in the selected cell fraction. In contrast, in the unselected cell population neuronal differentiation is enhanced. PMID:21437196

Anatomy of the dead sea transform from lithospheric to microscopic scale

USGS Publications Warehouse

Weber, M.; Abu-Ayyash, K.; Abueladas, A.; Agnon, A.; Alasonati-Tasarova, Z.; Al-Zubi, H.; Babeyko, A.; Bartov, Y.; Bauer, K.; Becken, M.; Bedrosian, P.A.; Ben-Avraham, Z.; Bock, G.; Bohnhoff, M.; Bribach, J.; Dulski, P.; Ebbing, J.; El-Kelani, R.; Forster, A.; Forster, H.-J.; Frieslander, U.; Garfunkel, Z.; Goetze, H.J.; Haak, V.; Haberland, C.; Hassouneh, M.; Helwig, S.; Hofstetter, A.; Hoffmann-Rotrie, A.; Jackel, K.H.; Janssen, C.; Jaser, D.; Kesten, D.; Khatib, M.; Kind, R.; Koch, O.; Koulakov, I.; Laske, Gabi; Maercklin, N.; Masarweh, R.; Masri, A.; Matar, A.; Mechie, J.; Meqbel, N.; Plessen, B.; Moller, P.; Mohsen, A.; Oberhansli, R.; Oreshin, S.; Petrunin, A.; Qabbani, I.; Rabba, I.; Ritter, O.; Romer, R.L.; Rumpker, G.; Rybakov, M.; Ryberg, T.; Saul, J.; Scherbaum, F.; Schmidt, S.; Schulze, A.; Sobolev, S.V.; Stiller, M.; Stromeyer, D.; Tarawneh, K.; Trela, C.; Weckmann, U.; Wetzel, U.; Wylegalla, K.

2009-01-01

Fault zones are the locations where motion of tectonic plates, often associated with earthquakes, is accommodated. Despite a rapid increase in the understanding of faults in the last decades, our knowledge of their geometry, petrophysical properties, and controlling processes remains incomplete. The central questions addressed here in our study of the Dead Sea Transform (DST) in the Middle East are as follows: (1) What are the structure and kinematics of a large fault zone? (2) What controls its structure and kinematics? (3) How does the DST compare to other plate boundary fault zones? The DST has accommodated a total of 105 km of leftlateral transform motion between the African and Arabian plates since early Miocene (???20 Ma). The DST segment between the Dead Sea and the Red Sea, called the Arava/ Araba Fault (AF), is studied here using a multidisciplinary and multiscale approach from the ??m to the plate tectonic scale. We observe that under the DST a narrow, subvertical zone cuts through crust and lithosphere. First, from west to east the crustal thickness increases smoothly from 26 to 39 km, and a subhorizontal lower crustal reflector is detected east of the AF. Second, several faults exist in the upper crust in a 40 km wide zone centered on the AF, but none have kilometer-size zones of decreased seismic velocities or zones of high electrical conductivities in the upper crust expected for large damage zones. Third, the AF is the main branch of the DST system, even though it has accommodated only a part (up to 60 km) of the overall 105 km of sinistral plate motion. Fourth, the AF acts as a barrier to fluids to a depth of 4 km, and the lithology changes abruptly across it. Fifth, in the top few hundred meters of the AF a locally transpressional regime is observed in a 100-300 m wide zone of deformed and displaced material, bordered by subparallel faults forming a positive flower structure. Other segments of the AF have a transtensional character with small pull-aparts along them. The damage zones of the individual faults are only 5-20 m wide at this depth range. Sixth, two areas on the AF show mesoscale to microscale faulting and veining in limestone sequences with faulting depths between 2 and 5 km. Seventh, fluids in the AF are carried downward into the fault zone. Only a minor fraction of fluids is derived from ascending hydrothermal fluids. However, we found that on the kilometer scale the AF does not act as an important fluid conduit. Most of these findings are corroborated using thermomechanical modeling where shear deformation in the upper crust is localized in one or two major faults; at larger depth, shear deformation occurs in a 20-40 km wide zone with a mechanically weak decoupling zone extending subvertically through the entire lithosphere. Copyright 2009 by the American Geophysical Union.

CXCL10 and IL-6: Markers of two different forms of intra-amniotic inflammation in preterm labor.

PubMed

Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Docheva, Nikolina; Dong, Zhong; Kim, Chong Jai; Kim, Yeon Mee; Kim, Jung-Sun; Qureshi, Faisal; Jacques, Suzanne M; Yoon, Bo Hyun; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S; Erez, Offer; Korzeniewski, Steven J

2017-07-01

To determine whether amniotic fluid (AF) CXCL10 concentration is associated with histologic chronic chorioamnionitis in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PROM). This study included 168 women who had an episode of PTL or preterm PROM. AF interleukin (IL)-6 and CXCL10 concentrations were determined by immunoassay. (i) Increased AF CXCL10 concentration was associated with chronic (OR: 4.8; 95% CI: 1.7-14), but not acute chorioamnionitis; (ii) increased AF IL-6 concentration was associated with acute (OR: 4.2; 95% CI: 1.3-13.7) but not chronic chorioamnionitis; and (iii) an increase in AF CXCL10 concentration was associated with placental lesions consistent with maternal anti-fetal rejection (OR: 3.7; 95% CI: 1.3-10.4). (iv) All patients with elevated AF CXCL10 and IL-6 delivered preterm. Increased AF CXCL10 concentration is associated with chronic chorioamnionitis or maternal anti-fetal rejection, whereas increased AF IL-6 concentration is associated with acute histologic chorioamnionitis. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.

Cardiovascular risk profile and management of atrial fibrillation in India: Real world data from RealiseAF survey.

PubMed

Narasimhan, C; Verma, Jagmohan Singh; Ravi Kishore, A G; Singh, Balbir; Dani, Sameer; Chawala, Kamaldeep; Haque, Azizul; Khan, Aftab; Nair, Mohan; Vora, Amit; Rajasekhar, V; Thomas, Joy M; Gupta, Anoop; Naik, Ajay; Prakash, V S; Naditch, Lisa; Gabriel Steg, P

Atrial fibrillation (AF) is the most common sustained arrhythmia with high risk for many cardiovascular (CV) complications. Adherence to recommended management guidelines is important to avoid complications. In India, there is little knowledge on how AF is managed in real world. This is a cross-sectional study of patients in India enrolled in RealiseAF survey between February 2010 and March 2010 with a diagnosis of AF within the last 12 months. From 15 centers, 301 patients {mean age 59.9 years (14.4); 52.5% males} were recruited. AF was controlled in 50% of patients with 77 (26.7%) in sinus rhythm and 67 (23.3%) with heart rate <80beats/min. Hypertension (50.8%), valvular heart disease (40.7%), heart failure (25.9%), and diabetes (20.4%) were the most common underlying CV diseases. Increased risk for stroke (CHADS 2 score≥2) was present in 36.6%. Most of the patients (85%) were symptomatic. AF was paroxysmal, persistent, and permanent in 28.7%, 22.7%, and 34.3% respectively. In 14%, AF was diagnosed as first episode. Forty-six percent of patients had rate control, 35.2% rhythm control, 0.3% both strategies, and 18.4% received no therapy for AF before the visit. At the end of the visit, adoption to rate control strategy increased to 52.3% and patients with no therapy decreased to 7%. AF in India is not adequately controlled. Concomitant CV risk factors and risk of stroke are high. The study underscores the need for improved adoption of guideline-directed management for optimal control of AF and reducing the risk of stroke. Copyright © 2016. Published by Elsevier B.V.

A Novel Application for the Detection of an Irregular Pulse using an iPhone 4S in Patients with Atrial Fibrillation

PubMed Central

McManus, David D.; Lee, Jinseok; Maitas, Oscar; Esa, Nada; Pidikiti, Rahul; Carlucci, Alex; Harrington, Josephine; Mick, Eric; Chon, Ki H.

2012-01-01

Background Atrial fibrillation (AF) is common and associated with adverse health outcomes. Timely detection of AF can be challenging using traditional diagnostic tools. Smartphone use is increasing and may provide an inexpensive and user-friendly means to diagnose AF. Objective To test the hypothesis that a smartphone-based application could detect an irregular pulse from AF. Methods 76 adults with persistent AF were consented for participation in our study. We obtained pulsatile time series recordings before and after cardioversion using an iPhone 4S camera. A novel smartphone application conducted real-time pulse analysis using 2 statistical methods [Root Mean Square of Successive RR Differences (RMSSD/mean); Shannon Entropy (ShE)]. We examined the sensitivity, specificity, and predictive accuracy of both algorithms using the 12-lead electrocardiogram as the gold standard. Results RMSDD/mean and ShE were higher in participants in AF compared with sinus rhythm. The 2 methods were inversely related to AF in regression models adjusting for key factors including heart rate and blood pressure (β coefficients per SD-increment in RMSDD/mean and ShE were −0.20 and −0.35; p<0.001). An algorithm combining the 2 statistical methods demonstrated excellent sensitivity (0.962), specificity (0.975), and accuracy (0.968) for beat-to-beat discrimination of an irregular pulse during AF from sinus rhythm. Conclusions In a prospectively recruited cohort of 76 participants undergoing cardioversion for AF, we found that a novel algorithm analyzing signals recorded using an iPhone 4S accurately distinguished pulse recordings during AF from sinus rhythm. Data are needed to explore the performance and acceptability of smartphone-based applications for AF detection. PMID:23220686

A novel application for the detection of an irregular pulse using an iPhone 4S in patients with atrial fibrillation.

PubMed

McManus, David D; Lee, Jinseok; Maitas, Oscar; Esa, Nada; Pidikiti, Rahul; Carlucci, Alex; Harrington, Josephine; Mick, Eric; Chon, Ki H

2013-03-01

Atrial fibrillation (AF) is common and associated with adverse health outcomes. Timely detection of AF can be challenging using traditional diagnostic tools. Smartphone use is increasing and may provide an inexpensive and user-friendly means to diagnoseAF. To test the hypothesis that a smartphone-based application could detect an irregular pulse fromAF. Seventy-six adults with persistent AF were consented for participation in our study. We obtained pulsatile time series recordings before and after cardioversion using an iPhone 4S camera. A novel smartphone application conducted real-time pulse analysis using 2 statistical methods: root mean square of successive RR difference (RMSSD/mean) and Shannon entropy (ShE). We examined the sensitivity, specificity, and predictive accuracy of both algorithms using the 12-lead electrocardiogram as the gold standard. RMSDD/mean and ShE were higher in participants in AF than in those with sinus rhythm. The 2 methods were inversely related to AF in regression models adjusting for key factors including heart rate and blood pressure (beta coefficients per SD increment in RMSDD/mean and ShE were-0.20 and-0.35; P<.001). An algorithm combining the 2 statistical methods demonstrated excellent sensitivity (0.962), specificity (0.975), and accuracy (0.968) for beat-to-beat discrimination of an irregular pulse during AF from sinus rhythm. In a prospectively recruited cohort of 76 participants undergoing cardioversion for AF, we found that a novel algorithm analyzing signals recorded using an iPhone 4S accurately distinguished pulse recordings during AF from sinus rhythm. Data are needed to explore the performance and acceptability of smartphone-based applications for AF detection. Copyright © 2013 Heart Rhythm Society. All rights reserved.

Dynamic and dual-site atrial pacing in the prevention of atrial fibrillation: The STimolazione Atrial DInamica Multisito (STADIM) Study.

PubMed

De Simone, Antonio; Senatore, Gaetano; Donnici, Giovanni; Turco, Pietro; Romano, Enrico; Gazzola, Carlo; Stabile, G

2007-01-01

The impact of new algorithms to consistently pace the atrium on the prevention of atrial fibrillation (AF) remains unclear. Our randomized, crossover study compared the efficacy of single- and dual-site atrial pacing, with versus without dynamic atrial overdrive pacing in preventing AF. We studied 72 patients (mean age = 69.6 +/- 6.5 years, 34 men) with sick sinus syndrome (SSS) and paroxysmal or persistent AF, who received dual-chamber pacemakers (PM) equipped with an AF prevention algorithm and two atrial leads placed in the right atrial appendage (RAA), by passive fixation, and in the coronary sinus ostium (CS), by active fixation, respectively. At implant, the patients were randomly assigned to unipolar CS versus RAA pacing. The PM was programmed in DDDR mode 1 month after implant. Each patient underwent four study phases of equal duration: (1) unipolar, single site (CS or RAA) pacing with the AF algorithm ON (atrial lower rate = 0 ppm); (2) unipolar, single site pacing with the AF algorithm OFF (atrial lower rate = 70 bpm); (3) bipolar, dual-site pacing with AF algorithm ON; (4) bipolar, dual-site pacing with the AF algorithm OFF. Among 40 patients (56%), who completed the follow-up (15 +/- 4 months) no difference was observed in the mean number of automatic mode switch (AMS) corrected for the duration of follow-up, in unipolar (5.6 +/- 22.8 vs 2.6 +/- 5.5) or bipolar mode (3.3 +/- 12.7 vs 2.1 +/- 4.9) with, respectively, the algorithm OFF or ON. With the AF prevention algorithm ON, the percentage of atrial pacing increased significantly from 78.7 +/- 22.1% to 92.4 +/- 4.9% (P < 0.001), while the average ventricular heart rate was significantly lower with the algorithm ON (62.4 +/- 17.5 vs 79.9 +/- 3 bpm (P < 0.001). The AF prevention algorithm increased the percentage of atrial pacing significantly, regardless of the atrial pulse configuration and pacing site, while maintaining a slower ventricular heart rate. It had no impact on the number of AMS in the unipolar and bipolar modes in patients with SSS.

Correlation of iodine uptake and perfusion parameters between dual-energy CT imaging and first-pass dual-input perfusion CT in lung cancer.

PubMed

Chen, Xiaoliang; Xu, Yanyan; Duan, Jianghui; Li, Chuandong; Sun, Hongliang; Wang, Wu

2017-07-01

To investigate the potential relationship between perfusion parameters from first-pass dual-input perfusion computed tomography (DI-PCT) and iodine uptake levels estimated from dual-energy CT (DE-CT).The pre-experimental part of this study included a dynamic DE-CT protocol in 15 patients to evaluate peak arterial enhancement of lung cancer based on time-attenuation curves, and the scan time of DE-CT was determined. In the prospective part of the study, 28 lung cancer patients underwent whole-volume perfusion CT and single-source DE-CT using 320-row CT. Pulmonary flow (PF, mL/min/100 mL), aortic flow (AF, mL/min/100 mL), and a perfusion index (PI = PF/[PF + AF]) were automatically generated by in-house commercial software using the dual-input maximum slope method for DI-PCT. For the dual-energy CT data, iodine uptake was estimated by the difference (λ) and the slope (λHU). λ was defined as the difference of CT values between 40 and 70 KeV monochromatic images in lung lesions. λHU was calculated by the following equation: λHU = |λ/(70 - 40)|. The DI-PCT and DE-CT parameters were analyzed by Pearson/Spearman correlation analysis, respectively.All subjects were pathologically proved as lung cancer patients (including 16 squamous cell carcinoma, 8 adenocarcinoma, and 4 small cell lung cancer) by surgery or CT-guided biopsy. Interobserver reproducibility in DI-PCT (PF, AF, PI) and DE-CT (λ, λHU) were relatively good to excellent (intraclass correlation coefficient [ICC]Inter = 0.8726-0.9255, ICCInter = 0.8179-0.8842; ICCInter = 0.8881-0.9177, ICCInter = 0.9820-0.9970, ICCInter = 0.9780-0.9971, respectively). Correlation coefficient between λ and AF, and PF were as follows: 0.589 (P < .01) and 0.383 (P < .05). Correlation coefficient between λHU and AF, and PF were as follows: 0.564 (P < .01) and 0.388 (P < .05).Both the single-source DE-CT and dual-input CT perfusion analysis method can be applied to assess blood supply of lung cancer patients. Preliminary results demonstrated that the iodine uptake relevant parameters derived from DE-CT significantly correlated with perfusion parameters derived from DI-PCT.

Clinical presentation, management, and outcomes in the Indian Heart Rhythm Society-Atrial Fibrillation (IHRS-AF) registry.

PubMed

Vora, A; Kapoor, A; Nair, M; Lokhandwala, Y; Narsimhan, C; Ravikishore, A G; Dwivedi, S K; Namboodiri, N; Hygriv, R; Saxena, A; Nabar, A; Garg, S; Bardoloi, N; Yadav, R; Nambiar, A; Pandurangi, U; Jhala, D; Naik, A; Nagmallesh; Rajagopal, S; Selvaraj, R; Arora, V; Thachil, A; Thomas, J; Panicker, G

A national atrial fibrillation (AF) registry was conducted under the aegis of the Indian Heart Rhythm Society (IHRS), to capture epidemiological data-type of AF, clinical presentation and comorbidities, current treatment practices, and 1-year follow-up outcomes. A total of 1537 patients were enrolled from 24 sites in India in the IHRS-AF registry from July 2011 to August 2012. Their baseline characteristics and follow-up data were recorded in case report forms and subsequently analyzed. The average age of Indian AF patients was 54.7 years. There was a marginal female preponderance - 51.5% females and 48.5% males. At baseline, 20.4% had paroxysmal AF; 33% had persistent AF; 35.1% had permanent AF and 11% had first AF episode. At one-year follow-up, 45.6% patients had permanent AF. Rheumatic valvular heart disease (RHD) was present in 47.6% of patients. Hypertension, heart failure, coronary artery disease, and diabetes were seen in 31.4%, 18.7%, 16.2%, and 16.1%, respectively. Rate control was the strategy used in 75.2% patients, digoxin and beta-blockers being the most frequently prescribed rate-control drugs. Oral anticoagulation (OAC) drugs were used in 70% of patients. The annual mortality was 6.5%, hospitalization 8%, and incidence of stroke 1%. In India, AF patients are younger and RHD is still the most frequent etiology. Almost two-third of the patients have persistent/permanent AF. At one-year follow-up, there is a significant mortality and morbidity in AF patients in India. Copyright © 2016. Published by Elsevier B.V.

Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up.

PubMed

Nyqvist, Johanna; Fransson, Per; Laurell, Göran; Hammerlid, Eva; Kjellén, Elisabeth; Franzén, Lars; Söderström, Karin; Wickart-Johansson, Gun; Friesland, Signe; Sjödin, Helena; Brun, Eva; Ask, Anders; Nilsson, Per; Ekberg, Lars; Björk-Eriksson, Thomas; Nyman, Jan; Lödén, Britta; Lewin, Freddi; Reizenstein, Johan; Lundin, Erik; Zackrisson, Björn

2016-02-01

Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, N0 glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1+2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Toward Streamlined Identification of Dioxin-like Compounds in Environmental Samples through Integration of Suspension Bioassay.

PubMed

Xiao, Hongxia; Brinkmann, Markus; Thalmann, Beat; Schiwy, Andreas; Große Brinkhaus, Sigrid; Achten, Christine; Eichbaum, Kathrin; Gembé, Carolin; Seiler, Thomas-Benjamin; Hollert, Henner

2017-03-21

Effect-directed analysis (EDA) is a powerful strategy to identify biologically active compounds in environmental samples. However, in current EDA studies, fractionation and handling procedures are laborious, consist of multiple evaporation steps, and thus bear the risk of contamination and decreased recoveries of the target compounds. The low resulting throughput has been one of the major bottlenecks of EDA. Here, we propose a high-throughput EDA (HT-EDA) work-flow combining reversed phase high-performance liquid chromatography fractionation of samples into 96-well microplates, followed by toxicity assessment in the micro-EROD bioassay with the wild-type rat hepatoma H4IIE cells, and chemical analysis of bioactive fractions. The approach was evaluated using single substances, binary mixtures, and extracts of sediment samples collected at the Three Gorges Reservoir, Yangtze River, China, as well as the rivers Rhine and Elbe, Germany. Selected bioactive fractions were analyzed by highly sensitive gas chromatography-atmospheric pressure laser ionization-time-of-flight-mass spectrometry. In addition, we optimized the work-flow by seeding previously adapted suspension-cultured H4IIE cells directly into the microplate used for fractionation, which makes any transfers of fractionated samples unnecessary. The proposed HT-EDA work-flow simplifies the procedure for wider application in ecotoxicology and environmental routine programs.

Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms.

PubMed

Lubitz, Steven A; Parsons, Owen E; Anderson, Christopher D; Benjamin, Emelia J; Malik, Rainer; Weng, Lu-Chen; Dichgans, Martin; Sudlow, Cathie L; Rothwell, Peter M; Rosand, Jonathan; Ellinor, Patrick T; Markus, Hugh S; Traylor, Matthew

2017-06-01

Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single-nucleotide polymorphisms associated with AF in a previous independent analysis across a range of preselected significance thresholds. There were 460 (19.4%) individuals with cardioembolic stroke, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) individuals with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association ( P =6×10 - 4 ) attributed to scores of 944 single-nucleotide polymorphisms (each associated with AF at P <1×10 - 3 in a previous analysis). Associations between AF genetic risk and stroke were enriched in the cardioembolic stroke subset (strongest P =1.2×10 - 9 , 944 single-nucleotide polymorphism score). In contrast, AF genetic risk was not significantly associated with noncardioembolic stroke subtypes. Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined pathogenesis. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke pathogeneses. © 2017 American Heart Association, Inc.

Increasing atrial fibrillation prevalence in acute ischemic stroke and TIA.

PubMed

Otite, Fadar Oliver; Khandelwal, Priyank; Chaturvedi, Seemant; Romano, Jose G; Sacco, Ralph L; Malik, Amer M

2016-11-08

To evaluate trends in atrial fibrillation (AF) prevalence in acute ischemic stroke (AIS) and TIA in the United States. We used the Nationwide Inpatient Sample to retrospectively compute weighted prevalence of AF in AIS (n = 4,355,140) and TIA (n = 1,816,459) patients admitted to US hospitals from 2004 to 2013. Multivariate-adjusted models were used to evaluate the association of AF with clinical factors, mortality, length of stay, and cost. From 2004 to 2013, AF prevalence increased by 22% in AIS (20%-24%) and by 38% in TIA (12%-17%). AF prevalence varied by age (AIS: 6% in 50-59 vs 37% in ≥80 years; TIA: 4% in 50-59 vs 24% in ≥80 years), sex (AIS: male 19% vs female 25%; TIA: male 15% vs female 14%), race (AIS: white 26% vs black 12%), and region (AIS: Northeast 25% vs South 20%). Advancing age, female sex, white race, high income, and large hospital size were associated with increased odds of AF in AIS. AF in AIS was a risk factor for in-hospital death (odds ratio 1.93, 95% confidence interval 1.89-1.98) but mortality in AIS with AF decreased from 11.6% to 8.3% (p < 0.001). Compared to no AF, AF was associated with increased cost of $2,310 and length of stay 1.1 days in AIS. AF prevalence in AIS and TIA has continued to increase. Disparity in AF prevalence in AIS and TIA exists by patient and hospital factors. AF is associated with increased mortality in AIS. Innovative AIS preventive strategies are needed in patients with AF, especially in the elderly. © 2016 American Academy of Neurology.

Extraction, characterization and antioxidant activities of Se-enriched tea polysaccharides.

PubMed

Wang, Yuanfeng; Li, Yongfu; Liu, Yangyang; Chen, Xueqing; Wei, Xinlin

2015-01-01

Se-polysaccharides from Se-enriched tea leaves were purified by DEAE-sepharose fast flow gel column (2.5×60cm) and three polysaccharide fractions (Se-TPS1, Se-TPS2, and Se-TPS3) were isolated and purified with yields of 6.5, 37.14, and 8.57%, respectively. The average sizes of Se-TPS1 and Se-TPS2 were determined by HPGPC system, with molecular weights of 1.1×10(5) and 2.4×10(5)Da, respectively. Se-TPS3 was a polysaccharide polymer with two peaks with molecular weights of 9.2×10(5) and 2.5×10(5)Da. Monosaccharide components analysis by ion chromatography revealed Se-polysaccharides were acidic polysaccharoses and different from each other in monosaccharide kinds and molar ratio. Elements of Se, C, H, N, S, and 14 kinds of mineral elements were analyzed by AFS, EA, and ICP-AES, respectively. Spectral analysis (IR and UV) indicated Se-polysaccharides were typical glycoproteins. Morphological analyses of the samples were determined by SEM and AFM. In addition, the DPPH and superoxide radicals scavenging activities were also discussed to assess antioxidant activities of the samples, and Se-polysaccharides showed higher antioxidant activities compared to the ordinary polysaccharides. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel intra-operative, high-resolution atrial mapping approach.

PubMed

Yaksh, Ameeta; van der Does, Lisette J M E; Kik, Charles; Knops, Paul; Oei, Frans B S; van de Woestijne, Pieter C; Bekkers, Jos A; Bogers, Ad J J C; Allessie, Maurits A; de Groot, Natasja M S

2015-12-01

A new technique is demonstrated for extensive high-resolution intra-operative atrial mapping that will facilitate the localization of atrial fibrillation (AF) sources and identification of the substrate perpetuating AF. Prior to the start of extra-corporal circulation, a 8 × 24-electrode array (2-mm inter-electrode distance) is placed subsequently on all the right and left epicardial atrial sites, including Bachmann's bundle, for recording of unipolar electrograms during sinus rhythm and (induced) AF. AF is induced by high-frequency pacing at the right atrial free wall. A pacemaker wire stitched to the right atrium serves as a reference signal. The indifferent pole is connected to a steal wire fixed to subcutaneous tissue. Electrograms are recorded by a computerized mapping system and, after amplification (gain 1000), filtering (bandwidth 0.5-400 Hz), sampling (1 kHz) and analogue to digital conversion (16 bits), automatically stored on hard disk. During the mapping procedure, real-time visualization secures electrogram quality. Analysis will be performed offline. This technique was performed in 168 patients of 18 years and older, with coronary and/or structural heart disease, with or without AF, electively scheduled for cardiac surgery and a ventricular ejection fraction above 40 %. The mean duration of the entire mapping procedure including preparation time was 9 ± 2 min. Complications related to the mapping procedure during or after cardiac surgery were not observed. We introduce the first epicardial atrial mapping approach with a high resolution of ≥1728 recording sites which can be performed in a procedure time of only 9±2 mins. This mapping technique can potentially identify areas responsible for initiation and persistence of AF and hopefully can individualize both diagnosis and therapy of AF.

Atrial fibrillation in cardiac resynchronization therapy with a defibrillator: a risk factor for mortality, appropriate and inappropriate shocks.

PubMed

van Boven, Nick; Theuns, Dominic; Bogaard, Kjell; Ruiter, Jaap; Kimman, Geert; Berman, Lily; VAN DER Ploeg, Tjeerd; Kardys, Isabella; Umans, Victor

2013-10-01

Knowledge about predictive factors for mortality and (in)appropriate shocks in cardiac resynchronization therapy with a defibrillator (CRT-D) should be available and updated to predict clinical outcome. We retrospectively analyzed 543 consecutive patients assigned to CRT-D in 2 tertiary medical centers. The aim of this study was to assess risk factors for all-cause mortality, appropriate and inappropriate shocks. Mean follow-up time was 3.2 (±1.8) years. A total of 110 (20%) patients died, 71 (13%) received ≥1 appropriate shocks, and 33 (6.1%) received ≥1 inappropriate shocks. No patients received a His bundle ablation and biventricular pacing percentage was not analyzed. Multivariable Cox regression analysis showed that a history of atrial fibrillation (AF) (HR 1.74 CI 1.06-2.86), higher creatinine (HR 1.12; CI 1.08-1.16), and a poorer left ventricular ejection fraction (LVEF) (HR 0.97; CI 0.94-1.01) independently predict all-cause mortality. In the entire cohort, history of AF and secondary prevention were independent predictors of appropriate shocks and variables associated with inappropriate shocks were history of AF and QRS ≥150 milliseconds. In primary prevention patients, history of AF also predicted appropriate shocks as did ischemic cardiomyopathy and poorer LVEF. History of AF, QRS ≥150 milliseconds, and lower creatinine were associated with inappropriate shocks in this subgroup. Appropriate shocks increased mortality risk, but inappropriate shocks did not. In symptomatic CHF patients treated with CRT-D, history of AF is an independent risk factor not only for mortality, but also for appropriate and inappropriate shocks. Further efforts in AF management may optimize the care in CRT-D patients. © 2013 Wiley Periodicals, Inc.

Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus

PubMed Central

van den Akker, Guus G. H.; Surtel, Don A. M.; Cremers, Andy; Richardson, Stephen M.; Hoyland, Judith A.; van Rhijn, Lodewijk W.

2016-01-01

Introduction Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Methods Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). Results The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. Conclusion We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair. PMID:26794306

Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus.

PubMed

van den Akker, Guus G H; Surtel, Don A M; Cremers, Andy; Richardson, Stephen M; Hoyland, Judith A; van Rhijn, Lodewijk W; Voncken, Jan Willem; Welting, Tim J M

2016-01-01

Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair.

