Inhibitory axons are targeted in hippocampal cell culture by anti-Caspr2 autoantibodies associated with limbic encephalitis

International audienceContactin-associated protein-like 2 (Caspr2), also known as CNTNAP2, is a cell adhesion molecule that clusters voltage-gated potassium channels (Kv1.1/1.2) at the juxtaparanodes of myelinated axons and may regulate axonal excitability. As a component of the Kv1 complex, Caspr2 has been identified as a target in neuromyotonia and Morvan syndrome, but also in some cases of autoimmune limbic encephalitis (LE). How anti-Caspr2 autoimmunity is linked with the central neurological symptoms is still elusive. In the present study, using anti-Caspr2 antibodies from seven patients affected by pure LE, we determined that IgGs in the cerebrospinal fluid of four out seven patients were selectively directed against the N-terminal Discoïdin and LamininG1 modules of Caspr2. Using live immunolabeling of cultured hippocampal neurons, we determined that serum IgGs in all patients strongly targeted inhibitory interneurons. Caspr2 was highly detected on GAD65-positive axons that are surrounding the cell bodies and at the VGAT-positive inhibitory presynaptic contacts. Functional assays indicated that LE autoantibodies may induce alteration of Gephyrin clusters at inhibitory synaptic contacts. Next, we generated a Caspr2-Fc chimera to reveal Caspr2 receptors on hippocampal neurons localized at the somato-dendritic compartment and post-synapse. Caspr2-Fc binding was strongly increased on TAG-1-transfected neurons and conversely, Caspr2-Fc did not bind hippocampal neurons from TAG-1-deficient mice. Our data indicate that Caspr2 may participate as a cell recognition molecule in the dynamics of inhibitory networks. This study provides new insight into the potential pathogenic effect of anti-Caspr2 autoantibodies in central hyperexcitability that may be related with perturbation of inhibitory interneuron activity

X-ray Ptychographic Imaging and Spectroscopic Studies of Plasma-Treated Plastic Films

Polyethylene terephthalate (PET) is a thermoplastic polyester with numerous applications in industry. However, it requires surface modification on an industrial scale for printing and coating processes and plasma treatment is one of the most commonly used techniques to increase the hydrophilicity of the PET films. Systematic improvement of the surface modification by adaption of the plasma process can be aided by a comprehensive understanding of the surface morphology and chemistry. However, imaging large surface areas (tens of microns) with a resolution that allows understanding the surface quality and modification is challenging. As a proof-of-principle, plasma-treated PET films were used to demonstrate the capabilities of X-ray ptychography, currently under development at the soft X-ray free-electron laser FLASH at DESY, for imaging macroscopic samples. In combination with scanning electron microscopy (SEM), this new technique was used to study the effects of different plasma treatment processes on PET plastic films. The studies on the surface morphology were complemented by investigations of the surface chemistry using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR). While both imaging techniques consistently showed an increase in roughness and change in morphology of the PET films after plasma treatment, X-ray ptychography can provide additional information on the three-dimensional morphology of the surface. At the same time, the chemical analysis shows an increase in the oxygen content and polarity of the surface without significant damage to the polymer, which is important for printing and coating processes

Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

The contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS.A panel of experts developed by consensus a modified set of diagnostic PNS criteria for clinical decision making and research purposes. The panel reappraised the 2004 criteria alongside new knowledge on PNS obtained from published and unpublished data generated by the different laboratories involved in the project.The panel proposed to substitute "classical syndromes" with the term "high-risk phenotypes" for cancer and introduce the concept of "intermediate-risk phenotypes." The term "onconeural antibody" was replaced by "high risk" (>70% associated with cancer) and "intermediate risk" (30%-70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided.The proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

Applications des plasmas froids à l’oncologie, approche expérimentale multidisciplinaire, modèles et modélisations physiques, chimiques et biologiques

