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Perampanel (PER) is a new-generation antiepileptic drug that has an occasional but significant shortcoming, psychiatric adverse effects (PAEs). Recently, antiepileptic drug-related adverse reactions, such as skin rash and even PAEs, have been discovered to be correlated with certain human leukocyte antigen (HLA) types. Thus, we aimed to analyze specific HLA alleles as risk factors for PER-PAEs. We prospectively enrolled 17 patients with epilepsy who were prescribed PER between May 2016 and Jul 2018 at Seoul National University Hospital and developed PAEs while taking PER. Their HLA types were analyzed compared to those of 19 patients in the PAE-tolerant group and the general Korean population. In silico docking was performed with two different computational programs, AutoDock Vina and SwissDock, to theoretically evaluate the binding affinity of PER in the grooves of the specific HLA alleles. The HLA-DQB1*06:01, DRB1*08:03, and B*54:01 alleles were significantly associated with the patients who developed PER-PAEs compared with the general Korean population (odds ratio [OR] 3.94, p = 0.008, OR 9.24, p = 0.037, and OR 3.25, p = 0.041, respectively). As a haplotype, the combination of the three alleles was significantly more frequent in the PER-PAE group than in both the PER-tolerant group and the general Korean population. DQB1*06:01 and B*54:01 also demonstrated higher docking scores with PER than other alleles. This is the first study to analyze the association of PER-PAEs with specific HLA genotypes. Our results suggest that an HLA-associated genetic predisposition and a possible immunological mechanism are involved in the occurrence of PER-PAEs.

The neural substrates related to periodic leg movements during sleep (PLMS) remain uncertain, and the specific brain regions involved in PLMS have not been evaluated. We investigated the brain regions associated with PLMS and their severity using the electroencephalographic (EEG) source localization method. Polysomnographic data, including electromyographic, electrocardiographic, and 19-channel EEG signals, of 15 patients with restless legs syndrome were analyzed. We first identified the source locations of delta-band (2–4 Hz) spectral power prior to the onset of PLMS using a standardized low-resolution brain electromagnetic tomography method. Next, correlation analysis was conducted between current densities and PLMS index. Delta power initially and most prominently increased before leg movement (LM) onset in the PLMS series. Sources of delta power at −4~−3 seconds were located in the right pericentral, bilateral dorsolateral prefrontal, and cingulate regions. PLMS index was correlated with current densities at the right inferior parietal, temporoparietal junction, and middle frontal regions. In conclusion, our results suggest that the brain regions activated before periodic LM onset or associated with their severity are the large-scale motor network and provide insight into the cortical contribution of PLMS pathomechanism.

The desired target steady-state average colistin concentration (Css,avg) to balance between therapeutic effectiveness and nephrotoxicity is largely unclear. The objective of this study was to evaluate the effect of the desired target colistin Css,avg on the effectiveness and safety of IV colistin therapy in critically ill patients. Overall, 153 critically ill patients (71% males) receiving IV colistin were retrospectively analyzed. The desired target colistin Css,avg was estimated based on the daily colistin dose and creatinine clearance of each patient. No significant predictor for clinical cure was identified. However, microbiological outcome was significantly associated with pneumonia compared to bacteremia (odds ratio [OR] 0.092, 95% confidence interval [CI] [0.033–0.251], P P = 0.027). Colistin-associated nephrotoxicity was significantly less likely to occur in patients who received inhaled colistin close to the time of IV colistin therapy (OR 0.331, CI [0.119–0.925], P = 0.035). The desired target Css,avg of colistin was not associated with treatment outcomes or the risk of nephrotoxicity. Loading dose and inhaled colistin use near the time of IV colistin therapy may be considered to maximize therapeutic effectiveness and minimize the risk of colistin-associated nephrotoxicity, respectively.

There is no known biomarker that predicts the response to immune therapy in autoimmune synaptic encephalitis. Thus, we investigated serum albumin as a prognostic biomarker of early immune therapies in patients with autoimmune encephalitis. We enrolled patients who were diagnosed with definite autoimmune encephalitis and underwent IVIg treatment at Seoul National University Hospital from 2012 to 2017. Patients were dichotomized according to serum albumin prior to IVIg administration with a cut-off level of 4.0 g/dL, which was the median value of 50% of patients. Seventeen (53.1%) of the 32 patients with definite autoimmune encephalitis who received IVIg treatment in our hospital had low serum albumin (

The optic nerve sheath diameter (ONSD) is considered as an indirect marker for intracranial pressure (ICP). However, the optimal cut-off value for an abnormal ONSD indicating elevated ICP and its associated factors have been unclear. Thus, we investigated normative values for the ONSD using ultrasonography and investigate the potential factors affecting it. We prospectively recruited healthy volunteers between September 2016 and March 2017. A total of 585 individuals were included, in which the mean ONSD was 4.11 mm [95% confidence interval (CI), 4.09–4.14 mm]. Although ONSD was correlated with sex (p = 0.015), height (p = 0.003), and eyeball transverse diameter (ETD) (p p

TREM2 plays a critical role in the alleviation of Alzheimer’s disease by promoting Aβ phagocytosis by microglia, but the detailed molecular mechanism underlying TREM2-induced direct phagocytic activity of Aβ remains to be revealed. We found that learning and memory functions were improved in aged TREM2 TG mice, with the opposite effects in KO mice. The amount of phagocytosed Aβ was significantly reduced in the primary microglia of KO mice. CD36 expression in primary microglia was greater in TG than in WT mice but was substantially decreased in KO mice. The expression of C/EBPα, an upstream transcriptional activator of CD36, was also elevated in primary microglia of TG mice but decreased in KO mice. The transcription of CD36 was markedly increased by TREM2 overexpression, and this effect was suppressed by a mutation of the C/EBPα binding site on the CD36 promoter. The TREM2-induced expression of CD36 and C/EBPα was inhibited by treatment with PI3K/AKT signaling blockers, and phosphorylation of AKT was elevated in TREM2-overexpressing BV2 cells. The present study provides evidence that TREM2 is required for preventing loss of memory and learning in Alzheimer’s disease by regulating C/EBPα-dependent CD36 expression and the consequent Aβ phagocytosis.

Graphene has been studied for various applications due to its excellent properties. Graphene film fabrication from solutions of graphene oxide (GO) have attracted considerable attention because these procedures are suitable for mass production. GO, however, is an insulator and therefore a reduction process is required to make the GO film conductive. These reduction procedures require chemical reducing agents or high temperature annealing. Herein, we report a novel direct and simple reduction procedure of GO by silicon, which is the most widely used material in the electronics industry. In this study, we also used silicon nanosheets (SiNSs) as reducing agents for GO. The reducing effect of silicon was confirmed by various characterization methods. Furthermore, the silicon wafer was also used as a reducing template to create a reduced GO (rGO) film on a silicon substrate. By this process, a pure rGO film can be formed without the impurities that normally come from chemical reducing agents. This is an easy and environmentally friendly method to prepare large scale graphene films on Si substrates.

Surface potential measurement on atomically thin MoS2 flakes revealed the thickness dependence in Schottky barriers formed between high work function metal electrodes and MoS2 thin flakes. Schottky diode devices using mono- and multi- layer MoS2 channels were demonstrated by employing Ti and Pt contacts to form ohmic and Schottky junctions respectively. Characterization results indicated n-type behavior of the MoS2 thin flakes and the devices showed clear rectifying performance. We also observed the layer dependence in device characteristics and asymmetrically enhanced responses to NH3 and NO2 gases based on the metal work function and the Schottky barrier height change.