Detection of atrial fibrillation in real world setting in patients with cryptogenic stroke and an implantable loop recorder.

INTRODUCTION: Implantable loop recorders (ILR) are used to screen for atrial fibrillation (AF) in patients with cryptogenic stroke (CS). However, there is limited real-world data regarding the long-term rate of AF detection using ILR and management consequences in patients with CS. The objective is to assess the rate of AF detection in patients with CS in a real-world study over 36 months of follow-up and its consequences on stroke prevention. METHODS: This retrospective study included patients with an ILR placed for CS at Baylor College of Medicine and Baylor St. Luke's Medical Center between January 2014 and July 2021. The primary outcome was AF detection in patients with ILR. The secondary outcome was the rate of subsequent strokes after ILR placement in patients with or without diagnosed AF. The AF detection rate in our cohort was compared to the rate in CRYSTAL-AF Trial at 36-month follow-up. The impact of AF detection on clinical management was examined. RESULTS: We identified 225 patients. 51.1% were women and 38.2% African American. Among 85 patients with ILR labeled AF, 43 patients had true AF, and 42 had incorrectly labeled AF (48.3% false positive). The estimated AF detection rate at 36 months follow-up was 28.6% (95% CI, 26.6%-30.6%). 58.1% of patients with AF were initiated on oral anticoagulation, 80.0% of whom were started on a direct oral anticoagulant. 13.8% of patients had recurrent strokes after ILR implantation; 4 of whom were diagnosed with AF. CONCLUSION: Compared to CRYSTAL-AF, the AF detection rate in our cohort is similar, but this cohort includes a higher proportion of female and African American patients. Most patients with recurrent strokes after ILR implant did not have AF during 36 months of monitoring.

Selective extraction of apixaban from plasma by dispersive solid-phase microextraction using magnetic metal organic framework combined with molecularly imprinted polymer nanocomposite.

This research aims to synthesize a specific and efficient sorbent to use in the extraction of apixaban from human plasma samples and its determination by high-performance liquid chromatography-tandem mass spectrometry. High specific surface area of metal-organic framework, magnetic property of iron oxide nanoparticles, selectively of molecular imprinted polymer toward the analyte, and the combination of dispersive solid-phase extraction method with a sensitive analysis system provided an efficient analytical method. In this study, first, a molecularly imprinted polymer combined with magnetic metal organic framework nanocomposite was prepared and then characterized using different techniques. Then the sorbent particles were used for selective extraction of the analyte from plasma samples. The efficiency of the method was improved by optimizing effective parameters. According to the validation results, wide linear range (1.02-200 ng mL-1 ), acceptable coefficient of determination (0.9938), low limit of detection (0.32 ng mL-1 ) and limit of quantification (1.02 ng mL-1 ), high extraction recovery (78%), and good precision (relative standard deviations ≤ 2.9% for intra- (n = 6) and interday (n = 6) precisions) were obtainable using the proposed method. These outcomes showed the high potential of the proposed method for screening apixaban in the human plasma samples.

Riboflavin as a green sorbent in dispersive micro-solid-phase extraction of several pesticides from fruit juices combined with dispersive liquid-liquid microextraction.

A vortex-assisted dispersive micro-solid-phase extraction procedure using a new and green sorbent was developed as a simple, fast, and efficient sample preparation method for the extracting five pesticides in several fruit juice samples. In this study, for the first time, riboflavin was used as an efficient sorbent. A few milligrams of riboflavin was directly added into the aqueous solution containing the analytes to adsorb them. After adsorption the analytes, they were desorbed and more concentrated by a dispersive liquid-liquid microextraction procedure. The influence of several effective parameters such as amount of riboflavin, pH, vortex time, eluent nature and volume, and extraction solvent type and volume on the extraction efficiency was investigated. In optimal conditions, linear ranges of the calibration curves were broad. The limits of detection and quantification were attained in the ranges of 0.56-1.5  and 1.9-0.52 ng mL-1 , respectively. The proposed method demonstrated to be suitable for concurrent extraction of the studied pesticides in various fruit juice samples with high enrichment factors (320-360) and precision (relative standard deviation ≤7.8% for intra- [n = 6] and interday [n = 4] precisions at a concentration of 25 ng mL-1 of each pesticide).

