Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Selective-area chemical beam epitaxy of in-plane InAs one-dimensional channels grown on InP(001), InP(111)B, and InP(110) surfaces

We report on the selective-area chemical beam epitaxial growth of InAs in-plane, one-dimensional (1-D) channels using patterned SiO$_{2}$-coated InP(001), InP(111)B, and InP(110) substrates to establish a scalable platform for topological superconductor networks. Top-view scanning electron micrographs show excellent surface selectivity and dependence of major facet planes on the substrate orientations and ridge directions, and the ratios of the surface energies of the major facet planes were estimated. Detailed structural properties and defects in the InAs nanowires (NWs) were characterized by transmission electron microscopic analysis of cross-sections perpendicular to the NW ridge direction and along the NW ridge direction. Electrical transport properties of the InAs NWs were investigated using Hall bars, a field effect mobility device, a quantum dot, and an Aharonov-Bohm loop device, which reflect the strong spin-orbit interaction and phase-coherent transport characteristic in the selectively grown InAs systems. This study demonstrates that selective-area chemical beam epitaxy is a scalable approach to realize semiconductor 1-D channel networks with the excellent surface selectivity and this material system is suitable for quantum transport studies

In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs

Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015

Exploring the psychology of trade-off decision-making in environmental impact assessment

Dealing with trade-offs lies at the heart of environmental impact assessment (EIA). However, there has been scant reflection to date on the concept of trade-offs within the EIA literature. This paper aims to contribute to the thinking about trade-offs by distilling key learning points from research conducted within the field of psychology. In particular, the paper explores three interrelated questions namely: When are trade-off decisions difficult? How do we react when faced with difficult trade-off decisions? And how can we deal with difficult trade-off decisions? The research confirms that EIA functions within a very difficult trade-off decision-making context and that observed behaviour related to these difficult decisions can be explained from a psychology perspective. In order to deal better with trade-off decisions, it is helpful to be able to predict decision difficulty and anticipate resultant behaviour. Moreover, the way we present and frame decisions affects their outcomes