3 Tesla MRI-detected brain lesions after pulmonary vein isolation for atrial fibrillation: results of the MACPAF study.

PubMed

Haeusler, Karl Georg; Koch, Lydia; Herm, Juliane; Kopp, Ute A; Heuschmann, Peter U; Endres, Matthias; Schultheiss, Heinz-Peter; Schirdewan, Alexander; Fiebach, Jochen B

2013-01-01

Left atrial catheter ablation (LACA) is an established therapeutic approach to abolish symptomatic atrial fibrillation (AF). Based on the prospective MACPAF study (clinicaltrials.gov NCT01061931) we report the rate of ischemic brain lesions postablation and their impact on cognitive function. Patients with symptomatic paroxysmal AF were randomized to LACA using the Arctic Front® or the HD Mesh Ablator® catheter. All patients underwent brain MRI at 3 Tesla, neurological, and neuropsychological examinations within 48 hours prior and after the ablation procedure. There was no clinically evident stroke in 37 patients (mean age 62.4 ± 8.4 years; 41% female; median CHADS2 score 1 [IQR 0-2]) after LACA but high-resolution diffusion-weighted imaging (DWI) detected new ischemic lesions in 15 (41%) patients after LACA. Four (27%) of the HD Mesh Ablator® patients and 11 (50%) of the Arctic Front® patients suffered a silent ischemic lesion (P = 0.19). In these 15 patients, there was a nonsignificant trend toward lower cardiac ejection fraction (P = 0.07) and AF episodes during LACA (P = 0.09), while activated clotting time levels, number of energy applications, periprocedural electrocardioversion or CHADS(2) score had no impact. Lesion volumes varied from 5 to 150 mm(3) and 1 to 5 lesions were detected per patient. However, acute brain lesions had no effect on cognitive performance immediately after LACA. Of the DWI lesions postablation 82% were not detectable on FLAIR images 6-9 months postablation. According to 3 Tesla high-resolution DWI, ischemic brain lesions after LACA were common but not associated with impaired cognitive function after the ablation procedure. © 2012 Wiley Periodicals, Inc.

Effects of Rosuvastatin Versus Atorvastatin, Alone or in Combination, on Lipoprotein (a).

PubMed

Vavlukis, Marija; Mladenovska, Kristina; Daka, Arlinda; Dimovski, Aleksandar; Domazetovska, Saska; Kuzmanovska, Sonja; Kedev, Sasko

2016-08-01

There are little evidences about the therapeutic efficacy of different lipid-lowering agents in the reduction of elevated lipoprotein(a) [Lp(a)]. testing the effect of different lipid-lowering agents on elevated Lp(a). prospective interventional study performed in patients with CAD, or high CAD risk, with Lp(a), >50 mg/dL. Lp(a), total cholesterol (C), HDL-C, LDL-C, triglycerides (TGs), apolipoprotein (Apo) A1, Apo B, enzymes of myocyte and hepatic injury were comparatively analyzed between 4 lipid-lowering strategies: rosuvastatin (R group) 40 mg, atorvastatin (A group) 80 mg, atorvastatin 40 mg add-on micronized fenofibrate (A+F group), and atorvastatin 40 mg add-on 1 g extended-release niacin (A+ERN group). Comparison was made for their therapeutic efficacy on Lp(a), and safety. 87 patients with mean Lp(a) 94.6 ± 39.6 mg/dL were analyzed. Groups: 25 patients in the R, 22 in the A, 20 in the A+F and 20 in A+ERN group. Significant reduction in all lipid fractions in all treatment groups was reported after 6 months. The average reduction of Lp(a) was 15.9 ± 21.0 mg/dL, with: 18.2 ± 24.8 (P = 0.001) in the R group, 17.3 ± 10.4 (P = 0.001) in A+F, 19.5 ± 10.9 (P = 0.001) in A+ERN and the lowest in the A group (11.24 ± 22.91, P = 0.032). No adverse effects were observed in any of the treatment groups. When compared with atorvastatin, it seems that rosuvastatin can achieve more significant decrease of Lp(a).The efficacy of the second one can be increased by adding fibrate or ERN. © The Author(s) 2016.

Sachon AFS K-4, Sacheon, Korea. Revised Uniform Summary of Surface Weather Observations (RUSSWO)

DTIC Science & Technology

1968-04-11

FREQUENCY OF WIND DIRECTION AND SPEED (FROM HOURLY OESERVATIONS) 41240 -- SACHON KflREALROK AFS K-4 55-67_________ APR UT"If STATION MANZ TSARS SON ?") ALL...KOREA/ROI( AFS K-4 55-67 ____APR SAINSTATION NAME YEARS MOSN ALL WEATHER 1500-1700 ~ LA $S NOUN$ (LST I ONITIOW (KNTSI 1 .3 4.6 7.10 11.-16 17.21 22...4S 1209 c~ ~iC4 1V/ . $ I - - ’~-4 V ~’ *-** La DATA PROCESSING DIVISION ElAc, UJSAF SURFACE WINDS ASHEVILLE, N. C. 28801 PERCENTAGE FREQUENCY OF

Interaction between sapwood and foliage area in alpine ash (Eucalyptus delegatensis) trees of different heights.

PubMed

Mokany, Karel; McMurtrie, Ross E; Atwell, Brian J; Keith, Heather

2003-10-01

In native stands of Eucalyptus delegatensis R. T. Baker, sapwood area (As) to foliage area (Af) ratios (As:Af) decreased as tree height increased, contradicting the common interpretation of the Pipe Model Theory as well as the generally observed trend of increasing As:Af ratios with tree height. To clarify this relationship, we estimated sapwood hydraulic conductivity theoretically based on measurements of sapwood vessel diameters and Poiseuille's law for fluid flow through pipes. Despite the observed decrease in As:Af ratios with tree height, leaf specific conductivity increased with total tree height, largely as a result of an increase in the specific conductivity of sapwood. This observation supports the proposition that the stem's ability to supply foliage with water must increase as trees grow taller, to compensate for the increased hydraulic path length. The results presented here highlight the importance of measuring sapwood hydraulic conductivity in analyses of sapwood-foliage interactions, and suggest that measurements of sapwood hydraulic conductivity may help to resolve conflicting observations of how As:Af ratios change as trees grow taller.

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats.

PubMed

Mobley, C Brooks; Toedebusch, Ryan G; Lockwood, Christopher M; Heese, Alexander J; Zhu, Conan; Krieger, Anna E; Cruthirds, Clayton L; Hofheins, John C; Company, Joseph M; Wiedmeyer, Charles E; Kim, Dae Y; Booth, Frank W; Roberts, Michael D

2014-01-01

We examined if a purported anti-inflammatory supplement (AF) abrogated Western-diet (WD)-induced liver pathology in rats. AF contained: 1) protein concentrates from bovine colostrum and avian egg yolk; 2) herbal adaptogens and antioxidants; and 3) acetyl-L-carnitine. Nine month-old male Brown Norway rats were allowed ad libitum access to WD for 41-43 days and randomly assigned to WD + AF feeding twice daily for the last 31-33 days (n = 8), or WD and water-placebo feeding twice daily for the last 31-33 days (n = 8). Rats fed a low-fat/low-sucrose diet (CTL, n = 6) for 41-43 days and administered a water-placebo twice daily for the last 31-33 days were also studied. Twenty-four hours following the last gavage-feed, liver samples were analyzed for: a) select mRNAs (via RT-PCR) as well as genome-wide mRNA expression patterns (via RNA-seq); b) lipid deposition; and, c) protein carbonyl and total antioxidant capacity (TAC). Serum was also examined for TAC, 8-isoprostane and clinical chemistry markers. WD + AF rats experienced a reduction in liver Tnf-α mRNA (-2.8-fold, p < 0.01). Serum and liver TAC was lower in WD + AF versus WD and CTL rats (p < 0.05), likely due to exogenous antioxidant ingredients provided through AF as evidenced by a tendency for mitochondrial SOD2 mRNA to increase in WD + AF versus CTL rats (p = 0.07). Liver fat deposition nor liver protein carbonyl content differed between WD + AF versus WD rats, although liver protein carbonyls tended to be lower in WD + AF versus CTL rats (p = 0.08). RNA-seq revealed that 19 liver mRNAs differed between WD + AF versus WD when both groups were compared with CTL rats (+/- 1.5-fold, p < 0.01). Bioinformatics suggest that AF prevented WD-induced alterations in select genes related to the transport and metabolism of carbohydrates in favor of select genes related to lipid transport and metabolism. Finally, serum clinical safety markers and liver pathology (via lesion counting) suggests that chronic consumption of AF was well tolerated. AF supplementation elicits select metabolic, anti-inflammatory, and anti-oxidant properties which was in spite of WD feeding and persisted up to 24 hours after receiving a final dose.

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats

PubMed Central

2014-01-01

Background We examined if a purported anti-inflammatory supplement (AF) abrogated Western-diet (WD)-induced liver pathology in rats. AF contained: 1) protein concentrates from bovine colostrum and avian egg yolk; 2) herbal adaptogens and antioxidants; and 3) acetyl-L-carnitine. Methods Nine month-old male Brown Norway rats were allowed ad libitum access to WD for 41–43 days and randomly assigned to WD + AF feeding twice daily for the last 31–33 days (n = 8), or WD and water-placebo feeding twice daily for the last 31–33 days (n = 8). Rats fed a low-fat/low-sucrose diet (CTL, n = 6) for 41–43 days and administered a water-placebo twice daily for the last 31–33 days were also studied. Twenty-four hours following the last gavage-feed, liver samples were analyzed for: a) select mRNAs (via RT-PCR) as well as genome-wide mRNA expression patterns (via RNA-seq); b) lipid deposition; and, c) protein carbonyl and total antioxidant capacity (TAC). Serum was also examined for TAC, 8-isoprostane and clinical chemistry markers. Results WD + AF rats experienced a reduction in liver Tnf-α mRNA (-2.8-fold, p < 0.01). Serum and liver TAC was lower in WD + AF versus WD and CTL rats (p < 0.05), likely due to exogenous antioxidant ingredients provided through AF as evidenced by a tendency for mitochondrial SOD2 mRNA to increase in WD + AF versus CTL rats (p = 0.07). Liver fat deposition nor liver protein carbonyl content differed between WD + AF versus WD rats, although liver protein carbonyls tended to be lower in WD + AF versus CTL rats (p = 0.08). RNA-seq revealed that 19 liver mRNAs differed between WD + AF versus WD when both groups were compared with CTL rats (+/- 1.5-fold, p < 0.01). Bioinformatics suggest that AF prevented WD-induced alterations in select genes related to the transport and metabolism of carbohydrates in favor of select genes related to lipid transport and metabolism. Finally, serum clinical safety markers and liver pathology (via lesion counting) suggests that chronic consumption of AF was well tolerated. Conclusions AF supplementation elicits select metabolic, anti-inflammatory, and anti-oxidant properties which was in spite of WD feeding and persisted up to 24 hours after receiving a final dose. PMID:24822076

1.4 times increase in atrial fibrillation-related ischemic stroke and TIA over 12years in a stroke center.

PubMed

Yang, Qiong; Churilov, Leonid; Fan, Dongsheng; Davis, Stephen; Yan, Bernard

2017-08-15

Prevalence of atrial fibrillation (AF) has quadrupled in the past 50years in the general population. However, there is uncertainty regarding prevalence of AF over time in ischemic stroke patients given the aging population and enhanced surveillance of AF. We aimed to explore the changing prevalence of AF as well as other risk factors, stroke subtypes, investigations and pre-stroke medications among ischemic stroke and transient ischemic attack (TIA) patients. We performed a retrospective analysis of data from a prospective database of consecutive patients with acute ischemic stroke and TIA from 2004 to 2015. Trends in risk factors and other variables year by year were analyzed using logistic regression or median regression. Among 6275 patients (median age [interquartile range] 74 [62-82] years, 56% males), the prevalence of AF increased 1.4 times over 12years (from 23.3% to 32.7%, P<0.001). The increase in the prevalence of AF remained significant after adjustment for age and the use of Holter monitoring. There was also a significant increase in prevalence of hypertension (67.4% to 77.3%), structural heart disease (9.8% to 10.5%), and previous TIA (10.9% to 13.7%) and a significant decrease in prevalence of dyslipidemia (71.8% to 49.4%). There was a 1.4 times increase in the prevalence of AF among consecutive ischemic stroke and TIA patients in the past 12years in a hospital-based registry. More active screening of the general population for AF may be warranted in order to decrease the overall stroke burden. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene expression of stem cells at different stages of ontological human development.

PubMed

Allegra, Adolfo; Altomare, Roberta; Curcio, Patrizia; Santoro, Alessandra; Lo Monte, Attilio I; Mazzola, Sergio; Marino, Angelo

2013-10-01

To compare multipotent mesenchymal stem cells (MSCs) obtained from chorionic villi (CV), amniotic fluid (AF) and placenta, with regard to their phenotype and gene expression, in order to understand if MSCs derived from different extra-embryonic tissues, at different stages of human ontological development, present distinct stemness characteristics. MSCs obtained from 30 samples of CV, 30 of AF and 10 placentas (obtained from elective caesarean sections) were compared. MSCs at second confluence cultures were characterized by immunophenotypic analysis with flow cytometry using FACS CANTO II. The expression of the genes Oct-4 (Octamer-binding transcription factor 4, also known as POU5F1), Sox-2 (SRY box-containing factor 2), Nanog, Rex-1 (Zfp-42) and Pax-6 (Paired Box Protein-6), was analyzed. Real-time quantitative PCR was performed by ABI Prism 7700, after RNA isolation and retro-transcription in cDNA. Statistical analysis was performed using non-parametric test Kruskal-Wallis (XLSTAT 2011) and confirmed by REST software, to estimate fold changes between samples. Each gene was defined differentially expressed if p-value was <0.05. Cells from all samples were negative for haematopoietic antigens CD45, CD34, CD117 and CD33 and positive for the typical MSCs antigens CD13, CD73 and CD90. Nevertheless, MSCs from AF and placentas showed different fluorescence intensity, reflecting the heterogeneity of these tissues. The gene expression of OCT-4, SOX-2, NANOG was not significantly different among the three groups. In AF, REX-1 and PAX-6 showed a higher expression in comparison to CV. MSCs of different extra-embryonic tissues showed no differences in immunophenotype when collected from second confluence cultures. The expression of OCT-4, NANOG and SOX-2 was not significantly different, demonstrating that all fetal sources are suitable for obtaining MSCs. These results open new possibilities for the clinical use of MSCs derived from easily accessible sources, in order to develop new protocols for clinical and experimental research. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Development of FDR-AF (Frictional Drag Reduction Anti-Fouling) Marine Coating

NASA Astrophysics Data System (ADS)

Lee, Inwon; Park, Hyun; Chun, Ho Hwan; GCRC-SOP Team

2013-11-01

In this study, a novel skin-friction reducing marine paint has been developed by mixing fine powder of PEO(PolyEthyleneOxide) with SPC (Self-Polishing Copolymer) AF (Anti-Fouling) paint. The PEO is well known as one of drag reducing agent to exhibit Toms effect, the attenuation of turbulent flows by long chain polymer molecules in the near wall region. The frictional drag reduction has been implemented by injecting such polymer solutions to liquid flows. However, the injection holes have been a significant obstacle to marine application. The present PEO-containing marine paint is proposed as an alternative to realize Toms effect without any hole on the ship surface. The erosion mechanism of SPC paint resin and the subsequent dissolution of PEO enable the controlled release of PEO solution from the coating. Various tests such as towing tank drag measurement of flat plate and turbulence measurement in circulating water tunnel demonstrated over 10% frictional drag reduction compared with conventional AF paint. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) through GCRC-SOP(No. 2011-0030013).

Optimizing Air Force Depot Programming to Maximize Operational Capability

DTIC Science & Technology

2014-03-27

MONITORING AGENCY NAME(S) AND ADDRESS(ES) AF/A4/ 7P Lt Col Dana C. Pelleltier, dana.c.pelletier2.mil@mail.mil, (703) 693-8395 Lt Col Robert L...Charlesworth, robert.charlesworth@pentagon.af.mi Maj Steven N. Lamb, steven.lamb@pentagon.mil, (703) 695-7049 10. SPONSOR/MONITOR’S ACRONYM(S) AF/A4/ 7P 11

Topological ferrimagnetic behaviours of coordination polymers containing manganese(II) chains with mixed azide and carboxylate bridges and alternating F/AF/AF'/AF'/AF interactions.

PubMed

Wang, Yan-Qin; Liu, Hou-Ting; Qi, Yan; Gao, En-Qing

2014-08-21

Two Mn(ii) complexes with azide and a new zwitterionic tetracarboxylate ligand 1,2,4,5-tetrakis(4-carboxylatopyridinium-1-methylene)benzene (L(1)), {[Mn5(L(1))2(N3)8(OH)2]·12H2O}n () and {[Mn5(L(1))2(N3)8(H2O)2](ClO4)2·6H2O}n (), have been synthesized and characterized crystallographically and magnetically. and contain similar alternating chains constructed by azide and carboxylate bridges. The independent sets of bridges alternate in an ABCCB sequence between adjacent Mn(ii) ions: (EO-N3)2 double bridges (EO = end-on) (denoted as A), [(EO-N3)(OCO)2] triple bridges (denoted as B) and [(EO-N3)(OCO)] double bridges (denoted as C). The alternating chains are interlinked into 2D coordination networks by the tetrapyridinium spacers. Magnetic studies demonstrate that the magnetic coupling through the double EO azide bridges is ferromagnetic and that through mixed azide/carboxylate bridges is antiferromagnetic. The unprecedented F/AF/AF'/AF'/AF coupling sequence along the chain dictates an uncompensated ground spin state (S = 5/2 per Mn5 unit) and leads to one-dimensional topological ferrimagnetism, which features a minimum in the χT versus T plot.

The incidence and distribution characteristics of MLL rearrangements in Chinese acute myeloid leukemia patients by multiplex nested RT-PCR.

PubMed

Yang, Hua; Cao, Tingting; Gao, Li; Wang, Lili; Zhu, Chengying; Xu, Yuanyuan; Jing, Yu; Zhu, Haiyan; Lv, Na; Yu, Li

2017-07-20

Occurrence of MLL (Mixed Lineage Leukemia) gene rearrangements indicates poor prognosis in acute myeloid leukemia (AML) patients. This is the first study to report the positive rate and distribution characteristics of MLL rearrangements in AML patients in north China. We used multiplex nested real time PCR (RT-PCR) to screen for incidence of 11 MLL rearrangements in 433 AML patients. Eleven MLL rearrangements included (MLL-PTD, MLL-AF9, MLL-ELL, MLL-AF10, MLL-AF17, MLL-AF6, MLL-ENL, MLL-AF1Q, MLL-CBP, MLL-AF1P, MLL-AFX1). There were 68 AML patients with MLL rearrangements, and the positive rate was 15.7%. MLL-PTD (4.84%) was detected in 21 patients, MLL-AF9 in 15, (3.46%), MLL-ELL in 10 (2.31%), MLL-AF10 in 8 (1.85%), MLL-AF1Q in 2 (0.46%), 3 cases each of MLL-AF17, MLL-AF6, MLL-ENL (0.69% each), a and single case each of MLL-CBP, MLL-AF1P, and MLL-AFX1 (0.23% each). The highest rate of MLL rearrangements was found in 24 patients with M5 subtype AML, occurring in 24 cases (35.3%). MLL rearrangements occurred in 21 patients with M2 subtype AML (30.9%), and in 10 patients with M4 subtype AML (14.7%). Screening fusion genes by multiplex nested RT-PCR is a convenient, fast, economical, and accurate method for diagnosis and predicting prognosis of AML.

Incidence of atrial fibrillation in whites and African-Americans: the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Alonso, Alvaro; Agarwal, Sunil K; Soliman, Elsayed Z; Ambrose, Marietta; Chamberlain, Alanna M; Prineas, Ronald J; Folsom, Aaron R

2009-07-01

To define the incidence and cumulative risk of atrial fibrillation (AF) in a population-based cohort of whites and African Americans. African-Americans reportedly have a lower risk of AF than whites despite their higher exposure to AF risk factors. However, precise estimates of AF incidence in African Americans have not been previously published. We studied the incidence of AF in the Atherosclerosis Risk in Communities (ARIC) study, which has followed up 15,792 men and women 45 to 65 years of age at baseline from 4 communities in the United States since 1987. Atrial fibrillation cases were identified from electrocardiograms conducted at baseline and 3 follow-up visits, and from hospitalizations and death certificates through the end of 2004. During follow-up, 1,085 new cases of AF were identified (196 in African Americans, 889 in whites). Crude incidence rates of AF were 6.7, 4.0, 3.9, and 3.0 per 1,000 persons per year in white men, white women, African-American men, and African-American women, respectively. Increasing age was exponentially associated with an elevated risk of AF. Compared to whites, African-Americans had a 41% (95% CI: 8%-62%) lower age- and sex-adjusted risk of being diagnosed with AF. The cumulative risk of AF at 80 years of age was 21% in white men, 17% in white women, and 11% in African-American men and women. In this population-based cohort, African Americans presented a lower risk of AF than whites. Still, the burden of AF among the former is substantial, with 1 in 9 receiving a diagnosis of AF before 80 years of age.

Aspergillus sensitization or carriage in cystic fibrosis patients.

PubMed

Fillaux, Judith; Brémont, François; Murris, Marlène; Cassaing, Sophie; Tétu, Laurent; Segonds, Christine; Pipy, Bernard; Magnaval, Jean-François

2014-07-01

Aspergillus fumigatus (Af) sensitization and persistent carriage are deleterious to lung function, but no consensus has been reached defining these medical entities. This work aimed to identify possible predictive factors for patients who become sensitized to Af, compared with a control group of non-sensitized Af carriers. Between 1995 and 2007, 117 pediatric patients were evaluated. Demographic data, CFTR gene mutations, body mass index and FEV1 were recorded. The presence of Af in sputum, the levels of Af-precipitin, total IgE (t-IgE) and specific IgE to Af (Af-IgE) were determined. Patients were divided into 2 groups: (1) "sensitization": level of Af-IgE > 0.35 IU/mL with t-IgE level < 500 IU/mL and (2) "persistent or transient carriage": Af-IgE level ≤ 0.35 IU/mL with either an Af transient or persistent positive culture. A survival analysis was performed with the appearance of Af-IgE in serum as an outcome variable. Severe mutation (hazard ratio = 3.2), FEV1 baseline over 70% of theoretical value (hazard ratio = 4.9), absence of Pa colonization, catalase activity and previous azithromycin administration (hazard ratio = 9.8, 4.1 and 1.9, respectively) were predictive factors for sensitization. We propose a timeline of the biological events and a tree diagram for risk calculation. Two profiles of cystic fibrosis patients can be envisaged: (1) patients with nonsevere mutation but low FEV1 baselines are becoming colonized with Af or (2) patients with high FEV1 baselines who present with severe mutation are more susceptible to the Af sensitization and then to the presentation of an allergic bronchopulmonary aspergillosis event.

Predictors of Long-term Success After Concomitant Surgical Ablation for Atrial Fibrillation.

PubMed

Pecha, Simon; Ghandili, Susanne; Hakmi, Samer; Willems, Stephan; Reichenspurner, Hermann; Wagner, Florian Mathias

2017-01-01

According to guidelines, atrial fibrillation (AF) ablation success should be measured by 24-hour Holter electrocardiogram (ECG). However, information on long-term success, especially obtained by 24-hour Holter ECG, is rare. We therefore analyzed rhythm course and long-term outcomes of our patients undergoing concomitant surgical AF ablation. Between January 2003 and April 2011, 486 patients underwent concomitant surgical AF ablation in our institution. Patients with 24-hour Holter ECG rhythm status available between 5 and 10 years postoperatively were included in this retrospective data analysis (n = 155). Ablation lesions were limited to either a pulmonary vein isolation (n = 31, 20%), a more complex left atrial lesion set (n = 89, 57%), or biatrial lesions (n = 35, 23%). Primary end point of the study was freedom from AF during long-term follow-up. Mean patient age was 68.1 ± 8.4 years; 57.4% were male. Mean follow-up time was 5.9 years. Surgical AF ablation provided freedom from AF rate of 56.6% during long-term follow-up, with significantly better results in patients with paroxysmal than in those with persistent AF (67.2% vs 51.8% P = 0.03). A stable rhythm course was observed during follow-up, without statistically significant differences between 12 months and latest follow-up (63.2% vs 56.6%; P = 0.25). In multivariate analysis, preoperative paroxysmal AF, duration of AF, and left atrial diameter were predictors of long-term ablation success. Surgical AF ablation provided freedom from AF rate of 56.6% during long-term follow-up. Statistically significant predictors of ablation success at latest follow-up were preoperative paroxysmal AF, duration of AF, and a preoperative smaller left atrial diameter. Copyright © 2017. Published by Elsevier Inc.

Atrial Fibrillation and Colonic Neoplasia in African Americans.

PubMed

Nouraie, Mehdi; Kansal, Vandana; Belfonte, Cassius; Ghazvini, Mohammad; Haidari, Tahmineh; Shahnazi, Anahita; Brim, Hassan; Soliman, Elsayed Z; Ashktorab, Hassan

2015-01-01

Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American. We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression. The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9-2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7-1.6, P = 0.7) were not significantly associated AF compared to control group. AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors.

Clinical, Electrocardiographic, and Echocardiographic Parameter Combination Predicts the Onset of Atrial Fibrillation.

PubMed

Soeki, Takeshi; Matsuura, Tomomi; Tobiume, Takeshi; Bando, Sachiko; Matsumoto, Kazuhisa; Nagano, Hiromi; Uematsu, Etsuko; Kusunose, Kenya; Ise, Takayuki; Yamaguchi, Koji; Yagi, Shusuke; Fukuda, Daiju; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Sata, Masataka

2018-05-30

The ability to identify risk markers for new-onset atrial fibrillation (AF) is critical to the development of preventive strategies, but it remains unknown whether a combination of clinical, electrocardiographic, and echocardiographic parameters predicts the onset of AF. In the present study, we evaluated the predictive value of a combined score that includes these parameters.Methods and Results:We retrospectively studied 1,040 patients without AF who underwent both echocardiography and 24-h Holter electrocardiography between May 2005 and December 2010. During a median follow-up period of 68.4 months (IQR, 49.9-93.3 months), we investigated the incidence of new-onset AF. Of the 1,040 patients, 103 (9.9%) developed AF. Patients who developed AF were older than patients who did not. Total heart beats, premature atrial contraction (PAC) count, maximum RR interval, and frequency of sinus pause quantified on 24-h electrocardiography were associated with new-onset AF. LA diameter (LAD) on echocardiography was also associated with the development of AF. On multivariate Cox analysis, age ≥58 years, PAC count ≥80 beats/day, maximum RR interval ≥1.64 s, and LAD ≥4.5 cm were independently associated with the development of AF. The incidence rate of new-onset AF significantly increased as the combined score (i.e., the sum of the risk score determined using hazard ratios) increased. A combined score that includes age, PAC count, maximum RR interval, and LAD could help characterize the risk of new-onset AF.

Incident Atrial Fibrillation and the Risk of Congestive Heart Failure, Myocardial Infarction, End-Stage Kidney Disease, and Mortality Among Patients With a Decreased Estimated GFR.