Improved magnetic solid-phase extraction based on magnetic sorbent obtained from sand for the extraction of pesticides from fruit juice.

BACKGROUND: A combination of magnetic solid-phase extraction using an efficient and cheap magnetic sorbent obtained from sand and dispersive liquid-liquid microextraction has been developed for the extraction of nine multiclass pesticides (clodinafop-propargyl, haloxyfop-R-methyl, fenoxaprop-P-ethyl, oxadiazon, penconazole, diniconazole, chlorpyrifos, fenazaquin, and fenpropathrin) from commercial fruit juices (sour cherry, pomegranate, grape, watermelon, orange, apricot, and peach juices). The enriched pesticides were determined by gas chromatography-flame ionization detector and gas chromatography-mass spectrometry. The sorbent was natural iron oxide entrapped in silica along with some impurities. In this method, to extract the analytes from the samples, an appropriate amount of the magnetic sorbent (at mg level) is added. Then the sorbent particles are isolated from the solution using an external magnetic field and the adsorbed analytes are desorbed from the sorbent by acetone. In the following, a dispersive liquid-liquid microextraction procedure is carried out to concentrate the analytes more and to reach low limits of detection. RESULTS: Under optimized extraction conditions, the method revealed satisfactory repeatability (relative standard deviation ≤8% for intra-day and inter-day precision), reasonable extraction recovery (43.3-55.9%), high enrichment factors (433-559), and low limits of detection (0.45-0.89 µg L-1 ). CONCLUSION: The method was applied in the analysis of pesticides in various fruit juices. Chlorpyrifos was found in peach juice at a concentration of 27 ± 2 µg L-1 (n = 3) using a gas chromatography-flame ionization detector. To verify the results, the peach juice was also injected into gas chromatography-mass spectrometry after applying the proposed extraction method. © 2022 Society of Chemical Industry.

Meta-analysis comparing outcomes of catheter ablation for ventricular arrhythmia in ischemic versus nonischemic cardiomyopathy.

BACKGROUND: Catheter ablation is an effective treatment for ventricular arrhythmia (VA) in ischemic cardiomyopathy (ICM). However, results in non-ICM (NICM) patients are not satisfactory, and studies comparing differences between NICM and ICM are limited. We conducted a meta-analysis of procedural characteristics and long-term outcomes of catheter ablation for VA, comparing results between ICM and NICM. METHODS: Studies in the PubMed, EMBASE, and Cochrane databases were systematically reviewed. Four studies reporting comparison of catheter ablation of VA between ICM and NICM were examined. The Newcastle-Ottawa Scale was used to appraise study quality. A random-effects model with inverse variance method was used for comparisons. RESULTS: Epicardial approach was significantly more undertaken for the NICM group than in the ICM group (odds ratio [OR]: 0.13; 95% confidence interval [CI]: 0.09-0.18; P < .00001). Mean ablation time (P = .54), fluoroscopy time (P = .55), and procedural time (P = .18) did not differ significantly between the ICM and NICM groups. Procedural failure rates (OR: 0.46; 95% CI: 0.24-0.89; P = .02) and VA recurrence rates (risk ratio [RR]: 0.68; 95% CI: 0.46-1.01; P = .06) were significantly higher in the NICM group than in the ICM group. However, all-cause mortality (RR: 1.37; 95% CI: 0.75-2.49; P = .31) did not differ significantly between groups. CONCLUSIONS: Procedural failure and VA recurrence rates were significantly higher in the NICM group, despite significantly more frequent epicardial access. These highlight the limitations of catheter ablation for VA in NICM, given our current knowledge.

Expression of DDX11 and DNM1L at the 12p11 Locus Modulates Systemic Lupus Erythematosus Susceptibility.

