Seronegative autoimmune encephalitis: clinical characteristics and factors associated with outcomes.

Seronegative autoimmune encephalitis is autoimmune encephalitis without any identifiable pathogenic antibody. Although it is a major subtype of autoimmune encephalitis, many unmet clinical needs exist in terms of clinical characteristics, treatments and prognosis. In this institutional cohort study, patients diagnosed with seronegative autoimmune encephalitis with available 2-year outcomes were analysed for the disease course, 2-year outcome prediction system, effect of immunotherapy, necessity of further immunotherapy at 6 or 12 months and pattern of brain atrophy. Seronegative autoimmune encephalitis was subcategorized into antibody-negative probable autoimmune encephalitis, autoimmune limbic encephalitis and acute disseminated encephalomyelitis. Poor 2-year outcome was defined by modified Rankin scale scores 3-6, and the 2-year serial data of Clinical Assessment Scales in Autoimmune Encephalitis score was used for longitudinal data analyses. A total of 147 patients were included. The frequency of achieving a good 2-year outcome (modified Rankin scale 0-2) was 56.5%. The antibody-negative probable autoimmune encephalitis subtype exhibited the poorest outcomes, although the baseline severity was similar among the subtypes. The RAPID score, consisting of five early usable clinical factors, refractory status epilepticus, age of onset ≥60 years, probable autoimmune encephalitis (antibody-negative probable autoimmune encephalitis subtype), infratentorial involvement and delay of immunotherapy ≥1 month, was associated with poorer 2-year outcomes. Any immunotherapy was associated with clinical improvement in the patients with low risk for poor 2-year outcomes (RAPID scores 0-1), and the combination immunotherapy of steroid, immunoglobulin, rituximab and tocilizumab was associated with better outcomes in the patients with high risk for poor 2-year outcomes (RAPID scores 2-5). In patients with persistent disease at 6 months, continuing immunotherapy was associated with more improvement, while the effect of continuing immunotherapy for more than 12 months was unclear. In the longitudinal analysis of MRI, the development of cerebellar atrophy indicated poor outcomes, while the absence of diffuse cerebral atrophy or medial temporal atrophy indicated the possibility of a good outcome. This study provides information about the clinical characteristics and courses, the effect of immunotherapy and its duration, and prognostic factors in seronegative autoimmune encephalitis.

Effects of CYP2C19 genetic polymorphisms on the pharmacokinetics of lacosamide in Korean patients with epilepsy.

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.

Tolerability of lacosamide rapid dose titration: A randomized, multicenter, prospective, open-label study.

OBJECTIVE: Currently recommended dosing of lacosamide often necessitates long titration periods. However, the use of a regimen consisting of initial loading dose of 200 mg followed by a maintenance dose of 200 mg/day in practice suggests tolerability of more rapid titration schedules. We aimed to clarify whether the shortened titration schedule affects tolerability of lacosamide. METHODS: We evaluated the safety of two rapid titration protocols designed to reach the target dose of 400 mg/day within 1 week, and the conventional weekly titration protocol (reaching the target dose of 400 mg/day in three weeks). The ≥50% responder rate and steady-state plasma concentration of lacosamide were also analyzed. Adverse events were assessed at 1 week and 5 weeks after reaching the target dose. RESULTS: Seventy-five patients with epilepsy were enrolled and evenly distributed to three titration protocols, from which 5 patients were lost to follow-up and excluded from the safety analysis. Discontinuation of lacosamide or dose reductions due to adverse events occurred in 32 patients (46%), of whom a large majority (74%) had experienced adverse events after reaching 400 mg/day, demonstrating apparent dose-dependency. There was no difference in safety outcomes among the three titration groups. Concomitant use of sodium channel blockers significantly increased the risk of adverse events. CONCLUSION: Rapid titration protocols for lacosamide were not associated with an increased risk of adverse events compared to the conventional weekly titration protocol. Uptitration of lacosamide at shorter intervals to an effective target dosage may be feasible in appropriate clinical situations.

Usefulness of saliva for perampanel therapeutic drug monitoring.

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.

Ions from Solution to the Gas Phase: A Molecular Dynamics Simulation of the Structural Evolution of Substance P during Desolvation of Charged Nanodroplets Generated by Electrospray Ionization.

