We investigated the therapeutic potential of the interleukin‐6 receptor inhibitor tocilizumab in 7 patients with new onset refractory status epilepticus (NORSE) who remained refractory to ...conventional immunotherapy with rituximab (n = 5) or without rituximab (n = 2). Status epilepticus (SE) was terminated after 1 or 2 doses of tocilizumab in 6 patients with a median interval of 3 days from the initiation. They had no recurrence of SE during the observation. However, 2 patients experienced severe adverse events related to infection during the tocilizumab therapy. Further prospective controlled studies are warranted to validate the efficacy and safety of tocilizumab in patients with NORSE. Ann Neurol 2018;84:940–945
Implantation of biodegradable wafers near the brain surgery site to deliver anti-cancer agents which target residual tumor cells by bypassing the blood-brain barrier has been a promising method for ...brain tumor treatment. However, further improvement in the prognosis is still necessary. We herein present novel materials and device technologies for drug delivery to brain tumors, i.e., a flexible, sticky, and biodegradable drug-loaded patch integrated with wireless electronics for controlled intracranial drug delivery through mild-thermic actuation. The flexible and bifacially-designed sticky/hydrophobic device allows conformal adhesion on the brain surgery site and provides spatially-controlled and temporarily-extended drug delivery to brain tumors while minimizing unintended drug leakage to the cerebrospinal fluid. Biodegradation of the entire device minimizes potential neurological side-effects. Application of the device to the mouse model confirms tumor volume suppression and improved survival rate. Demonstration in a large animal model (canine model) exhibited its potential for human application.
Forest trees are a major source of biogenic volatile organic compounds (BVOCs). Terpenes and terpenoids are known as the main BVOCs of forest aerosols. These compounds have been shown to display a ...broad range of biological activities in various human disease models, thus implying that forest aerosols containing these compounds may be related to beneficial effects of forest bathing. In this review, we surveyed studies analyzing BVOCs and selected the most abundant 23 terpenes and terpenoids emitted in forested areas of the Northern Hemisphere, which were reported to display anti-inflammatory activities. We categorized anti-inflammatory processes related to the functions of these compounds into six groups and summarized their molecular mechanisms of action. Finally, among the major 23 compounds, we examined the therapeutic potentials of 12 compounds known to be effective against respiratory inflammation, atopic dermatitis, arthritis, and neuroinflammation among various inflammatory diseases. In conclusion, the updated studies support the beneficial effects of forest aerosols and propose their potential use as chemopreventive and therapeutic agents for treating various inflammatory diseases.
Hierarchical hollow spheres of Fe2O3@polyaniline are fabricated by template‐free synthesis of iron oxides followed by a post in‐ and exterior construction. A combination of large surface area with ...porous structure, fast ion/electron transport, and mechanical integrity renders this material attractive as a lithium‐ion anode, showing superior rate capability and cycling performance.
Forest bathing is suggested to have beneficial effects on various aspects of human health. Terpenes, isoprene based-phytochemicals emitted from trees, are largely responsible for these beneficial ...effects of forest bathing. Although the therapeutic effects of terpenes on various diseases have been revealed, their effects on neuronal health have not yet been studied in detail. Here, we screened 16 terpenes that are the main components of Korean forests using Drosophila Alzheimer’s disease (AD) models to identify which terpenes have neuroprotective effects. Six out of the 16 terpenes, ρ-cymene, limonene (+), limonene (−), linalool, α-pinene (+), and β-pinene (−), partially suppressed the beta amyloid 42 (Aβ42)-induced rough eye phenotype when fed to Aβ42-expressing flies. Among them, limonene (+) restored the decreased survival of flies expressing Aβ42 in neurons during development. Limonene (+) treatment did not affect Aβ42 accumulation and aggregation, but did cause to decrease cell death, reactive oxygen species levels, extracellular signal-regulated kinase phosphorylation, and inflammation in the brains or the eye imaginal discs of Aβ42-expressing flies. This neuroprotective effect of limonene (+) was not associated with autophagic activity. Our results suggest that limonene (+) has a neuroprotective function against the neurotoxicity of Aβ42 and, thus, is a possible therapeutic reagent for AD.