PubMed

Massicotte-Azarniouch, David; Kuwornu, John Paul; Carrero, Juan-Jesus; Lam, Ngan N; Molnar, Amber O; Zimmerman, Deborah; McCallum, Megan K; Garg, Amit X; Sood, Manish M

2018-02-01

The association of atrial fibrillation (AF), estimated glomerular filtration rate (eGFR), and adverse events remains unknown. Population-based retrospective cohort study from Ontario, Canada. 1,422,978 adult residents with eGFRs < 90mL/min/1.73m 2 from April 1, 2006, through March 31, 2015. A diagnosis of AF at hospitalization. Congestive heart failure (CHF), myocardial infarction (MI), end-stage kidney disease, all-cause mortality. All adverse events were more frequent in individuals with AF (93,414 propensity score matched) compared to no AF, and this difference was more pronounced within the first 6 months of the index date (CHF: 3.04% [AF] vs 0.28% [no AF], subdistribution HR [sHR] of 11.57 [95% CI, 10.26-13.05]; MI: 0.97% [AF] vs 0.21% [no AF], sHR of 4.76 [95% CI, 4.17-5.43]; end-stage kidney disease: 0.16% [AF] vs 0.03% [no AF], sHR of 5.84 [95% CI, 3.82-8.93]; and all-cause mortality: 6.11% [AF] vs 2.50% [no AF], HR of 2.62 [95% CI, 2.50-2.76]) than in the period more than 6 months after the index date (CHF: 6.87% [AF] vs 2.87% [no AF], sHR of 2.64 [95% CI, 2.55-2.74]; MI: 2.21% [AF] vs 1.81% [no AF], sHR of 1.24 [95% CI, 1.18-1.30]; end-stage kidney disease: 0.52% [AF] vs 0.32% [no AF], sHR of 1.75 [95% CI, 1.57-1.95]; and all-cause mortality: 15.55% [AF] vs 15.10% [no AF], HR of 1.07 [95% CI, 1.04-1.10]). The results accounted for the competing risk for mortality. eGFR level modified the effect of AF on CHF (P for interaction < 0.05). Observational study design does not permit determination of causality; only a single outpatient eGFR measure was used; medication data were not included. Incident AF is associated with a high risk for adverse outcomes in patients with eGFRs < 90mL/min/1.73m 2 . Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Risk Factors For Bradycardia Requiring Pacemaker Implantation In Patients With Atrial Fibrillation

PubMed Central

Barrett, Tyler W.; Abraham, Robert L.; Jenkins, Cathy A.; Russ, Stephan; Storrow, Alan B.; Darbar, Dawood

2012-01-01

Symptomatic bradycardia may complicate atrial fibrillation (AF) and necessitate a permanent pacemaker. Identifying patients at increased risk for symptomatic bradycardia may reduce associated morbidities and healthcare costs. We investigated predictors for developing bradycardia requiring a permanent pacemaker among AF patients. We reviewed records of all patients treated for AF/flutter in an academic hospital’s emergency department from 8/1/2005 to 8/30/2008. We determined survival and presence of a pacemaker as of 11/1/2011. Cases were defined as patients with pacemakers placed for bradycardia after their AF diagnoses. Patients without a pacemaker who were followed at our hospital comprised the controls. We identified a priori variables for the logistic regression analysis. We fit a post-hoc model adjusting for AF type and atrioventricular nodal blocker (AVN) use. Of the 362 patients in our cohort, 119 cases had permanent pacemakers implanted for bradycardia subsequent to AF diagnosis and 243 controls were alive without a pacemaker. Median and interquartile range follow-up time was 4.5 (3.8 – 5.4) years. Odds ratios and 95% confidence intervals were determined for age at time of AF diagnosis (1.02 [1, 1.04]), female (1.58 [0.95, 2.63]), prior heart failure (2.72 [1.47, 5.01]), and African-American (0.33 [0.12, 0.94]). Post-hoc model identified permanent AF (2.99 [1.61, 5.57]) and AVN use (1.43 [0.85, 2.4]). In conclusion, among AF patients, heart failure and permanent AF each nearly triple the odds of developing bradycardia requiring a permanent pacemaker; while not statistically significant, our results suggest that women are more likely and African-Americans less likely to develop bradycardia requiring pacemaker implantation. PMID:22840846

Cone Photoreceptor Abnormalities Correlate with Vision Loss in Patients with Stargardt Disease

PubMed Central

Chen, Yingming; Ratnam, Kavitha; Sundquist, Sanna M.; Lujan, Brandon; Ayyagari, Radha; Gudiseva, V. Harini; Roorda, Austin

2011-01-01

Purpose. To study the relationship between macular cone structure, fundus autofluorescence (AF), and visual function in patients with Stargardt disease (STGD). Methods. High-resolution images of the macula were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography in 12 patients with STGD and 27 age-matched healthy subjects. Measures of retinal structure and AF were correlated with visual function, including best-corrected visual acuity, color vision, kinetic and static perimetry, fundus-guided microperimetry, and full-field electroretinography. Mutation analysis of the ABCA4 gene was completed in all patients. Results. Patients were 15 to 55 years old, and visual acuity ranged from 20/25–20/320. Central scotomas were present in all patients, although the fovea was spared in three patients. The earliest cone spacing abnormalities were observed in regions of homogeneous AF, normal visual function, and normal outer retinal structure. Outer retinal structure and AF were most normal near the optic disc. Longitudinal studies showed progressive increases in AF followed by reduced AF associated with losses of visual sensitivity, outer retinal layers, and cones. At least one disease-causing mutation in the ABCA4 gene was identified in 11 of 12 patients studied; 1 of 12 patients showed no disease-causing ABCA4 mutations. Conclusions. AOSLO imaging demonstrated abnormal cone spacing in regions of abnormal fundus AF and reduced visual function. These findings provide support for a model of disease progression in which lipofuscin accumulation results in homogeneously increased AF with cone spacing abnormalities, followed by heterogeneously increased AF with cone loss, then reduced AF with cone and RPE cell death. (ClinicalTrials.gov number, NCT00254605.) PMID:21296825

Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060

PubMed Central

Krijthe, Bouwe P.; Kunst, Anton; Benjamin, Emelia J.; Lip, Gregory Y.H.; Franco, Oscar H.; Hofman, Albert; Witteman, Jacqueline C.M.; Stricker, Bruno H.; Heeringa, Jan

2013-01-01

Aims Since atrial fibrillation (AF) is associated with increased risks of cardiovascular and cerebrovascular complications, estimations on the number of individuals with AF are relevant to healthcare planning. We aimed to project the number of individuals with AF in the Netherlands and in the European Union from 2000 to 2060. Methods and results Age- and sex-specific AF prevalence estimates were obtained from the prospective community-based Rotterdam Study. Population projections for the Netherlands and the European Union were obtained from the European Union's statistics office. In the age stratum of 55–59 years, the prevalence of AF was 1.3% in men (95% CI: 0.4–3.6%) and 1.7% in women (95% CI: 0.7–4.0%). The prevalence of AF increased to 24.2% in men (95% CI: 18.5–30.7%), and 16.1% in women (95% CI: 13.1–19.4%), for those >85 years of age. This age- and sex-specific prevalence remained stable during the years of follow-up. Furthermore, we estimate that in the European Union, 8.8 million adults over 55 years had AF in 2010 (95% CI: 6.5–12.3 million). We project that this number will double by 2060 to 17.9 million (95% CI: 13.6–23.7 million) if the age- and sex-specific prevalence remains stable. Conclusion We estimate that from 2010 to 2060, the number of adults 55 years and over with AF in the European Union will more than double. As AF is associated with significant morbidities and mortality, this increasing number of individuals with AF may have major public health implications. PMID:23900699

Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060.

PubMed

Krijthe, Bouwe P; Kunst, Anton; Benjamin, Emelia J; Lip, Gregory Y H; Franco, Oscar H; Hofman, Albert; Witteman, Jacqueline C M; Stricker, Bruno H; Heeringa, Jan

2013-09-01

Since atrial fibrillation (AF) is associated with increased risks of cardiovascular and cerebrovascular complications, estimations on the number of individuals with AF are relevant to healthcare planning. We aimed to project the number of individuals with AF in the Netherlands and in the European Union from 2000 to 2060. Age- and sex-specific AF prevalence estimates were obtained from the prospective community-based Rotterdam Study. Population projections for the Netherlands and the European Union were obtained from the European Union's statistics office. In the age stratum of 55-59 years, the prevalence of AF was 1.3% in men (95% CI: 0.4-3.6%) and 1.7% in women (95% CI: 0.7-4.0%). The prevalence of AF increased to 24.2% in men (95% CI: 18.5-30.7%), and 16.1% in women (95% CI: 13.1-19.4%), for those >85 years of age. This age- and sex-specific prevalence remained stable during the years of follow-up. Furthermore, we estimate that in the European Union, 8.8 million adults over 55 years had AF in 2010 (95% CI: 6.5-12.3 million). We project that this number will double by 2060 to 17.9 million (95% CI: 13.6-23.7 million) if the age- and sex-specific prevalence remains stable. We estimate that from 2010 to 2060, the number of adults 55 years and over with AF in the European Union will more than double. As AF is associated with significant morbidities and mortality, this increasing number of individuals with AF may have major public health implications.

Low Serum Magnesium and the Development of Atrial Fibrillation in the Community: The Framingham Heart Study

PubMed Central

Khan, Abigail May; Lubitz, Steven A.; Sullivan, Lisa M.; Sun, Jenny X.; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; Ellinor, Patrick T.; Benjamin, Emelia J.; Wang, Thomas J.

2012-01-01

Background Low serum magnesium has been linked to increased risk of atrial fibrillation (AF) following cardiac surgery. It is unknown whether hypomagnesemia predisposes to AF in the community. Methods and Results We studied 3,530 participants (mean age, 44 years; 52% women) from the Framingham Offspring Study who attended a routine examination, and were free of AF and cardiovascular disease. We used Cox proportional hazard regression analysis to examine the association between serum magnesium at baseline and risk of incident AF. Analyses were adjusted for conventional AF risk factors, use of antihypertensive medications, and serum potassium. During up to 20 years of follow-up, 228 participants developed AF. Mean serum magnesium was 1.88 mg/dl. The age- and sex-adjusted incidence rate of AF was 9.4 per 1,000 person-years (95% confidence interval, 6.7 to 11.9) in the lowest quartile of serum magnesium (≤1.77 mg/dl), compared with 6.3 per 1,000 person-years (95% confidence interval, 4.1 to 8.4) in the highest quartile (≥1.99 mg/dl). In multivariable-adjusted models, individuals in the lowest quartile of serum magnesium were approximately 50% more likely to develop AF (adjusted hazard ratio, 1.52, 1.00 to 2.31; P=0.05), compared with those in the upper quartiles. Results were similar after excluding individuals on diuretics. Conclusion Low serum magnesium is moderately associated with the development of AF in individuals without cardiovascular disease. Because hypomagnesemia is common in the general population, a link with AF may have potential clinical implications. Further studies are warranted to confirm our findings and elucidate the underlying mechanisms. PMID:23172839

Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.

PubMed

Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja; Larsson, Henrik B W; Rostrup, Egill

2014-11-01

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Two spin-canting textures in the antiferromagnetic phase AF1 of MnWO4 based on the new polar atomistic model in P2

NASA Astrophysics Data System (ADS)

Park, S.-H.; Liu, B.-Q.; Behal, D.; Pedersen, B.; Schneidewind, A.

2018-04-01

The low temperature antiferromagnetic (AF) phase of MnWO4 (the so-called AF1 phase) exhibits different spin-canting configurations at two Mn2+ sublattices of the (3  +  1)-dimensional magnetic structure. The suggested superspace group {{\\boldsymbol P}}2.1^\\prime(α, 1/2, γ)0s is a significant consequence of the polar space group {{\\boldsymbol P}} 2 true for the nuclear structure of MnWO4. Density functional theory calculations showed that its ground state prefers this two spin-canting system. The structural difference between two independent atomic sites for Mn (Mn a , Mn b ) is too small to allow microscopically detectable electric polarisation. However, this hidden intrinsic polar character allows AF1 two commensurately modulated spin-canting textures. This is considered as the prerequisite onset of the improper ferroelectricity enhanced by the helical spin order in the multiferroic phase AF2 of MnWO4.

Flecainide-metoprolol combination reduces atrial fibrillation clinical recurrences and improves tolerability at 1-year follow-up in persistent symptomatic atrial fibrillation.

PubMed

Capucci, Alessandro; Piangerelli, Luca; Ricciotti, Jenny; Gabrielli, Domenico; Guerra, Federico

2016-11-01

Atrial fibrillation (AF) affects ∼2% of the total population. In order to prevent AF recurrences, many anti-arrhythmic drugs are currently available, but most of them are burdened by serious side effects and suboptimal efficacy. The aim of the present study was to test efficacy and safety of a combination of flecainide and metoprolol in preventing AF clinical recurrences. This study is a monocentric, prospective, randomized, open-blinded trial on 173 patients with a recent episode of paroxysmal or persistent AF. Patients were randomized into group A (flecainide + metoprolol; n = 80), group B (flecainide only; n = 72), or group C (metoprolol only; n = 21). Main exclusion criteria were recent acute coronary syndrome, heart failure New York Heart Association class III-IV, left ventricular ejection fraction <0.40, atrioventricular conduction disorders, and severe bradycardia. Primary endpoint was symptomatic recurrence over 1-year follow-up. Secondary endpoint was quality of life (QoL) over 1-year follow-up, as assessed by the SF-36 and Atrial Fibrillation Severity Scale questionnaires. Combination therapy with flecainide and metoprolol significantly reduced recurrences at 1-year follow-up when compared with flecainide alone in the whole population (66.7 vs. 46.8%; P < 0.001) and in patients with persistent AF (71.1 vs. 43.6%; P = 0.025) while adding beta-blocker therapy to paroxysmal AF showed no benefit over IC anti-arrhythmic drug-only. Patients randomized to combination therapy experienced a significant improvement of QoL when compared with those assigned to a flecainide-only regimen irrespective of AF type. Flecainide-metoprolol combination therapy improves effectiveness of rhythm control in persistent symptomatic AF and increases tolerability, with a concomitant reduction of side effects and a better compliance. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

The Left, The Better: White-Matter Brain Integrity Predicts Foreign Language Imitation Ability.

PubMed

Vaquero, Lucía; Rodríguez-Fornells, Antoni; Reiterer, Susanne M

2017-08-01

Speech imitation is crucial for language acquisition and second-language learning. Interestingly, large individual differences regarding the ability in imitating foreign-language sounds have been observed. The origin of this interindividual diversity remains unknown, although it might be partially explained by structural predispositions. Here we correlated white-matter structural properties of the arcuate fasciculus (AF) with the performance of 52 German-speakers in a Hindi sentence- and word-imitation task. First, a manual reconstruction was performed, permitting us to extract the mean values along the three branches of the AF. We found that a larger lateralization of the AF volume toward the left hemisphere predicted the performance of our participants in the imitation task. Second, an automatic reconstruction was carried out, allowing us to localize the specific region within the AF that exhibited the largest correlation with foreign language imitation. Results of this reconstruction also showed a left lateralization trend: greater fractional anisotropy values in the anterior half of the left AF correlated with the performance in the Hindi-imitation task. From the best of our knowledge, this is the first time that foreign language imitation aptitude is tested using a more ecological imitation task and correlated with DTI tractography, using both a manual and an automatic method. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

VLDL from Metabolic Syndrome Individuals Enhanced Lipid Accumulation in Atria with Association of Susceptibility to Atrial Fibrillation.

PubMed

Lee, Hsiang-Chun; Lin, Hsin-Ting; Ke, Liang-Yin; Wei, Chi; Hsiao, Yi-Lin; Chu, Chih-Sheng; Lai, Wen-Ter; Shin, Shyi-Jang; Chen, Chu-Huang; Sheu, Sheng-Hsiung; Wu, Bin-Nan

2016-01-20

Metabolic syndrome (MetS) represents a cluster of metabolic derangements. Dyslipidemia is an important factor in MetS and is related to atrial fibrillation (AF). We hypothesized that very low density lipoproteins (VLDL) in MetS (MetS-VLDL) may induce atrial dilatation and vulnerability to AF. VLDL was therefore separated from normal (normal-VLDL) and MetS individuals. Wild type C57BL/6 male mice were divided into control, normal-VLDL (nVLDL), and MetS-VLDL (msVLDL) groups. VLDL (15 µg/g) and equivalent volumes of saline were injected via tail vein three times a week for six consecutive weeks. Cardiac chamber size and function were measured by echocardiography. MetS-VLDL significantly caused left atrial dilation (control, n = 10, 1.64 ± 0.23 mm; nVLDL, n = 7, 1.84 ± 0.13 mm; msVLDL, n = 10, 2.18 ± 0.24 mm; p < 0.0001) at week 6, associated with decreased ejection fraction (control, n = 10, 62.5% ± 7.7%, vs. msVLDL, n = 10, 52.9% ± 9.6%; p < 0.05). Isoproterenol-challenge experiment resulted in AF in young msVLDL mice. Unprovoked AF occurred only in elderly msVLDL mice. Immunohistochemistry showed excess lipid accumulation and apoptosis in msVLDL mice atria. These findings suggest a pivotal role of VLDL in AF pathogenesis for MetS individuals.

Preoperative atrial fibrillation increases risk of thromboembolic events after left ventricular assist device implantation.

PubMed

Stulak, John M; Deo, Salil; Schirger, John; Aaronson, Keith D; Park, Soon J; Joyce, Lyle D; Daly, Richard C; Pagani, Francis D

2013-12-01

Because no series has specifically analyzed the impact of preoperative atrial fibrillation (AF) on patients already at higher risk of thromboembolism after implantation of a left ventricular assist device (LVAD), we review our experience with these patients. Between July 2003 and September 2011, 389 patients (308 male) underwent implantation of a continuous flow LVAD at University of Michigan Hospital and Mayo Clinic. Median age at implant was 60 years (range, 18 to 79 years). Preoperative AF was present in 120 patients (31%). Outcomes were analyzed for the association of preoperative AF and postoperative thromboembolic (TE) events defined as stroke, transient ischemic attack, hemolysis, or pump thrombosis. Thromboembolic events occurring within the first 30 days were not counted. One hundred thirty-eight TEs events occurred in 97/389 patients (25%) for an event rate of 0.31 TE events/patient-years of support. Freedom from a TE event in patients with preoperative AF was 62% at 1 year and 46% at 2 years compared with 79% and 72% at 1 and 2 years, respectively, in patients without preoperative AF (p < 0.001). Median survival was 10 months (maximum 7.2 years, total 439 patient-years). Preoperative AF did not decrease late survival at 1 and 2 years after LVAD implant (preop AF: 85% and 70% versus no preop AF: 82% and 70%, respectively; p = 0.55). Patients with preoperative AF have a lower freedom from TE events after LVAD implant. While overall late survival was not significantly reduced in these patients, refinement in anticoagulation strategies after VAD implant may be required. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Enhancing uranium uptake by amidoxime adsorbent in seawater: An investigation for optimum alkaline conditioning parameters

DOE PAGES

Das, Sadananda; Tsouris, Costas; Zhang, Chenxi; ...

2015-09-07

A high-surface-area polyethylene-fiber adsorbent (AF160-2) has been developed at the Oak Ridge National Laboratory by radiation-induced graft polymerization of acrylonitrile and itaconic acid. The grafted nitriles were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with potassium hydroxide (KOH) by varying different reaction parameters such as KOH concentration (0.2, 0.44, and 0.6 M), duration (1, 2, and 3 h), and temperature (60, 70, and 80 °C). Adsorbent screening was then performed with simulated seawater solutions containing sodium chloride and sodium bicarbonate, at concentrations found in seawater, and uranium nitrate at a uranium concentration ofmore » ~7–8 ppm and pH 8. Fourier transform infrared spectroscopy and solid-state NMR analyses indicated that a fraction of amidoxime groups was hydrolyzed to carboxylate during KOH conditioning. The uranium adsorption capacity in the simulated seawater screening solution gradually increased with conditioning time and temperature for all KOH concentrations. It was also observed that the adsorption capacity increased with an increase in concentration of KOH for all the conditioning times and temperatures. AF160-2 adsorbent samples were also tested with natural seawater using flow-through experiments to determine uranium adsorption capacity with varying KOH conditioning time and temperature. Based on uranium loading capacity values of several AF160-2 samples, it was observed that changing KOH conditioning time from 3 to 1 h at 60, 70, and 80 °C resulted in an increase of the uranium loading capacity in seawater, which did not follow the trend found in laboratory screening with stimulated solutions. Longer KOH conditioning times lead to significantly higher uptake of divalent metal ions, such as calcium and magnesium, which is a result of amidoxime conversion into less selective carboxylate. The scanning electron microscopy showed that long conditioning times may also lead to adsorbent degradation.« less

Enhancing Uranium Uptake by Amidoxime Adsorbent in Seawater: An investigation for optimum alkaline conditioning parameters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, S.; Tsouris, Constantinos; Zhang, C.

2016-04-20

A high-surface-area polyethylene-fiber adsorbent (AF160-2) has been developed at the Oak Ridge National Laboratory (ORNL) by radiation-induced graft polymerization of acrylonitrile and itaconic acid. The grafted nitriles were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with potassium hydroxide (KOH) by varying different reaction parameters such as KOH concentration (0.2, 0.44, and 0.6 M), duration (1, 2, and 3 h), and temperature (60, 70, and 80 ºC). Adsorbent screening was then performed with simulated seawater solutions containing sodium chloride and sodium bicarbonate, at concentrations found in seawater, and uranium nitrate at a uranium concentrationmore » of ~ 7-8 ppm and pH 8. FTIR and solid state NMR indicated that a fraction of amidoxime groups was hydrolyzed to carboxylate during KOH conditioning. The uranium adsorption capacity in the simulated seawater screening solution gradually increased with conditioning time and temperature for all KOH concentrations. It was also observed that the adsorption capacity increased with an increase in concentration of KOH for all the conditioning times and temperatures. AF160-2 adsorbent samples were also tested with natural seawater using flow-through experiments to determine uranium adsorption capacity with varying KOH conditioning time and temperature. Based on uranium loading capacity values of several AF160-2 samples, it was observed that changing KOH conditioning time from 3 to 1 h at 60, 70, and 80 ºC resulted in increase of the uranium loading capacity in seawater, which did not follow the trend found in laboratory screening with stimulated solutions. Longer KOH conditioning times lead to significantly higher uptake of divalent metal ions, such as calcium and magnesium, which is a result of amidoxime conversion into less selective carboxylate. Scanning electron microscopy showed that long conditioning times may also lead to adsorbent degradation« less

Volume fraction instability in an oscillating non-Brownian iso-dense suspension.

NASA Astrophysics Data System (ADS)

Roht, Y. L.; Gauthier, G.; Hulin, J. P.; Salin, D.; Chertcoff, R.; Auradou, H.; Ippolito, I.

2017-06-01

The instability of an iso-dense non-Brownian suspension of polystyrene beads of diameter 40 μm dispersed in a water-glycerol mixture submitted to a periodic square wave oscillating flow in a Hele-Shaw cell is studied experimentally. The instability gives rise to stationary bead concentration waves transverse to the flow. It has been observed for average particle volume fractions between 0.25 and 0.4, for periods of the square wave flow variation between 0.4 and 10 s and in finite intervals of the amplitude of the fluid displacement. The study shows that the wavelength λ increases roughly linearly with the amplitude of the oscillatory flow; on the other hand, λ is independent of the particle concentration and of the period of oscillation of the flow although the minimum threshold amplitude for observing the instability increases with the period.

Electrocardiographic Predictors of Incident Atrial Fibrillation

PubMed Central

Nguyen, Kaylin T.; Vittinghoff, Eric; Dewland, Thomas A.; Mandyam, Mala C.; Stein, Phyllis K.; Soliman, Elsayed Z.; Heckbert, Susan R.; Marcus, Gregory M.

2017-01-01

Atrial fibrillation (AF) is likely secondary to multiple different pathophysiological mechanisms that are increasingly, but incompletely understood. Motivated by the hypothesis that 3 previously described electrocardiographic (ECG) predictors of AF identify distinct AF mechanisms, we sought to determine if these ECG findings independently predict incident disease. Among Cardiovascular Health Study participants without prevalent AF, we determined whether left anterior fascicular block (LAFB), a prolonged QTC, and atrial premature complexes (APCs) each predicted AF after adjusting for each other. We then calculated the attributable risk in the exposed for each ECG marker. LAFB and QTC intervals were assessed on baseline 12-lead ECG (n=4,696). APC count was determined using 24-hour Holter recordings obtained in a random subsample (n=1,234). After adjusting for potential confounders and each ECG marker, LAFB (hazard ratio [HR. 2.1, 95% confidence interval [CI. 1.1–3.9, p=0.023), a prolonged QTC (HR 2.5, 95% CI 1.4–4.3, p=0.002), and every doubling of APC count (HR 1.2, 95% CI 1.1–1.3, p<0.001) each remained independently predictive of incident AF. The attributable risk of AF in the exposed was 35% (95% CI 13–52%) for LAFB, 25% (95% CI 0.6–44%) for a prolonged QTC, and 34% (95% CI 26–42%) for APCs. In conclusion, in a community-based cohort, 3 previously established ECG-derived AF predictors were each independently associated with incident AF, suggesting they may represent distinct mechanisms underlying the disease. PMID:27448684

Reduction of atrial fibrillation by Tanshinone IIA in chronic heart failure.

PubMed

He, Zhifeng; Sun, Changzheng; Xu, Yi; Cheng, Dezhi

2016-12-01

The aim of the present study was to confirm the effect of Tanshinone IIA (TAN) on the prevention of AF in chronic heart failure (CHF), and to elucidate the underlying electrophysiological mechanisms for the antiarrhythmic effects of TAN at the level of the atrium in an experimental model of CHF. In 10 female rabbits, CHF was induced by rapid ventricular pacing, leading to a significant decrease in ejection fraction in the presence of a dilated left ventricle and atrial enlargement. Twelve rabbits were sham-operated and served as controls. Isolated hearts were perfused using the Langendorff method. Burst pacing was used to induce AF. Monophasic action potential recordings showed an increase of atrial action potential duration (aAPD) and effective refractory period (aERP) in CHF hearts compared with sham hearts. Infusion of acetylcholine (1μm) and isoproterenol (1μm) led to AF in all failing hearts and in 11 sham hearts. Simultaneous infusion of TAN (10μm) remarkably reduced inducibility of AF in 50% of sham and 50% of failing hearts. TAN had no effect on aAPD but significantly increased aERP, leading to a marked increase in atrial post-repolarization refractoriness. Moreover, TAN application moderately increased interatrial conduction time. TAN has been shown to be effective in reducing the inducibility of AF in an experimental model of AF. The antiarrhythmic effect is mainly due to prolongations of atrial post-repolarization refractoriness and a moderate increase in interatrial conduction time. Copyright © 2016. Published by Elsevier Masson SAS.

Laser Processing for Interconnect Technology

DTIC Science & Technology

1992-02-27

2.1 0.0002 - available in film ethylene- - insoluble propylene (FEP) Perfluoroalkoxy ( PFA ) Teflon AF Amorphous DuPont 1.9 0.0002 - soluble form...t,) where the pulse is sorption coefficient, hv is the photon energy, and f is the a maximum at the surface at time t0. The distance marker fraction

40 CFR Table Hh-4 to Subpart Hh of... - Landfill Methane Oxidation Fractions

Code of Federal Regulations, 2014 CFR

2014-07-01

... gas sent off-site). If a single monitoring location is used to monitor volumetric flow and CH4... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Landfill Methane Oxidation Fractions... (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Municipal Solid Waste Landfills Pt...

A Bibliography of Selected Publications: Project Air Force, 5th Edition

DTIC Science & Technology

1989-05-01

Dyna - R-3028-AF. A Dynamic Retention Model for Air Force Officers: METRIC’s DL and and Pipeilne Variability. M. J. Carrillo. Theory and Estimates. G...Theorem and Dyna - and Support. METRIC’s Demand and Pipeline Variability. R-3255-AF. Aircraft Airframe Cost Estimating Relationships: N-2283/1-AF...U). 1970-1985. N-2409-AF. Tanker Splitting Across the SlOP Bomber Force R-3389-AF. Dyna -METRIC Version 4: Modeling Worldwide (U). Logistics Support of

Biochemical validity of imaging techniques (X-ray, MRI, and dGEMRIC) in degenerative disc disease of the human cervical spine-an in vivo study.

PubMed

Bostelmann, Richard; Bostelmann, Tamara; Nasaca, Adrian; Steiger, Hans Jakob; Zaucke, Frank; Schleich, Christoph

2017-02-01

On a molecular level, maturation or degeneration of human intervertebral disc is among others expressed by the content of glycosaminoglycans (GAGs). According to the degenerative status, the disc content can differ in nucleus pulposus (NP) and annulus fibrosus (AF), respectively. Research in this area was conducted mostly on postmortem samples. Although several radiological classification systems exist, none includes biochemical features. Therefore, we focused our in vivo study on a widely spread and less expensive imaging technique for the cervical spine and the correlation of radiological patterns to biochemical equivalents in the intervertebral discs. The aim of this pilot study was to (1) measure the GAG content in human cervical discs, (2) to investigate whether a topographic biochemical GAG pattern can be found, and (3) whether there is a correlation between imaging data (X-ray and magnetic resonance imaging [MRI] including delayed gadolinium-enhanced MRI of cartilage [dGEMRIC] as a special imaging technique of cartilage) and the biochemical data. We conducted a prospective experimental pilot study. Only non-responders to conservative therapy were included. All subjects were physically and neurologically examined, and they completed their questionnaires. Visual analogue scale neck and arm, Neck Disability Index score, radiological parameters (X-rays, MRI, dGEMRIC), and the content of GAG in the cervical disc were assessed. After surgical removal of 12 discs, 96 fractions of AF and NP were biochemically analyzed for the GAG content using dimethylmethylene blue assay. A quantitative pattern of GAGs in the human cervical disc was identified. There were (1) significantly (p<.001) higher values of GAGs (µg GAG/mg tissue) in the NP (169.9 SD 37.3) compared with the AF (132.4 SD 42.2), and (2) significantly (p<.005) higher values of GAGs in the posterior (right/left: 149.9/160.2) compared with the anterior (right/left: 112.0/120.2) part of the AF. Third, we found in dGEMRIC imaging a significantly (p<.008) different distribution of GAGs in the cervical disc (NP 1083.3 ms [SD 248.6], AF 925.9 ms [SD 137.6]). Finally, we found that grading of disc degeneration in X-ray and MRI was significantly correlated with neither AF- nor NP-GAG content. The GAG content in human cervical discs can be detected in vivo and is subject to a significantly (p<.05) region-specific pattern (AF vs. NP; anterior vs. posterior in the AF). Up to the levels of AF and NP, this is reproducible in MRI in dGEMRIC technique, but not in X-ray or standard MRI sequences. Potentially, the MRI in dGEMRIC technique can be used as a non-invasive in vivo indicator for disc degeneration in the cervical spine. Copyright © 2016 Elsevier Inc. All rights reserved.

Countercurrent flow of supercritical anti-solvent in the production of pure xanthophylls from Nannochloropsis oculata.

PubMed

Cho, Yueh-Cheng; Wang, Yuan-Chuen; Shieh, Chwen-Jen; Lin, Justin Chun-Te; Chang, Chieh-Ming J; Han, Esther

2012-08-10

This study examined pilot scaled elution chromatography coupled with supercritical anti-solvent precipitation (using countercurrent flow) in generating zeaxanthin-rich particulates from a micro-algal species. Ultrasonic agitated acetone extract subjected to column fractionation successfully yielded a fraction containing 349.4 mg/g of zeaxanthin with a recovery of 85%. Subsequently, supercritical anti-solvent (SAS) precipitation of the column fraction at 150 bar and 343 K produced submicron-sized particulates with a concentration of 845.5mg/g of zeaxanthin with a recovery of 90%. Experimental results from a two-factor response surface method SAS precipitation indicated that purity, mean size and morphology of the precipitates were significantly affected by the flow type configuration, feed flow rate and injection time. Copyright © 2012 Elsevier B.V. All rights reserved.

Automated system for on-line determination of dimethylarsinic and inorganic arsenic by hydride generation-atomic fluorescence spectrometry.

PubMed

Chaparro, L L; Ferrer, L; Cerdà, V; Leal, L O

2012-09-01

A multisyringe flow-injection approach has been coupled to hydride generation-atomic fluorescence spectrometry (HG-AFS) with UV photo-oxidation for dimethylarsinic (DMA), inorganic As and total As determination, depending on the pre-treatment given to the sample (extraction or digestion). The implementation of a UV lamp allows on-line photo-oxidation of DMA and the following arsenic detection, whereas a bypass leads the flow directly to the HG-AFS system, performing inorganic arsenic determination. DMA concentration is calculated by the difference of total inorganic arsenic and measurement of the photo-oxidation step. The detection limits for DMA and inorganic arsenic were 0.09 and 0.47 μg L(-1), respectively. The repeatability values accomplished were of 2.4 and 1.8%, whereas the injection frequencies were 24 and 28 injections per hour for DMA and inorganic arsenic, respectively. This method was validated by means of a solid reference material BCR-627 (muscle of tuna) with good agreement with the certified values. Satisfactory results for DMA and inorganic arsenic determination were obtained in several water matrices. The proposed method offers several advantages, such as increasing the sampling frequency, low detection limits and decreasing reagents and sample consumption, which leads to lower waste generation.