Molecular dynamics (MD) simulations are used to model changes in the conformational preferences of a model peptide during the transition from a hydrated environment (charged nanodroplet generated by electrospray ionization) to the solvent-free peptide ion. The charged droplet consists of ∼2400 water molecules, 22 hydronium ions, and 10 chloride and contains a single Substance P (SP) [SP + 3H]3+ ion (SP3+; amino acid sequence RPKPQQFFGLM-NH2). Initially, droplet shrinkage involves a combination of solvent evaporation and ejection of excess charge, primarily hydronium ions. Further droplet shrinkage leads to a series of fission events, which includes the loss of some Cl- ions. SP3+ ions adapt to the smaller size droplet through small conformational changes that result in coiling of the hydrophobic C-terminus of the peptide on or near the droplet surface, intramolecular interactions involving the hydrophilic N-terminus of the peptide, and water-mediated interactions between the SP3+ ion and H3O+ and Cl- ions. Calculated collision cross sections (CCS) for SP3+ ions at various stages of desolvation are consistent with the results obtained from cryogenic ion mobility-mass spectrometry (cryo-IM-MS) measurements. Specifically, early in the decay of the charged droplet SP3+ ions favor an extended conformation, whereas a compact conformer is favored during the final stages of dehydration.

Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG.

The azinomycins are a family of potent antitumor agents with the ability to form interstrand cross-links with DNA. This study reports on the unusual biosynthetic formation of the 5-methyl naphthoate moiety, which is essential for effective DNA association. While sequence analysis predicts that the polyketide synthase (AziB) catalyzes the formation of this naphthoate, 2-methylbenzoic acid, a truncated single-ring product, is formed instead. We demonstrate that the thioesterase (AziG) acts as a chain elongation and cyclization (CEC) domain and is required for the additional two rounds of chain extension to form the expected product.

Increasing Ubiquitin Ion Resistance to Unfolding in the Gas Phase Using Chloride Adduction: Preserving More "Native-Like" Conformations Despite Collisional Activation.

Electrospray ionization (ESI) of ubiquitin from acidified (0.1%) aqueous solution produces abundant ubiquitin-chloride adduct ions, [M + nH + xCl]((n - x)+), that upon mild heating react via elimination of neutral HCl. Ion mobility collision cross section (CCS) measurements show that ubiquitin ions retaining chloride adducts exhibit CCS values similar to those of the "native-state" of the protein. Coupled with results from recent molecular dynamics (MD) simulations for the evolution of a salt-containing electrospray droplet, this study provides a more complete picture for how the presence of salts affects the evolution of protein conformers in the final stages of dehydration of the ESI process and within the instrument.

Predictors of survival for patients with cancer after cryptogenic stroke.

Patients with active cancer experience ischemic stroke via cryptogenic mechanisms, with cancer-associated hypercoagulability being considered a major contributor to such strokes. Despite the remarkably shortened survival of these patients, the clinical predictors of survival are poorly understood. We determined the clinical factors including D-dimer levels serving as the predictors of overall survival in these patients. Retrospective study was conducted on cancer patients who visited our hospital for acute ischemic stroke with cryptogenic mechanisms from April 2012 through November 2014. Demographics, clinical characteristics, imaging and laboratory results including coagulation markers were collected, and overall survival was calculated from the patient medical records and a governmental national database. A high D-dimer level was defined as a D-dimer level exceeding the median value from the study population (>5.50 µg/ml). A total of 93 patients were identified, with a median survival of 62 days (interquartile range 32-223 days). A high D-dimer level (p = 0.004; hazard ratio [HR] 2.01, 95 % confidence interval [CI] 1.26-3.21), systemic metastases (p = 0.02; HR 2.08, 95 % CI 1.11-3.90), and diabetes mellitus (p = 0.03; HR 1.78, 95 % CI 1.03-3.10) were identified as independent predictors of poor overall survival using multivariate Cox proportional hazard analysis. Most of the patients (87 %) were primarily treated with low-molecular-weight heparin (dalteparin, n = 49; enoxaparin, n = 32). The type of low-molecular-weight heparin had no association with survival. A high D-dimer level, systemic metastases, and diabetes are independent predictors of poor survival in cancer patients with cryptogenic stroke.

Orthostatic intolerance symptoms are associated with depression and diminished quality of life in patients with postural tachycardia syndrome.