Plasma-medicine is the field of research describing the medical applications of plasmas, mainly at atmospheric pressure. Cold plasmas are a state of matter characterized by the presence of free electrons with a kinetic energy of several electron volts even though the ions and neutrals may be at room temperature. This transient state, apart from thermal equilibrium, produces highly reactive chemical species. The objective of this multidisciplinary work was to evaluate the anti-tumor potential of cold plasmas. Two types of devices have been designed and manufactured by 3D-printing: Dielectric Barrier Discharge and plasma-jets. In-vitro and in-vivo studies were conducted with TC1 and CT26 cell lines. The production of reactive species produced in a liquid exposed to plasma has been studied in order to understand the in-vitro results and to compare the plasma devices with those of other teams. Various plasma devices have been made to study the effect of the energy deposited during the in-vivo treatment of skin and subcutaneous tumors. A device cooled with liquid nitrogen has been developed to limit skin damage induced by heating. Finally, a numerical simulation modeling the heat transfers of tumors and tissues under plasmas exposure enables to quantify the hyperthermia and the associated lesions by validating the model on experimental results. A critical review of in-vivo plasma-medicine studies published in the literature is proposed to evaluate the role of hyperthermia in the therapeutic effects reported.« La médecine- plasma» est le domaine de recherche décrivant les applications médicales des plasmas, principalement à pression atmosphérique. Les plasmas froids sont un état de la matière caractérisé par la présence d'électrons libres ayant une énergie cinétique de plusieurs eV alors même que les ions et les neutres peuvent être à température ambiante. Cet état transitoire, hors équilibre thermique, produit des espèces chimiques très réactives. L’objectif de ce travail multidisciplinaire a été d’évaluer le potentiel anti-tumoral des plasmas-froids. Deux types de dispositifs ont été conçus et fabriqués par impression 3D: des Décharges à Barrière Diélectrique et des jets plasmas. Des études in-vitro et in-vivo ont été menées avec les lignées cellulaires TC1 et CT26. La production d’espèces réactives produites dans un liquide exposé à un plasma a été étudiée afin de comprendre les résultats in-vitro et de comparer les dispositifs plasma entre eux. Différents dispositifs à plasmas ont été réalisés afin d’étudier in-vivo, l’effet de l’énergie déposée lors du traitement sur la peau et les tumeurs. Afin de limiter l’échauffement cutané et les lésions induites un dispositif refroidi à l’azote liquide a été développé. Enfin, une simulation numérique modélisant les transferts thermiques des tumeurs et tissus sous exposition plasmas a permis de quantifier l’hyperthermie et les lésions associées en validant le modèle sur des résulats expérimentaux. Une revue critique d’études in-vivo de « médecine plasma » publiées dans la littérature est proposée afin d’évaluer le rôle de l’hyperthermie dans les effets thérapeutiques observés

Investigation of key plasma species on germination boosting of Mung bean

International audienceAtmospheric-pressure dielectric barrier discharge (DBD) plasma array has been used to treat mung bean seeds and mustard to explore the responses of them in terms of germination rate under direct and indirect plasma treatment methods. Plasma stimulation could selectively affect germination of mung bean and mustard seeds. Plasma indirect treatment showed a positive germination promotion both in mung bean and mustard seeds, while plasma direct treatment only increased mung bean germination rate, inhibit that of mustard. This enhancement of germination was related with plasma produced activated ions both including long life ions and short life oxidative radicals in liquid condition. Short life radicals, e.g. hydroxyl radical etc, played a more sensitive promoting effect because of their stronger chemical and biological activities

Generation and quantification of nitrogen species in plasma activated water

International audienceThe plasma activation of liquid media such as water to store reactive oxygen (nitrogen) species (e.g. H2O2, O3, O2-, NO2-, NO3-, NO) gains rising interest in cold plasma community owing to their great potential in medical applications (such as blood coagulation, oncology) but also in agriculture so as to face with contemporary and prospective issues such as organic fertilizers replacement, plants growth velocity increase and seeds dormancy reduction. Effects of cold atmospheric plasma (CAP) treatment have already been demonstrated on seeds germination and on seedling growth. CAP treatments appear therefore as a fast and pollution-free alternative to improve seeds performance and crop yield