Small ICBM Area Narrowing Report. Volume 1. Hard Mobile Launcher in Random Movement Basing Mode

DTIC Science & Technology

1986-01-01

WHICH STATE INSTALLATION SERVICE ELIMINATED DE DOVER AIR FORCE BASE AF 4 DE REC AREA, FIRST ARMY ARMY 3 FL AVON PARK AIR FORCE RANGE AF 3 FL CAPE...PLANT NO. 47 AF 3 OH COLUMBUS DEF CONST SUPPLY CTR ARMY 4 OH COLUMBUS WEAPONS IND RES PLANT NAVY 3 OH EVANDALE PLANT NO. 36 AF 3 OH LIMA ARMY TANK...BLANK I I I I i I I I D-19 SENSITIVE FOR OFFICIAL USE ONLY 29I 331 J11 31 Alabam .._ _ . _ _ ............. _ . BAY MNETI ALLENTOW DE FUNII X0 LAN AT NO

Atrial fibrillation detection using an iPhone 4S.

PubMed

Lee, Jinseok; Reyes, Bersain A; McManus, David D; Maitas, Oscar; Mathias, Oscar; Chon, Ki H

2013-01-01

Atrial fibrillation (AF) affects three to five million Americans and is associated with significant morbidity and mortality. Existing methods to diagnose this paroxysmal arrhythmia are cumbersome and/or expensive. We hypothesized that an iPhone 4S can be used to detect AF based on its ability to record a pulsatile photoplethysmogram signal from a fingertip using the built-in camera lens. To investigate the capability of the iPhone 4S for AF detection, we first used two databases, the MIT-BIH AF and normal sinus rhythm (NSR) to derive discriminatory threshold values between two rhythms. Both databases include RR time series originating from 250 Hz sampled ECG recordings. We rescaled the RR time series to 30 Hz so that the RR time series resolution is 1/30 (s) which is equivalent to the resolution from an iPhone 4S. We investigated three statistical methods consisting of the root mean square of successive differences (RMSSD), the Shannon entropy (ShE) and the sample entropy (SampE), which have been proved to be useful tools for AF assessment. Using 64-beat segments from the MIT-BIH databases, we found the beat-to-beat accuracy value of 0.9405, 0.9300, and 0.9614 for RMSSD, ShE, and SampE, respectively. Using an iPhone 4S, we collected 2-min pulsatile time series from 25 prospectively recruited subjects with AF pre- and postelectrical cardioversion. Using derived threshold values of RMSSD, ShE and SampE from the MIT-BIH databases, we found the beat-to-beat accuracy of 0.9844, 0.8494, and 0.9522, respectively. It should be recognized that for clinical applications, the most relevant objective is to detect the presence of AF in the data. Using this criterion, we achieved an accuracy of 100% for both the MIT-BIH AF and iPhone 4S databases.

Evaluation of the Crack Growth Gage Concept as an Individual Aircraft Tracking Device. Volume 2

DTIC Science & Technology

1983-09-01

102 A4. Crack Growth Data for Carrier AF-48 104 A5. Crack Growth Data for Carrier AF-29 106 A6. Crack Growth Data for Carrier AF-49 108 A7. Crack...BNr..76 X 3.0 _RIH.2 X RHB /BI=.eB 02.0 -I o _ . UNIFORM THICKNESS 1.0 --__ - -a---S•j.A- , 0.0 - 0.0 0.2 0.4 0.6 0.8, 1.0 2X/BN 4 Figure 9 Effect of

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

PubMed

Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

2008-05-01

Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

The Long and Short Term Impact of Elevated Body Mass Index on Risk of New Atrial Fibrillation in the Women’s Health Study

PubMed Central

Tedrow, Usha B; Conen, David; Ridker, Paul M; Cook, Nancy R; Koplan, Bruce A; Manson, JoAnn E; Buring, Julie E; Albert, Christine M

2010-01-01

Objectives To characterize the relationship between changes in body mass index (BMI) and incident atrial fibrillation (AF) in a large cohort of women. Background Obesity and AF are increasing public health problems. The importance of dynamic obesity-associated AF risk is uncertain, and mediators are not well characterized. Methods Cases of AF were confirmed by medical record review in 34,309 participants in the Women’s Health Study. Baseline and updated measures of BMI were obtained from periodic questionnaires. Results Over 12.9 +/− 1.9 years of follow-up, 834 AF events were confirmed. BMI was linearly associated with AF risk, with a 4.7% (95% CI 3.4, 6.1, p<0.0001) increase in risk with each kg/m2. Adjustment for inflammatory markers minimally attenuated this risk. When updated measures of BMI were utilized to estimate dynamic risk, overweight (HR 1.22 95%CI 1.02, 1.45, p=0.03) and obesity (HR 1.65 95%CI 1.36, 2.00, p<0.0001) were associated with adjusted short term elevations in AF risk. Participants becoming obese during the first 60 months had a 41% adjusted increase in risk of developing AF (p=0.02) compared to those maintaining BMI <30 kg/m2. The prevalence of overweight and obesity increased over time. The adjusted proportion of incident AF attributable to short term elevations in BMI was substantial (18.3%). Conclusions In this population of apparently healthy women, BMI was associated with short and long term elevations in AF risk, accounting for a large proportion of incident AF independent of traditional risk factors. A strategy of weight control may reduce the increasing incidence of AF. PMID:20488302

Association of left ventricular late gadolinium enhancement with left atrial low voltage areas in patients with atrial fibrillation.

PubMed

Stegmann, Clara; Jahnke, Cosima; Paetsch, Ingo; Hilbert, Sebastian; Arya, Arash; Bollmann, Andreas; Hindricks, Gerhard; Sommer, Philipp

2018-02-06

Presence of late gadolinium enhancement (LGE) is related to adverse cardiovascular outcome. Many patients suffering from atrial fibrillation (AF) undergo cardiovascular magnetic resonance (CMR) imaging prior to ablation. Since quantification of atrial fibrosis still lacks reproducibility, we sought to investigate risk factors for the presence of left ventricular (LV)-LGE and a possible correlation between ventricular fibrosis as defined by positive LGE and pathological atrial voltage maps evaluated by 3D mapping systems. Between May 2015 and January 2017, 241 patients with AF (73% persistent AF, 71% male, mean age 62.8 ± 10.1 years, Redo procedure in 24%, AF history 4.5 ± 5.2 years) underwent CMR including LV LGE prior to pulmonary vein (PV) isolation at Heart Center Leipzig. Depending on CMR results, two groups were separated: 'LV-LGE negative' (Group A, n = 197, 82%) and 'LV-LGE positive' (Group B, n = 44, 18%). To identify low voltage areas (LVA), a 3D electro-anatomic map was created during PV isolation. Multivariate analysis revealed male gender [odds ratio (OR) 7.6, 95% confidence interval (95% CI) 2.4-23.9, P = 0.001] and an increased CHA2DS2VASc Score (OR 1.6, 95% CI 1.2-2.2, P = 0.004) as significantly associated with LV-LGE. Impaired left ventricular ejection fraction, LV dilatation, larger LA size and, enlarged septum diameter occurred significantly more often in the 'LGE positive' group. Low voltage areas were detected in 83 patients overall (34%): Group A: n = 64/197 (33%), Group B: n = 19/44 (43%) (P = 0.177). Male gender and high CHA2DS2VASc Score are significantly associated with presence of LV-LGE, but LV-LGE is not associated with left atrial LVA. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

Pulmonary Vein Isolation Compared to Rate Control in Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

PubMed

Vaidya, Kaivan; Arnott, Clare; Russell, Anne; Masson, Philip; Sy, Raymond W; Patel, Sanjay

2015-08-01

Atrial fibrillation (AF) often coexists with congestive cardiac failure (CCF), with multiple treatment options available. Systematic review and meta-analysis of randomised control trials (RCT) comparing pulmonary vein isolation (PVI), pharmacological rate control, and atrioventricular junction ablation with pacemaker insertion (AVJAP) for AF, with a subgroup analysis in patients with CCF. We analysed changes in left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, six-minute walk distance (6MWD), treadmill exercise time, and treatment complications. Results were expressed as weighted mean differences (WMD) with 95% Confidence-Intervals (95%CI). We included seven RCT (425 participants). PVI was associated with a greater increase in LVEF (WMD+6.5%, 95%CI:+0.6to+12.5) and decrease in MLHFQ score (WMD-11.0, 95%CI:-2.6to-19.4) than pharmacological rate control in patients with CCF. PVI was also associated with a greater increase in LVEF (WMD+9.0%, 95%CI:+6.3to+11.7) and 6MWD (WMD+55.0metres, 95%CI:+34.9to+75.1), and decrease in MLHFQ score (WMD-22.0, 95%CI:-17.0to-27.0), compared to AVJAP in patients with CCF. Irrespective of cardiac function, pharmacological rate control had similar effects to AVJAP on LVEF (WMD+0.6%, 95%CI:-8.3to+9.4) and treadmill exercise time (WMD+0.5minutes, 95%CI:-0.4to+1.3). Our results support the clinical implementation of PVI over AVJAP or pharmacological rate control in AF patients with CCF, who may or may not have already trialled pharmacological rhythm control. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Discharge flow of a granular media from a silo: effect of the packing fraction and of the hopper angle

NASA Astrophysics Data System (ADS)

Benyamine, Mebirika; Aussillous, Pascale; Dalloz-Dubrujeaud, Blanche

2017-06-01

Silos are widely used in the industry. While empirical predictions of the flow rate, based on scaling laws, have existed for more than a century (Hagen 1852, translated in [1] - Beverloo et al. [2]), recent advances have be made on the understanding of the control parameters of the flow. In particular, using continuous modeling together with a mu(I) granular rheology seem to be successful in predicting the flow rate for large numbers of beads at the aperture (Staron et al.[3], [4]). Moreover Janda et al.[5] have shown that the packing fraction at the outlet plays an important role when the number of beads at the apeture decreases. Based on these considerations, we have studied experimentally the discharge flow of a granular media from a rectangular silo. We have varied two main parameters: the angle of the hopper, and the bulk packing fraction of the granular material by using bidisperse mixtures. We propose a simple physical model to describe the effect of these parameters, considering a continuous granular media with a dilatancy law at the outlet. This model predicts well the dependance of the flow rate on the hopper angle as well as the dependance of the flow rate on the fine mass fraction of a bidisperse mixture.

Improving atrial fibrillation detection in patients with implantable cardiac devices by means of a remote monitoring and management application.

PubMed

Zoppo, Franco; Facchin, Domenico; Molon, Giulio; Zanotto, Gabriele; Catanzariti, Domenico; Rossillo, Antonio; Baccillieri, Maria Stella; Menard, Cecile; Comisso, Jennifer; Gentili, Alessandra; Grammatico, Andrea; Bertaglia, Emanuele; Proclemer, Alessandro

2014-12-01

Atrial fibrillation (AF) is common in patients with cardiac implantable electronic devices (CIED) and has been associated with an increased stroke risk. The aim of our project was to assess the clinical value of a web-based application, Discovery Link AFinder, in improving AF detection in CIED patients. Seven Italian hospitals performed an observational study consisting of four phases. During phase 1, expert nurses and cardiologists prospectively followed-up CIED patients via in-hospital examinations and remote monitoring, and classified clinically relevant events, particularly AF occurrence. During phase 2, Discovery Link AFinder was exploited to identify patients who had suffered AF in the previous 12 months through the systematic scanning of device data remote transmissions. Phases 3 and 4 were repetitions of phases 1 and 2, respectively, and were implemented 6 months after the previous phases. A total of 472 consecutive patients were included in phase 1; AF occurred in 170 patients, 61 of whom were identified as new AF patients. Evidence of AF during this phase prompted prescription of oral anticoagulation (OAC) therapy in 30 patients. In phase 2, AFinder uncovered new AF, unidentified in phase 1, in 54 patients and prompted implementation of OAC therapy in 11 patients. During phase 3, 30 new AF patients were identified by means of remote monitoring, while during phase 4, a further three AF patients were identified by AFinder only. The AFinder web-based software, applied on top of standard in-hospital and remote monitoring, improved AF detection and enabled OAC treatment to be undertaken. ©2014 Wiley Periodicals, Inc.

Systems Biology Graphical Notation: Activity Flow language Level 1 Version 1.2.

PubMed

Mi, Huaiyu; Schreiber, Falk; Moodie, Stuart; Czauderna, Tobias; Demir, Emek; Haw, Robin; Luna, Augustin; Le Novère, Nicolas; Sorokin, Anatoly; Villéger, Alice

2015-09-04

The Systems Biological Graphical Notation (SBGN) is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD), Entity Relationship (ER) and Activity Flow (AF), allow for the representation of different aspects of biological and biochemical systems at different levels of detail. The SBGN Activity Flow language represents the influences of activities among various entities within a network. Unlike SBGN PD and ER that focus on the entities and their relationships with others, SBGN AF puts the emphasis on the functions (or activities) performed by the entities, and their effects to the functions of the same or other entities. The nodes (elements) describe the biological activities of the entities, such as protein kinase activity, binding activity or receptor activity, which can be easily mapped to Gene Ontology molecular function terms. The edges (connections) provide descriptions of relationships (or influences) between the activities, e.g., positive influence and negative influence. Among all three languages of SBGN, AF is the closest to signaling pathways in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

Elevated admission N-terminal pro-brain natriuretic peptide level predicts the development of atrial fibrillation in general surgical intensive care unit patients.

PubMed

Chokengarmwong, Nalin; Yeh, Daniel Dante; Chang, Yuchiao; Ortiz, Luis Alfonso; Kaafarani, Haytham M A; Fagenholz, Peter; King, David R; DeMoya, Marc; Butler, Kathryn; Lee, Jarone; Velmahos, George; Januzzi, James Louis; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent

2017-09-01

New onset atrial fibrillation (AF) in critically ill surgical patients is associated with significant morbidity and increased mortality. N-terminal pro-B type natriuretic peptide (NT-proBNP) is released by cardiomyocytes in response to stress and may predict AF development after surgery. We hypothesized that elevated NT-proBNP level at surgical intensive care unit (ICU) admission predicts AF development in a general surgical and trauma population. From July to October 2015, NT-proBNP concentrations were measured at ICU admission. Abnormal NT-proBNP concentrations were defined by age-adjusted cut-offs. We examined the relationship between the development of AF and demographics, clinical variables, and NT-proBNP level using univariate analysis and a multivariable logistic regression model. Three hundred eighty-seven subjects were included in the cohort, none of whom were in AF at ICU admission. The median age was 63 years (52-73 years), and 40.3% were women. The risk of developing AF was higher for abnormal versus normal NT-proBNP (22% vs. 4%; p < 0.0001). Using optimal derived cutoffs (regardless of age), the risk of developing AF was 2% for NT-proBNP less than 600 ng/L, 15% for NT-proBNP of 600 ng/L to 1,999 ng/L, and 27% for NT-proBNP of 2,000 ng/L or greater. Multiple logistic regression analysis identified three independent predictors for new-onset AF: age, older than 70 years (odds ratio [OR], 3.7, 95% confidence interval [CI], 1.5-9.3), history of AF (OR, 25.3; 95% CI, 9.6-67.0), and NT-proBNP of 600 or greater (OR, 4.3; 95% CI, 1.3-14.2). When none or only one predictor was present, AF incidence was less than 1%. When all three predictors were present, AF incidence was 66%. For subjects 70 years or older but no history of AF, AF incidence was 12.8% when NT-proBNP was 600 or greater compared with 0% when NT-proBNP was less than 600. For subjects younger than 70 years with a history of AF, AF incidence was 44.4% when NT-proBNP was 600 or higher compared to 0% when NT-proBNP was less than 600. Elevated NT-proBNP at ICU admission in general surgical and trauma patients is predictive of AF development in the first 3 ICU days. Addition of NT-proBNP measurement to known risk factors can improve predictive power and identify patients who might potentially benefit from evidence-based prophylactic treatment for AF.

Relativistically Skewed Iron Emission and Disk Reflection in Galactic Microquasar XTE J1748-288

NASA Technical Reports Server (NTRS)

Miller, J. M.; Fox, D. W.; DiMatteo, T.; Wijnands, R.; Belloni, T.; Kouveliotou, C.; Lewin, W. H. G.

2000-01-01

We report evidence for an Fe K-alpha fluorescence line feature in the Very High, High, and Low state X-ray spectra of the galactic microquasar XTE JI748-288 during its June 1998 outburst. Spectral analyses were made on observations spread across the outburst, gathered with the Rossi X-ray Timing Explorer. Gaussian line. disk emission line, relativistic disk emission line, and disk reflection models are fit to the data. In the Very High State, the line profile is strongly redshifted and consistent with emission from the innermost radius of a maximally rotating Kerr black hole, 1.235 R(sub g). The line profile is less redshifted in the High State, but increasingly prominent. In the Low State, the line profile is very strong and centered af approx. 6.7 keV; disk line emission models constrain the inner edge of the disk to fluctuate between approx.20 and approx.59 R(sub g). We trace the disk reflection fraction across the full outburst of this source, and find well-constrained fractions below those observed in AGN in the Very High and High States, but consistent with other galactic sources in the Low State. We discuss the possible implications for black hole X-ray binary system dynamics and accretion flow geometry.

Amniotic fluid stem cells provide considerable advantages in epidermal regeneration: B7H4 creates a moderate inflammation microenvironment to promote wound repair.

PubMed

Sun, Qing; Li, Fang; Li, Hong; Chen, Rui-Hua; Gu, Yan-Zheng; Chen, Ying; Liang, Han-Si; You, Xin-Ran; Ding, Si-Si; Gao, Ling; Wang, Yun-Liang; Qin, Ming-De; Zhang, Xue-Guang

2015-06-23

The current treatments for severe skin injury all involve skin grafting. However, there is a worldwide shortage of donor skin tissue. In this study, we examined the advantages of using human amniotic fluid stem (hAFS) cells in skin wound healing. In vitro, hAFS cells differentiate into keratinocytes (termed hAFS-K). Like keratinocytes, hAFS-K cells express the markers K5, K14, K10 and involucrin; display typical cellular structure, including a tonofibril-rich cytoplasm; and construct a completely pluristratified epithelium in 3D culture. In vivo, in a mouse excisional wound model, GFP-positive hAFS cells participate in wound repair. Co-localization of GFP/K14 and GFP/K10 in the repaired epidermis demonstrated that hAFS cells can differentiate into keratinocytes. Real-time PCR results confirmed that hAFS cells can initiate and promote early-stage repair of skin damage. During wound repair, hAFS cells did not directly secrete repair-related factors, such as bFGF, VEGF, CXCL12, TGF-β1 and KGF, and provided a moderate inflammation reaction with lower expression of IL-1β, IL-6, TNF-α, Cox2 and Mac3. In hAFS cells, the negative co-stimulatory molecule B7H4 regulates low immunogenicity, which can provide a modest inflammatory reaction microenvironment for wound repair. Furthermore, with their uniquely high proliferation rate, hAFS cells offer a promising alternative for epidermal regeneration.

Synthesis and isomerization of acridine substituted 1,3-thiazolidin-4-ones and 4-oxo-1,3-thiazolidin-5-ylidene acetates. An experimental and computational study

NASA Astrophysics Data System (ADS)

Bečka, Michal; Vilková, Mária; Šoral, Michal; Potočňák, Ivan; Breza, Martin; Béres, Tibor; Imrich, Ján

2018-02-01

Acridine thiosemicarbazones 3a-g, obtained through a two-step reaction between aromatic isothiocyanates and hydrazine followed by the treatment with acridin-9-carbaldehyde, in reaction with bifunctional reagents; methyl bromoacetate (MBA) and diethyl acetylenedicarboxylate (DEAD) afforded acridin-thiazolidinone derivatives 4a-g and 7a-f and not their regioisomers 6a-g and 9a-f. Derivatives 4a-g and 7a-f exhibit ZC2N6EN7C8 configuration. Upon standing in DMSO-d6 the thiazolidinones 4a-g and 7a-f spontaneously isomerized into ZC2N6ZN7C8 isomers 5a-g and 8a-f to give a mixture of the both stereoisomers. All compounds were fully characterized by multinuclear NMR, mass spectrometry (MS) and X-ray crystal structure of 4b is also described. X-ray diffraction study revealed that the representative compound 4b crystallized in the monoclinic crystal system with the C2/c space group and Z = 4. Intramolecular C1‧sbnd H1‧⋯N-7 hydrogen bond between the acridine proton H-1‧ and nitrogen N-7 of linker existed. This hydrogen bond is responsible for the E isomerism on C-8 atom which was observed in the NMR experiments. Quantum-chemical calculations and NOESY experiments confirmed ZC2N6ZN7C8 configuration of the transformed stereoisomers 5a-g and 8a-f.

Purification and characterization of a novel endo-β-1,4-glucanases , AfEG22, from the giant snail, Achatina fulica frussac.

PubMed

Teng, Yigang; Yin, Qiuyu; ding, Ming; Zhao, Fukun

2010-10-01

In this study, we confirmed that at least three endo-β-1,4-glucanases existed in the digestive juice of the giant snail, Achatina fulica ferussac, by Congo red staining assay. One of these enzymes, a novel endo-β-1,4-glucanase (AfEG22), was purified 29.5-fold by gel filtration, anion exchange, and hydrophobic interaction chromatography. The carboxymethyl cellulose (CMC) hydrolytic activity of the purified enzyme was 12.3 U/mg protein. The molecular mass of AfEG22 was 22081 Da determined by MALDI-TOF. N-terminal amino acid sequencing revealed a sequence of EQRCTNQGGILKYYNT, which did not have significant homology with any proteins in BLAST database. The optimal pH and temperature for hydrolytic activity toward CMC were pH 4.0 and 50°C, respectively. AfEG22 was stable between pH 3.0 and pH 12.0 when incubated at 4°C for 3 h or at 37°C for 1 h. The enzyme remained more than 80% activity between pH 4.5 and pH 7.0 after incubation at 50°C for 1 h. AfEG22 possessed excellent thermostability as more than 70% activity was remained after incubation at 60°C for 3 h. Substrate specific analysis revealed that AfEG22 was a typical endo-β-1,4-glucanase. This is the first time to report a novel endo-β-1,4-glucanase with high stability from the digestive juice of A. fulica.

Dynamics of Dengue Virus (DENV)–Specific B Cells in the Response to DENV Serotype 1 Infections, Using Flow Cytometry With Labeled Virions

PubMed Central

Woda, Marcia; Friberg, Heather; Currier, Jeffrey R.; Srikiatkhachorn, Anon; Macareo, Louis R.; Green, Sharone; Jarman, Richard G.; Rothman, Alan L.; Mathew, Anuja

2016-01-01

Background. The development of reagents to identify and characterize antigen-specific B cells has been challenging. Methods. We recently developed Alexa Fluor–labeled dengue viruses (AF DENVs) to characterize antigen-specific B cells in the peripheral blood of DENV-immune individuals. Results. In this study, we used AF DENV serotype 1 (AF DENV-1) together with AF DENV-2 on peripheral blood mononuclear cells (PBMCs) from children in Thailand with acute primary or secondary DENV-1 infections to analyze the phenotypes of antigen-specific B cells that reflected their exposure or clinical diagnosis. DENV serotype-specific and cross-reactive B cells were identified in PBMCs from all subjects. Frequencies of AF DENV+ class-switched memory B cells (IgD−CD27+ CD19+ cells) reached up to 8% during acute infection and early convalescence. AF DENV–labeled B cells expressed high levels of CD27 and CD38 during acute infection, characteristic of plasmablasts, and transitioned into memory B cells (CD38−CD27+) at the early convalescent time point. There was higher activation of memory B cells early during acute secondary infection, suggesting reactivation from a previous DENV infection. Conclusions. AF DENVs reveal changes in the phenotype of DENV serotype–specific and cross-reactive B cells during and after natural DENV infection and could be useful in analysis of the response to DENV vaccination. PMID:27443614

Investigation of the Effects of Cathode Flow Fraction and Position on the Performance and Operation of the High Voltage Hall Accelerator

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Huang, Wensheng; Haag, Thomas

2014-01-01

The National Aeronautics and Space Administration (NASA) Science Mission Directorate In- Space Propulsion Technology office is sponsoring NASA Glenn Research Center (GRC) to develop a 4 kW-class Hall thruster propulsion system for implementation in NASA science missions. Tests were performed within NASA GRC Vacuum Facility 5 at background pressure levels that were six times lower than what has previously been attained in other vacuum facilities. A study was conducted to assess the impact of varying the cathode-to-anode flow fraction and cathode position on the performance and operational characteristics of the High Voltage Hall Accelerator (HiVHAc) thruster. In addition, the impact of injecting additional xenon propellant in the vicinity of the cathode was also assessed. Cathode-to-anode flow fraction sensitivity tests were performed for power levels between 1.0 and 3.9 kW. It was found that varying the cathode flow fraction from 5 to approximately 10% of the anode flow resulted in the cathode-to-ground voltage becoming more positive. For an operating condition of 3.8 kW and 500 V, varying the cathode position from a distance of closest approach to 600 mm away did not result in any substantial variation in thrust but resulted in the cathode-to-ground changing from -17 to -4 V. The change in the cathode-to-ground voltage along with visual observations indicated a change in how the cathode plume was coupling to the thruster discharge. Finally, the injection of secondary xenon flow in the vicinity of the cathode had an impact similar to increasing the cathode-to-anode flow fraction, where the cathode-to-ground voltage became more positive and discharge current and thrust increased slightly. Future tests of the HiVHAc thruster are planned with a centrally mounted cathode in order to further assess the impact of cathode position on thruster performance.

MRI of the wrist at 7 tesla using an eight-channel array coil combined with parallel imaging: preliminary results.

PubMed

Chang, Gregory; Friedrich, Klaus M; Wang, Ligong; Vieira, Renata L R; Schweitzer, Mark E; Recht, Michael P; Wiggins, Graham C; Regatte, Ravinder R

2010-03-01

To determine the feasibility of performing MRI of the wrist at 7 Tesla (T) with parallel imaging and to evaluate how acceleration factors (AF) affect signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and image quality. This study had institutional review board approval. A four-transmit eight-receive channel array coil was constructed in-house. Nine healthy subjects were scanned on a 7T whole-body MR scanner. Coronal and axial images of cartilage and trabecular bone micro-architecture (3D-Fast Low Angle Shot (FLASH) with and without fat suppression, repetition time/echo time = 20 ms/4.5 ms, flip angle = 10 degrees , 0.169-0.195 x 0.169-0.195 mm, 0.5-1 mm slice thickness) were obtained with AF 1, 2, 3, 4. T1-weighted fast spin-echo (FSE), proton density-weighted FSE, and multiple-echo data image combination (MEDIC) sequences were also performed. SNR and CNR were measured. Three musculoskeletal radiologists rated image quality. Linear correlation analysis and paired t-tests were performed. At higher AF, SNR and CNR decreased linearly for cartilage, muscle, and trabecular bone (r < -0.98). At AF 4, reductions in SNR/CNR were:52%/60% (cartilage), 72%/63% (muscle), 45%/50% (trabecular bone). Radiologists scored images with AF 1 and 2 as near-excellent, AF 3 as good-to-excellent (P = 0.075), and AF 4 as average-to-good (P = 0.11). It is feasible to perform high resolution 7T MRI of the wrist with parallel imaging. SNR and CNR decrease with higher AF, but image quality remains above-average.

Functional characterization of GH7 endo-1,4-β-glucanase from Aspergillus fumigatus and its potential industrial application.

PubMed

Bernardi, Aline Vianna; de Gouvêa, Paula Fagundes; Gerolamo, Luis Eduardo; Yonamine, Deborah Kimie; de Lourdes de Lima Balico, Laís; Uyemura, Sergio Akira; Dinamarco, Taisa Magnani

2018-04-30

A gene encoding an endo-1,4-β-glucanase (Afu6g01800) from A. fumigatus was cloned into the vector pET-28a(+) and expressed in the E. coli strain RosettaTM (DE3) pLysS. Sequence analysis indicated that the enzyme Af-EGL7 belonged to the GH7 family. The gene Af-egl7 encoded a protein comprising 460 amino acids, with a CBM1 domain at residues 424-460 and molecular mass of 52 kDa, as estimated by SDS-PAGE. This enzyme was optimally active at pH and temperatures ranging from 4.5 to 5.5 and from 40 to 60 °C, respectively. Mn 2+ addition significantly enhanced the Af-EGL7 cellulase activity by 233%, whereas SDS addition fully inhibited this activity. Higher activity was observed toward β-glucan than toward xyloglucan and CM-Cellulose, suggesting that the enzyme corresponds to a β-1,3-1,4-glucanase. qRT-PCR in different culture media helped to establish the time-course expression profile. Different polysaccharides induced the gene Af-egl7 in a time-dependent manner; in the particular case of the substrate sugarcane exploded bagasse (SEB), Af-egl7 was induced 2500-fold. Upon addition to a commercial cellulase cocktail, Af-EGL7 significantly improved SEB saccharification, which suggested that the enzyme Af-EGL7 had great potential to hydrolyze complex biomass. From a biotechnological point of view, A. fumigatus Af-EGL7 is a promising candidate to enhance enzyme cocktails used in biorefineries such as consolidated bioprocessing. Copyright © 2018 Elsevier Inc. All rights reserved.

Real-time dominant frequency mapping and ablation of dominant frequency sites in atrial fibrillation with left-to-right frequency gradients predicts long-term maintenance of sinus rhythm.