BACKGROUND: Patients with postural tachycardia syndrome often appear depressive and report diminished quality of life (QOL). In the current study, we first evaluated if the maximal heart rate (HR) increment after standing is associated with the clinical symptoms in patients with excessive orthostatic tachycardia (OT). Next, we investigated the correlations among the symptoms of orthostatic intolerance (OI), depression, and health-related QOL in these patients. Finally we assessed if patients with minimal OI symptoms suffer from depression or diminished QOL. METHODS: We performed a comprehensive questionnaire-based assessment of symptoms in 107 patients with excessive OT with a ≥ 30 beats/min heart rate increment (or ≥ 40 beats/min in individuals aged between 12 and 19) within 10 min after standing up. An existing orthostatic intolerance questionnaire (OIQ), the Beck depression inventory-II (BDI-II), and the 36 Item Short-Form Health Survey were completed prior to any treatment. Correlation analyses among the items of the questionnaires and other parameters were performed. Additionally, patients with minimal OI symptoms were analysed separately. RESULTS: The maximal orthostatic HR increment was not associated with the clinical symptoms. The OI symptoms were significantly correlated with depression and diminished QOL. The BDI-II score demonstrated a positive linear relationship with total OIQ score (r = 0.516), and both physical and mental component summary scales of SF-36 showed a negative linear relationship with total OIQ score (r = -0.542 and r = -0.440, respectively; all p <0.001). Some OI symptoms were more strongly associated with depression, and others were more strongly related to QOL. Chest discomfort and concentration difficulties were the most influential OI symptoms for depression, while nausea and concentration difficulties were the most influential symptoms for physical and mental QOL, respectively. Dizziness and headache were the two most common complaints in patients with mild to moderate OI symptoms. In addition, subjects with minimal OI symptoms also had considerable deterioration in QOL. CONCLUSION: The OI symptoms, but not the maximal HR increment, are significantly correlated with depression and diminished QOL in patients with excessive OT. Therefore, pervasive history taking is important when encountering patients with excessive OT.

Bioelectric medicine: unveiling the therapeutic potential of micro-current stimulation.

Bioelectric medicine (BEM) refers to the use of electrical signals to modulate the electrical activity of cells and tissues in the body for therapeutic purposes. In this review, we particularly focused on the microcurrent stimulation (MCS), because, this can take place at the cellular level with sub-sensory application unlike other stimuli. These extremely low-level currents mimic the body's natural electrical activity and are believed to promote various physiological processes. To date, MCS has limited use in the field of BEM with applications in several therapeutic purposes. However, recent studies provide hopeful signs that MCS is more scalable and widely applicable than what has been used so far. Therefore, this review delves into the landscape of MCS, shedding light on the multifaceted applications and untapped potential of MCS in the realm of healthcare. Particularly, we summarized the hierarchical mediation from cell to whole body responses by MCS including its physiological applications. Our final objective of this review is to contribute to the growing body of literature that unveils the captivating potential of BEM, with MCS poised at the intersection of technological innovation and the intricacies of the human body.

Evaluation of the adsorption performance and thermal treatment-associated regeneration of adsorbents for formaldehyde removal.

Indoor air pollution remains a major concern, with formaldehyde (HCHO) a primary contributor due to its long emission period and associated health risks, including skin allergies, coughing, and bronchitis. This study evaluated the adsorption performance and economic efficiency of various adsorbents (biochar, activated carbon, zeolites A, X, and Y) selected for HCHO removal. The impact of thermal treatment on adsorbent regeneration was also assessed. The experimental apparatus featured an adsorption column and HCHO concentration meter with an electrochemical sensor designed for adsorption analysis. Zeolite X exhibited the highest adsorption performance, followed by zeolite A, zeolite Y, activated carbon, and biochar. All adsorbents displayed increased HCHO removal rates with an extended length/diameter (L/D) ratio of the adsorption column. Zeolite A demonstrated the highest economic efficiency, followed by zeolite X, activated carbon, zeolite Y, and biochar. Higher L/D ratios improved economic efficiency and prolonged the replacement cycle (the optimal timing for adsorbent replacement to maintain high adsorption performance). Sensitivity analysis of adsorbent regeneration under varying thermal treatment conditions (150, 120, and 80°C) and durations (60, 45, and 30 min) revealed minimal changes in adsorption efficiency (±3%). The results indicated the potential of adsorbent regeneration under energy-efficient thermal treatment conditions (80°C, 30 min). In conclusion, this study underscores the importance of a comprehensive assessment, considering factors such as adsorption performance, replacement cycle, economic efficiency, and regeneration performance for the selection of optimal adsorbents for HCHO adsorption and removal.Implications: This study underscores the importance of adsorption technology for the removal of formaldehyde and similar volatile organic compounds (VOCs), highlighting the potential of alternative adsorbents, such as environmentally friendly biochar, in addition to traditional strategies, such as activated carbon and zeolites. Our findings demonstrate the feasibility of adsorbent regeneration under energy-efficient thermal treatment conditions. These results hold promise for improving indoor air quality, reducing environmental pollutants, and enhancing responses to air contaminants like fine dust and VOCs.

