A Review of Pneumatic Actuators Used for the Design of Medical Simulators and Medical Tools

International audienc

Commande d'un robot de télé-échographie par asservissement visuel

Les robots légers utilisés pour la télé-échographie robotisée permettent, à l'expert médical, d'orienter à distance une sonde ultrasonore 2D. L'analyse en temps réel de l'image ultrasonore du patient, reçue via un lien de communication, permet à l'expert de définir un diagnostic. Les validations cliniques du concept de télé-échographie robotisée montrent qu'il est ainsi possible de pallier le manque d'experts en ultrasonographie sur des sites médicalement isolés. Le robot porte-sonde est positionné et maintenu sur le corps du patient par un assistant à partir des informations communiquées par le spécialiste via visioconférence. Cependant, la faible masse du robot, le fait qu'il soit maintenu par un assistant sur le corps du patient et les mouvements physiologiques du patient provoquent des perturbations dans la position de la sonde et engendrent ainsi des pertes des sections d'intérêt des organes étudiés. Les travaux de cette thèse ont consisté à développer une approche par asservissement visuel basé sur les moments d'image ultrasonore 2D. Le calcul des moments 2D étant basé sur les points du contour de la section d'intérêt, un algorithme de traitement d'images efficace est nécessaire pour détecter et suivre le contour d'intérêt en mouvement. Pour cela, une méthode de contour actif paramétrique basée sur les descripteurs de Fourier est présentée. Les lois de commandes correspondant à trois tâches autonomes autorisant la recherche et le maintien de visibilité d'un organe lors de l'acte médical télé-opéré sont implémentées et validées sur la plateforme robotique du projet ANR Prosit.The light weight robots used for robotized tele-echography allow the medical expert to remotely operate a 2D-ultrasound probe. The real-time analysis of the patient's ultrasound images, received via a standard communication link, provides the expert with relevant information to define a diagnosis. The clinical validations of the robotized tele-echography concept show that it is possible to overcome the lack of sonographers in medically isolated sites. The robot probe-holder is usually positioned and held on the patient's body by a paramedical staff based on information provided by the specialist via videoconferencing. However, the small mass of the robot, the fact that it is held by an assistant on the patient's body and the patient's physiological movements cause disturbances in the position of the probe ; this thus can generate a loss of the region of interest of the organ being under investigation during the teleoperated medical act. This thesis work focuses on the development of a visual servoing approach based on 2D ultrasound image moments. 2D moments calculation is based on the contour points of the image section of interest, therefore an image-processing algorithm is needed to effectively detect and follow the contour of interest in motion. For this reason, a parametric active contour method based on Fourier descriptors is presented. The control laws, corresponding to three independent autonomous tasks to search and maintain the visibility of an organ within a given ultrasound plane during the tele-operated medical act are implemented and validated on robotic platform project ANR Prosit.RENNES1-Bibl. électronique (352382106) / SudocSudocFranceF

Characterization of antibody-mediated neutralization directed against the hypervariable region 1 of hepatitis C virus E2 glycoprotein

The hypervariable region 1 (HVR1) comprising the first 27 aa of E2 glycoprotein is a target for neutralizing antibodies against hepatitis C virus (HCV), but the mechanisms of this neutralization in the cell-culture-infectious genotype 2a strain JFH1 HCV virus (HCVcc) system are unknown. Two rabbit polyclonal sera, R1020 and R140, recognizing the HVR1 of the genotype 1a isolates H77c and Glasgow (Gla), respectively, and a Gla HVR1-specific mouse mAb AP213 have been described previously. However, attempts to generate of antibodies to the JFH1 HVR1 were unsuccessful. Therefore, this study produced chimeric JFH1 HCVcc viruses harbouring the H77c or Gla HVR1 to assess the reactivity of antibodies to this region and their effects on virus infectivity. The inter-genotypic HVR1 swap did not significantly affect virus infectivity. The genotype 1a HVR1-specific antibodies neutralized chimeric viruses in an isolate-dependent manner, underlining the role of HVR1 in HCV infection. The neutralizing antibodies reacted mainly with the C-terminal portion of HVR1, and detailed mapping identified A17, F20 and Q21 in the Gla HVR1 sequence and T21 (and possibly L20) in the corresponding H77c sequence as key epitope residues for AP213 and R140, and R1020, respectively. Importantly, none of the antibodies inhibited in vitro binding of viral envelope glycoproteins to the best-characterized HCV receptor, CD81, or to the glycosaminoglycan attachment factors. However, the HVR1 antibodies were capable of post-attachment neutralization. Overall, this study emphasizes the role of HVR1 in HCVcc entry and provides new tools to study this region further in the context of complete virions