OBJECTIVES: This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes. METHODS: Four hundred and ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Confirmatory qPCR on SLE monocytes was performed. The entire 12p11 locus was investigated for genetic association using two additional GWAS. Expression of 150 genes at this locus was assessed. Based on this significance, qPCRs for DNM1L and KRAS were performed. RESULTS: Fifty genes were differentially expressed in at least two SLE GEO-datasets, with all probes directionally aligned. DDX11, an RNA helicase involved in genome stability, was downregulated in both GEO and Cordoba datasets. The most significant SNP, rs3741869 in OASIS locus 12p11.21, containing DDX11, was a cis-eQTL regulating DDX11 expression. DDX11 was found repressed. The entire 12p11 locus showed three association peaks. Gene expression in GEO datasets identified DNM1L and KRAS, besides DDX11. Confirmatory qPCR validated DNM1L as an SLE susceptibility gene. DDX11, DNM1L and KRAS interact with each other and multiple known SLE genes including STAT1/STAT4 and major components of IFN-dependent gene expression, and are responsible for signal transduction of cytokines, hormones, and growth-factors, deregulation of which is involved in SLE-development. CONCLUSION: A genomic convergence approach with OASIS analysis of multiple GWAS and expression datasets identified DDX11 and DNM1L as novel SLE-genes, the expression of which is altered in monocytes from SLE patients. This study lays the foundation for understanding the pathogenic involvement of DDX11 and DNM1L in SLE by identifying them using a systems-biology approach, while the 12p11 locus harboring these genes was previously missed by four independent GWAS.

Antimicrobial activity of different plants extracts against Staphylococcus aureus and Escherichia coli.

BACKGROUND: Microbial pathogens, mainly bacteria, are a major cause of food spoilage resulting in several foodborne diseases. Food spoilage can be prevented by the application of chemical preservatives in the food industry but such process has harmful effects on human health and causes the introduction of chemicals in several food chains, leading to toxicity and long-term complications. Due to such adverse effects, the need to find natural preservatives that are safer to use, effective and less complicated is increasing. OBJECTIVES: This study is based on plant extracts that play a major role in microbicidal action (the use of natural preservatives is preferred over chemical ones). Antimicrobial action of different plant extracts was assessed using Staphylococcus aureus and Escherichia coli as experimental bacterial strains. MATERIAL AND METHODS: Ethanolic extracts of different plants like Punica granatum, Acacia catechu and Phyllanthus emblica were highly effective against the both analyzed bacterial strains at a dosage of 10 mg/mL, while the extracts of Ocimum bacilicum and Quercus infectoria were effective only against S. aureus and E. coli, respectively. RESULTS: Punica granatum and Phyllanthus emblica extracts were found to be the most effective and exhibited bacteriostatic and bactericidal activities against the highly infectious strains of pathogenic bacteria causing food spoilage, with minimum inhibitory concentration (MIC) of 2.5 mg/mL and minimum bactericidal concentration (MBC) of 5 mg/mL. CONCLUSIONS: The plant extracts used in the study were highly effective in reducing bacterial contamination and can be used as an alternative to chemical preservatives to avoid and control foodborne diseases and for preservation of food with no health-related hazards caused by chemicals.

Fractal genomics of SOD1 evolution.

To understand the fundamental processes of gene evolution such as the impact of point mutations and segmental duplications on statistical topography, superoxide dismutase-1 (SOD1) orthologous sequences (n = 50) are studied. These demonstrate scale invariant self-similarity patterns and long-range correlations (LRCs) indicating fractal organization. Phylogenetic hierarchies change when SOD1 orthologs are grouped according to fractal measures, indicating that statistical topographies can be used to study gene evolution. Sliding window k-mer analysis show that majority of k-mers across all SOD1 orthologs are unique, with very few duplications. Orthologs from simpler species contribute minimally (< 1% of k-mers) to more complex species. Both simple and complex random processes fail to produce significant matching k-mer sequences for SOD1 orthologs. Point mutations causing amyotrophic lateral sclerosis do not impact the fractal organization of human SOD1. Hence, SOD1 did not evolve by a patchwork of repetitive sequences modified by point mutations. Moreover, fractal and other methods described here can be used to study the origin and evolution of genomes.

