Objective
There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to ...verify the reliability and validity of the developed scale.
Methods
The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38).
Results
A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient ICC = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92).
Interpretation
CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352–358.
Color conversion, long‐wavelength light emission by absorbing short‐wavelength light, is an attractive approach for developing a broad‐color expression technology and is widely used in solid‐state ...lighting, dye‐lasers, and colorful displays. Up to now, many papers have been published reporting various mechanoluminescent materials emitting color of ultraviolet, blue, green, orange, and red. However, the strategies of previous reports have focused on color‐tuning of mechanoluminescent material itself through newly developing inorganic mechanoluminescent compounds. Here, a new strategy for the color manipulation of mechanoluminescence (ML) is introduced by physically combining fluorescent dyes with existing mechanoluminescent materials. An elastomeric zinc sulfide (ZnS) composite is prepared in a polydimethylsiloxane framework with spontaneously diffused 4‐(dicyanomethylene)‐2‐t‐butyl‐6‐(1,1,7,7‐tetramethyljulolidyl‐9‐enyl)‐4H‐pyran (DCJTB), and red luminescence by complete color conversion via DCJTB is demonstrated, which fully absorbed green ML from ZnS. Based on this approach, color‐tuning of ML from red to green is successfully achieved and color expression range is expanded by employing electroluminescence (EL). Various‐color‐emitting EL/ML electromechanical display is demonstrated using color discrepancy between DCJTB employed EL and ML. As the implementation is fairly straightforward, it is believed that present color conversion is a viable and common method to manipulate broader color expression for future ML applications.
A new strategy is shown for a candy‐inspired (left image) mechanoluminescence (ML) color manipulation by combining organic red fluorescent dye and zinc sulfide ML material. A red‐dye‐diffused elastomeric bilayer film consisting of a color conversion layer and a green ML light source layer emits clear red luminescence by complete color conversion process when it is stretched (right figure).
Although carbon nanotubes (CNTs) are remarkable materials with many exceptional characteristics, their poor chemical functionality limits their potential applications. Herein, a strategy is proposed ...for functionalizing CNTs, which can be achieved with any functional group (FG) without degrading their intrinsic structure by using a deoxyribonucleic acid (DNA)‐binding peptide (DBP) anchor. By employing a DBP tagged with a certain FG, such as thiol, biotin, and carboxyl acid, it is possible to introduce any FG with a controlled density on DNA‐wrapped CNTs. Additionally, different types of FGs can be introduced on CNTs simultaneously, using DBPs tagged with different FGs. This method can be used to prepare CNT nanocomposites containing different types of nanoparticles (NPs), such as Au NPs, magnetic NPs, and quantum dots. The CNT nanocomposites decorated with these NPs can be used as reusable catalase‐like nanocomposites with exceptional catalytic activities, owing to the synergistic effects of all the components. Additionally, the unique DBP–DNA interaction allows the on‐demand detachment of the NPs attached to the CNT surface; further, it facilitates a CNT chirality‐specific NP attachment and separation using the sequence‐specific programmable characteristics of oligonucleotides. The proposed method provides a novel chemistry platform for constructing new functional CNTs suitable for diverse applications.
This work reports a simple and generalizable method to introduce diverse functional groups on carbon nanotube (CNT) surfaces and construct heterogeneous CNT nanocomposites using deoxyribonucleic acid (DNA) binding peptide anchors. Using this strategy, any desired functional group of choice, such as thiol, biotin, and carboxylic acid, can be easily introduced on CNT surfaces with controlled density and ratio.
Metasurfaces have been continuously garnering attention in both scientific and industrial fields, owing to their unprecedented wavefront manipulation capabilities using arranged subwavelength ...artificial structures. To date, research has mainly focused on the full control of electromagnetic characteristics, including polarization, phase, amplitude, and even frequencies. Consequently, versatile possibilities of electromagnetic wave control have been achieved, yielding practical optical components such as metalenses, beam-steerers, metaholograms, and sensors. Current research is now focused on integrating the aforementioned metasurfaces with other standard optical components (e.g., light-emitting diodes, charged-coupled devices, micro-electro-mechanical systems, liquid crystals, heaters, refractive optical elements, planar waveguides, optical fibers, etc.) for commercialization with miniaturization trends of optical devices. Herein, this review describes and classifies metasurface-integrated optical components, and subsequently discusses their promising applications with metasurface-integrated optical platforms including those of augmented/virtual reality, light detection and ranging, and sensors. In conclusion, this review presents several challenges and prospects that are prevalent in the field in order to accelerate the commercialization of metasurfaces-integrated optical platforms.
Objective
Many pharmacokinetic studies of lacosamide (LCM) have been reported, but no large‐scale clinical study has been conducted on genetic polymorphisms that affect the metabolism of LCM. ...Therefore, we designed a pharmacogenetic study of LCM to explore the effect of genetic polymorphisms on serum LCM concentration. We evaluated the pharmacodynamic characteristics of LCM, including clinical efficacy and toxicity.
Methods
Adult patients with epilepsy who received LCM at Seoul National University Hospital were enrolled. Blood samples were obtained from 115 patients taking LCM for more than 1 month with unchanged doses and were used to analyze the serum LCM concentration, the concentration/dose (C/D) ratio and the single nucleotide polymorphisms (SNPs) of the cytochrome P450 (CYP)2C9 and CYP2C19 genes. In addition, clinical information—including efficacy, toxicity, and concomitant drugs—was collected.