The incorporation of carbon nanotubes (CNTs) in Ultra-High Performance Concrete (UHPC) was investigated with regard to the dispersion, mechanical properties, and electromagnetic shielding ...effectiveness (SE). Dispersed CNT solution (0–2.0 wt%) was prepared by sonication and subsequent shear mixing with superplasticizer to achieve the high flowability for UHPC slurry. The dispersion method was effective to manufacture CNT-UHPC composite up to the critical incorporation concentration (CIC). Conducted experiments revealed that CNTs below the CIC improve the mechanical properties of UHPC through pore filling, bridging, and a denser C–S–H structure. CNTs substantially improve the electrical conductivity and resulting SE up to the percolation threshold. Two methods of ASTM D4935-18 and IEEE-STD-299 with electromagnetic compatibility (EMC) theory verified the result and suggested that larger specimen with sufficient incident area should be fabricated to accurately evaluate the SE of actual structures. Otherwise, the ability of SE of UHPC-CNT composites could be biased.
To treat intractable cases of autoimmune encephalitis, the need for novel immunotherapy that penetrates the blood‐brain barrier (BBB) is increasing. Tofacitinib is a Janus kinase (JAK) inhibitor used ...to treat refractory immune‐mediated diseases that effectively penetrates the BBB. Accordingly, tofacitinib could be a new option for patients with refractory autoimmune encephalitis. Patients treated with tofacitinib were selected from Seoul National University Hospital cohort for autoimmune encephalitis from April 2019 until July 2020. We retrospectively analyzed the efficacy of tofacitinib in patients with autoimmune encephalitis who showed insufficient responses to multimodal conventional immunotherapies. Tofacitinib was administered orally at a dose of 5 mg twice daily. A total of eight patients were treated with tofacitinib; two had good responses (clinical global impression‐improvement score CGI‐I = 1 or 2), three had partial responses (CGI‐I = 3), and three showed no significant improvements (CGI‐I = 4) in response to tofacitinib. The two good responders showed the improvement of chronic autoimmune meningoencephalitis and the cessation of the new‐onset refractory status epilepticus in anti‐myelin oligodendrocyte glycoprotein (MOG)–associated disorder, which was previously intractable to anesthetics and the other immunotherapies. No patients had serious side effects. Our findings suggest the potential of tofacitinib as a therapeutic option for central nervous system autoimmune diseases.
The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune ...encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.
The hard X-ray free-electron laser at the Pohang Accelerator Laboratory (PAL-XFEL) in the Republic of Korea achieved saturation of a 0.144 nm free-electron laser beam on 27 November 2016, making it ...the third hard X-ray free-electron laser in the world, following the demonstrations of the Linac Coherent Light Source (LCLS) and the SPring-8 Angstrom Compact Free Electron Laser (SACLA). The use of electron-beam-based alignment incorporating undulator radiation spectrum analysis has allowed reliable operation of PAL-XFEL with unprecedented temporal stability and dispersion-free orbits. In particular, a timing jitter of just 20 fs for the free-electron laser photon beam is consistently achieved due to the use of a state-of-the-art design of the electron linear accelerator and electron-beam-based alignment. The low timing jitter of the electron beam makes it possible to observe Bi(111) phonon dynamics without the need for timing-jitter correction, indicating that PAL-XFEL will be an extremely useful tool for hard X-ray time-resolved experiments. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) in South Korea has now entered operation with a timing jitter of just 20 fs.
The thermodynamic state of H2 adsorbed on Pt in the aqueous phase was determined by kinetic analysis of H2 reacting with D2O to HDO, HD, and D2, and by DFT‐based ab initio molecular dynamics ...simulations of H2 adsorption on Pt(111), Pt(110), and Pt nanoparticles. Dissociative adsorption of H2 on Pt is significantly weakened in the aqueous phase compared to adsorption at gas–solid interfaces. Water destabilizes the adsorbed H atoms, decreasing the heat of adsorption by 19–22 kJ molH2-1
while inducing an additional entropy loss of 50–70 J molH2-1
K−1. Upon dissociative adsorption of H2, the average distance of water from the Pt surface increases and the liquid adopts a structure that is more ordered than before close to the Pt surface, which limits the translation mobility of the adsorbed H atoms. The presence of hydrated hydronium ions next to the Pt surface further lowers the H−Pt bond strength.
The thermodynamic state of H2 adsorbed on Pt in the aqueous phase was determined via kinetic analysis of H2 reacting with D2O and by DFT‐based ab initio molecular dynamics simulations of H2 adsorption on Pt(111). Compared to the gas–solid interface, the presence of liquid water weakens the dissociative adsorption by decreasing the heat of adsorption and inducing a larger loss of entropy.
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