Slow-pathway visualization by using voltage-time relationship: A novel technique for identification and fluoroless ablation of atrioventricular nodal reentrant tachycardia.

BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is treatable by catheter ablation. Advances in mapping-system technology permit fluoroless workflow during ablations. As national practice trends toward fluoroless approaches, easily obtained, reproducible methods of slow-pathway identification, and ablation become increasingly important. We present a novel method of slow-pathway identification and initial ablation results from this method. METHODS AND RESULTS: We examined AVNRT ablations performed at our institution over a 12-month period. In these cases, the site of the slow pathway was predicted by latest activation in the inferior triangle of Koch during sinus rhythm. Ablation was performed in this region. Proximity of the predicted site to the successful ablation location, complication rates, and patient outcomes were recorded. Junctional rhythm was seen in 40/41 ablations (98%) at the predicted site (mean, 1.3 lesions and median, 1 lesion per case). One lesion was defined as 5 mm of ablation. The initial ablation was successful in 39/41 cases (95%); in two cases, greater or equal to 2 echo beats were detected after the initial ablation, necessitating further lesion expansion. In 8/41 cases (20%), greater than one lesion was placed during initial ablation before attempted reinduction. Complications included one transient heart block and one transient PR prolongation. During follow-up (median, day 51), one patient had lower-extremity deep-vein thrombosis and pulmonary embolus, and one had a lower-extremity superficial venous thrombosis. There was one tachycardia recurrence, which prompted a redo ablation. CONCLUSIONS: Mapping-system detection of late-activation, low-amplitude voltage during sinus rhythm provides an objective, and fluoroless means of identifying the slow pathway in typical AVNRT.

Development of a liquid-nitrogen-induced homogeneous liquid-liquid microextraction of Co(II) and Ni(II) from water and fruit juice samples followed by atomic absorption spectrometry detection.

In this study, a simple and rapid sample preparation method named liquid-nitrogen-induced homogeneous liquid-liquid microextraction has been developed for the extraction and pre-concentration of Co(II) and Ni(II) ions before their analysis by flame atomic absorption spectrometry. For this purpose, first, acetonitrile containing 8-hydroxyquinoline is added into a sample solution and the mixture is vortexed. As a result, a homogeneous solution is formed. Subsequently, the solution is cooled using liquid nitrogen for a few seconds. By this process, due to difference in the freezing point of acetonitrile and water, the homogeneous state is broken and the analytes (as oxinate complexes) are extracted into liquid acetonitrile phase collected on top of the frozen aqueous phase. The linear dynamic ranges obtained for Ni(II) and Co(II) were 1.0-30 and 0.50-20 µg L-1, respectively. The obtained limits of detection were 0.36 and 0.20 µg L-1 for Ni(II) and Co(II), respectively.

Confirming pericardial access by using impedance measurements from a micropuncture needle.

BACKGROUND: Pericardial access is complicated by two difficulties: confirming when the needle tip is in the pericardial space, and avoiding complications during access, such as inadvertently puncturing other organs. Conventional imaging tools are inadequate for addressing these difficulties, as they lack soft-tissue markers that could be used as guidance during access. A system that can both confirm access and avoid inadvertent organ injury is needed. METHODS: A 21G micropuncture needle was modified to include two small electrodes at the needle tip. With continuous bioimpedance monitoring from the electrodes, the needle was used to access the pericardium in porcine models (n  =  4). The needle was also visualized in vivo by using an electroanatomical map (n  =  2). Bioimpedance data from different tissues were analyzed retrospectively. RESULTS: Bioimpedance data collected from the subcutaneous space (992.8 ± 13.1 Ω), anterior mediastinum (972.2 ± 14.2 Ω), pericardial space (323.2 ± 17.1 Ω), mid-myocardium (349.7 ± 87.6 Ω), right ventricular cavity (235.0 ± 9.7 Ω), lung (1142.0 ± 172.0 Ω), liver (575.0 ± 52.6 Ω), and blood (177.5 ± 1.9 Ω) differed significantly by tissue type (P < .01). Phase data in the frequency domain correlated well with the needle being in the pericardial space. A simple threshold analysis effectively separated lung (threshold  =  1120.0 Ω) and blood (threshold  =  305.9 Ω) tissues from the other tissue types. CONCLUSIONS: Continuous bioimpedance monitoring from a modified micropuncture needle during pericardial access can be used to clearly differentiate tissues. Combined with traditional imaging modalities, this system allows for confirming access to the pericardial space while avoiding inadvertent puncture of other organs, creating a safer and more efficient needle-access procedure.

