Hepatocyte Permissiveness to Plasmodium Infection Is Conveyed by a Short and Structurally Conserved Region of the CD81 Large Extracellular Domain

Invasion of hepatocytes by Plasmodium sporozoites is a prerequisite for establishment of a malaria infection, and thus represents an attractive target for anti-malarial interventions. Still, the molecular mechanisms underlying sporozoite invasion are largely unknown. We have previously reported that the tetraspanin CD81, a known receptor for the hepatitis C virus (HCV), is required on hepatocytes for infection by sporozoites of several Plasmodium species. Here we have characterized CD81 molecular determinants required for infection of hepatocytic cells by P. yoelii sporozoites. Using CD9/CD81 chimeras, we have identified in CD81 a 21 amino acid stretch located in a domain structurally conserved in the large extracellular loop of tetraspanins, which is sufficient in an otherwise CD9 background to confer susceptibility to P. yoelii infection. By site-directed mutagenesis, we have demonstrated the key role of a solvent-exposed region around residue D137 within this domain. A mAb that requires this region for optimal binding did not block infection, in contrast to other CD81 mAbs. This study has uncovered a new functionally important region of CD81, independent of HCV E2 envelope protein binding domain, and further suggests that CD81 may not interact directly with a parasite ligand during Plasmodium infection, but instead may regulate the function of a yet unknown partner protein

Deep-brain stimulation in Parkinson's disease: long-term efficacy and safety - What happened this year?

International audiencePURPOSE OF REVIEW: Deep-brain high-frequency stimulation of the thalamus was introduced in 1987 to treat tremor, and was applied in 1993 to the subthalamic nucleus to treat advanced Parkinson's disease. High-frequency stimulation of the subthalamic nucleus has become the surgical therapy of choice. This review concentrates on recent data on long-term results and side-effects, after 12 years of practice using this technique. RECENT FINDINGS: A literature search produced 260 papers from February 2004 to March 2005. The stable efficacy of high-frequency stimulation of the subthalamic nucleus on Parkinson's disease motor symptoms is confirmed. Evidence for a neuroprotective effect is still lacking. There are transient neuropsychological disturbances, but no cognitive impairment over time. Complications are rare and mild, mortality is extremely low and hardware complications are highly variable. SUMMARY: The safety and innocuity of the method legitimizes earlier operations, before impairment of the quality of life. Depression and suicide are related to pre-existing co-morbidities and multifactorial causes that could become contraindications. Neuropsychological effects should be documented, to determine whether they are caused by an alteration of high-frequency stimulation of the subthalamic nucleus, or inappropriate electrode placement. There is an urgent need for the organization of research and reports, and no need to report small series replicating well-established conclusions. Clinical reports should concentrate on unobserved effects in relation to causative parameters, based on the precise location of electrodes, and on clinical reports comparable between teams and on methods to optimize and facilitate the tuning of parameters and postoperative evaluations in order to make this treatment easier to provide for the neurologist

Frameless ROSA (R) robot-assisted lead implantation for deep brain stimulation: Technique and accuracy

International audienceBACKGROUND: Frameless robotic-assisted surgery is an innovative technique for deep brain stimulation (DBS) that has not been assessed in a large cohort of patients.OBJECTIVE: To evaluate accuracy of DBS lead placement using the ROSA$^{(R)}$ robot (Zimmer Biomet) and a frameless registration.METHODS: All patients undergoing DBS surgery in our institution between 2012 and 2016 were prospectively included in an open label single-center study. Accuracy was evaluated by measuring the radial error (RE) of the first stylet implanted on each side and the RE of the final lead position at the target level. RE was measured on intraoperative telemetric X-rays (group 1), on intraoperative O-Arm$^{(R)}$ (Medtronic) computed tomography (CT) scans (group 2), and on postoperative CT scans or magnetic resonance imaging (MRI) in both groups.RESULTS: Of 144 consecutive patients, 119 were eligible for final analysis (123 DBS; 186 stylets; 192 leads). In group 1 (76 patients), the mean RE of the stylet was 0.57 $\pm$ 0.02 mm, 0.72 $\pm$ 0.03 mm for DBS lead measured intraoperatively, and 0.88 $\pm$ 0.04 mm for DBS lead measured postoperatively on CT scans. In group 2 (43 patients), the mean RE of the stylet was 0.68 $\pm$ 0.05 mm, 0.75 $\pm$ 0.04 mm for DBS lead measured intraoperatively; 0.86 $\pm$ 0.05 mm and 1.10 $\pm$ 0.08 mm for lead measured postoperatively on CT scans and on MRI, respectively No statistical difference regarding the RE of the final lead position was found between the different intraoperative imaging modalities and postoperative CT scans in both groups. CONCLUSION: Frameless ROSA (R) robot-assisted technique for DBS reached submillimeter accuracy. Intraoperative CT scans appeared to be reliable and sufficient to evaluatethe final lead position

[Sulcal identification and neuronavigation in supratentorial cavernoma surgery]

International audienceWe present the use of cortical sulci, segmented from magnetic resonance imaging, in image guided neurosurgery. Sulcal information was transferred to a surgical microscope with enhanced reality features. This assistance was used for the resection of supratentorial cavernomas (7 patients). Sulci were semi-automatically segmented from 3D MRI data sets. Sulci close to the cavernoma were selected and transferred to the neuronavigation system which allows the superimposition of graphics into the right ocular of the microscope. Selected sulci were displayed on the workstation and superimposed into the ocular of the microscope. Cortical sulci proved to be useful for the recognition of the anatomical environment. The superimposed sulci helped to optimize location and size of the skin incision as well as to guide the access to the cavernoma by using the course of a sulcus as indirect trajectory