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The temporal behavior and consistency of bipolar atrial electrograms in human persistent atrial fibrillation

Abstract

The unstable temporal behavior of atrial electrical activity during persistent atrial fibrillation (persAF) might influence ablation target identification, which could explain the conflicting persAF ablation outcomes in previous studies. We sought to investigate the temporal behavior and consistency of atrial electrogram (AEG) fractionation using different segment lengths. Seven hundred ninety-seven bipolar AEGs were collected with three segment lengths (2.5, 5,and 8 s) from 18 patients undergoing persAF ablation. The AEGs with 8-s duration were divided into three 2.5-s consecutive segments. AEG fractionation classification was applied off-line to all cases following the CARTO criteria; 43% of the AEGs remained fractionated for the three consecutive AEG segments, while nearly 30% were temporally unstable. AEG classification within the consecutive segments had moderate correlation (segment 1 vs 2: Spearman’s correlation ρ = 0.74, kappa score κ = 0.62; segment 1 vs 3: ρ = 0.726, κ = 0.62; segment 2 vs 3: ρ = 0.75, κ = 0.68). AEG classifications were more similar between AEGs with 5 and 8 s (ρ = 0.96, κ = 0.87) than 2.5 versus 5 s (ρ = 0.93, κ = 0.84) and 2.5 versus 8 s (ρ = 0.90, κ = 0.78). Our results show that the CARTO criteria should be revisited and consider recording duration longer than 2.5 s for consistent ablation target identification in persAF.

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Vaccines, Vol. 5, Pages 16: The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection

Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182–186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting.

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IJGI, Vol. 6, Pages 198: Assessing Performance of Three BIM-Based Views of Buildings for Communication and Management of Vertically Stratified Legal Interests

Multistorey buildings typically include stratified legal interests which provide entitlements to a community of owners to lawfully possess private properties and use communal and public properties. The spatial arrangements of these legal interests are often defined by multiplexing cognitively outlined spaces and physical elements of a building. In order to support 3D digital management and communication of legal arrangements of properties, a number of spatial data models have been recently developed in Geographic Information Systems (GIS) and Building Information Modelling (BIM) domains. While some data models, such as CityGML, IndoorGML or IFC, provide a merely physical representation of the built environment, others, e.g., LADM, mainly rely on legal data elements to support a purely legal view of multistorey buildings. More recently, spatial data models integrating legal and physical notions of multistorey buildings have been proposed to overcome issues associated with purely legal models and purely physical ones. In previous investigations, it has been found that the 3D digital data environment of BIM has the flexibility to utilize either only physical elements or only legal spaces, or an integrated view of both legal spaces and physical elements to represent spatial arrangements of stratified legal interests. In this article, the performance of these three distinct BIM-based representations of legal interests defined inside multistorey buildings is assessed in the context of the Victorian jurisdiction of Australia. The assessment metrics are a number of objects and geometry batches, visualization speed in terms of frame rate, query time, modelling legal boundaries, and visual communication of legal boundaries.

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Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System

Background. Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect. Methods. Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2, 2 μg). Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE2 injection. Results. Aripiprazole (100 μg/paw) injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50 μg/paw), a nonselective opioid receptor antagonist. The role of μ-, δ-, and κ-opioid receptors was investigated using the selective antagonists, clocinnamox (40 μg/paw), naltrindole (15, 30, and 60 μg/paw), and nor-binaltorphimine (200 μg/paw), respectively. The data indicated that only the δ-opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400 μg), an aminopeptidase-N inhibitor, significantly enhanced low-dose (25 μg/paw) aripiprazole-induced peripheral antinociception. Conclusion. The results suggest the participation of the opioid system via δ-opioid receptor in the peripheral antinociceptive effect induced by aripiprazole.

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Hypothalamo-pituitary-adrenal axis after a single epidural triamcinolone injection

Abstract

Purpose

To quantify adrenocorticotropin and cortisol secretion after epidural glucocorticoid injection.

Methods

Eight men (ages 25–63 year) were studied at baseline, 1, 4, and 12 weeks after triamcinolone (80 mg) injection epidurally. Adrenocorticotropin (pg/mL) and cortisol (µg/dL) were measured every 10 min for 4 h, and after Corticotropin-releasing hormone (CRH) (1 µg/kg) injection.

Results

Epidural triamcinolone markedly suppressed: (1) pre-CRH injection ACTH (from 18 ± 3.1 to 4.8 ± 0.4: P < 0.01) and cortisol (from 12.2 ± 1.6 to 1.6 ± 0.3: P < 0.0001) at week 1, with recovery at 4 weeks, and (2) CRH-stimulated 3-h summed ACTH (from 633 ± 116 to 129 ± 10 pg/mL, P < 0.0001), and 3-h summed cortisol at week 1 (from 385 ± 29 to 56 ± 22 µg/dL, P < 0.0001) and 4 weeks (284 ± 53; P < 0.01). Serum cortisol was <18 µg/dL in eight of eight men at 4 weeks, and six of eight men at week 12. Urinary-free cortisol (µg/24 h) remained low at week 12: baseline (60 ± 6.5); week 1 (9.0 ± 1.3, P < 0.01); week 4 (36 ± 8.6) and week 12 (38 ± 4.1). Urinary cortisol/cortisone ratios rose at week 4 only. Serum triamcinolone peaked at week 1 (16/16 samples), declining at week 4 (13/16 samples) and week 12 (6/16 samples).

Limitations

Relatively small group.

Conclusion

Epidural triamcinolone suppresses unstimulated and CRH-stimulated ACTH and cortisol secretion for 1–4 weeks but urinary free cortisol ≥12 weeks. Suppression of ACTH and cortisol after glucocorticoid treatment is thus complex.

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The Bold and the Beautiful: a Neurotoxicity Comparison of New World Coral Snakes in the Micruroides and Micrurus Genera and Relative Neutralization by Antivenom

Abstract

Coral snake envenomations are well characterized to be lethally neurotoxic. Despite this, few multispecies, neurotoxicity and antivenom efficacy comparisons have been undertaken and only for the Micrurus genus; Micruroides has remained entirely uninvestigated. As the USA’s supplier of antivenom has currently stopped production, alternative sources need to be explored. The Mexican manufacturer Bioclon uses species genetically related to USA species, thus we investigated the efficacy against Micrurus fulvius (eastern coral snake), the main species responsible for lethal envenomations in the USA as well as additional species from the Americas. The use of Coralmyn® coral snake antivenom was effective in neutralizing the neurotoxic effects exhibited by the venom of M. fulvius but was ineffective against the venoms of Micrurus tener, Micrurus spixii, Micrurus pyrrhocryptus, and Micruroides euryxanthus. Our results suggest that the Mexican antivenom may be clinically useful for the treatment of M. fulvius in the USA but may be of only limited efficacy against the other species studied.

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