Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing

The sodium-activated potassium channel Slack (K_Na1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I_KNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I_KNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I_KNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.     

SLA-aware operational efficiency in AI-enabled service chains: challenges ahead

Information Systems and e-Business Management - Service providers compose services in service chains that require deep integration of core operational information systems across organizations....     

Silk proteins for biomedical applications: Bioengineering perspectives

Biomaterials of either natural or synthetic origin are used to fabricate implantable devices, as carriers for bioactive molecules or as substrates to facilitate tissue regeneration. For the design of medical devices it is fundamental to use materials characterized by non-immunogenicity, biocompatibility, slow and/or controllable biodegradability, non-toxicity, and structural integrity. The success of biomaterial-derived biodevices tends to be based on the biomimetic architecture of the materials. Recently, proteins from natural precursors that are essentially structural and functional polymers, have gained popularity as biomaterials. The silks produced by silkworms or spiders are of particular interest as versatile protein polymers. These form the basis for diverse biomedical applications that exploit their unique biochemical nature, biocompatibility and high mechanical strength. This review discusses and summarizes the latest advances in the engineering of silk-based biomaterials, focusing specifically on the fabrication of diverse bio-mimetic structures such as films, hydrogels, scaffolds, nanofibers and nanoparticles; their functionalization and potential for biomedical applications.     

The Reactivity of Difluorocarbene with Hydroxylamines: Synthesis of Carbamoyl Fluorides

Carbamoyl fluorides are formed in reactions of hydroxylamines with difluorocarbene generated from sodium bromodifluoroacetate as readily available and non‐toxic carbene precursor. The process shows a high functional group tolerance, and the reaction path has been rationalized by computational calculations.

     

Comparative study of membrane filtration methods for the isolation of group D streptococci from water

An evaluation of two membrane filtration media (KF-streptococcus agar and bile esculin azide agar) incubated at two temperatures (37 and 44°C) was undertaken as a collaborative study involving nine laboratories. A wide variety of samples: sewage, secondary effluent, chlorinated effluent, surface water, stored water and almost fully treated drinking water, were used. Bacteria from all the media studied, were subcultured and classified as group D streptococci if they were catalase negative and able to grow at 45°C. It was demonstrated that the latter characteristic showed a very good correlation with the presence or absence of the group D antigen.There was a marked difference in selectivity between the two media tested. On bile esculin azide agar significantly fewer typical colonies (81 vs 94%) were formed by group D streptococci than on KF. In addition, the suppression of the background flora was insufficient. Selectivity of the two media was not improved by incubation at 44°C instead of the usual 37°C, but the recovery at the higher temperature was significantly less, especially if chlorine-damaged bacteria were present. Therefore, the use of KF-streptococcus agar at 37°C is preferred for membrane filtration.     

Heavy metal exposure in patients suffering from electromagnetic hypersensitivity

Background

Risks from electromagnetic devices are of considerable concern. Electrohypersensitive (EHS) persons attribute a variety of rather unspecific symptoms to the exposure to electromagnetic fields. The pathophysiology of EHS is unknown and therapy remains a challenge.

Objectives

Heavy metal load has been discussed as a potential factor in the symptomatology of EHS patients. The main objective of the study was to test the hypothesis of a link between EHS and heavy metal exposure.

Methods

We measured lead, mercury and cadmium concentrations in the blood of 132 patients (n = 42 males and n = 90 females) and 101 controls (n = 34 males and n = 67 females).

Results

Our results show that heavy metal load is of no concern in most cases of EHS but might play a role in exceptional cases.

Conclusions

The data do not support the general advice to heavy metal detoxification in EHS.     

3D Printed Anatomical Nerve Regeneration Pathways

A 3D printing methodology for the design, optimization, and fabrication of a custom nerve repair technology for the regeneration of complex peripheral nerve injuries containing bifurcating sensory and motor nerve pathways is introduced. The custom scaffolds are deterministically fabricated via a microextrusion printing principle using 3D models, which are reverse engineered from patient anatomies by 3D scanning. The bifurcating pathways are augmented with 3D printed biomimetic physical cues (microgrooves) and path‐specific biochemical cues (spatially controlled multicomponent gradients). In vitro studies reveal that 3D printed physical and biochemical cues provide axonal guidance and chemotractant/chemokinetic functionality. In vivo studies examining the regeneration of bifurcated injuries across a 10 mm complex nerve gap in rats showed that the 3D printed scaffolds achieved successful regeneration of complex nerve injuries, resulting in enhanced functional return of the regenerated nerve. This approach suggests the potential of 3D printing toward advancing tissue regeneration in terms of: (1) the customization of scaffold geometries to match inherent tissue anatomies; (2) the integration of biomanufacturing approaches with computational modeling for design, analysis, and optimization; and (3) the enhancement of device properties with spatially controlled physical and biochemical functionalities, all enabled by the same 3D printing process.     

Thermal interaction between limestone and silica

A thermodynamic analysis of the interaction between limestone and silica is carried out under normal pressure with the use of the TERRA program system. An equilibrium system is considered. The thermodynamic parameters are calculated with a step-by-step increase in temperature. The temperature of calcium silicate synthesis with respect to the initial mixture composition is found. At all possible ratios between limestone and silica, the products of the chemical reaction are determined. The reaction heat, synthesis temperature, enthalpy increment, and heat content are determined. It is shown that wollastonite isothermal synthesis proceeds at 550 K at a constant heat content, and rankinite isothermal synthesis proceeds at 750 K at a constant heat content as well. The reaction heat increases with rising limestone content until rankinite starts to form and then decreases to zero. The interaction between limestone and silica produces carbon dioxide gas, whose content grows simultaneously with the rising reaction heat. When the rankinite yield is maximal, the amount of carbon dioxide diminishes to zero, because free limestone forms and CO₂ is buried. On the basis of the results, the conclusion is drawn that the reaction proceeds with a latent exotherm due to latent limestone dissociation and formation of lime during the thermal interaction between limestone and silica.     

Analysis of microbending of CuZn37 brass foils based on strain gradient hardening models

Microbending experiments of brass foils were conducted and demonstrated clear size effects, i.e., the normalized bending moment increased with the reduction of foil thickness. The experiments were modeled using the classical plasticity model and three strain-gradient plasticity models. A modified Nix-Gao model was proposed to consider the number of twins across the thickness direction in strain hardening. It was found that the proposed model could better predict the normalized bending moment for both fine-grain and coarse-grain foils and the proposed equation for material intrinsic length could better capture the physics of material deformation. Furthermore, micro-hardness distributions in the bending area were measured and obvious lower-hardness region was found in the middle layer of fine-grain foils instead of coarse-grain foils. This indicates that the modified Nix-Gao model and the assumption of fully plastic bending worked better for coarse-grain foils than for fine-grain foils.