Results
The serum LCM concentration showed a linear correlation with the daily dose (r = .66, p < .001). In genetic analysis, 43 patients (38.7%) were extensive metabolizers (EMs), 51 (45.9%) were intermediate metabolizers (IMs), and 17 (15.3%) were poor metabolizers (PMs). In the group comparison, mean serum concentrations and the C/D ratio showed significant differences between the three groups (p = .01 and p < .001, respectively). The C/D ratios of IM (27.78) and PM (35.6) were 13% and 39% higher than those of EM (25.58), respectively. In the pharmacodynamic subgroup analysis, patients in the ineffective LCM group had significantly lower serum concentrations (6.39 ± 3.25 vs. 8.44 ± 3.68 μg/ml, p = .024), whereas patients with adverse events had higher serum concentrations than those without adverse events (11.03 ± 4.32 vs. 7.4 ± 3.1 μg/ml, p < .001). Based on this, we suggest a reference range for LCM in the Korean population (6–9 μg/ml).
Significance
Genetic polymorphisms of the CYP2C19 gene affect the serum LCM concentration. Because efficacy and toxicity are apparently related to serum LCM levels, the genetic phenotype of CYP2C19 should be considered when prescribing LCM for patients with epilepsy.
Objective
Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) helps optimize drug management for patients with epilepsy. Salivary testing is both noninvasive and easy, and has several ...other advantages. Due to technical advances, salivary TDM has become feasible for several drugs, including AEDs, and its value has been investigated. Until recently, saliva TDM of perampanel (PER) had not been reported. The purpose of our study was to confirm whether saliva is a biological substitute for plasma in PER TDM.
Methods
Adult patients diagnosed with epilepsy who received PER from August 2018 to March 2019 at Seoul National University Hospital were enrolled. Total and free PER were measured in simultaneously obtained plasma and saliva samples using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) and high‐performance liquid chromatographic (HPLC). We examined the correlations between saliva and plasma PER concentrations and whether the use of concomitant medications classified as cytochrome P450 (CYP)3A4 inducers affected the correlations.
Results
Thirty patients were enrolled, aged 16 to 60; 10 (33%) were women. Patients received 2 to 12 mg (mean, 6 mg) of PER. The average total and free concentrations of PER were 343.02 (46.6‐818.0) and 1.53 (0.51‐2.92) ng/mL in plasma and 9.74 (2.21‐33.0) and 2.83 (1.01‐6.8) ng/mL in saliva, respectively. A linear relationship was observed between the total PER concentrations in saliva and the total and free PER concentrations in plasma (both P < .001; r = .678 and r = .619, respectively). The change in the PER concentration caused by the CYP3A4 inducer did not affect the correlation between saliva and plasma concentrations (all P < .001).
Significance
The PER concentration in saliva was correlated with that in plasma. This correlation was not affected by CYP3A4 inducers. Our results demonstrate for the first time that PER is measurable in saliva and suggest the potential for the clinical application of the saliva PER TDM matrix.
Abstract The purpose of this study was to investigate the chondrogenic features of human induced pluripotent stem cells (hiPSCs) and examine the differences in the chondrogenesis between hiPSCs and ...human bone marrow-derived MSCs (hBMMSCs). Embryoid bodies (EBs) were formed from undifferentiated hiPSCs. After EBs were dissociated into single cells, chondrogenic culture was performed in pellets and alginate hydrogel. Chondro-induced hiPSCs were implanted in osteochondral defects created on the patellar groove of immunosuppressed rats and evaluated after 12 weeks. The ESC markers NANOG, SSEA4 and OCT3/4 disappeared while the mesodermal marker BMP-4 appeared in chondro-induced hiPSCs. After 21 days of culture, greater glycosaminoglycan contents and better chondrocytic features including lacuna and abundant matrix formation were observed from chondro-induced hiPSCs compared to chondro-induced hBMMSCs. The expression of chondrogenic markers including SOX-9, type II collagen, and aggrecan in chondro-induced hiPSCs was comparable to or greater than chondro-induced hBMMSCs. A remarkably low level of hypertrophic and osteogenic markers including type X collagen, type I collagen and Runx-2 was noted in chondro-induced hiPSCs compared to chondro-induced hBMMSCs. hiPSCs had significantly greater methylation of several CpG sites in COL10A1 promoter than hBMMSCs in either undifferentiated or chondro-induced state, suggesting an epigenetic cause of the difference in hypertrophy. The defects implanted with chondro-induced hiPSCs showed a significantly better quality of cartilage repair than the control defects, and the majority of cells in the regenerated cartilage consisted of implanted hiPSCs.
3D interference printing enables the single‐step production of multilayered ultralong nanochannel arrays with nanoscale regularity. The superior depth‐of‐focus of this technique realizes a ...state‐of‐the‐art nanostructure which has intensively stacked 32 layers of inch‐long, horizonontal nanochannels with sub‐100 nm holes in a monolithic matrix (≈15 μm). This exceptional structure can be integrated into microfluidic devices, facilitating high‐flux rheological platforms using nanocapillarity.
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