A User Interface for Mobile Robotized Tele-echography

Ultrasound imaging allows the evaluation of the degree of emergency of a patient. However, in many situations no experienced sonographer is available to perform such echography. To cope with this issue, the OTELO project “mObile Tele-Echography using an ultra-Light rObot” (OTELO) aims to develop a fully integrated end-to-end mobile tele-echography system using an ultralight, remotely controlled six degree-of-freedom (DOF) robot. In this context, this paper deals with the user interface environment of the OTELO system, composed by the following parts: an ultrasound video transmission system providing real-time images of the scanned area at each moment, an audio/video conference to communicate with the paramedical assistant and the patient, and finally a virtual reality environment, providing visual and haptic feedback to the expert, while capturing the expert's hand movements with a one-DOF hand free input device

The next challenge for world wide robotized tele-echography experiment (WORTEX 2012): from engineering success to healthcare delivery.

Access to good quality healthcare remains difficult for many patients whether they live in developed or developing countries. In developed countries, specialist medical expertise is concentrated in major hospitals in urban settings both to improve clinical outcomes and as a strategy to reduce the costs of specialist healthcare delivery. In developing countries, millions of people have limited, if any, routine access to a healthcare system and due to economic and cultural factors the accessibility of any services may be restricted. In both cases, geographical, socio-political, cultural and economic factors produce ‘medically isolated areas’ where patients find themselves disadvantaged in terms of timely diagnosis and expert and/or expensive treatment. The robotized teleechography approach, also referred to as robotized teleultrasound, offers a potential solution to diagnostic imaging in medically isolated areas. It is designed for patients requiring ultrasound scans for routine care (e.g., ante natal care) and for diagnostic imaging to investigate acute and medical emergencies conditions, including trauma care and responses to natural disasters such as earthquakes. The robotized teleechography system can hold any standard ultrasound probe; this lightweight system is positioned on the patient’s body by a healthcare assistant. The medical expert, a clinician with expertise in ultrasound imaging and diagnosis, is in a distant location and, using a dedicated joystick, remotely controls the scanning via any available communication link (Internet, satellite). The WORTEX2012 intercontinental trials of the system conducted last year successfully demonstrated the feasibility of remote robotized tele-echography in a range of cultural, technical and clinical contexts. In addition to the engineering success, these trials provided positive feedback from the participating clinicians and patients on using the system and on the system’s perceived potential to transform healthcare in medically isolated areas. The next challenge is to show evidence that this innovative technology can deliver on its promise if introduced into routine healthcare

Ion-channel function and cross-species determinants in viral assembly of nonprimate hepacivirus p7