PubMed

Atienza, Felipe; Almendral, Jesús; Jalife, José; Zlochiver, Sharon; Ploutz-Snyder, Robert; Torrecilla, Esteban G; Arenal, Angel; Kalifa, Jérôme; Fernández-Avilés, Francisco; Berenfeld, Omer

2009-01-01

Spectral analysis identifies localized sites of high-frequency activity during atrial fibrillation (AF). This study sought to determine the effectiveness of using real-time dominant frequency (DF) mapping for radiofrequency ablation of maximal DF (DFmax) sites and elimination of left-to-right frequency gradients in the long-term maintenance of sinus rhythm (SR) in AF patients. DF mapping was performed in 50 patients during ongoing AF (32 paroxysmal, 18 persistent), acquiring a mean of 117 +/- 38 points. Ablation was performed targeting DFmax sites, followed by circumferential pulmonary vein isolation. Ablation significantly reduced DFs (Hz) in the LA (7.9 +/- 1.4 vs. 5.7 +/- 1.3, P <.001), coronary sinus (CS) (5.7 +/- 1.1 vs. 5.3 +/- 1.2, P = .006), and RA (6.3 +/- 1.4 vs. 5.4 +/- 1.3, P <.001) abolishing baseline left-to-right atrial DF gradient (1.7 +/- 1.7 vs. 0.2 +/- 0.9; P <.001). Only a significant reduction in DFs in all chambers with a loss of the left-to-right atrial gradient after ablation was associated with a higher probability of long-term SR maintenance in both paroxysmal and persistent AF patients. After a mean follow-up of 9.3 +/- 5.4 months, 88% of paroxysmal and 56% of persistent AF patients were free of AF (P = .02). Ablation of DFmax sites was associated with a higher probability of remaining both free of arrhythmias (78% vs. 20%; P = .001) and free of AF (88% vs. 30%; P <.001). Radiofrequency ablation leading to elimination of LA-to-RA frequency gradients predicts long-term SR maintenance in AF patients.

Systolic MOLLI T1 mapping with heart-rate-dependent pulse sequence sampling scheme is feasible in patients with atrial fibrillation.

PubMed

Zhao, Lei; Li, Songnan; Ma, Xiaohai; Greiser, Andreas; Zhang, Tianjing; An, Jing; Bai, Rong; Dong, Jianzeng; Fan, Zhanming

2016-03-15

T1 mapping enables assessment of myocardial characteristics. As the most common type of arrhythmia, atrial fibrillation (AF) is often accompanied by a variety of cardiac pathologies, whereby the irregular and usually rapid ventricle rate of AF may cause inaccurate T1 estimation due to mis-triggering and inadequate magnetization recovery. We hypothesized that systolic T1 mapping with a heart-rate-dependent (HRD) pulse sequence scheme may overcome this issue. 30 patients with AF and 13 healthy volunteers were enrolled and underwent cardiovascular magnetic resonance (CMR) at 3 T. CMR was repeated for 3 patients after electric cardioversion and for 2 volunteers after lowering heart rate (HR). A Modified Look-Locker Inversion Recovery (MOLLI) sequence was acquired before and 15 min after administration of 0.1 mmol/kg gadopentetate dimeglumine. For AF patients, both the fixed 5(3)3/4(1)3(1)2 and the HRD sampling scheme were performed at diastole and systole, respectively. The HRD pulse sequence sampling scheme was 5(n)3/4(n)3(n)2, where n was determined by the heart rate to ensure adequate magnetization recovery. Image quality of T1 maps was assessed. T1 times were measured in myocardium and blood. Extracellular volume fraction (ECV) was calculated. In volunteers with repeated T1 mapping, the myocardial native T1 and ECV generated from the 1st fixed sampling scheme were smaller than from the 1st HRD and 2nd fixed sampling scheme. In healthy volunteers, the overall native T1 times and ECV of the left ventricle (LV) in diastolic T1 maps were greater than in systolic T1 maps (P < 0.01, P < 0.05). In the 3 AF patients that had received electrical cardioversion therapy, the myocardial native T1 times and ECV generated from the fixed sampling scheme were smaller than in the 1st and 2nd HRD sampling scheme (all P < 0.05). In patients with AF (HR: 88 ± 20 bpm, HR fluctuation: 12 ± 9 bpm), more T1 maps with artifact were found in diastole than in systole (P < 0.01). The overall native T1 times and ECV of the left ventricle (LV) in diastolic T1 maps were greater than systolic T1 maps, either with fixed or HRD sampling scheme (all P < 0.05). Systolic MOLLI T1 mapping with heart-rate-dependent pulse sequence scheme can improve image quality and avoid T1 underestimation. It is feasible and with further validation may extend clinical applicability of T1 mapping to patients with atrial fibrillation.

[Electrophysiological findings and ablation strategies in patients with atrial tachyarrhythmias after left atrial circumferential ablation in the treatment of atrial fibrillation].

PubMed

Chen, Ming-long; Yang, Bing; Xu, Dong-jie; Zou, Jian-gang; Shan, Qi-jun; Chen, Chun; Chen, Hong-wu; Li, Wen-qi; Cao, Ke-jiang

2007-02-01

To report the electrophysiological findings and the ablation strategies in patients with atrial tachyarrhythmias (ATAs) or atrial fibrillation (AF) recurrence after left atrial circumferential ablation (LACA) in the treatment of AF. 91 patients with AF had LACA procedure from April 2004 to May 2006, 19 of which accepted the second ablation procedure due to ATAs or AF recurrence. In all the 19 patients [17 male, 2 female, age 25 - 65 (53 +/- 12) years], 11 presented with paroxysmal AF before the first ablation procedure, 2 with persistent AF and 6 with permanent AF. Pulmonary vein potentials (PVP) were investigated in both sides in all the patients. Delayed PVP was identified inside the left circular line in 5 patients, in the right in 1 and both in 2 during sinus rhythm. "Gap" conduction was found and successfully closed guided by circular mapping catheter. In 3 cases, irregular left atrial tachycardia was caused by fibrillation rhythm inside the left ring via decremental "gap" conduction. Reisolation was done successfully again guided by 3-D mapping and made the left atrium in sinus rhythm but the fibrillation rhythm was still inside the left ring. Pulmonary vein tachycardia with 1:1 conduction to the left atrium presented in one case and reisolation stopped the tachycardia. No PVP was discovered in both sides in 4 patients but other tachycardias could be induced, including two right atrial scar related tachycardias, two supraventricular tachycardias mediated by concealed accessory pathway, one cavo-tricuspid isthmus dependent atrial flutter and one focal atrial tachycardia near the coronary sinus ostium. All the tachycardias in these 4 patients were successfully ablated with the help of routine and 3-D mapping techniques. In the rest 3, which were in AF rhythm, LACA was successfully done again. After a mean follow-up of 4 - 26 (11.5 +/- 8.5) months, 16 patients were symptom free without anti-arrhythmic drug therapy; 1 of them had frequent palpitation attack with Holter recording of atrial premature contractions; 2 of them with permanent AF became paroxysmal in one, and still in AF in the other. Reconduction between the left atrium and the pulmonary veins is the dominant factor for post-LACA ATAs and AF recurrence. Other forms of atrial tachycardias or supraventricular tachycardias may coexist with AF or sometimes trigger AF. LACA can not sufficiently modify AF substrate in some permanent AF patients.

Clinical Characteristics, Management, and Outcomes of Japanese Patients Hospitalized for Heart Failure With Preserved Ejection Fraction　- A Report From the Japanese Heart Failure Syndrome With Preserved Ejection Fraction (JASPER) Registry.

PubMed

Nagai, Toshiyuki; Yoshikawa, Tsutomu; Saito, Yoshihiko; Takeishi, Yasuchika; Yamamoto, Kazuhiro; Ogawa, Hisao; Anzai, Toshihisa

2018-05-25

Despite the specific characteristics of heart failure with preserved ejection fraction (HFpEF) having been demonstrated predominantly from registries in Western countries, important international differences exist in terms of patient characteristics, management and medical infrastructure between Western and Asian countries.Methods and Results:We performed nationwide registration of consecutive Japanese hospitalized HFpEF patients with left ventricular EF ≥50% from 15 sites between November 2012 and March 2015. Follow-up data were obtained up to 2 years post-discharge. A total of 535 patients were registered. The median age was 80 years and 50% were female. The most common comorbid conditions were hypertension (77%) and atrial fibrillation (AF: 62%), but body mass index was relatively low. In-hospital mortality rate was 1.3% and the median length of hospitalization was 16 days. By 2 years post-discharge, 40.8% of patients had all-cause death or HF hospitalization. Approximately one-half of deaths had a cardiac cause. Lower serum albumin on admission was one of the strongest independent determinants of worse clinical outcome. Japanese HFpEF patients were less obese, but had a substantially higher prevalence of AF and lower incidence of subsequent events compared with previous reports. Our findings indicated that specific preventative and therapeutic strategies focusing on AF and nutritional status might need to be considered for Japanese hospitalized patients with HFpEF.

Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial.

PubMed

1996-09-07

Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). However, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism. 1044 patients with AF and with at least one thromboembolic risk factor (congestive heart failure or left ventricular fractional shortening < or = 25%, previous thromboembolism, systolic blood pressure of more than 160 mm Hg at study enrollment, or being a woman aged over 75 years) were randomly assigned either a combination of low-intensity, fixed-dose warfarin (international normalised ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open-labelled. The mean INR during follow-up of patients taking combination therapy (n = 521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n = 523). During follow-up, 54% of INRs in patients taking combination therapy were 1.2-1.5 and 34% were less than 1.2. The trial was stopped after a mean, follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism (primary events) in patients given combination therapy (7.9% per year) was significantly higher than in those given adjusted-dose warfarin (1.9% per year) at an interim analysis (p < 0.0001), an absolute reduction of 6.0% per year (95% Cl 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p = 0.0007) and of primary event or vascular death (11.8% vs 6.4%, p = 0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups. Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients.

Effects of ventricular rate and regularity on the velocity and magnitude of left atrial appendage flow in atrial fibrillation

PubMed Central

Obel, O A; Luddington, L; Maarouf, N; Aytemir, K; Ekwall, C; Malik, M; Camm, A J

2005-01-01

Objective: To prospectively determine whether ventricular rate and regularity are significant determinants of the velocity and magnitude of left atrial appendage (LAA) flow. Design and patients: 12 patients with atrial fibrillation (AF), high degree atrioventricular block, and indwelling permanent pacemakers were studied. Setting: Cardiology department of a tertiary referral centre. Interventions: Pacing was triggered by an external programmable transcutaneous device. Patients were paced at 60, 120, and 150 beats/min in both regular and irregular rhythm. LAA flow velocity and magnitude were assessed with transoesophageal Doppler echocardiography. Main outcome measures: Peak and mean LAA inflow and outflow velocity, and time-velocity interval (TVI) of LAA flow. Results: Increasing ventricular rate was associated with significantly lower peak inflow (p < 0.01), peak outflow (p < 0.05), mean inflow (p < 0.01), and mean outflow (p < 0.05) velocities and with a lower TVI of LAA filling and emptying velocities (p < 0.01). This effect was noted at rates of 60 beats/min compared with both 120 and 150 beats/min. At a pacing rate of 120 beats/min there was a significantly higher total TVI when pacing at a regular than at an irregular rhythm (40.16 (14.6) cm v 30.74 (10.9) cm, p < 0.05). Conclusions: In this study, LAA filling velocities in patients in AF were significantly influenced by paced ventricular rate and to a much lesser extent ventricular rhythm. These results suggest that rapid ventricular rates may predispose to stasis in the LAA in AF. PMID:15894771

Interatrial block and interatrial septal thickness in patients with paroxysmal atrial fibrillation undergoing catheter ablation: Long-term follow-up study.

PubMed

Gul, Enes E; Pal, Raveen; Caldwell, Jane; Boles, Usama; Hopman, Wilma; Glover, Benedict; Michael, Kevin A; Redfearn, Damian; Simpson, Chris; Abdollah, Hoshiar; Baranchuk, Adrian

2017-07-01

Interatrial block (IAB) is a strong predictor of recurrence of atrial fibrillation (AF). IAB is a conduction delay through the Bachman region, which is located in the upper region of the interatrial space. During IAB, the impulse travels from the right atrium to the interatrial septum (IAS) and coronary sinus to finally reach the left atrium in a caudocranial direction. No relation between the presence of IAB and IAS thickness has been established yet. To determine whether a correlation exists between the degree of IAB and the thickness of the IAS and to determine whether IAS thickness predicts AF recurrence. Sixty-two patients with diagnosis of paroxysmal AF undergoing catheter ablation were enrolled. IAB was defined as P-wave duration ≥120 ms. IAS thickness was measured by cardiac computed tomography. Among 62 patients with paroxysmal AF, 45 patients (72%) were diagnosed with IAB. Advanced IAB was diagnosed in 24 patients (39%). Forty-seven patients were male. During a mean follow-up period of 49.8 ± 22 months (range 12-60 months), 32 patients (51%) developed AF recurrence. IAS thickness was similar in patients with and without IAB (4.5 ± 2.0 mm vs. 4.0 ± 1.4 mm; p = .45) and did not predict AF. Left atrial size was significantly enlarged in patients with IAB (40.9 ± 5.7 mm vs. 37.2 ± 4.0 mm; p = .03). Advanced IAB predicted AF recurrence after the ablation (OR: 3.34, CI: 1.12-9.93; p = .03). IAS thickness was not significantly correlated to IAB and did not predict AF recurrence. IAB as previously demonstrated was an independent predictor of AF recurrence. © 2016 Wiley Periodicals, Inc.

Effect of kumquat (Fortunella crassifolia) pericarp on natural killer cell activity in vitro and in vivo.

PubMed

Nagahama, Kiyoko; Eto, Nozomu; Shimojo, Tomofumi; Kondoh, Tomomi; Nakahara, Keiko; Sakakibara, Yoichi; Fukui, Keiichi; Suiko, Masahito

2015-01-01

Natural killer (NK) cells play a key role in innate immune defense against infectious disease and cancer. A reduction of NK activity is likely to be associated with increased risk of these types of disease. In this study, we investigate the activation potential of kumquat pericarp acetone fraction (KP-AF) on NK cells. It is shown to significantly increase IFN-γ production and NK cytotoxic activity in human KHYG-1 NK cells. Moreover, oral administration of KP-AF significantly improves both suppressed plasma IFN-γ levels and NK cytotoxic activity per splenocyte in restraint-stressed mice. These results indicate that raw kumquat pericarp activates NK cells in vitro and in vivo. To identify the active constituents, we also examined IFN-γ production on KHYG-1 cells by the predicted active components. Only β-cryptoxanthin increased IFN-γ production, suggesting that NK cell activation effects of KP-AF may be caused by carotenoids such as β-cryptoxanthin.

Optical Magnetic Induction Tomography of the Heart

NASA Astrophysics Data System (ADS)

Marmugi, Luca; Renzoni, Ferruccio

2016-04-01

Atrial Fibrillation (AF) affects a significant fraction of the ageing population, causing a high level of morbidity and mortality. Despite its significance, the causes of AF are still not uniquely identified. This, combined with the lack of precise diagnostic and guiding tools, makes the clinical treatment of AF sub-optimal. We identify magnetic induction tomography as the most promising technique for the investigation of the causes of fibrillation and for its clinical practice. We therefore propose a novel optical instrument based on optical atomic magnetometers, fulfilling the requirements for diagnostic mapping of the heart’s conductivity. The feasibility of the device is here discussed in view of the final application. Thanks to the potential of atomic magnetometers for miniaturisation and extreme sensitivity at room temperature, a new generation of compact and non-invasive diagnostic instrumentation, with both bedside and intra-operative operation capability, is envisioned. Possible scenarios both in clinical practice and biomedical research are then discussed. The flexibility of the system makes it promising also for application in other fields, such as neurology and oncology.

Features of intrinsic ganglionated plexi in both atria after extensive pulmonary isolation and their clinical significance after catheter ablation in patients with atrial fibrillation.

PubMed

Kurotobi, Toshiya; Shimada, Yoshihisa; Kino, Naoto; Ito, Kazato; Tonomura, Daisuke; Yano, Kentaro; Tanaka, Chiharu; Yoshida, Masataka; Tsuchida, Takao; Fukumoto, Hitoshi

2015-03-01

The features of intrinsic ganglionated plexi (GP) in both atria after extensive pulmonary vein isolation (PVI) and their clinical implications have not been clarified in patients with atrial fibrillation (AF). The purpose of this study was to assess the features of GP response after extensive PVI and to evaluate the relationship between GP responses and subsequent AF episodes. The study population consisted of 216 consecutive AF patients (104 persistent AF) who underwent an initial ablation. We searched for the GP sites in both atria after an extensive PVI. GP responses were determined in 186 of 216 patients (85.6%). In the left atrium, GP responses were observed around the right inferior GP in 116 of 216 patients (53.7%) and around the left inferior GP in 57 of 216 (26.4%). In the right atrium, GP responses were observed around the posteroseptal area: inside the CS in 64 of 216 patients (29.6%), at the CS ostium in 150 of 216 (69.4%), and in the lower right atrium in 45 of 216 (20.8%). The presence of a positive GP response was an independent risk factor for AF recurrence (hazard ratio 4.04, confidence interval 1.48-11.0) in patients with paroxysmal, but not persistent, AF. The incidence of recurrent atrial tachyarrhythmias in patients with paroxysmal AF with a positive GP response was 51% vs 8% in those without a GP response (P = .002). The presence of GP responses after extensive PVI was significantly associated with increased AF recurrence after ablation in patients with paroxysmal AF. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Correlations Among Near-Infrared and Short-Wavelength Autofluorescence and Spectral-Domain Optical Coherence Tomography in Recessive Stargardt Disease

PubMed Central

Duncker, Tobias; Marsiglia, Marcela; Lee, Winston; Zernant, Jana; Tsang, Stephen H.; Allikmets, Rando; Greenstein, Vivienne C.; Sparrow, Janet R.

2014-01-01

Purpose. Short-wavelength (SW) fundus autofluorescence (AF) is considered to originate from lipofuscin in retinal pigment epithelium (RPE) and near-infrared (NIR) AF from melanin. In patients with recessive Stargardt disease (STGD1), we correlated SW-AF and NIR-AF with structural information obtained by spectral-domain optical coherence tomography (SD-OCT). Methods. Twenty-four STGD1 patients (45 eyes; age 8 to 61 years) carrying confirmed disease-associated ABCA4 mutations were studied prospectively. Short-wavelength AF, NIR-AF, and SD-OCT images were acquired. Results. Five phenotypes were identified according to features of the central lesion and extent of fundus change. Central zones of reduced NIR-AF were typically larger than areas of diminished SW-AF and reduced NIR-AF usually approximated areas of ellipsoid zone (EZ) loss identified by SD-OCT (group 1; r, 0.93, P < 0.0001). In patients having a central lesion with overlapping parafoveal rings of increased NIR-AF and SW-AF (group 3), the extent of EZ loss was strongly correlated with the inner diameter of the NIR-AF ring (r, 0.89, P < 0.0001) and the eccentricity of the outer border of the NIR-AF ring was greater than that of the SW-AF ring. Conclusions. Lesion areas were more completely delineated in NIR-AF images than with SW-AF. In most cases, EZ loss was observed only at locations where NIR-AF was reduced or absent, indicating that RPE cell atrophy occurs in advance of photoreceptor cell degeneration. Because SW-AF was often increased within the central area of EZ disruption, degenerating photoreceptor cells may produce lipofuscin at accelerated levels. Consideration is given to mechanisms underlying hyper–NIR-AF in conjunction with increased SW-AF. PMID:25342616

Neutron imaging of diabatic two-phase flows relevant to air conditioning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geoghegan, Patrick J; Sharma, Vishaldeep

The design of the evaporator of an air conditioning system relies heavily on heat transfer coefficients and pressure drop correlations that predominantly involve an estimate of the changing void fraction and the underlying two-phase flow regime. These correlations dictate whether the resulting heat exchanger is oversized or not and the amount of refrigerant charge necessary to operate. The latter is particularly important when dealing with flammable or high GWP refrigerants. Traditional techniques to measure the void fraction and visualize the flow are either invasive to the flow or occur downstream of the evaporator, where some of the flow distribution willmore » have changed. Neutron imaging has the potential to visualize two-phase flow in-situ where an aluminium heat exchanger structure becomes essentially transparent to the penetrating neutrons. The subatomic particles are attenuated by the passing refrigerant flow. The resulting image may be directly related to the void fraction and the overall picture provides a clear insight into the flow regime present. This work presents neutron images of the refrigerant Isopentane as it passes through the flow channels of an aluminium evaporator at flowrates relevant to air conditioning. The flow in a 4mm square macro channel is compared to that in a 250 m by 750 m rectangular microchannel in terms of void fraction and regime. All neutron imaging experiments were conducted at the High Flux Isotope Reactor, an Oak Ridge National Laboratory facility« less

New-onset atrial fibrillation in bacteremia is not associated with C-reactive protein, but is an indicator of increased mortality during hospitalization.

PubMed

Kindem, Ingvild A; Reindal, Eva K; Wester, Astrid L; Blaasaas, Karl G; Atar, Dan

2008-01-01

Several studies have associated elevated C-reactive protein (CRP) levels to the occurrence of atrial fibrillation (AF). We sought to estimate the frequency and prognostic impact of AF in patients with bacteremia, and to study the possible association between AF and CRP as well as between AF and mortality in this population. We retrospectively evaluated patient charts of patients with bacteremia with Escherichia coli or Streptococcus pneumoniae admitted to the Aker University Hospital in Oslo between 1994 and 2004. Known cardiac risk factors for AF, signs and mode of conversion of AF, and, if applicable, date of death were registered, as were characteristics of infection, such as systemic inflammatory response syndrome and white blood cell count. Initial CRP values were categorized into 4 strata. Odds ratios of the 3 highest CRP categories compared with the lowest were obtained from logistic models adjusting for known cardiac risk factors for AF as well as possible factors that may have had an impact on the odds ratios for the different CRP levels. Cox regression analysis was used to compare new-onset AF and death during the first 2 weeks after hospitalization. A total of 672 patient charts were studied; 104 patients (15.4%) had new-onset AF. Peak incidence of new-onset AF occurred on the day of admission. Peak CRP values were reached during the following 2 days. High CRP level at admission did not predict the occurrence of AF. The observed mortality was higher among patients with new-onset AF (p = 0.001) during the first 2 weeks after hospitalization, but this effect disappears when adjusted for relevant factors. The frequency of new-onset AF in bacteremia is substantial. Initial CRP levels or white blood cell count do not seem to predict new-onset AF, as opposed to systemic inflammatory response syndrome. On the other hand, in patients with bacteremia, new-onset AF should be viewed as an indicator of increased mortality and morbidity. Copyright 2008 S. Karger AG, Basel.

Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.

PubMed

Lowres, Nicole; Neubeck, Lis; Salkeld, Glenn; Krass, Ines; McLachlan, Andrew J; Redfern, Julie; Bennett, Alexandra A; Briffa, Tom; Bauman, Adrian; Martinez, Carlos; Wallenhorst, Christopher; Lau, Jerrett K; Brieger, David B; Sy, Raymond W; Freedman, S Ben

2014-06-01

Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered.

Baseline Demographics, Safety, and Patient Acceptance of an Insertable Cardiac Monitor for Atrial Fibrillation Screening: The REVEAL-AF Study.

PubMed

Conti, Sergio; Reiffel, James A; Gersh, Bernard J; Kowey, Peter R; Wachter, Rolf; Halperin, Jonathan L; Kaplon, Rachelle E; Pouliot, Erika; Verma, Atul

2017-01-01

Given the high prevalence and risk of stroke associated with atrial fibrillation (AF), detection strategies have important public health implications. The ongoing prospective, single-arm, open-label, multicenter REVEAL AF trial is evaluating the incidence of previously undetected AF using an insertable cardiac monitor (ICM) in patients without prior AF or device implantation, but who could be at risk for AF due to their demographic characteristics, +/- non-specific but compatible symptoms. Enrollment required an elevated AF risk profile defined as CHADS2≥3 or CHADS 2 =2 plus one or more of the following: coronary artery disease, renal impairment, sleep apnea or chronic obstructive pulmonary disease. Exclusions included stroke or transient ischemic attack occurring in the previous year. Of 450 subjects screened, 399 underwent a device insertion attempt, and 395 were included in the final analysis (Reveal XT: n=122; Reveal LINQ: n=273; excluded: n=4). Participants were primarily identified by demographic characteristics and the presence of nonspecific symptoms, but without prior documentation of "overt" AF. The most common symptoms were palpitations (51%), dizziness/lightheadedness/pre-syncope (36%), and shortness of breath (36%). Over 100 subjects were enrolled in each pre-defined CHADS2 subgroup (2, 3 and ≥4). AF risk factors not included in the CHADS2 score were well represented (prevalence≥15%). Procedure and/or device related serious adverse events were low, with the miniaturized Reveal LINQ ICM having a more favorable safety profile than the predicate Reveal XT (all: n=13 [3.3%]; LINQ: n=6 [2.2%]; XT: n=7 [5.7%]). These data demonstrate that REVEAL AF was successful in enrolling its target population, high risk patients were willing to undergo ICM monitoring for AF screening, and ICM use in this group is becoming increasingly safe with advancements in technology. A clinically meaningful incidence of device detected AF in this study will inform clinical decisions regarding ICM use for AF screening in patients at risk.

Multidetector thermal field-flow fractionation as a novel tool for the microstructure separation of polyisoprene and polybutadiene.

PubMed

Greyling, Guilaume; Pasch, Harald

2014-11-01

For the first time, it is demonstrated that thermal field-flow fractionation (ThFFF) is an efficient tool for the fractionation of polyisoprene (PI) and polybutadiene (PB) with regard to molecular microstructure. ThFFF analysis of 1,4- and 3,4-PI as well as 1,4- and 1,2-PB samples in tetrahydrofuran (THF), THF/cyclohexane, and cyclohexane reveals that isomers of the same polymer family having similar molar masses exhibit different Soret coefficients depending on microstructure for each solvent. The separation according to microstructure is found to be based on the cooperative influence of the normal and the thermal diffusion coefficient. Of the three solvents, cyclohexane has the greatest influence on the fractionation of the isomers. In order to determine the distribution of isomeric structures in the PI and PB samples, the samples are fractionated by ThFFF in cyclohexane and subsequently analyzed by (1) H NMR. The isomeric distributions determined from NMR data correlate well with ThFFF retention data of the samples and thus further highlight the unique fractionating capabilities of ThFFF. The interplay of the normal and thermal diffusion coefficients that are influenced by temperature and the mobile phase opens the way to highly selective fractionations without the drawbacks of column-based separation methods. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of C-reactive protein levels in patients who do and do not develop atrial fibrillation during electrophysiologic study.

PubMed

Pirat, Bahar; Atar, Ilyas; Ertan, Cagatay; Bozbas, Huseyin; Gulmez, Oyku; Müderrisoglu, Haldun; Ozin, Bulent

2007-11-15

C-reactive protein (CRP) was increased in patients with atrial fibrillation (AF). The aim of this study was to evaluate CRP after inducing AF in 39 patients undergoing electrophysiologic study (EPS). After a diagnostic EPS, programmed atrial stimulation with 3 extra stimuli from the right atrium was performed in all patients. CRP was measured before and 6 and 24 hours after the procedure. Patients in whom AF was induced were monitored for 24 hours. AF was induced in 18 of 39 patients. Twenty-one patients without a tachyarrhythmia constituted the control group. Groups were similar with regard to age, gender, incidences of hypertension and diabetes, and history of coronary artery disease. On average, AF lasted 4.8 hours, and spontaneous conversion to sinus rhythm was observed in all patients. There were no statistically significant differences with respect to baseline and 6-hour CRP values between groups. However, mean CRP at 24 hours was significantly higher in patients with AF compared with controls (10 +/- 11 and 3.9 +/- 4.2 mg/L; p = 0.04). In conclusion, induction of AF during EPS led to increased CRP. This finding suggested that increased CRP may be the consequence of AF.

Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

PubMed

Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

2016-10-04

To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover, when applied/used as an antifungal agent. [68 FR 41541, July 14...

Effects of Cooling Conditions on Tensile and Charpy Impact Properties of API X80 Linepipe Steels

NASA Astrophysics Data System (ADS)

Han, Seung Youb; Shin, Sang Yong; Lee, Sunghak; Kim, Nack J.; Bae, Jin-Ho; Kim, Kisoo

2010-02-01

In this study, four API X80 linepipe steel specimens were fabricated by varying the cooling rate and finish cooling temperature, and their microstructures and crystallographic orientations were analyzed to investigate the effects of the cooling conditions on the tensile and Charpy impact properties. All the specimens consisted of acicular ferrite (AF), granular bainite (GB), and martensite-austenite (MA) constituents. The volume fraction of MA increased with an increasing cooling rate, and the volume fraction and size of MA tended to decrease with an increasing finish cooling temperature. According to the crystallographic orientation analysis data, the effective grain size and unit crack path decreased as fine ACs having a large amount of high-angle grain boundaries were homogeneously formed, thereby leading to the improvement in the Charpy impact properties. The specimen fabricated with the higher cooling rate and lower finish cooling temperature had the highest upper-shelf energy (USE) and the lowest energy transition temperature (ETT), because it contained a large amount of MA homogeneously distributed inside fine AFs, while its tensile properties remained excellent.

Calculation of absorbed fractions to human skeletal tissues due to alpha particles using the Monte Carlo and 3-D chord-based transport techniques.

PubMed

Hunt, J G; Watchman, C J; Bolch, W E

2007-01-01

Absorbed fraction (AF) calculations to the human skeletal tissues due to alpha particles are of interest to the internal dosimetry of occupationally exposed workers and members of the public. The transport of alpha particles through the skeletal tissue is complicated by the detailed and complex microscopic histology of the skeleton. In this study, both Monte Carlo and chord-based techniques were applied to the transport of alpha particles through 3-D microCT images of the skeletal microstructure of trabecular spongiosa. The Monte Carlo program used was 'Visual Monte Carlo--VMC'. VMC simulates the emission of the alpha particles and their subsequent energy deposition track. The second method applied to alpha transport is the chord-based technique, which randomly generates chord lengths across bone trabeculae and the marrow cavities via alternate and uniform sampling of their cumulative density functions. This paper compares the AF of energy to two radiosensitive skeletal tissues, active marrow and shallow active marrow, obtained with these two techniques.