Prolongation of the lifetime of guided discharges triggered in atmospheric air by femtosecond laser filaments up to 130 μs

International audienceThe triggering and guiding of electric discharges produced in atmospheric air by a compact 100 kV Marx generator is realized in laboratory using an intense femtosecond laser pulse undergoing filamentation. We describe here an approach allowing extending the lifetime of the discharges by injecting a current with an additional circuit. Laser guiding discharges with a length of 8.5 cm and duration of 130 μs were obtained

Non-thermal DBD plasma array on seed germination of different plant species

International audienceA dielectric barrier discharge (DBD) reactor producing cold plasma at atmospheric pressure has been used to treat seeds of eight different species and investigate their responses in term of germination. The device is made of nine cylindrical DBDs organized in a array and partially immersed in water. O2, N2, and air were flown in the device; the cold plasma from such gas is formed in the bubbles and touch liquid surface. Seeds were either located inside the water during plasma treatment process (direct treatment) or were watered by the water exposed to cold plasma beforehand (indirect treatment). Such plasma activated water contains reactive oxygen species and reactive nitrogen species. The statistical analysis shows that the probability of germinating of treated mung bean, mustard and radish is significantly higher than in control groups (p&#8201;&#8201;<&#8201;&#8201;0.05) for indirect treatments. A comparison of different treatment modalities (direct versus indirect treatment and gas composition) on germination boost has been completed on mung bean seeds. It is shown that direct plasma treatment using different gas (O2, N2, and air) give a strong enhancement of the mung bean germination probability compared to the control group; in the case of indirect treatment, only plasma air-treated water lead to a significant germination boost compared to the control group; this effect is still smaller than the one obtained using a direct treatment

Potential side effect of propofol and sevoflurane for anesthesia of anti-NMDA-R encephalitis.

International audienceBACKGROUND: Many anesthetic drugs interact with the NMDA receptor and may therefore alter the clinical presentation of anti-NMDA-R encephalitis. CASE PRESENTATION: A 24-year-old woman was admitted to hospital for decreased consciousness and hyperthermia. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis, and elevated protein. Cultures were negative. Patient state worsened with agitation, facial dyskinesia, ocular deviation, and limb dystonia. Diagnosis of anti-NMDA-R encephalitis was evidenced by specific antibodies. High doses of methylprednisolone were administered. CT scan disclosed an ovarian teratoma and tumor resection was scheduled under anesthesia with propofol, sufentanil, atracurium and sevoflurane. Sedation after surgery was maintained with propofol. Rapidly after surgery, patient's condition deteriorated with increase of dyskinesias, and two tonic-clonic generalized seizure events. CONCLUSION: In patients with anti-NMDA-R encephalitis, anesthesia using benzodiazepines, opiates and curares, which fail to interfere with the NMDA pathway, should be preferred

X-ray Ptychographic Imaging and Spectroscopic Studies of Plasma-Treated Plastic Films

Polyethylene terephthalate (PET) is a thermoplastic polyester with numerous applications in industry. However, it requires surface modification on an industrial scale for printing and coating processes and plasma treatment is one of the most commonly used techniques to increase the hydrophilicity of the PET films. Systematic improvement of the surface modification by adaption of the plasma process can be aided by a comprehensive understanding of the surface morphology and chemistry. However, imaging large surface areas (tens of microns) with a resolution that allows understanding the surface quality and modification is challenging. As a proof-of-principle, plasma-treated PET films were used to demonstrate the capabilities of X-ray ptychography, currently under development at the soft X-ray free-electron laser FLASH at DESY, for imaging macroscopic samples. In combination with scanning electron microscopy (SEM), this new technique was used to study the effects of different plasma treatment processes on PET plastic films. The studies on the surface morphology were complemented by investigations of the surface chemistry using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR). While both imaging techniques consistently showed an increase in roughness and change in morphology of the PET films after plasma treatment, X-ray ptychography can provide additional information on the three-dimensional morphology of the surface. At the same time, the chemical analysis shows an increase in the oxygen content and polarity of the surface without significant damage to the polymer, which is important for printing and coating processes