Nonprimate hepacivirus (NPHV), the closest homolog of hepatitis C virus (HCV) described to date, has recently been discovered in horses. Even though the two viruses share a similar genomic organization, conservation of the encoded hepaciviral proteins remains undetermined. The HCV p7 protein is localized within endoplasmic reticulum (ER) membranes and is important for the production of infectious particles. In this study, we analyzed the structural and functional features of NPHV p7 in addition to its role during virus assembly. Three-dimensional homology models for NPHV p7 using various nuclear magnetic resonance spectroscopy (NMR) structures were generated, highlighting the conserved residues important for ion channel function. By applying a liposome permeability assay, we observed that NPHV p7 exhibited liposome permeability features similar to those of HCV p7, indicative of similar ion channel activity. Next, we characterized the viral protein using a p7-based trans-complementation approach. A similar subcellular localization pattern at the ER membrane was observed, although production of infectious particles was likely hindered by genetic incompatibilities with HCV proteins. To further characterize these cross-species constraints, chimeric viruses were constructed by substituting different regions of HCV p7 with NPHV p7. The N terminus and transmembrane domains were nonexchangeable and therefore constitute a cross-species barrier in hepaciviral assembly. In contrast, the basic loop and the C terminus of NPHV p7 were readily exchangeable, allowing production of infectious trans-complemented viral particles. In conclusion, comparison of NPHV and HCV p7 revealed structural and functional homology of these proteins, including liposome permeability, and broadly acting determinants that modulate hepaciviral virion assembly and contribute to the host-species barrier were identified

A novel method for the measurement of hepatitis C virus infectious titres using the IncuCyte ZOOM and its application to antiviral screening

Summary: Hepatitis C virus (HCV) is a significant human pathogen infecting 3% of the world population. An infectious molecular clone capable of replicating and releasing infectious virions in cell culture has only been available since 2005, leaving a significant knowledge gap concerning post-RNA replication events such as particle assembly, trafficking and release. Thus, a fast, efficient and accurate method of measuring infectious viral titres is highly desirable. Current methods rely upon manual counting of infected cell foci and so are both labour-intensive and susceptible to human error. Here, we report a novel protocol, which utilises the IncuCyte ZOOM instrument and related software to accurately count infected cells and extrapolation of this data to produce an infectious titre, reported as infectious units per millilitre (IU/mL). This method reduces cost, time and error in experiments. We also demonstrate that this approach is amenable to high-throughput compound screening, thereby expediting the identification of novel antivirals

Neutralizing antibodies and pathogenesis of hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The interplay between the virus and host innate and adaptive immune responses determines the outcome of infection. There is increasing evidence that host neutralizing responses play a relevant role in the resulting pathogenesis. Furthermore, viral evasion from host neutralizing antibodies has been revealed to be an important contributor in leading both to viral persistence in acute liver graft infection following liver transplantation, and to chronic viral infection. The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. The understanding of these mechanisms will ultimately contribute to the development of novel antiviral preventive strategies for liver graft infection and an urgently needed vaccine. This review summarizes recent concepts of the role of neutralizing antibodies in viral clearance and protection, and highlights consequences of viral escape from neutralizing antibodies in the pathogenesis of HCV infection

Cell Culture Replication of a Genotype 1b Hepatitis C Virus Isolate Cloned from a Patient Who Underwent Liver Transplantation

The introduction of the genotype 2a isolate JFH1 was a major breakthrough in the field of hepatitis C virus (HCV), allowing researchers to study the complete life cycle of the virus in cell culture. However, fully competent culture systems encompassing the most therapeutically relevant HCV genotypes are still lacking, especially for the highly drug-resistant genotype 1b. For most isolated HCV clones, efficient replication in cultured hepatoma cells requires the introduction of replication-enhancing mutations. However, such mutations may interfere with viral assembly, as occurs in the case of the genotype 1b isolate Con1. In this study, we show that a clinical serum carrying a genotype 1b virus with an exceptionally high viral load was able to infect Huh7.5 cells. Similar to previous reports, inoculation of Huh7.5 cells by natural virus is very inefficient compared to infection by cell culture HCV. A consensus sequence of a new genotype 1b HCV isolate was cloned from the clinical serum (designated Barcelona HCV1), and then subjected to replication studies. This virus replicated poorly in a transient fashion in Huh7.5 cells after electroporation with in vitro transcribed RNA. Nonetheless, approximately 3 weeks post electroporation and thereafter, core protein-positive cells were detected by immunofluorescence. Surprisingly, small amounts of core protein were also measurable in the supernatant of electroporated cells, suggesting that HCV particles might be assembled and released. Our findings not only enhance the current method of cloning in vitro HCV replication-competent isolates, but also offer valuable insights for the realization of fully competent culture systems for HCV