A compact x-ray system for two-phase flow measurement

NASA Astrophysics Data System (ADS)

Song, Kyle; Liu, Yang

2018-02-01

In this paper, a compact x-ray densitometry system consisting of a 50 kV, 1 mA x-ray tube and several linear detector arrays is developed for two-phase flow measurement. The system is capable of measuring void fraction and velocity distributions with a spatial resolution of 0.4 mm per pixel and a frequency of 1000 Hz. A novel measurement model has been established for the system which takes account of the energy spectrum of x-ray photons and the beam hardening effect. An improved measurement accuracy has been achieved with this model compared with the conventional log model that has been widely used in the literature. Using this system, void fraction and velocity distributions are measured for a bubbly and a slug flow in a 25.4 mm I.D. air-water two-phase flow test loop. The measured superficial gas velocities show an error within  ±4% when compared with the gas flowmeter for both conditions.

Clinical impact of rotor ablation in atrial fibrillation: a systematic review.

PubMed

Parameswaran, Ramanathan; Voskoboinik, Aleksandr; Gorelik, Alexandra; Lee, Geoffrey; Kistler, Peter M; Sanders, Prashanthan; Kalman, Jonathan M

2018-01-11

Rotor mapping and ablation have gained favour over the recent years as an emerging ablation strategy targeting drivers of atrial fibrillation (AF). Their efficacy, however, has been a topic of great debate with variable outcomes across centres. The aim of this study was to systematically review the recent medical literature to determine the medium-term outcomes of rotor ablation in patients with paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation (PeAF). A systematic search of the contemporary scientific literature (PubMed and EMBASE) was performed in August 2017. Only studies assessing arrhythmia-free survival from rotor ablation of AF were included. We used the random-effects model to assess the primary outcome of pooled medium-term single-procedure AF-free survival for both PAF and PeAF. Success rates from multiple procedures and complication rates were also examined. We included 11 observational studies (4 PAF and 10 PeAF) with a total of 556 patients (166 PAF and 390 PeAF). Pooled single-procedure freedom from AF was 37.8% [95% confidence interval 5.6-86.3%] at a mean follow-up period of 13.8 ± 1.8 months for PAF and 59.2% (95% CI 41.4-74.9%) at a mean follow-up period of 12.9 ± 6 months for PeAF. There was a marked heterogeneity between studies (I2 = 93.8% for PAF and 88.3% for PeAF). The mean complication rate of rotor ablation among the reported studies was 3.4%. The wide variability in success rate between different centres performing rotor ablations suggests that the optimal ablation strategy, particularly targeting rotors, is unclear. Results from randomized studies are necessary before this technique can be considered as an established clinical tool. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China.

PubMed

Yang, Xiaomeng; Li, Shuya; Zhao, Xingquan; Liu, Liping; Jiang, Yong; Li, Zixiao; Wang, Yilong; Wang, Yongjun

2017-12-04

Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define the true frequency of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF in Chinese stroke patients, and to elucidate predictors of newly detected AF. Patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled in a prospective, multicenter cohort study of 6-day Holter monitoring within 7 days after stroke onset at 20 sites in China between 2013 and 2015. Independent predictors of newly-detected AF were determined by multivariate analysis. Among 1511 patients with ischemic stroke and TIA (mean age 63 years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring (56/1262, 4.4%). A history of heart failure (OR = 4.70, 95%CI, 1.64-13.5), advanced age (OR = 1.06, 95%CI, 1.04-1.09), NIHSS at admission (OR = 1.06, 95%CI, 1.02-1.10), blood high density lipoprotein (HDL) (OR = 1.52, 95%CI, 1.09-2.13), together with blood triglycerides (OR = 0.64, 95%CI, 0.45-0.91) were independently associated with newly-detected AF. Contrary to previous reports, AF-associated stroke is frequent (20%) in China if systemically sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF detection in patients with recent ischemic stroke and TIA in China. Advanced age, history of heart failure, and higher admission NIHSS and higher level of HDL were independent indicators of newly-detected AF. NCT02156765 (June 5, 2014).

Comparison of Risk of Atrial Fibrillation Among Employed Versus Unemployed (from the REasons for Geographic and Racial Differences in Stroke Study).

PubMed

Soliman, Elsayed Z; Zhang, Zhu-Ming; Judd, Suzanne; Howard, Virginia J; Howard, George

2017-10-15

Involuntary unemployment due to job loss has been associated with increased risk of cardiovascular events. Whether it also is associated with increased risk of atrial fibrillation (AF) is currently unknown. Therefore, we examined this association in 8,812 participants residing mainly in the Southeastern United States (mean age 58.1 ± 7.8 years; 63.2%; women; 43.2% black) with data on employment status who were enrolled in the REasons for Geographic And Racial Differences in Stroke study between 2003 and 2007 after excluding those with voluntary unemployment (retiree, homemakers, and students). AF was identified by electrocardiogram and past medical history at the same period. The cross-sectional association between status and type of unemployment with AF was examined in multivariable logistic regression models. Additional analysis in 4,273 participants without baseline AF and with data on incident AF collected in a follow-up visit occurred after a median of 9.4 years from baseline was also conducted. In a model adjusted for socio-demographics, health insurance, income, perceived stress, and cardiovascular risk factors, unemployment was associated with 60% increased odds of AF (odds ratio [95% confidence interval] 1.60 (1.24, 2.07)). This association was consistent in subgroups stratified by median age, gender, race, education, income, and health insurance status. Similarly, unemployment was associated with AF in those without AF at baseline who developed incident AF (odds ratio [95% confidence interval] 1.54 (1.04, 2.37)). In conclusion, involuntary unemployment is associated with increased risk of AF. This may call for considering socioeconomic determinants such as unemployment as part of the preventive strategies for AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Size and elemental distributions of nano- to micro-particulates in the geochemically-stratified Great Salt Lake

USGS Publications Warehouse

Diaz, X.; Johnson, W.P.; Fernandez, D.; Naftz, D.L.

2009-01-01

The characterization of trace elements in terms of their apportionment among dissolved, macromolecular, nano- and micro-particulate phases in the water column of the Great Salt Lake carries implications for the potential entry of toxins into the food web of the lake. Samples from the anoxic deep and oxic shallow brine layers of the lake were fractionated using asymmetric flow field-flow fractionation (AF4). The associated trace elements were measured via online collision cell inductively-coupled plasma mass spectrometry (CC-ICP-MS). Results showed that of the total (dissolved + particulate) trace element mass, the percent associated with particulates varied from negligible (e.g. Sb), to greater than 50% (e.g. Al, Fe, Pb). Elements such as Cu, Zn, Mn, Co, Au, Hg, and U were associated with nanoparticles, as well as being present as dissolved species. Particulate-associated trace elements were predominantly associated with particulates larger than 450 nm in size. Among the smaller nanoparticulates (<450 nm), some trace elements (Ni, Zn, Au and Pb) showed higher percent mass (associated with nanoparticles) in the 0.9-7.5 nm size range relative to the 10-250 nm size range. The apparent nanoparticle size distributions were similar between the two brine layers; whereas, important differences in elemental associations to nanoparticles were discerned between the two layers. Elements such as Zn, Cu, Pb and Mo showed increasing signal intensities from oxic shallow to anoxic deep brine, suggesting the formation of sulfide nanoparticles, although this may also reflect association with dissolved organic matter. Aluminum and Fe showed greatly increased concentration with depth and equivalent size distributions that differed from those of Zn, Cu, Pb and Mo. Other elements (e.g. Mn, Ni, and Co) showed no significant change in signal intensity with depth. Arsenic was associated with <2 nm nanoparticles, and showed no increase in concentration with depth, possibly indicating dissolved arsenite. Mercury was associated with <2 nm nanoparticles, and showed greatly increased concentration with depth, possibly indicating association with dissolved organic matter. ?? 2009 Elsevier Ltd.

Beta1 integrin inhibits apoptosis induced by cyclic stretch in annulus fibrosus cells via ERK1/2 MAPK pathway.

PubMed

Zhang, Kai; Ding, Wei; Sun, Wei; Sun, Xiao-jiang; Xie, You-zhuan; Zhao, Chang-qing; Zhao, Jie

2016-01-01

Low back pain is associated with intervertebral disc degeneration (IVDD) due to cellular loss through apoptosis. Mechanical factors play an important role in maintaining the survival of the annulus fibrosus (AF) cells and the deposition of extracellular matrix. However, the mechanisms that excessive mechanical forces lead to AF cell apoptosis are not clear. The present study was to look for how AF cells sense mechanical changes. In vivo experiments, the involvement of mechanoreceptors in apoptosis was examined by RT-PCR and/or immunoblotting in the lumbar spine of rats subjected to unbalanced dynamic and static forces. In vitro experiments, we investigated apoptotic signaling pathways in untransfected and transfected AF cells with the lentivirus vector for rat β1 integrin overexpression after cyclic stretch. Apoptosis in AF cells was assessed using flow cytometry, Hoechst 33258 nuclear staining. Western blotting was used to analyze expression of β1 integrin and caspase-3 and ERK1/2 MAPK signaling molecules. In the rat IVDD model, unbalanced dynamic and static forces induced apoptosis of disc cells, which corresponded to decreased expression of β1 integrin. Cyclic stretch-induced apoptosis in rat AF cells correlated with the activation of caspase-3 and with decreased levels of β1 integrin and the phosphorylation levels of ERK1/2 activation level. However, the overexpression of β1 integrin in AF cells ameliorated cyclic stretch-induced apoptosis and decreased caspase-3 activation. Furthermore, ERK1/2-specific inhibitor promotes apoptosis in vector β1-infected AF cells. These results suggest that the disruption of β1 integrin signaling may underlie disc cell apoptosis induced by mechanical stress. Further work is necessary to fully elucidate the pathophysiological mechanisms that underlie IVDD caused by unbalanced dynamic and static forces.

Factors effecting impact of Aspergillus fumigatus sensitization in cystic fibrosis.

PubMed

Kanthan, Senthooran Kathirgama; Bush, Andrew; Kemp, Michael; Buchdahl, Roger

2007-09-01

The clinical impact of Aspergillus fumigatus (Af) sensitization in cystic fibrosis (CF) is controversial. We examined the effect of Af sensitization (Afs) on pulmonary function and growth using a retrospective cohort analysis over two 5-year study periods: 1996-2000 (19 Afs cases and 19 controls) and 2001-2005 (24 Afs cases and 23 controls). Sensitization was defined as Af specific radioallergosorbent test (RAST) >or= 17.5 iu/ml and total serum IgE level >or=150 iu/ml. We examined the impact of changing treatment schedules over these periods. Afs cases had lower median FEV(1) %predicted (%PR) compared to matched controls 1996: 67 versus 80, P < 0.01; 2001: 78 versus 93, P < 0.01. Afs cases in the 2001 cohort had a higher FEV(1) %PR compared to Afs cases in the 1996 cohort: 78 versus 67, P < 0.01. For the 1996 Afs cohort FEV(1) %PR fell significantly over 5 years but not for the 2001 Afs cohort. Af RAST and total IgE reflected the changes in pulmonary function. Children in the 2001 Afs cohort were prescribed significantly more oral antifungal treatment (odds ratio 4.3, 95%CI 1.2-15.7, P = 0.03). Afs children continue to have poorer lung function compared to controls but this observational, hypothesis generating study, suggests that the use of antifungal treatment is associated with better lung function. (c) 2007 Wiley-Liss, Inc.

Clinical, biomarker, and genetic predictors of specific types of atrial fibrillation in a community-based cohort: data of the PREVEND study.

PubMed

Hobbelt, Anne H; Siland, Joylene E; Geelhoed, Bastiaan; Van Der Harst, Pim; Hillege, Hans L; Van Gelder, Isabelle C; Rienstra, Michiel

2017-02-01

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation.

PubMed

Magrì, Damiano; Agostoni, Piergiuseppe; Corrà, Ugo; Passino, Claudio; Scrutinio, Domenico; Perrone-Filardi, Pasquale; Correale, Michele; Cattadori, Gaia; Metra, Marco; Girola, Davide; Piepoli, Massimo F; Iorio, AnnaMaria; Emdin, Michele; Raimondo, Rosa; Re, Federica; Cicoira, Mariantonietta; Belardinelli, Romualdo; Guazzi, Marco; Limongelli, Giuseppe; Clemenza, Francesco; Parati, Gianfranco; Frigerio, Maria; Casenghi, Matteo; Scardovi, Angela B; Ferraironi, Alessandro; Di Lenarda, Andrea; Bussotti, Maurizio; Apostolo, Anna; Paolillo, Stefania; La Gioia, Rocco; Gargiulo, Paola; Palermo, Pietro; Minà, Chiara; Farina, Stefania; Battaia, Elisa; Maruotti, Antonello; Pacileo, Giuseppe; Contini, Mauro; Oliva, Fabrizio; Ricci, Roberto; Sinagra, Gianfranco

2015-08-01

Oxygen uptake at the anaerobic threshold (VO2AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO2AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. We tested the prognostic role of VO2AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p = 0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO2) showed a prognostic capacity (C-index) similar to that obtained including VO2AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO2AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. VO2AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO2AT cut-off values between SR and AF HF patients should be adopted. © The European Society of Cardiology 2014.

Impact of obesity on atrial fibrillation ablation: Patient characteristics, long-term outcomes, and complications.

PubMed

Winkle, Roger A; Mead, R Hardwin; Engel, Gregory; Kong, Melissa H; Fleming, William; Salcedo, Jonathan; Patrawala, Rob A

2017-06-01

There is an association between obesity and atrial fibrillation (AF). The impact of obesity on AF ablation procedures is unclear. The purpose of this study was to evaluate the influence of body mass index (BMI) on patient characteristics, long-term ablation outcomes, and procedural complications. We evaluated 2715 patients undergoing 3742 AF ablation procedures. BMI was ≥30 kg/m 2 in 1058 (39%) and ≥40 kg/m 2 in 129 (4.8%). Patients were grouped by BMI ranges (<25, 25-<30, 30-<35, 35-<40, and ≥40 kg/m 2 ). As BMI increased from <25 to ≥40 kg/m 2 , age decreased from 65.3 ± 11.2 to 61.2 ± 9.2 years (P < .001), left atrial size increased from 3.91 ± 0.68 to 4.72 ± 0.62 cm (P < .005), and CHADS 2 scores increased from 1.24 ± 1.10 to 1.62 ± 1.09 (P < .001). As BMI increased, paroxysmal AF decreased from 48.0% to 16.3% (P < .0001) and there was an increase in dilated cardiomyopathy (from 7.6% to 12.4%; P < .0001), hypertension (from 41.0% to 72.9%; P < .0001), diabetes (from 4.3% to 23.3%; P < .0001), and sleep apnea (from 7.0% to 46.9%; P < .0001). For the entire cohort, for BMI ≥35 kg/m 2 the 5-year ablation freedom from AF decreased from 67%-72% to 57% (P = .036). For paroxysmal AF, when BMI was ≥40 kg/m 2 ablation success decreased from 79%-82% to 60% (P = .064), and for persistent AF, when BMI was ≥35 kg/m 2 ablation success decreased from 64%-70% to 52%-57% (P = .021). For long-standing AF, there was no impact of BMI on outcomes (P = .624). In multivariate analysis, BMI ≥35 kg/m 2 predicted worse outcomes (P = .036). Higher BMI did not impact major complication rates (P = .336). However, when BMI was ≥40 kg/m 2 , minor (from 2.1% to 4.4%; P = .035) and total (from 3.5% to 6.7%; P = .023) complications increased. In patients undergoing AF ablation, increasing BMI is associated with more patient comorbidities and more persistent and long-standing AF. BMI ≥35 kg/m 2 adversely impacts ablation outcomes, and BMI ≥40 kg/m 2 increases minor complications. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Direct Proof of Endo-Epicardial Asynchrony of the Atrial Wall During Atrial Fibrillation in Humans.

PubMed

de Groot, Natasja; van der Does, Lisette; Yaksh, Ameeta; Lanters, Eva; Teuwen, Christophe; Knops, Paul; van de Woestijne, Pieter; Bekkers, Jos; Kik, Charles; Bogers, Ad; Allessie, Maurits

2016-05-01

The presence of focal fibrillation waves during atrial fibrillation (AF) can, besides ectopic activity, also be explained by asynchronous activation of the atrial endo- and epicardial layer and transmurally propagating fibrillation waves. To provide direct proof of endo-epicardial asynchrony, we performed simultaneous high-resolution mapping of the right atrial endo- and epicardial wall during AF in humans. Intraoperative mapping of the endo- and epicardial right atrial wall was performed during (induced) AF in 10 patients with AF (paroxysmal: n=3; persistent: n=4; and longstanding persistent: n=3) and 4 patients without a history of AF. A clamp made of 2 rectangular 8×16 electrode arrays (interelectrode distance 2 mm) was inserted into the incision in the right atrial appendage. Recordings of 10 seconds of AF were analyzed to determine the incidence of asynchronous endo-epicardial activation times (≥15 ms) of opposite electrodes. Asynchronous endo-epicardial activation ranged between 0.9 and 55.9% without preference for either side. Focal waves appeared equally frequent at endocardium and epicardium (11% versus 13%; ITALIC! P=0.18). Using strict criteria for breakthrough (presence of an opposite wave within 4 mm and ≤14 ms before the origin of the focal wave), the majority (65%) of all focal fibrillation waves could be attributed to endo-epicardial excitation. We provided the first evidence for asynchronous activation of the endo-epicardial wall during AF in humans. Endo-epicardial asynchrony may play a major role in the pathophysiology of AF and may offer an explanation why in some patients therapy fails. © 2016 American Heart Association, Inc.

Atrial fibrillation ablation using a closed irrigation radiofrequency ablation catheter.

PubMed

Golden, Keith; Mounsey, John Paul; Chung, Eugene; Roomiani, Pahresah; Morse, Michael Andew; Patel, Ankit; Gehi, Anil

2012-05-01

Catheter ablation is an effective therapy for symptomatic, medically refractory atrial fibrillation (AF). Open-irrigated radiofrequency (RF) ablation catheters produce transmural lesions at the cost of increased fluid delivery. In vivo models suggest closed-irrigated RF catheters create equivalent lesions, but clinical outcomes are limited. A cohort of 195 sequential patients with symptomatic AF underwent stepwise AF ablation (AFA) using a closed-irrigation ablation catheter. Recurrence of AF was monitored and outcomes were evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mean age was 59.0 years, 74.9% were male, 56.4% of patients were paroxysmal and mean duration of AF was 5.4 years. Patients had multiple comorbidities including hypertension (76.4%), tobacco abuse (42.1%), diabetes (17.4%), and obesity (mean body mass index 30.8). The median follow-up was 55.8 weeks. Overall event-free survival was 73.6% with one ablation and 77.4% after reablation (reablation rate was 8.7%). Median time to recurrence was 26.9 weeks. AF was more likely to recur in patients being treated with antiarrhythmic therapy at the time of last follow-up (recurrence rate 30.3% with antiarrhythmic drugs, 13.2% without antiarrhythmic drugs; hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.1-4.4, P = 0.024) and in those with a history of AF greater than 2 years duration (HR 2.7, 95% CI 1.1-6.9, P = 0.038). Our study represents the largest cohort of patients receiving AFA with closed-irrigation ablation catheters. We demonstrate comparable outcomes to those previously reported in studies of open-irrigation ablation catheters. Given the theoretical benefits of a closed-irrigation system, a large head-to-head comparison using this catheter is warranted. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Fundus Autofluorescence in the Abca4−/− Mouse Model of Stargardt Disease—Correlation With Accumulation of A2E, Retinal Function, and Histology

PubMed Central

Charbel Issa, Peter; Barnard, Alun R.; Singh, Mandeep S.; Carter, Emma; Jiang, Zhichun; Radu, Roxana A.; Schraermeyer, Ulrich; MacLaren, Robert E.

2013-01-01

Purpose. To investigate fundus autofluorescence (AF) characteristics in the Abca4−/− mouse, an animal model for AMD and Stargardt disease, and to correlate findings with functional, structural, and biochemical assessments. Methods. Blue (488 nm) and near-infrared (790 nm) fundus AF images were quantitatively and qualitatively analyzed in pigmented Abca4−/− mice and wild type (WT) controls in vivo. Functional, structural, and biochemical assessments included electroretinography (ERG), light and electron microscopic analysis, and A2E quantification. All assessments were performed across age groups. Results. In Abca4−/− mice, lipofuscin-related 488 nm AF increased early in life with a ceiling effect after 6 months. This increase was first paralleled by an accumulation of typical lipofuscin granules in the retinal pigment epithelium (RPE). Later, lipofuscin and melanin granules decreased in number, whereas melanolipofuscin granules increased. This increase in melanolipofuscin granules paralleled an increase in melanin-related 790 nm AF. Old Abca4−/− mice revealed a flecked fundus AF pattern at both excitation wavelengths. The amount of A2E, a major lipofuscin component, increased 10- to 12-fold in 6- to 9-month-old Abca4−/− mice compared with controls, while 488 nm AF intensity only increased 2-fold. Despite pronounced lipofuscin accumulation in the RPE of Abca4−/− mice, ERG and histology showed a slow age-related thinning of the photoreceptor layer similar to WT controls up to 12 months. Conclusions. Fundus AF can be used to monitor lipofuscin accumulation and melanin-related changes in vivo in mouse models of retinal disease. High RPE lipofuscin may not adversely affect retinal structure or function over prolonged time intervals, and melanin-related changes (melanolipofuscin formation) may occur before the decline in retinal function. PMID:23761084

[The contribution of endogenous vasodilators to the control of glomerular hemodynamics].

PubMed

Arima, S; Ito, S; Abe, K

1994-06-01

Preglomerular afferent (Af-) and postglomerular efferent arterioles (Ef-Arts) are crucial vascular segments in the control of glomerular hemodynamics. However, their vascular reactivity is not fully understood. We examined: 1) their responses to angiotensin II (AII) or norepinephrine (NE), and 2) the possible modulatory roles of nitric oxide (NO) and prostaglandins (PGs) in these responses. Rabbit Af- or Ef-Arts were microperfused in vitro. Ef-Arts were perfused in either the orthograde direction from the distal end of Af-Arts through the glomerulus (OP) or the retrograde direction from its distal end to eliminate the influence of the glomerulus (RP). Although AII and NE constricted both arterioles in a dose-dependent manner, sensitivity to AII was higher in Ef-Arts. AII began to cause significant (P < 0.01) constriction from 10(-9) M (11 +/- 3%, n = 11) in Af-Arts, and from 10(-11) M in Ef-Arts (OP; 11 +/- 4%, n = 9. RP; 10 +/- 2%, n = 5). In addition, both AII and NE produced stronger constriction of Ef-Arts in RP than OP; AII at 10(-8) M or NE at 10(-6) M decreased the diameter by 35 +/- 4% or 25 +/- 4% in OP and 74 +/- 4% or 62 +/- 7% in RP. NO synthesis inhibitor nitro-L-arginine (L-NAME; 10(-4) M) increased the sensitivity of Af-Art to AII without affecting the reactivity of Ef-Art; in L-NAME-pretreated Af-Arts, AII began to cause significant constriction from 10(-10) M (14 +/- 4%, n = 9, P < 0.01). Thus, L-NAME-pretreatment significantly decreased the differences in sensitivity to AII between Af- and Ef-Arts without affecting different vascular responses between OP and RP. Indomethacin (5 x 10(-5) M) significantly augmented the AII- or NE-induced Ef-Art constriction only in OP; AII at 10(-8) M or NE at 10(-6) M decreased the diameter by 72 +/- 5% (n = 8) or 48 +/- 3% (n = 7). Thus, indomethacin-pretreatment markedly diminished the differences in responses between OP and RP. These results suggest that 1) NO modulates AII action only in the Af-Art, contributing to the difference in sensitivity to AII between Af- and Ef-Art, and 2) the glomerulus controls vascular reactivity of the downstream Ef-Art by releasing PGs.

Relationship of Preexisting Cardiovascular Comorbidities to Newly Diagnosed Atrial Fibrillation After Ischemic Stroke.

PubMed

Bisson, Arnaud; Clementy, Nicolas; Bodin, Alexandre; Angoulvant, Denis; Babuty, Dominique; Lip, Gregory Y H; Fauchier, Laurent

2017-10-01

There remains uncertainty as whether newly diagnosed atrial fibrillation (AF) after ischemic stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms. We aimed to determine whether cardiovascular comorbidities in patients with new AF after ischemic stroke differ from patients with previous known AF or without AF. This French longitudinal cohort study was based on the database covering hospital care from 2009 to 2012 for the entire population. Of 336 291 patients with ischemic stroke, 240 459 (71.5%) had no AF and 95 832 (28.5%) had previously known AF at baseline. Patients without previous AF had a mean CHA 2 DS 2 -VASc score of 4.98±1.63 SD. During a mean follow-up of 7.9±11.5 months, 14 095 (5.9%) of these patients had incident AF, representing an annual incidence of AF after ischemic stroke of 8.9 per 100 person-years (95% confidence interval, 8.8-9.0). New AF patients had higher CHA 2 DS 2 -VASc score, more likely comorbidities, and more frequent history of previous transient ischemic attack than patients with previous known AF or without AF. Preexisting cardiovascular comorbidities underlie AF newly diagnosed after stroke. Consequently, these high-risk patients should be closely monitored for incident AF to facilitate an earlier diagnosis of AF and avoid stroke with appropriate thromboprophylaxis. © 2017 American Heart Association, Inc.

Impact of Atrial Fibrillation Ablation on Left Ventricular Filling Pressure and Left Atrial Remodeling

PubMed Central

dos Santos, Simone Nascimento; Henz, Benhur Davi; Zanatta, André Rodrigues; Barreto, José Roberto; Loureiro, Kelly Bianca; Novakoski, Clarissa; dos Santos, Marcus Vinícius Nascimento; Giuseppin, Fabio F.; Oliveira, Edna Maria; Leite, Luiz Roberto

2014-01-01

Background Left ventricular (LV) diastolic dysfunction is associated with new-onset atrial fibrillation (AF), and the estimation of elevated LV filling pressures by E/e' ratio is related to worse outcomes in patients with AF. However, it is unknown if restoring sinus rhythm reverses this process. Objective To evaluate the impact of AF ablation on estimated LV filling pressure. Methods A total of 141 patients underwent radiofrequency (RF) ablation to treat drug-refractory AF. Transthoracic echocardiography was performed 30 days before and 12 months after ablation. LV functional parameters, left atrial volume index (LAVind), and transmitral pulsed and mitral annulus tissue Doppler (e' and E/e') were assessed. Paroxysmal AF was present in 18 patients, persistent AF was present in 102 patients, and long-standing persistent AF in 21 patients. Follow-up included electrocardiographic examination and 24-h Holter monitoring at 3, 6, and 12 months after ablation. Results One hundred seventeen patients (82.9%) were free of AF during the follow-up (average, 18 ± 5 months). LAVind reduced in the successful group (30.2 mL/m2 ± 10.6 mL/m2 to 22.6 mL/m2 ± 1.1 mL/m2, p < 0.001) compared to the non-successful group (37.7 mL/m2 ± 14.3 mL/m2 to 37.5 mL/m2 ± 14.5 mL/m2, p = ns). Improvement of LV filling pressure assessed by a reduction in the E/e' ratio was observed only after successful ablation (11.5 ± 4.5 vs. 7.1 ± 3.7, p < 0.001) but not in patients with recurrent AF (12.7 ± 4.4 vs. 12 ± 3.3, p = ns). The success rate was lower in the long-standing persistent AF patient group (57% vs. 87%, p = 0.001). Conclusion Successful AF ablation is associated with LA reverse remodeling and an improvement in LV filling pressure. PMID:25590928

Surgical RF ablation of atrial fibrillation in patients undergoing mitral valve repair for Barlow disease.

PubMed

Rostagno, Carlo; Droandi, G; Gelsomino, S; Carone, E; Gensini, G F; Stefàno, P L

2013-01-01

At present, limited experience exists on the treatment of atrial fibrillation (AF) in patients undergoing mitral valve repair (MVR) for Barlow disease. The aim of this investigation was to prospectively evaluate the radiofrequency ablation of AF in patients undergoing MVR for severe regurgitation due to Barlow disease. From January 1, 2007 to December 31, 2010, out of 85 consecutive patients with Barlow disease, 27 with AF underwent RF ablation associated with MVR. They were examined every 4 months in the first year after surgery and thereafter twice yearly. At follow-up, AF was observed in 4/25 (16.0%). NYHA (New York Heart Association) functional class improved significantly, with no patients in class III or IV (before surgery, 81.5% had been). Otherwise, among 58 patients in sinus rhythm, 6 (11%) developed AF during follow-up. No clinical or echocardiographic predictive factor was found in this subgroup. Results from our investigation suggest that radiofrequency ablation of AF in patients with Barlow disease undergoing MVR for severe regurgitation is effective and should be considered in every patient with Barlow disease and AF undergoing valve surgical repair. Copyright © 2013 S. Karger AG, Basel.

Adiabatic Compression Sensitivity of AF-M315E (Briefing Charts)

DTIC Science & Technology

2015-07-27

Charts 3. DATES COVERED (From - To) July 2015-July 2015 4. TITLE AND SUBTITLE Adiabatic Compression Sensitivity of AF - M315E (Briefing Charts) 5a...PA#15402. 14. ABSTRACT The Air Force Research Laboratory developed monopropellant, AF - M315E , has been selected for demonstration under the NASA...Pollux Drive, Edwards AFB, CA 93524-7048. Adiabatic Compression Sensitivity of AF - M315E Phu Quach ERC, Incorporated Air Force Research Laboratory

Antimutagens in gaiyou (Artemisia argyi levl. et vant.).