Application of a clean-up procedure using a ternary liquid phase system combined with pre-concentration by microextraction in the analysis of seven pesticides from soya milk.

BACKGROUND: A method has been developed based on a three-phase system, followed by dispersive liquid-liquid microextraction for the extraction of seven pesticides from soya milk prior to analysis by gas chromatography-flame ionization detection. The base of this method is the different extraction capability of the components of soya milk according to each of the phases involved. In this procedure, a homogeneous solution consisting of soya milk and a water-miscible solvent (acetonitrile) is separated into two phases in the presence of Na2 SO4 and the analytes are extracted into the produced acetonitrile droplets. The acetonitrile phase is mixed with a pre-concentration solvent to perform the next microextraction procedure for further enrichment of the analytes. RESULTS: Limits of detection and quantification were reached in the ranges of 0.11-0.35 and 0.35-1.20 µg L-1 , respectively. Enrichment factors and extraction recoveries were in the ranges of 562-933 and 56-93%, respectively. Relative standard deviations were ≤7% for intra- (n = 6) and inter-day (n = 5) precisions at two concentrations of 10 and 50 µg L-1 of each analyte. CONCLUSION: The proposed method was applied to the analysis of pesticides in soya milk samples at µg L-1 concentrations. © 2019 Society of Chemical Industry.

Locus and gene-based GWAS meta-analysis identifies new diabetic nephropathy genes.

Objective Assimilation of SNPs Interacting in Synchrony (OASIS) is a locus-based clustering algorithm recently described that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders. Diabetic nephropathy (DN) is incompletely understood due to a paucity of genes identified despite several GWAS. OASIS was applied to three DN dbGAP GWAS datasets (4725 subjects; 1.06 million SNPs). OASIS identified 19 DN genes which were verified using single variant replication in a standard association study and gene-based analysis using GATES. CARS and FRMD3 were confirmed as DN genes, and five known diabetes-associated genes, viz. NLRP3, INPPL1, PIK3C2G, NRXN3, and TBC1D4, not previously identified using these datasets were discovered. Furthermore, three additional novel DN genes were found which replicated in two sets of analysis, viz. NTN1, EBF2, and DNAH11. Hence, composite analysis with OASIS, gene-based, and single variant association testing can be universally applied to existing GWAS datasets for the identification of new genes.

Genomic convergence of locus-based GWAS meta-analysis identifies AXIN1 as a novel Parkinson's gene.

Parkinson's disease (PD) is a common, disabling neurodegenerative disorder with significant genetic underpinnings. Multiple genome-wide association studies (GWAS) have been conducted with identification of several PD loci. However, these only explain about 25% of PD genetic risk indicating that additional loci of modest effect remain to be discovered. Association clustering methods such as gene-based tests are more powerful than single-variant analysis for identifying modest genetic effects. Combined with the locus-based algorithm, OASIS, the most significant association signals can be homed in. Here, two dbGAP GWAS datasets (7415 subjects (2750 PD and 4845 controls) genotyped for 0.78 million SNPs) were analyzed using combined clustering algorithms to identify 88 PD candidate genes in 24 loci. These were further investigated for gene expression in substantia nigra (SN) of PD and control subjects on GEO datasets. Expression differences were also assessed in normal brains SN versus white matter on BRAINEAC datasets. This genetic and functional analysis identified AXIN1, a key regulator of Wnt/ß-catenin signaling, as a novel PD gene. This finding links PD with inflammation. Other significantly associated genes were CSMD1, CLDN1, ZNF141, ZNF721, RHOT2, RICTOR, KANSL1, and ARHGAP27. Novel PD genes were identified using genomic convergence of gene-wide and locus-based tests and expression studies on archived datasets.

