Development of a remote-control system for catheterization capable of high-speed force feedback.

PURPOSE: There is a growing interest in minimally invasive surgery as interventional radiology (IVR), which decreases the burden on a patient. However, occupational exposure is a problem because the treatment is performed using X-ray fluoroscopic images. This problem can be solved by the development of a teleoperation system, but rapid force presentation is important to perform safe surgery. The purpose of this study is to develop a new teleoperation system that can be controlled at a high speed and can provide feedback force sensation within 20 ms delay. METHODS: A master-slave-type remote-control system for catheterization was developed. A compact and high-speed force feedback system is realized using a novel electro-attractive material (EAM) device by which the resistance force is generated by the magnitude of the voltage applied. The linear and rotational movement of master is transferred to the slave device by UDP communication with the LAN cable, and the same movement is performed by two motors. The collision force of catheter or guidewire, detected by the sensor inside the slave device, is also transmitted to the master device. Two voltage-based methods for EAM: the ON/OFF and linear control methods, were implemented. RESULTS: After the collision force is detected by the slave sensor, the voltage is applied to the EAM in the master device for an average of 10.33 ms and 15.64 ms by the ON/OFF and linear control methods, respectively. These delays are less than required 20 ms. The movement of the master was stopped by the resistance force of EAM, and that of the slave was also stopped accordingly. CONCLUSION: A master-slave-type remote-control system for catheterization that is capable of high-speed force feedback was developed. With a low delay, the developed system achieved the requirements of 20 ms that was aimed for this study. Therefore, this system may facilitate the realization of IVR surgery that is safe for both doctors and patients.

Thrombomodulin alfa attenuates the procoagulant effect and cytotoxicity of extracellular histones through the promotion of protein C activation.

INTRODUCTION: Extracellular histones are reported to increase thrombin generation in the plasma and induce endothelial cell death in vitro. These effects of histones were suggested to involve histone-induced inhibition of TM-dependent activated protein C (APC) generation. Therefore, we hypothesized that TM alfa, a recombinant human soluble TM, attenuates these effects of histones by promoting the generation of APC. In the present study, we investigated the effects of TM alfa on the histone-induced decrease in APC generation, an increase in thrombin generation, and endothelial cell death in vitro. METHODS: APC generation was investigated using a chromogenic substrate based assay. Thrombin generation in plasma was studied by using a calibrated automated thrombogram method. Histone cleavage was detected by western blot analysis. Histone-induced endothelial cell death was evaluated by the trypan blue exclusion test. RESULTS: Histones decreased APC generation and increased thrombin generation in the presence of endothelial cells. TM alfa increased APC generation and decreased thrombin generation in the presence of histones and endothelial cells. TM alfa with thrombin and protein C cleaved histone H3, and attenuated histone-induced endothelial cell death. Antithrombin, an endogenous thrombin inhibitor, and gabexate mesilate, a synthetic protease inhibitor, inhibited thrombin generation, decreased APC generation, and did not have any effect on histone H3 cleavage or histone-induced endothelial cell death. CONCLUSIONS: TM alfa attenuated the histone-induced increase in thrombin generation and endothelial cell death by promoting APC generation in vitro.

The Presence of Two Receptor-Binding Proteins Contributes to the Wide Host Range of Staphylococcal Twort-Like Phages.

UNLABELLED: Thanks to their wide host range and virulence, staphylococcal bacteriophages (phages) belonging to the genus Twortlikevirus (staphylococcal Twort-like phages) are regarded as ideal candidates for clinical application for Staphylococcus aureus infections due to the emergence of antibiotic-resistant bacteria of this species. To increase the usability of these phages, it is necessary to understand the mechanism underlying host recognition, especially the receptor-binding proteins (RBPs) that determine host range. In this study, we found that the staphylococcal Twort-like phage ΦSA012 possesses at least two RBPs. Genomic analysis of five mutant phages of ΦSA012 revealed point mutations in orf103, in a region unique to staphylococcal Twort-like phages. Phages harboring mutated ORF103 could not infect S. aureus strains in which wall teichoic acids (WTAs) are glycosylated with α-N-acetylglucosamine (α-GlcNAc). A polyclonal antibody against ORF103 also inhibited infection by ΦSA012 in the presence of α-GlcNAc, suggesting that ORF103 binds to α-GlcNAc. In contrast, a polyclonal antibody against ORF105, a short tail fiber component previously shown to be an RBP, inhibited phage infection irrespective of the presence of α-GlcNAc. Immunoelectron microscopy indicated that ORF103 is a tail fiber component localized at the bottom of the baseplate. From these results, we conclude that ORF103 binds α-GlcNAc in WTAs, whereas ORF105, the primary RBP, is likely to bind the WTA backbone. These findings provide insight into the infection mechanism of staphylococcal Twort-like phages. IMPORTANCE: Staphylococcus phages belonging to the genus Twortlikevirus (called staphylococcal Twort-like phages) are considered promising agents for control of Staphylococcus aureus due to their wide host range and highly lytic capabilities. Although staphylococcal Twort-like phages have been studied widely for therapeutic purposes, the host recognition process of staphylococcal Twort-like phages remains unclear. This work provides new findings about the mechanisms of host recognition of the staphylococcal Twort-like phage ΦSA012. The details of the host recognition mechanism of ΦSA012 will allow us to analyze the mechanisms of infection and expand the utility of staphylococcal Twort-like phages for the control of S. aureus.