PubMed

Nakasugi, T; Nakashima, M; Komai, K

2000-08-01

Antimutagens from gaiyou (Artemisia argyi Levl. et Vant., Compositae) were examined. The methanol extract prepared from aerial parts of this plant strongly reduced the mutagenicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), when Salmonella typhimurium TA98 was used in the presence of the rat liver microsomal fraction. The antimutagens were purified chromatographically while monitoring the antimutagenic activity against Trp-P-2 with a modified Ames test employing a plate method. This purification resulted in the isolation of four strong antimutagens, 5,7-dihydroxy-6,3',4'-trimethoxyflavone (eupatilin), 5, 7,4'-trihydroxy-6,3'-dimethoxyflavone (jaceosidin), 5,7, 4'-trihydroxyflavone (apigenin) and 5,7, 4'-trihydroxy-3'-methoxyflavone (chrysoeriol) from the methanol extract. These antimutagenic flavones exhibited strong antimutagenic activity against not only Trp-P-2 but also against other heterocyclic amines, such as 3-amino-1,4-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P-1), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA(alpha)C) in S. typhimurium TA98. In contrast, they did not exhibit antimutagenic activity against benzo[a]pyrene (B[a]P), 4-nitroquinoline-1-oxide (4-NQO), 2-aminofluorene (2-AF), 2-nitrofluorene (2-NF) or furylfuramide (AF-2) in S. typhimurium TA98, or B[a]P, 4-NQO, 2-NF, AF-2, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or sodium azide (SA) in Salmonella typhimurium TA100, whereas they decreased the mutagenicity caused by aflatoxin B(1) (AFB(1)) and 2-aminoanthracene (2-AA) in both of these tester strains. Regarding the structure-activity relationship, the tested flavones had distinct differences in the intensities of their antimutagenic activities according to the differences of their substitution patterns. Namely, the intensity of antimutagenic activities against Trp-P-2 decreased in the order of: 5,7,3',4'-tetrasubstituted flavones (IC(50): <0.1 mmol/plate), 5,7,4'-trisubstituted flavones (IC(50): 0.120-0.260 mmol/plate), 5,6,7,3',4'-pentasubstituted flavones (IC(50): 0.440-0. 772 mmol/plate). The four isolated flavones were also studied regarding their antimutagenic mechanisms with preincubation methods of the modified Ames test and emission spectroscopic analysis. The results suggested that all isolated flavones were desmutagens which directly inactivated Trp-P-2 or inhibited its metabolic activation.

Benefits of Atrial Substrate Modification Guided by Electrogram Similarity and Phase Mapping Techniques to Eliminate Rotors and Focal Sources Versus Conventional Defragmentation in Persistent Atrial Fibrillation.

PubMed

Lin, Yenn-Jiang; Lo, Men-Tzung; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chao, Tze-Fan; Chung, Fa-Po; Liao, Jo-Nan; Lin, Chin-Yu; Kuo, Huan-Yu; Chang, Yi-Chung; Lin, Chen; Tuan, Ta-Chuan; Vincent Young, Hsu-Wen; Suenari, Kazuyoshi; Dan Do, Van Buu; Raharjo, Suunu Budhi; Huang, Norden E; Chen, Shih-Ann

2016-11-01

This prospective study compared the efficacy of atrial substrate modification guided by a nonlinear phase mapping technique with that of conventional substrate ablation. The optimal ablation strategy for persistent atrial fibrillation (AF) was unknown. In phase 1 study, we applied a cellular automation technique to simulate the electrical wave propagation to improve the phase mapping algorithm, involving analysis of high-similarity electrogram regions. In addition, we defined rotors and focal AF sources, using the physical parameters of the divergence and curvature forces. In phase 2 study, we enrolled 68 patients with persistent AF undergoing substrate modification into 2 groups, group-1 (n = 34) underwent similarity index (SI) and phase mapping techniques; group-2 (n = 34) received complex fractionated atrial electrogram ablation with commercially available software. Group-1 received real-time waveform similarity measurements in which a phase mapping algorithm was applied to localize the sources. We evaluated the single-procedure freedom from AF. In group-1, we identified an average of 2.6 ± 0.89 SI regions per chamber. These regions involved rotors and focal sources in 65% and 77% of patients in group-1, respectively. Group-1 patients had shorter ablation procedure times, higher termination rates, and significant reduction in AF recurrence compared to group-2 and a trend toward benefit for all atrial arrhythmias. Multivariate analysis showed that substrate mapping using nonlinear similarity and phase mapping was the independent predictor of freedom from AF recurrence (hazard ratio: 0.26; 95% confidence interval: 0.09 to 0.74; p = 0.01). Our study showed that for persistent AF ablation, a specified substrate modification guided by nonlinear phase mapping could eliminate localized re-entry and non-pulmonary focal sources after pulmonary vein isolation. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Three-Dimensional Echocardiographic Assessment of Left Heart Chamber Size and Function with Fully Automated Quantification Software in Patients with Atrial Fibrillation.

PubMed

Otani, Kyoko; Nakazono, Akemi; Salgo, Ivan S; Lang, Roberto M; Takeuchi, Masaaki

2016-10-01

Echocardiographic determination of left heart chamber volumetric parameters by using manual tracings during multiple beats is tedious in atrial fibrillation (AF). The aim of this study was to determine the usefulness of fully automated left chamber quantification software with single-beat three-dimensional transthoracic echocardiographic data sets in patients with AF. Single-beat full-volume three-dimensional transthoracic echocardiographic data sets were prospectively acquired during consecutive multiple cardiac beats (≥10 beats) in 88 patients with AF. In protocol 1, left ventricular volumes, left ventricular ejection fraction, and maximal left atrial volume were validated using automated quantification against the manual tracing method in identical beats in 10 patients. In protocol 2, automated quantification-derived averaged values from multiple beats were compared with the corresponding values obtained from the indexed beat in all patients. Excellent correlations of left chamber parameters between automated quantification and the manual method were observed (r = 0.88-0.98) in protocol 1. The time required for the analysis with the automated quantification method (5 min) was significantly less compared with the manual method (27 min) (P < .0001). In protocol 2, there were excellent linear correlations between the averaged left chamber parameters and the corresponding values obtained from the indexed beat (r = 0.94-0.99), and test-retest variability of left chamber parameters was low (3.5%-4.8%). Three-dimensional transthoracic echocardiography with fully automated quantification software is a rapid and reliable way to measure averaged values of left heart chamber parameters during multiple consecutive beats. Thus, it is a potential new approach for left chamber quantification in patients with AF in daily routine practice. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Imaging Lenticular Autofluorescence in Older Subjects.

PubMed

Charng, Jason; Tan, Rose; Luu, Chi D; Sadigh, Sam; Stambolian, Dwight; Guymer, Robyn H; Jacobson, Samuel G; Cideciyan, Artur V

2017-10-01

To evaluate whether a practical method of imaging lenticular autofluorescence (AF) can provide an individualized measure correlated with age-related lens yellowing in older subjects undergoing tests involving shorter wavelength lights. Lenticular AF was imaged with 488-nm excitation using a confocal scanning laser ophthalmoscope (cSLO) routinely used for retinal AF imaging. There were 75 older subjects (ages 47-87) at two sites; a small cohort of younger subjects served as controls. At one site, the cSLO was equipped with an internal reference to allow quantitative AF measurements; at the other site, reduced-illuminance AF imaging (RAFI) was used. In a subset of subjects, lens density index was independently estimated from dark-adapted spectral sensitivities performed psychophysically. Lenticular AF intensity was significantly higher in the older eyes than the younger cohort when measured with the internal reference (59.2 ± 15.4 vs. 134.4 ± 31.7 gray levels; P < 0.05) as well as when recorded with RAFI without the internal reference (10.9 ± 1.5 vs. 26.1 ± 5.7 gray levels; P < 0.05). Lenticular AF was positively correlated with age; however, there could also be large differences between individuals of similar age. Lenticular AF intensity correlated well with lens density indices estimated from psychophysical measures. Lenticular AF measured with a retinal cSLO can provide a practical and individualized measure of lens yellowing, and may be a good candidate to distinguish between preretinal and retinal deficits involving short-wavelength lights in older eyes.

Both Hypothyroidism and Hyperthyroidism Increase Atrial Fibrillation Inducibility in Rats

PubMed Central

Zhang, Youhua; Dedkov, Eduard I.; Teplitsky, Diana; Weltman, Nathan Y.; Pol, Christine J.; Rajagopalan, Viswanathan; Lee, Bianca; Gerdes, A. Martin

2014-01-01

Background Evidence indicates that cardiac hypothyroidism may contribute to heart failure (HF) progression. It is also known that HF is associated with an increased risk of atrial fibrillation (AF). While it is established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is unclear. This study investigated the effects of different thyroid hormone levels, ranging from hypothyroidism to hyperthyroidism on AF inducibility in thyroidectomized rats. Methods and Results Thyroidectomized rats with serum confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid (n=9), euthyroid (n=9) and hyperthyroid (n=9) groups. Rats received placebo, 3.3mg L-thyroxine (T4), or 20 mg T4 pellets (60 day release form) for 2 months, respectively. At the end of treatment, hypothyroid, euthyroid and hyperthyroid status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced cardiac systolic and diastolic function, while hyperthyroid rats exhibited cardiac hypertrophy and increased cardiac function. Hypothyroidism and hyperthyroidism produced opposite electrophysiological changes in heart rates and atrial effective refractory period, but both significantly increased AF susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the duration of induced AF was also longer, compared with 11% in the euthyroid group (all p<0.05). Hypothyroidism increased atrial interstitial fibrosis, but connexin 43 was not affected. Conclusions Both hypothyroidism and hyperthyroidism lead to increased AF vulnerability in a rat thyroidectomy model. Our results stress that normal thyroid hormone levels are required to maintain normal cardiac electrophysiology and prevent cardiac arrhythmias and AF. PMID:24036190

Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility in rats.

PubMed

Zhang, Youhua; Dedkov, Eduard I; Teplitsky, Diana; Weltman, Nathan Y; Pol, Christine J; Rajagopalan, Viswanathan; Lee, Bianca; Gerdes, A Martin

2013-10-01

Evidence indicates that cardiac hypothyroidism may contribute to heart failure progression. It is also known that heart failure is associated with an increased risk of atrial fibrillation (AF). Although it is established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is unclear. This study investigated the effects of different thyroid hormone levels, ranging from hypothyroidism to hyperthyroidism on AF inducibility in thyroidectomized rats. Thyroidectomized rats with serum-confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid (N=9), euthyroid (N=9), and hyperthyroid (N=9) groups. Rats received placebo, 3.3-mg l-thyroxine (T4), or 20-mg T4 pellets (60-day release form) for 2 months, respectively. At the end of treatment, hypothyroid, euthyroid, and hyperthyroid status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced cardiac systolic and diastolic functions, whereas hyperthyroid rats exhibited cardiac hypertrophy and increased cardiac function. Hypothyroidism and hyperthyroidism produced opposite electrophysiological changes in heart rates and atrial effective refractory period, but both significantly increased AF susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the duration of induced AF was also longer, compared with 11% in the euthyroid group (all P<0.05). Hypothyroidism increased atrial interstitial fibrosis, but connexin 43 was not affected. Both hypothyroidism and hyperthyroidism lead to increased AF vulnerability in a rat thyroidectomy model. Our results stress that normal thyroid hormone levels are required to maintain normal cardiac electrophysiology and to prevent cardiac arrhythmias and AF.

Tractography of Association Fibers Associated with Language Processing.

PubMed

Egger, K; Yang, S; Reisert, M; Kaller, C; Mader, I; Beume, L; Weiller, C; Urbach, H

2015-10-01

Several major association fiber tracts are known to be part of the language processing system. There is evidence that high angular diffusion-based MRI is able to separate these fascicles in a constant way. In this study, we wanted to proof this thesis using a novel whole brain "global tracking" approach and to test for possible lateralization. Global tracking was performed in six healthy right-handed volunteers for the arcuate fascicle (AF), the medial longitudinal fascicle (MdLF), the inferior fronto-occipital fascicle (IFOF), and the inferior longitudinal fascicle (ILF). These fiber tracts were characterized quantitatively using the number of streamlines (SL) and the mean fractional anisotropy (FA). We were able to characterize the AF, the MdLF, the IFOF, and the ILF consistently in six healthy volunteers using global tracking. A left-sided dominance (LI > 0.2) for the AF was found in all participants. The MdLF showed a left-sided dominance in four participants (one female, three male). Regarding the FA, no lateralization (LI > 0.2) could be shown in any of the fascicles. Using a novel global tracking algorithm we confirmed that the courses of the primary language processing associated fascicles can consistently be differentiated. Additionally we were able to show a streamline-based left-sided lateralization in the AF of all right-handed healthy subjects.

Flow Field Investigations of a Simulated Weapons Cavity at Mach 3.

DTIC Science & Technology

1981-12-01

AD-Alll 843 ARMO" ENGINEERING. DEVELOPMENT CENTER ARNOLD AFS TN F/9 14/2 FLOW FIELD INVESTIGATIONS OF A SIMULATED WEAPONS CAVITY AT MACN--ETC(U) DEC...TEST CHART .. AEDC-TSR-81-V37 FLOW FIELD INVESTIGATIONS OF A _____SIMULATED WEAPONS CAVITY AT MACH 3 _~W. A. Crosby Calspan Field Services, Inc...TYPE OF REPORT & PERIOD COVERED Final Report FLOW FIELD INVESTIGATIONS OF A SIMULATED WEAPONS 27 October 1981 CAVITY AT MACH 3 6. PERFORMING O1G

Beacon Editor: Capturing Signal Transduction Pathways Using the Systems Biology Graphical Notation Activity Flow Language.

PubMed

Elmarakeby, Haitham; Arefiyan, Mostafa; Myers, Elijah; Li, Song; Grene, Ruth; Heath, Lenwood S

2017-12-01

The Beacon Editor is a cross-platform desktop application for the creation and modification of signal transduction pathways using the Systems Biology Graphical Notation Activity Flow (SBGN-AF) language. Prompted by biologists' requests for enhancements, the Beacon Editor includes numerous powerful features for the benefit of creation and presentation.

Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

PubMed

Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

2016-01-01

A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts. Copyright © 2016 Elsevier Inc. All rights reserved.

Management of atrial fibrillation in Greece: the MANAGE-AF study.

PubMed

Andrikopoulos, George; Pastromas, Sokratis; Mantas, Ioannis; Sakellariou, Dimitris; Kyrpizidis, Christos; Makridis, Pantelis; Goumas, Georgios; Stakos, Dimitris; Gotsis, Alexandros; Kartalis, Athanasios; Kazianis, Georgios; Babalis, Dimitrios; Toli, Konstantina; Tzeis, Stylianos; Papavasileiou, Maria; Kalogeropoulos, Petros; Vardas, Panos

2014-01-01

Although atrial fibrillation (AF) is a highly prevalent health problem with high morbidity and mortality, data regarding the clinical characteristics and management of AF in the Greek population are scarce. The "Current Clinical Practice in the MANAGEment of Atrial Fibrillation in Greece" study (MANAGEAF) aimed to assess the epidemiological features as well as the daily clinical practice in the management of Greek patients with AF. Taking into consideration the distribution of the Greek population, 603 consecutive patients over 18 years of age, with any type of AF, presenting at the emergency departments or outpatient clinics of 27 different centers, were included in our study. The mean age of the patients was 68.5 ± 12.1 years, with male patients representing 52.5% of the study population. The most common AF type in our cohort was non-paroxysmal AF (60%), including the patients with permanent (24.1%), persistent (17.4%), long-standing (4.8%) and first diagnosed AF (13.8%). Hypertension was the most common comorbidity (70.3%). A history of stroke or transient ischemic attack was detected in 9.2% of the patients, while 6.2% had a history of gastrointestinal bleeding. About half of the patients (49.3%) were treated with anticoagulant drugs, mainly vitamin K antagonists (46.9%), while 34.2% were on antiplatelet drugs, aspirin and/or clopidogrel. The mean INR level (1.7 ± 0.8) was sub-therapeutic, although the mean values for CHADS2 and CHA2DS2-VASc scores were 1.6 ± 1.2 and 3.0 ± 1.7, respectively. The MANAGE-AF baseline results indicate unsatisfactory levels of compliance with the current guidelines for the management of AF in Greece. Considering the undisputed effectiveness of anticoagulant treatment for preventing AF-related strokes, MANAGE-AF demonstrates the need for optimization of our therapeutic strategies for the management of cardioembolic stroke risk.

The splicing factor U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jeonghee; Chung, In Kwon, E-mail: topoviro@yonsei.ac.kr

Highlights: •Identification of U2AF65 as a novel TRF1-interacting protein. •U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. •U2AF65 interferes with the interaction between TRF1 and Fbx4. •U2AF65 represents a new route for modulating TRF1 function at telomeres. -- Abstract: The human telomeric protein TRF1 is a component of the six-subunit protein complex shelterin, which provides telomere protection by organizing the telomere into a high-order structure. TRF1 functions as a negative regulator of telomere length by controlling the access of telomerase to telomeres. Thus, the cellular abundance of TRF1 at telomeres should be maintained and tightly regulated to ensure propermore » telomere function. Here, we identify U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor 65 (U2AF65), an essential pre-mRNA splicing factor, as a novel TRF1-interacting protein. U2AF65 interacts with TRF1 in vitro and in vivo and is capable of stabilizing TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. We also found that U2AF65 interferes with the interaction between TRF1 and Fbx4, an E3 ubiquitin ligase for TRF1. Depletion of endogenous U2AF65 expression by short interfering RNA (siRNA) reduced the stability of endogenous TRF1 whereas overexpression of U2AF65 significantly extended the half-life of TRF1. These findings demonstrate that U2AF65 plays a critical role in regulating the level of TRF1 through physical interaction and ubiquitin-mediated proteolysis. Hence, U2AF65 represents a new route for modulating TRF1 function at telomeres.« less

Using new non-invasive quick method to detect Borrelia Burgdorferi (B.B.) infection from specific parts of the heart in "seemingly normal" ECGs, and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are found to have: 1) Significant B.B. infection, 2) Markedly increased ANP, 3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4 factors were mainly localized at infected areas of the SA node area, R-&L-Atria & pulmonary veins at the L-atrium.

PubMed

Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

2015-01-01

Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224-600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224-600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100-400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4-6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times/day + Taurine 175mg x 3 times/day, with or without EPA 180 mg & DHA 120 mg, to avoid serious current limitations in the use of Doxycycline 100 mg 2 times/day, for 4 weeks.

Dynamics of Dengue Virus (DENV)-Specific B Cells in the Response to DENV Serotype 1 Infections, Using Flow Cytometry With Labeled Virions.

PubMed

Woda, Marcia; Friberg, Heather; Currier, Jeffrey R; Srikiatkhachorn, Anon; Macareo, Louis R; Green, Sharone; Jarman, Richard G; Rothman, Alan L; Mathew, Anuja

2016-10-01

The development of reagents to identify and characterize antigen-specific B cells has been challenging. We recently developed Alexa Fluor-labeled dengue viruses (AF DENVs) to characterize antigen-specific B cells in the peripheral blood of DENV-immune individuals. In this study, we used AF DENV serotype 1 (AF DENV-1) together with AF DENV-2 on peripheral blood mononuclear cells (PBMCs) from children in Thailand with acute primary or secondary DENV-1 infections to analyze the phenotypes of antigen-specific B cells that reflected their exposure or clinical diagnosis. DENV serotype-specific and cross-reactive B cells were identified in PBMCs from all subjects. Frequencies of AF DENV(+) class-switched memory B cells (IgD(-)CD27(+) CD19(+) cells) reached up to 8% during acute infection and early convalescence. AF DENV-labeled B cells expressed high levels of CD27 and CD38 during acute infection, characteristic of plasmablasts, and transitioned into memory B cells (CD38(-)CD27(+)) at the early convalescent time point. There was higher activation of memory B cells early during acute secondary infection, suggesting reactivation from a previous DENV infection. AF DENVs reveal changes in the phenotype of DENV serotype-specific and cross-reactive B cells during and after natural DENV infection and could be useful in analysis of the response to DENV vaccination. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Risk of stroke and heart failure attributable to atrial fibrillation in middle-aged and elderly people: Results from a five-year prospective cohort study of Japanese community dwellers.

PubMed

Ohsawa, Masaki; Okamura, Tomonori; Tanno, Kozo; Ogasawara, Kuniaki; Itai, Kazuyoshi; Yonekura, Yuki; Konishi, Kazuki; Omama, Shinichi; Miyamatsu, Naomi; Turin, Tanvir Chowdhury; Morino, Yoshihiro; Itoh, Tomonori; Onoda, Toshiyuki; Sakata, Kiyomi; Ishibashi, Yasuhiro; Makita, Shinji; Nakamura, Motoyuki; Tanaka, Fumitaka; Kuribayashi, Toru; Ohta, Mutsuko; Okayama, Akira

2017-08-01

The relative and absolute risks of stroke and heart failure attributable to atrial fibrillation (AF) have not been sufficiently examined. A prospective study of 23,731 community-dwelling Japanese individuals was conducted. Participants were divided into two groups based on the presence or absence of prevalent AF (n = 338 and n = 23,393, respectively). Excess events (EE) due to AF and relative risks (RRs) determined using the non-AF group as the reference for incident stroke and heart failure were estimated using Poisson regression stratified by age groups (middle-aged: 40-69 years old; elderly: 70 years of age or older) after adjustment for sex and age. There were 611 cases of stroke and 98 cases of heart failure during the observation period (131,088 person-years). AF contributed to a higher risk of stroke both in middle-aged individuals (EE 10.4 per 1000 person-years; RR 4.88; 95% confidence interval [CI], 2.88-8.29) and elderly individuals (EE 18.3 per 1000 person-years; RR 3.05; 95% CI, 2.05-4.54). AF also contributed to a higher risk of heart failure in middle-aged individuals (EE 3.7 per 1000 person-years; RR 8.18; 95% CI, 2.41-27.8) and elderly individuals (EE 15.4 per 1000 person-years; RR 7.82; 95% CI, 4.11-14.9). Results obtained from multivariate-adjusted analysis were similar (stroke: EE 8.9 per 1000 person-years; RR 4.40; 95% CI, 2.57-7.55 in middle-aged and EE 17.4 per 1000 person-years; RR 2.97; 95% CI, 1.99-4.43 in elderly individuals; heart failure: EE 3.1 per 1000 person-years; RR 7.22; 95% CI, 2.06-25.3 in middle-aged and EE 14.1 per 1000 person-years; RR 7.41; 95% CI, 3.86-14.2 in elderly individuals). AF increased the risk of stroke by the same magnitude as that reported previously in Western countries. AF increased the RR of heart failure more than that in Western populations. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

A novel approach to restore atrial function after the maze procedure in patients with an enlarged left atrium.

PubMed

Marui, Akira; Tambara, Keiichi; Tadamura, Eiji; Saji, Yoshiaki; Sasahashi, Nozomu; Ikeda, Tadashi; Nishina, Takeshi; Komeda, Masashi

2007-08-01

Left atrial (LA) volume reduction surgery concomitant with the maze procedure has been reported to facilitate sinus rhythm recovery even in patients with refractory atrial fibrillation (AF) with an enlarged LA. However, it is unknown whether the procedures can also restore effective atrial function of the enlarged LA with over-stretched myocardium. The maze procedures in association with mitral valve surgery were performed to 57 AF patients with an enlarged LA (LA diameter >or=60mm). Among them, 32 patients had concomitant LA volume reduction surgery (VR group). Another 25 patients did not have the volume reduction (control group). Three months postoperatively LA end-diastolic volume (LAEDV, ml) assessed by magnetic resonance (MR) imaging was larger in the VR group than that in the control group (291+/-117 vs 223+/-81 ml, p<0.05). Postoperatively, sinus rhythm recovery rate was better (84 vs 68%, p<0.05) and LAEDV was drastically smaller (118+/-48 vs 203+/-76 ml, p<0.001) in the VR group than those in the control group. Among the patients with sinus rhythm recovery in both groups, LA contraction ejection fraction (%) improved in the VR group but not in the control group (22.3+/-7.8 vs 10.3+/-4.7%, p<0.001). The LA volume reduction surgery concomitant with the maze procedure restored contraction of the enlarged LA; however, the maze procedure alone did not restore LA contraction in spite of successful sinus rhythm recovery. LA volume reduction surgery may be desirable to the patients with refractory AF with over-stretched LA.

Validation of a next-generation sequencing assay for clinical molecular oncology.

PubMed

Cottrell, Catherine E; Al-Kateb, Hussam; Bredemeyer, Andrew J; Duncavage, Eric J; Spencer, David H; Abel, Haley J; Lockwood, Christina M; Hagemann, Ian S; O'Guin, Stephanie M; Burcea, Lauren C; Sawyer, Christopher S; Oschwald, Dayna M; Stratman, Jennifer L; Sher, Dorie A; Johnson, Mark R; Brown, Justin T; Cliften, Paul F; George, Bijoy; McIntosh, Leslie D; Shrivastava, Savita; Nguyen, Tudung T; Payton, Jacqueline E; Watson, Mark A; Crosby, Seth D; Head, Richard D; Mitra, Robi D; Nagarajan, Rakesh; Kulkarni, Shashikant; Seibert, Karen; Virgin, Herbert W; Milbrandt, Jeffrey; Pfeifer, John D

2014-01-01

Currently, oncology testing includes molecular studies and cytogenetic analysis to detect genetic aberrations of clinical significance. Next-generation sequencing (NGS) allows rapid analysis of multiple genes for clinically actionable somatic variants. The WUCaMP assay uses targeted capture for NGS analysis of 25 cancer-associated genes to detect mutations at actionable loci. We present clinical validation of the assay and a detailed framework for design and validation of similar clinical assays. Deep sequencing of 78 tumor specimens (≥ 1000× average unique coverage across the capture region) achieved high sensitivity for detecting somatic variants at low allele fraction (AF). Validation revealed sensitivities and specificities of 100% for detection of single-nucleotide variants (SNVs) within coding regions, compared with SNP array sequence data (95% CI = 83.4-100.0 for sensitivity and 94.2-100.0 for specificity) or whole-genome sequencing (95% CI = 89.1-100.0 for sensitivity and 99.9-100.0 for specificity) of HapMap samples. Sensitivity for detecting variants at an observed 10% AF was 100% (95% CI = 93.2-100.0) in HapMap mixes. Analysis of 15 masked specimens harboring clinically reported variants yielded concordant calls for 13/13 variants at AF of ≥ 15%. The WUCaMP assay is a robust and sensitive method to detect somatic variants of clinical significance in molecular oncology laboratories, with reduced time and cost of genetic analysis allowing for strategic patient management. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

d,l-Sotalol reverses abbreviated atrial refractoriness and prevents promotion of atrial fibrillation in a canine model with left ventricular dysfunction induced by atrial tachypacing.

PubMed

Sakamoto, Tamotsu; Fujiki, Akira; Nakatani, Yosuke; Sakabe, Masao; Mizumaki, Koichi; Hashimoto, Norio; Inoue, Hiroshi

2009-10-01

This study evaluated antiarrhythmic effects of d,l-sotalol in a canine atrial fibrillation (AF) model with left ventricular dysfunction. Thirteen beagles (Sotalol group n=7 and Control group n=6) were subjected to atrial tachypacing (ATP) (400 beats/min) with intact atrioventricular conduction for 4 weeks. Oral d,l-sotalol (2 mg/kg) was administered 1 week after starting ATP and continued throughout the experiment. One week after starting ATP, atrial effective refractory periods (AERPs) were shortened in both groups. However, d,l-sotalol treatment gradually prolonged AERP, resulting in a significant prolongation of AERP compared with the Control group at 4 weeks (Control 76 +/-4 and Sotalol 126 +/-5 ms, p<0.01). d,l-Sotalol treatment showed lower AF inducibility and shorter AF duration at 4 weeks. In the control group, expressions of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA were downregulated by 46.2% and 43.0%, respectively, after 4 weeks of ATP; d,l-sotalol treatment did not affect these changes. d,l-Sotalol treatment prolonged AERP, even after atrial electrical remodeling had developed, and prevented AF perpetuation without affecting downregulated expression of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA in an ATP-induced canine AF model.

Does a patent foramen ovale matter when using a remote-controlled magnetic system for pulmonary vein isolation?