Gastrocardiac syndrome: A forgotten entity.

Symptomatic bradycardia due to gastric distension is a rarely reported entity in the field of medicine. The mechanism of gastrointestinal distention that contributes to bradycardia is complex. A 75-year-old female with recurrent episodes of dizziness in the setting of gastric distension was found to have severe sinus bradycardia which resolved upon resolution of gastric distension. No structural or functional abnormality of heart was found. The patient was treated with permanent pacemaker implantation due to recurrent episodes of dizziness in the setting of sinus bradycardia.

Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets.

Systemic lupus erythematosus (SLE) is a complex disorder. Genetic association studies of complex disorders suffer from the following three major issues: phenotypic heterogeneity, false positive (type I error), and false negative (type II error) results. Hence, genes with low to moderate effects are missed in standard analyses, especially after statistical corrections. OASIS is a novel linkage disequilibrium clustering algorithm that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders such as SLE. OASIS was applied to two SLE dbGAP GWAS datasets (6077 subjects; ∼0.75 million single-nucleotide polymorphisms). OASIS identified three known SLE genes viz. IFIH1, TNIP1, and CD44, not previously reported using these GWAS datasets. In addition, 22 novel loci for SLE were identified and the 5 SLE genes previously reported using these datasets were verified. OASIS methodology was validated using single-variant replication and gene-based analysis with GATES. This led to the verification of 60% of OASIS loci. New SLE genes that OASIS identified and were further verified include TNFAIP6, DNAJB3, TTF1, GRIN2B, MON2, LATS2, SNX6, RBFOX1, NCOA3, and CHAF1B. This study presents the OASIS algorithm, software, and the meta-analyses of two publicly available SLE GWAS datasets along with the novel SLE genes. Hence, OASIS is a novel linkage disequilibrium clustering method that can be universally applied to existing GWAS datasets for the identification of new genes.

Lupus pathobiology based on genomics.

Systemic lupus erythematosus (SLE) is an autoimmune disorder with complex genetic underpinnings. This review attempts to assemble the myriad of genomic findings to build a clearer picture of the pathobiology of SLE to serve as a guide for therapeutics. Over 100 genes are now known for SLE, and several more penetrant ones have led to the emergence of more defined lupus phenotypes. Also discussed here are the targeted therapies that have come up on the horizon and the specific biologic mechanisms of more traditional therapies which have only recently been explored. The diagnostic toolbox has been enhanced by the addition of new antibodies, gene expression signatures, and mutation panels. This provides an opportunity to piece together the lupus puzzle and even revisit the clinical classification of SLE.

Near-field impedance accurately distinguishes among pericardial, intracavitary, and anterior mediastinal position.

INTRODUCTION: Epicardial catheter ablation is increasingly used to treat arrhythmias with an epicardial component. Nevertheless, percutaneous epicardial access remains associated with a significant risk of major complications. Developing a technology capable of confirming proper placement within the pericardial space could decrease complication rates. The purpose of this study was to examine differences in bioimpedance among the pericardial space, anterior mediastinum, and right ventricle. METHODS: An ovine model (n = 3) was used in this proof-of-concept study. A decapolar catheter was used to collect bipolar impedance readings; data were collected between each of five electrode pairs of varying distances. Data were collected from three test regions: the pericardial space, anterior mediastinum, and right ventricle. A control region in the inferior vena cava was used to normalize the data from the test regions. Analysis of variance was used to test for differences among regions. RESULTS: A total of 10 impedance values were collected in each animal between each of the five electrode pairs in the three test regions (n = 340) and the control region (n = 145). The average normalized impedance values were significantly different among the pericardial space (1.760 ± 0.370), anterior mediastinum (3.209 ± 0.227), and right ventricle (1.024 ± 0.207; P < 0.0001). In post hoc testing, the differences between each pair of regions were significant, as well (P < 0.001 for all). CONCLUSION: Impedance values are significantly different among these three anatomical compartments. Therefore, impedance can be potentially used as a means to guide percutaneous epicardial access.