PubMed

Gate-Martinet, Alexie; Da Costa, Antoine; Romeyer-Bouchard, Cécile; Bisch, Laurence; Levallois, Marie; Isaaz, Karl

2014-02-01

Pulmonary vein isolation (PVI) takes longer when using a patent foramen ovale (PFO) compared with a transseptal puncture in paroxysmal atrial fibrillation (AF) with manual catheter ablation. To our knowledge, no data exist concerning the impact of a PFO on AF ablation procedure variables when using a remote magnetic navigation (RMN) system. To assess the impact of a PFO when using an RMN system in patients requiring AF ablation. Between December 2011 and December 2012, catheter ablation was performed remotely using the CARTO(®) 3 system in 167 consecutive patients who underwent PVI for symptomatic drug-refractory AF. The radiofrequency generator was set to a fixed power ≤ 35 W. The primary endpoint was wide-area circumferential PVI confirmed by spiral catheter recording during ablation for all patients and including additional lesion lines (left atrial roof) or complex fractionated atrial electrograms for persistent AF. Secondary endpoints included procedural data. Mean age 58±10 years; 18% women; 107 (64%) patients with symptomatic paroxysmal AF; 60 (36%) with persistent AF; CHA2DS2-VASc score 1.2 ± 1. The PFO presence was evidenced in 49/167 (29.3%) patients during the procedure but in only 26/167 (16%) by transoesophageal echocardiography. Median procedure time 2.5 ± 1 hours; median total X-ray exposure time 14 ± 7 minutes; transseptal puncture and catheter positioning time 7.5 ± 5 minutes; left atrium electroanatomical reconstruction time 3 ± 2.3 minutes; catheter ablation time 3 ± 3 minutes. No procedure time or X-ray exposure differences were observed between patients with or without a PFO during magnetic navigation catheter ablation. X-ray exposure time was significantly reduced using a PFO compared with double transseptal puncture access. A PFO does not affect magnetic navigation during AF ablation; procedure times and X-ray exposure were similar. Septal catheter probing is mandatory to limit X-ray exposure and prevent potential complications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Associations Between Neutrophil Gelatinase Associated Lipocalin, Neutrophil-to-Lymphocyte Ratio, Atrial Fibrillation and Renal Dysfunction in Chronic Heart Failure

PubMed Central

Argan, Onur; Ural, Dilek; Kozdag, Guliz; Sahin, Tayfun; Bozyel, Serdar; Aktas, Mujdat; Karauzum, Kurtulus; Yılmaz, Irem; Dervis, Emir; Agir, Aysen

2016-01-01

Background Atrial fibrillation (AF) and renal dysfunction are two common comorbidities in patients with chronic heart failure with reduced ejection fraction (HFrEF). This study evaluated the effect of permanent AF on renal function in HFrEF and investigated the associations of atrial fibrillation, neutrophil gelatinase-associated lipocalin (NGAL), and neutrophil-to-lymphocyte ratio (NLR) with adverse clinical outcome. Material/Methods Serum NGAL levels measured by ELISA and NLR were compared between patients with sinus rhythm (HFrEF-SR, n=68), with permanent AF (HFrEF-AF, n=62), and a healthy control group (n=50). Results Mean eGFR levels were significantly lower, and NLR and NGAL levels were significantly higher in the HFrEF patients than in the control patients but the difference between HFrEF-SR and HFrEF-AF was not statistically significant (NGAL: 95 ng/mL in HFrEF-SR, 113 ng/mL in HFrEF-AF and 84 ng/mL in the control group; p<0.001). Independent associates of baseline eGFR were age, hemoglobin, NLR, triiodothyronine, and pulmonary artery systolic pressure. In a mean 16 months follow-up, adverse clinical outcome defined as progression of kidney dysfunction and composite of all-cause mortality and re-hospitalization were not different between HFrEF-SR and HFrEF-AF patients. Although NGAL was associated with clinical endpoints in the univariate analysis, Cox regression analysis showed that independent predictors of increased events were the presence of signs right heart failure, C-reactive protein, NLR, triiodothyronine, and hemoglobin. In ROC analysis, a NLR >3 had a 68% sensitivity and 75% specificity to predict progression of kidney disease (AUC=0.72, 95% CI 0.58–0.85, p=0.001). Conclusions Presence of AF in patients with HFrEF was not an independent contributor of adverse clinical outcome (i.e., all-cause death, re-hospitalization) or progression of renal dysfunction. Renal dysfunction in HFrEF was associated with both NLR and NGAL levels, but systemic inflammation reflected by NLR seemed to be a more important determinant of progression of kidney dysfunction. PMID:27918494

Atrial Fibrillation Detection During 24-Hour Ambulatory Blood Pressure Monitoring: Comparison With 24-Hour Electrocardiography.

PubMed

Kollias, Anastasios; Destounis, Antonios; Kalogeropoulos, Petros; Kyriakoulis, Konstantinos G; Ntineri, Angeliki; Stergiou, George S

2018-07-01

This study assessed the diagnostic accuracy of a novel 24-hour ambulatory blood pressure (ABP) monitor (Microlife WatchBP O3 Afib) with implemented algorithm for automated atrial fibrillation (AF) detection during each ABP measurement. One hundred subjects (mean age 70.6±8.2 [SD] years; men 53%; hypertensives 85%; 17 with permanent AF; 4 paroxysmal AF; and 79 non-AF) had simultaneous 24-hour ABP monitoring and 24-hour Holter monitoring. Among a total of 6410 valid ABP readings, 1091 (17%) were taken in ECG AF rhythm. In reading-to-reading ABP analysis, the sensitivity, specificity, and accuracy of ABP monitoring in detecting AF were 93%, 87%, and 88%, respectively. In non-AF subjects, 12.8% of the 24-hour ABP readings indicated false-positive AF, of whom 27% were taken during supraventricular premature beats. There was a strong association between the proportion of false-positive AF readings and that of supraventricular premature beats ( r =0.67; P <0.001). Receiver operating characteristic curve revealed that in paroxysmal AF and non-AF subjects, AF-positive readings at 26% during 24-hour ABP monitoring had 100%/85% sensitivity/specificity (area under the curve 0.91; P <0.01) for detecting paroxysmal AF. These findings suggest that in elderly hypertensives, a novel 24-hour ABP monitor with AF detector has high sensitivity and moderate specificity for AF screening during routine ABP monitoring. Thus, in elderly hypertensives, a 24-hour ABP recording with at least 26% of the readings suggesting AF indicates a high probability for AF diagnosis and should be regarded as an indication for performing 24-hour Holter monitoring. © 2018 American Heart Association, Inc.

Characterizing Enterovirus 71 and Coxsackievirus A16 virus-like particles production in insect cells.

PubMed

Somasundaram, Balaji; Chang, Cindy; Fan, Yuan Y; Lim, Pei-Yin; Cardosa, Jane; Lua, Linda

2016-02-15

Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are two viruses commonly responsible for hand, foot and mouth disease (HFMD) in children. The lack of prophylactic or therapeutic measures against HFMD is a major public health concern. Insect cell-based EV71 and CVA16 virus-like particles (VLPs) are promising vaccine candidates against HFMD and are currently under development. In this paper, the influence of insect cell line, incubation temperature, and serial passaging effect and stability of budded virus (BV) stocks on EV71 and CVA16 VLP production was investigated. Enhanced EV71 and CVA16 VLP production was observed in Sf9 cells compared to High Five™ cells. Lowering the incubation temperature from the standard 27°C to 21°C increased the production of both VLPs in Sf9 cells. Serial passaging of CVA16 BV stocks in cell culture had a detrimental effect on the productivity of the structural proteins and the effect was observed with only 5 passages of BV stocks. A 2.7× higher production yield was achieved with EV71 compared to CVA16. High-resolution asymmetric flow field-flow fractionation couple with multi-angle light scattering (AF4-MALS) was used for the first time to characterize EV71 and CVA16 VLPs, displaying an average root mean square radius of 15±1nm and 15.3±5.8 nm respectively. This study highlights the need for different approaches in the design of production process to develop a bivalent EV71 and CVA16 vaccine. Copyright © 2015 Elsevier Inc. All rights reserved.

Analytical assessment about the simultaneous quantification of releasable pharmaceutical relevant inorganic nanoparticles in tap water and domestic waste water.

PubMed

Krystek, Petra; Bäuerlein, Patrick S; Kooij, Pascal J F

2015-03-15

For pharmaceutical applications, the use of inorganic engineered nanoparticles is of growing interest while silver (Ag) and gold (Au) are the most relevant elements. A few methods were developed recently but the validation and the application testing were quite limited. Therefore, a routinely suitable multi element method for the identification of nanoparticles of different sizes below 100 nm and elemental composition by applying asymmetric flow field flow fraction (AF4) - inductively coupled plasma mass spectrometry (ICPMS) is developed. A complete validation model of the quantification of releasable pharmaceutical relevant inorganic nanoparticles based on Ag and Au is presented for the most relevant aqueous matrices of tap water and domestic waste water. The samples are originated from locations in the Netherlands and it is of great interest to study the unwanted presence of Ag and Au as nanoparticle residues due to possible health and environmental risks. During method development, instability effects are observed for 60 nm and 70 nm Ag ENPs with different capping agents. These effects are studied more closely in relation to matrix effects. Besides the methodological aspects, the obtained analytical results and relevant performance characteristics (e.g. measuring range, limit of detection, repeatability, reproducibility, trueness, and expanded uncertainty of measurement) are determined and discussed. For the chosen aqueous matrices, the results of the performance characteristics are significantly better for Au ENPs in comparison to Ag ENPs; e.g. repeatability and reproducibility are below 10% for all Au ENPs respectively maximal 27% repeatability for larger Ag ENPs. The method is a promising tool for the simultaneous determination of releasable pharmaceutical relevant inorganic nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

Extensive Ameloblastic Fibroma in an Adolescent Patient: A Case Report with a Follow-Up of 4 Years

PubMed Central

Pitak-Arnnop, Poramate; Chaine, André; Dhanuthai, Kittipong; Bertrand, Jacques-Charles; Bertolus, Chloé

2009-01-01

Ameloblastic fibroma (AF) is a rare odontogenic tumour of the jaw which usually occurs in the first 2 decades of life. The common clinical manifestation is a slow-growing swelling. We report a case of a 16-year-old male patient presenting with extensive AF of the mandible. He underwent a conservative enucleation. The tumour recurred 2 years after the initial surgery, requiring the second enucleation. The patient has continued to be followed closely and has been disease-free for 4 years. Recent evidence suggests that the recurrent rate of AF is relatively high, and malignant transformation of AF may occur after recurrences or multiple surgeries. A conservative treatment approach with close surveillance is recommended. Anatomical limitations should be taken into account, especially when enucleation of AF in the posterior portion of the jaw is performed. Current surgical pathologic issues of the tumour are also discussed. PMID:19756198

An Application of Quality Control Theory to Vendor-Supplied Parts at an Aerospace Manufacturing Company.

DTIC Science & Technology

1985-08-01

presently used on the ATF3-6, TFE731 -2, -3, TPE331, GTCP660 and TSCP700 engines. Substantiation Metallurgical V Testing Tnstructions Control Part Name Part... TFE731 -2, -3 Fan 3072162 Ti-6-4 5001 C1.-2 L’$S52458 1st Stg.Comp. 3072193 Ti-6-4 5001 C1.-l AF5395 2nd Stg.Comp. 3072191 Ti-6-4 5001 CI.-I AF5395 W...Control Part Nam~e Part No. material (STIT~eouirernents Specification TFE731 -2, -3 4th Stg.Conp. 3072.93 Ti-6-4 5001 C1.-1 AF5395 HP Comp. 3072639 Ti-6-2

Reduction of Aspergillus spp. and aflatoxins in peanut sauce processing by oil-less frying of chilli powder and retort processing.

PubMed

Farawahida, A H; Jinap, S; Nor-Khaizura, M A R; Samsudin, N I P

2017-12-01

Among the many roles played by small and medium enterprises (SMEs) in the food industry is the production of heritage foods such as peanut sauce. Unfortunately, the safety of peanut sauce is not always assured as the processing line is not controlled. Peanut sauce is usually made of peanuts and chilli, and these commodities are normally contaminated with Aspergillus spp. and aflatoxins (AFs). Hence, the objective of this study was to evaluate the practices related to reduction of AF hazard and the effect of interventions in peanut sauce processing. Peanut samples were collected from each step of peanut sauce processing from a small peanut sauce company according to four designs: (1) control; (2) oil-less frying of chilli powder; (3) addition of retort processing; and (4) combination of oil-less frying of chilli powder and retort processing. Oil-less frying of chilli powder (Design 2) reduced total AFs by 33-41%, retort processing (Design 3) reduced total AFs by 49%, while combination of these two thermal processes (Design 4) significantly reduced total AFs, by 57%. The present work demonstrated that Design 4 yielded the highest reduction of total AFs and is therefore recommended to be employed by SME companies.

A systematic approach to designing reliable VV optimization methodology: assessment of internal validity of echocardiographic, electrocardiographic and haemodynamic optimization of cardiac resynchronization therapy.

PubMed

Kyriacou, Andreas; Li Kam Wa, Matthew E; Pabari, Punam A; Unsworth, Beth; Baruah, Resham; Willson, Keith; Peters, Nicholas S; Kanagaratnam, Prapa; Hughes, Alun D; Mayet, Jamil; Whinnett, Zachary I; Francis, Darrel P

2013-08-10

In atrial fibrillation (AF), VV optimization of biventricular pacemakers can be examined in isolation. We used this approach to evaluate internal validity of three VV optimization methods by three criteria. Twenty patients (16 men, age 75 ± 7) in AF were optimized, at two paced heart rates, by LVOT VTI (flow), non-invasive arterial pressure, and ECG (minimizing QRS duration). Each optimization method was evaluated for: singularity (unique peak of function), reproducibility of optimum, and biological plausibility of the distribution of optima. The reproducibility (standard deviation of the difference, SDD) of the optimal VV delay was 10 ms for pressure, versus 8 ms (p=ns) for QRS and 34 ms (p<0.01) for flow. Singularity of optimum was 85% for pressure, 63% for ECG and 45% for flow (Chi(2)=10.9, p<0.005). The distribution of pressure optima was biologically plausible, with 80% LV pre-excited (p=0.007). The distributions of ECG (55% LV pre-excitation) and flow (45% LV pre-excitation) optima were no different to random (p=ns). The pressure-derived optimal VV delay is unaffected by the paced rate: SDD between slow and fast heart rate is 9 ms, no different from the reproducibility SDD at both heart rates. Using non-invasive arterial pressure, VV delay optimization by parabolic fitting is achievable with good precision, satisfying all 3 criteria of internal validity. VV optimum is unaffected by heart rate. Neither QRS minimization nor LVOT VTI satisfy all validity criteria, and therefore seem weaker candidate modalities for VV optimization. AF, unlinking interventricular from atrioventricular delay, uniquely exposes resynchronization concepts to experimental scrutiny. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Oral gold compound auranofin triggers arachidonate release and cyclooxygenase metabolism in the alveolar macrophage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters-Golden, M.; Shelly, C.

1988-12-01

We examined the effect of in vitro incubation with the oral gold compound auranofin (AF) on arachidonic acid (AA) release and metabolism by rat alveolar macrophages (AMs). AF stimulated dose- and time-dependent release of /sup 14/C-AA from prelabeled AMs, which reached 4.7 +/- 0.3% (mean +/- SEM) of incorporated radioactivity at 10 micrograms/ml for 90 min, as compared to 0.5 +/- 0.1% release following control incubation for 90 min (p less than 0.001). Similar dose- and time-dependent synthesis of thromboxane (Tx) A2 (measured as TxB2) and prostaglandin (PG) E2 was demonstrated by radioimmunoassay of medium from unlabeled cultures, reaching 18-foldmore » and 9-fold, respectively, of the control values at 10 micrograms/ml AF for 90 min (p less than 0.001 for both). AF-induced TxB2 and PGE2 synthesis was inhibited by indomethacin as well as by pretreatment with methylprednisolone. No increase in the synthesis of immunoreactive leukotrienes (LT) B4 or C4 was noted at any dose or time of AF. High performance liquid chromatographic separation of /sup 14/C-eicosanoids synthesized by prelabeled AMs confirmed that AF induced the release of free AA and its metabolism to cyclooxygenase, but not 5-lipoxygenase, metabolites. The ability of AF to trigger macrophage AA metabolism may be relevant to the exacerbation of certain inflammatory processes which sometimes accompany gold therapy.« less

POW/MIA Issues. Volume 3. Appendixes

DTIC Science & Technology

1994-01-01

RANDS Johansen Charles SSgt/AF- 4 July 52 TFRM A611 RMC B-29/Photo op Vernon 19124748 TFRS 91st Strat RANDM Recon RANDS Rivers Bernard SSgt/AF- 4 July 52...Pvt Bellar, Bennie E. RA14326111 Cpl Beller, James E. RA18333098 Pvt Bernard , Elton J RA18281438 Cpl Besemer, Robert L. RA16263944 Cpl Billigmeier... Bernard AF31378023 Airman 1st class Mooradian, Ara A0932011 Capt Moore, John G. A0886003 Capt Myers, Thomas E. 13136A Capt Nelson, Lawrence A. A02221692

One-pot formation of 1,3,4-oxadiazol-2(3H)-ones and dibenzo[c,e]azepines by concomitant cathodic reduction of diazonium salts and phenanthrenequinones.

PubMed

Batanero, Belen; Barba, Fructuoso; Martin, Avelino

2013-09-20

The one-pot concomitant electrochemical reduction of phenanthrenequinones (1, 2) and arenediazonium salts (3a-f) led to the formation of 1,3,4-oxadiazol-2(3H)-ones (4a-f, 5a) and dibenzo[c,e]azepines (6a-f) when N-methylformamide was used as the solvent. A new pathway, different from those previously described with other aprotic solvents, is proposed. The experimental data support a radical mechanism for the electrochemical process followed by an internal rearrangement to give the products.

The cost savings of newer oral anticoagulants in atrial fibrillation-related stroke prevention
.

PubMed

Masbah, Norliana; Macleod, Mary Joan

2017-03-01

Newer oral anticoagulants (NOACs) are considered as better alternatives compared to warfarin for stroke prevention in atrial fibrillation (AF) in terms of clinical effectiveness although the drug acquisition cost is more substantial. This study determined the direct stroke costs based on inpatient hospitalization in a subgroup of the National Health Service (NHS) Grampian, Scotland, stroke patients, to evaluate the differences in costs related to AF stroke, and to ascertain whether the use of NOACs within this study population would produce greater cost savings. Hospitalization records over 5 years involving 3,601 stroke patients were analyzed. Direct costs were based on the costs of inpatient length of stay per day. The potential cost savings if AF patients had been on NOACs were estimated using efficacy data from a landmark clinical trial involving rivaroxaban. Out of the total stroke cases, 29.5% of total stroke cases were secondary to AF, and these cases were more severe with longer hospitalizations. Only 254 patients (39.4%) with confirmed AF were anticoagulated with warfarin prior to admission. AF patients incurred higher median costs (£4,719 (interquartile range (IQR) £1,815 - £12,452) compared to non-AF patients (£3,267 (IQR £1,175 - £11,368)), although the association was statistically insignificant. The use of NOACs in AF-related patients with ischemic strokes would potentially prevent more strokes (leading to 58 fewer cases in comparison to warfarin), resulting in 17.1% in total cost reduction. AF stroke patients incurred higher total direct costs compared to non-AF cases. However, more cost savings were evident with NOACs, due to more strokes being prevented through the use of NOACs compared to warfarin.
.

Atrial ectopy predicts late recurrence of atrial fibrillation after pulmonary vein isolation.

PubMed

Gang, Uffe J O; Nalliah, Chrishan J; Lim, Toon Wei; Thiagalingam, Aravinda; Kovoor, Pramesh; Ross, David L; Thomas, Stuart P

2015-06-01

Late recurrence of atrial fibrillation (AF) after radiofrequency ablation remains significant. Asymptomatic recurrence poses a difficult clinical problem as it is associated with an equally increased risk of stroke and death compared with symptomatic AF events. Meta-analyses reveal that no single preablation patient characteristic efficiently predicts these AF recurrences. This study aimed to evaluate the prognostic value of premature atrial complex (PAC) occurrence with regard to the risk of late AF recurrence after radiofrequency ablation. The study cohort consisted of 124 patients with 7-day Holter recordings at 6 months post radiofrequency ablation for AF. No patients had AF recurrence before this time. Patients were followed-up every 6 months. Holter-detected PACs were defined as any supraventricular complexes occurring >30% earlier than expected. During a median follow-up of 4.2 years (first quartile to third quartile [Q1-Q3]=1.6-4.5), 32 patients (26%) had late recurrences of AF at a median of 462 days (Q1-Q3=319-1026) post radiofrequency ablation. The number of PACs per 24 hours was 248 (Q1-Q3=62-1026) in patients with and 77 (Q1-Q3=24-448) in patients without recurrence of AF (P=0.02). Multivariate analysis of the risk of late AF recurrence found ≥142 PACs per 24 hours to have a hazard ratio 2.84 (confidence interval, 1.26-6.43), P=0.01. This study showed that occurrence of ≥142 PACs per day at 6 months after PVI was independently associated with a significantly increased risk of late AF recurrence. These results could have important clinical implications for the design of post-PVI follow-up. URL: http://www.anzctr.org.au. Unique identifier: ACRTN12606000467538. © 2015 American Heart Association, Inc.

Quantitative fundus autofluorescence in recessive Stargardt disease.

PubMed

Burke, Tomas R; Duncker, Tobias; Woods, Russell L; Greenberg, Jonathan P; Zernant, Jana; Tsang, Stephen H; Smith, R Theodore; Allikmets, Rando; Sparrow, Janet R; Delori, François C

2014-05-01

To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1). A total of 42 STGD1 patients (ages: 7-52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III. Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease. Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials.

Quantitative Fundus Autofluorescence in Recessive Stargardt Disease

PubMed Central

Burke, Tomas R.; Duncker, Tobias; Woods, Russell L.; Greenberg, Jonathan P.; Zernant, Jana; Tsang, Stephen H.; Smith, R. Theodore; Allikmets, Rando; Sparrow, Janet R.; Delori, François C.

2014-01-01

Purpose. To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1). Methods. A total of 42 STGD1 patients (ages: 7–52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III. Results. Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease. Conclusions. Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials. PMID:24677105

Birth weight and the risk of atrial fibrillation in whites and African Americans: the Atherosclerosis Risk In Communities (ARIC) study.

PubMed

Lawani, Sherifat O; Demerath, Ellen W; Lopez, Faye L; Soliman, Elsayed Z; Huxley, Rachel R; Rose, Kathryn M; Alonso, Alvaro

2014-05-26

Low birth weight (LBW) has been associated with an increased risk of cardiovascular disease (CVD). A previous study, however, found higher risk of atrial fibrillation (AF) in individuals with higher birth weight (BW). To further understand this apparent paradox, we examined the relationship between AF and BW in the Atherosclerosis Risk in Communities (ARIC) cohort. The analysis included 10,132 individuals free of AF at baseline (1996-1998), who provided BW information, were not born premature, and were not a twin. Self-reported BW was categorized as low (<2.5 kg), medium (2.5-4 kg), and high (>4.0 kg). AF incidence was ascertained from hospital discharge codes and death certificates. We used multivariable Cox proportional hazard models to determine the hazard ratios (HR) and 95% confidence intervals (CI) of AF across BW groups. During an average follow-up of 10.3 years, we identified 882 incident AF cases. LBW was associated with higher risk of AF. Compared to individuals in the medium BW category, the HR (95% CI) of AF was 1.33 (0.99, 1.78) for LBW and 1.00 (0.81, 1.24) for high BW after adjusting for sociodemographic variables (p for trend = 0.29). Additional adjustment for CVD risk factors did not attenuate the associations (HR 1.42, 95% CI 1.06, 1.90 for LBW and HR 0.86, 95% CI 0.69-1.07 for high BW, compared to medium BW, p for trend = 0.01). LBW was associated with a higher risk of AF. This association was independent of known predictors of AF and is consistent with that observed for other cardiovascular diseases.

Atrial rhythm influences catheter tissue contact during radiofrequency catheter ablation of atrial fibrillation: comparison of contact force between sinus rhythm and atrial fibrillation.

PubMed

Matsuda, Hisao; Parwani, Abdul Shokor; Attanasio, Philipp; Huemer, Martin; Wutzler, Alexander; Blaschke, Florian; Haverkamp, Wilhelm; Boldt, Leif-Hendrik

2016-09-01

Catheter tissue contact force (CF) is an important factor for durable lesion formation during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Since CF varies in the beating heart, atrial rhythm during RFCA may influence CF. A high-density map and RFCA points were obtained in 25 patients undergoing RFCA of AF using a CF-sensing catheter (Tacticath, St. Jude Medical). The operators were blinded to the CF information. Contact type was classified into three categories: constant, variable, and intermittent contact. Average CF and contact type were analyzed according to atrial rhythm (SR vs. AF) and anatomical location. A total of 1364 points (891 points during SR and 473 points during AF) were analyzed. Average CFs showed no significant difference between SR (17.2 ± 11.3 g) and AF (17.2 ± 13.3 g; p = 0.99). The distribution of points with an average CF of ≥20 and <10 g also showed no significant difference. However, the distribution of excessive CF (CF ≥40 g) was significantly higher during AF (7.4 %) in comparison with SR (4.2 %; p < 0.05). At the anterior area of the right inferior pulmonary vein (RIPV), the average CF during AF was significantly higher than during SR (p < 0.05). Constant contact was significantly higher during AF (32.2 %) when compared to SR (9.9 %; p < 0.01). Although the average CF was not different between atrial rhythms, constant contact was more often achievable during AF than it was during SR. However, excessive CF also seems to occur more frequently during AF especially at the anterior part of RIPV.

ACUTE TERMINATION OF HUMAN ATRIAL FIBRILLATION BY IDENTIFICATION AND CATHETER ABLATION OF LOCALIZED ROTORS AND SOURCES

PubMed Central

Shivkumar, Kalyanam; Ellenbogen, Kenneth A.; Hummel, John D.; Miller, John M.; Steinberg, Jonathan S.

2012-01-01

Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets. METHODS We prospectively enrolled the first (n=14, 11 males) consecutive patients undergoing FIRM guided ablation for persistent (n=11) and paroxysmal AF at 5 centers. A 64 pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10 % cycle length prolongation). Conventional ablation was performed only after FIRM guided ablation. RESULTS 12/14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9±0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n=8 (4.9±3.9 min at the primary source), and organization in n=4. Total FIRM time for all patients was 12.3±8.6 min. CONCLUSIONS FIRM guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation. PMID:23130890

Prevalence, Management, and Long-Term (6-Year) Outcomes of Atrial Fibrillation Among Patients Receiving Drug-Eluting Coronary Stents.

PubMed

Choi, Hyo-In; Ahn, Jung-Min; Kang, Se Hun; Lee, Pil Hyung; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Lee, Cheol Whan; Park, Seong-Wook; Park, Duk-Woo; Park, Seung-Jung

2017-06-12

This study sought to investigate the incidence, management, and clinical relevance of atrial fibrillation (AF) during and after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and evaluate outcomes of different antithrombotic strategies. Uncertainty exists regarding the optimal antithrombotic strategy in patients with AF who are undergoing PCI with DES. Using a consecutive series of 10,027 patients who underwent DES implantation between 2003 and 2011, we evaluated the overall prevalence and clinical impact of AF. In addition, we compared the efficacy and safety of dual antiplatelet therapy (DAPT) (aspirin plus clopidogrel) and triple therapy (DAPT plus warfarin) among patients with AF. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. Overall, 711 (7.1%) patients had a diagnosis of AF at the index PCI. Patients with AF were older, had more comorbid conditions, and more often had a history of strokes; most patients with AF (88.4%) received DAPT rather than triple therapy (10.5%) at discharge. The rate of primary outcome after PCI during the 6-year follow-up period was significantly higher in patients with AF than in those without AF (22.1% vs. 8.0%; p < 0.001). This trend was consistent for major bleeding (4.5% vs. 1.5%; p < 0.001). After multivariable adjustment, the presence of AF was significantly associated with a higher risk of primary outcome (hazard ratio [HR]: 2.33; 95% confidence interval [CI]: 1.95 to 2.79; p < 0.001) and major bleeding (HR: 2.01; 95% CI: 1.32 to 3.06; p = 0.001). Among patients with AF, adjusted risk for the primary outcome was similar between the DAPT group and the triple therapy group (HR: 1.01; 95% CI: 0.60 to 1.69; p = 0.98), but triple therapy was associated with a significantly higher risk of hemorrhagic stroke (HR: 7.73; 95% CI: 2.14 to 27.91; p = 0.002) and major bleeding (HR: 4.48; 95% CI: 1.81 to 11.08; p = 0.001). Among patients receiving DES implantation, AF was not rare and was associated with increased ischemic and bleeding risk. In patients with AF, triple therapy was not associated with decreased ischemic events but was associated with increased bleeding risk compared to DAPT. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Smart Systems for Logistics Command and Control (SSLC2)

DTIC Science & Technology

2004-06-01

design options 12 AFRL Risk Abatement (continued) • Awareness of key development projects: • AF Portal • GCSS-AF • TBMCS-UL • Enterprise Data Warehouse ... Logistics Enterprise Architecture • Early identification of Transition Agents 13 Collaboration Partners • AF-ILMM • AMC/A-4 • AFC2ISRC • AFMC LSO

Atrial fibrillation, CHA2DS2-VASc score, antithrombotics and risk of traffic accidents: A population-based cohort study.

PubMed

Lai, Hui-Chin; Chien, Wu-Chien; Chung, Chi-Hsiang; Lee, Wen-Lieng; Wang, Kuo-Yang; Wu, Tsu-Juey; Liu, Chia-Ning; Liu, Tsun-Jui

2015-10-15

Traffic accidents account for a substantial proportion of premature disabilities and deaths. Whether atrial fibrillation (AF) provokes while antithrombotics prevent from such events remains un-investigated. All patients ≥40years with newly diagnosed AF in 2005 were scrutinized from the "Longitudinal Health Insurance Database 2005" (1 million beneficiaries) of Taiwan's National Health Insurance Institute as the AF group. Four-fold number of age-, gender-, and comorbidity-matched patients but without AF served as the Non-AF controls. Patients were followed till occurrence of hospitalization-requiring traffic injury, death, withdrawal from insurance, or the end of 2010. Cumulative incidence of traffic accidents was compared between groups, and predictors and preventive role of antithrombotics for these accidents were identified by Cox regression analysis. Within a mean follow-up of 4.3years, traffic injury occurred significantly more often in patients with AF (N=1724) than those without it (N=6896) (5.4 vs. 4.9 per 1000 person-years, log-rank p=0.012, HR 1.110, 95% CI 1.013-1.572). Cox models identified age ≧65years, hypertension, coronary artery disease, stroke, liver cirrhosis and CHADS2VASC score≧1 as risk factors for traffic injury in AF patients, whereas oral anticoagulants (HR 0.576, 95% CI 0.285-0.791, p=0.002) used in patients with CHADS2VASC score ≧1 but not antiplatelet therapy (p=0.197) as negative predictors. Patients with AF are more vulnerable to traffic accidents especially when with higher CHADS2VASC scores and other comorbidities. This tendency to traffic accidents, however, could be ameliorated by oral anticoagulation in specialized cases but not by antiplatelet therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.