Accuracy of Voltage Signal Measurement During Radiofrequency Delivery Through the SMARTTOUCH Catheter.

INTRODUCTION: Current methods for measuring voltage during radiofrequency (RF) ablation (RFA) necessitate turning off the ablation catheter. If voltage could be accurately read without signal attenuation during RFA, turning off the catheter would be unnecessary, allowing continuous ablation. We evaluated the accuracy of the Thermocool SMARTTOUCH catheter for measuring voltage while RF traverses the catheter. METHODS AND RESULTS: We studied 26 patients undergoing RFA for arrhythmias. A 7.5F SMARTTOUCH catheter was used for sensing voltage and performing RFA. Data were collected from the Carto-3 3-dimensional mapping system. Voltages were measured during ablation (RF-ON) and immediately before or after ablation (RF-OFF). In evaluating the accuracy of RF-ON measurements, we utilized the RF-OFF measure as the gold standard. We measured 465 voltage signals. The median values were 0.2900 and 0.3100 for RF-ON and RF-OFF, respectively. Wilcoxon signed rank testing showed no significant difference in these values (P = 0.608). The intraclass correlation coefficient (ICC) was 0.96, indicating that voltage measurements were similarly accurate during RF-OFF versus RF-ON. Five patients had baseline atrial fibrillation (AF), for whom 82 ablation points were measured; 383 additional ablation points were measured for the remaining patients. The voltages measured during RF-ON versus RF-OFF were similar in the presence of AF (P = 0.800) versus non-AF rhythm (P = 0.456) (ICC, 0.96 for both). CONCLUSION: Voltage signal measurement was similarly accurate during RF-ON versus RF-OFF independent of baseline rhythm. Physicians should consider not turning off the SMARTTOUCH ablation catheter when measuring voltage during RFA.

Polyphenolic Polymersomes of Temperature-Sensitive Poly(N-vinylcaprolactam)-block-Poly(N-vinylpyrrolidone) for Anticancer Therapy.

We report a versatile synthesis for polyphenolic polymersomes of controlled submicron (<500 nm) size for intracellular delivery of high and low molecular weight compounds. The nanoparticles are synthesized by stabilizing the vesicular morphology of thermally responsive poly(N-vinylcaprolactam)n-b-poly(N-vinylpyrrolidone)m (PVCLn-PVPONm) diblock copolymers with tannic acid (TA), a hydrolyzable polyphenol, via hydrogen bonding at a temperature above the copolymer's lower critical solution temperature (LCST). The PVCL179-PVPONm diblock copolymers are produced by controlled reversible addition-fragmentation chain transfer (RAFT) polymerization of PVPON using PVCL as a macro-chain transfer agent. The size of the TA-locked (PVCL179-PVPONm) polymersomes at room temperature and upon temperature variations are controlled by the PVPON chain length and TA:PVPON molar unit ratio. The particle diameter decreases from 1000 to 950, 770, and 250 nm with increasing PVPON chain length (m = 107, 166, 205, 234), and it further decreases to 710, 460, 290, and 190 nm, respectively, upon hydrogen bonding with TA at 50 °C. Lowering the solution temperature to 25 °C results in a slight size increase for vesicles with longer PVPON. We also show that TA-locked polymersomes can encapsulate and store the anticancer drug doxorubicin (DOX) and higher molecular weight fluorescein isothiocyanate (FITC)-dextran in a physiologically relevant pH and temperature range. Encapsulated DOX is released in the nuclei of human alveolar adenocarcinoma tumor cells after 6 h incubation via biodegradation of the TA shell with the cytotoxicity of DOX-loaded polymersomes being concentration-dependent. Our approach offers biocompatible and intracellular degradable nanovesicles of controllable size for delivery of a variety of encapsulated materials. Considering the particle monodispersity, high loading capacity, and a facile two-step aqueous assembly based on the reversible temperature-responsiveness of PVCL, these polymeric vesicles have significant potential as novel drug nanocarriers and provide a new perspective for fundamental studies on thermo-triggered polymer assemblies in solutions.