Grouping of unused agricultural by-product biomass for fuel conversion in South Korea through multivariate analysis.

While biomass holds significance as a resource, its abundance in South Korea is limited. Therefore, in this study analyzed the chemical characteristics of agricultural by-products produced and evaluated their fuel potentiality. To achieve this objective, multivariate analysis was utilized to create biomass clusters with diverse feature. All investigated biomass types showed heating values of at least 12.6 MJ/kg, adhering to South Korea's Bio-solid recovered fuel (SRF) standard, once the moisture content was reduced to 20 % or less. However, the biomasses only met the heating value of Level 3 of the European standard for SRF, which is at least 15 MJ/kg. Groups were formed based on a multivariate analysis using four variables: the high heating value, and carbon, nitrogen, and ash contents. The groups were centered around wood chips and hog fuel, with a cluster of lignocellulosic biomass materials surrounding them. The clusters formed around four groups. When the biomasses in each group were mixed, the combustion characteristics were compared to the ignition, maximum, and burn-out temperatures. Utilizing biomass grouping, by-products from agriculture and livestock in South Korea can be effectively employed as energy sources.

Micro-current stimulation could inhibit IL-1ß-induced inflammatory responses in chondrocytes and protect knee bone cartilage from osteoarthritis.

This study aimed to evaluate the inhibitory effects of micro-current stimulation (MCS) on inflammatory responses in chondrocytes and degradation of extracellular matrix (ECM) in osteoarthritis (OA). To determine the efficacy of MCS, IL-1ß-treated chondrocytes and monosodium iodoacetate (MIA)-induced OA rat model were used. To evaluate the cytotoxicity and nitric oxide (NO) production in SW1353 cells, the presence or absence of IL-1ß treatment or various levels of MCS were applied. Immunoblot analysis was conducted to evaluate whether MCS can modulate IL-1R1/MyD88/NF-κB signaling pathway and various indicators involved in ECM degradation. Additionally, to determine whether MCS alleviates subchondral bone structure destruction caused by OA, micro-CT analysis, immunoblot analysis, and ELISA were conducted using OA rat model. 25 and 50 µA levels of MCS showed effects in cell proliferation and NO production. The MCS group with IL-1ß treatment lead to significant inhibition of protein expression levels regarding IL-1R1/MyD88/NF-κB signaling and reduction of the nucleus translocation of NF-κB. In addition, the protein expression levels of MMP-1, MMP-3, MMP-13, and IL-1ß decreased, whereas collagen II and aggrecan increased. In animal results, morphological analysis of subchondral bone using micro-CT showed that MCS induced subchondral bone regeneration and improvement, as evidenced by increased thickness and bone mineral density of the subchondral bone. Furthermore, MCS-applied groups showed decreases in the protein expression of MMP-1 and MMP-3, while increases in collagen-II and aggrecan expressions. These findings suggest that MCS has the potential to be used as a non-pharmaceutical method to alleviate OA.

RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts.

Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled border. However, the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely unknown. Here, we show with GeneChip analysis that RUN and FYVE domain-containing protein 4 (RUFY4) is strongly upregulated during osteoclastogenesis. Mice lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in vivo. Furthermore, deleting Rufy4 did not affect osteoclast differentiation, but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes, their trafficking to the membrane, and their secretion of cathepsin K into the extracellular space. Mechanistically, RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary lysosomes. Consequently, Rufy4-deficient mice were highly protected from lipopolysaccharide- and ovariectomy-induced bone loss. Thus, RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.

From solution to the gas phase: stepwise dehydration and kinetic trapping of substance P reveals the origin of peptide conformations.

Past experimental results and molecular dynamics simulations provide evidence that, under some conditions, electrospray ionization (ESI) of biomolecules produces ions that retain elements of solution phase structures. However, there is a dearth of information regarding the question raised by Breuker and McLafferty, "for how long, under what conditions, and to what extent, can solution structure be retained without solvent?" (Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 18145). Here, we use cryogenic ion mobility-mass spectrometry to experimentally probe the structural evolution of the undecapeptide substance P (SP) during the final stages of ESI. The results reveal that anhydrous SP conformers originate from evaporation of cluster ions, specifically, [SP + 2H](2+) (H2O)n (n = 0 to ∼50) and [SP + 3H](3+) (H2O)n (n = 0 to ∼30), and that major structural changes do not occur during the evaporative process. In the case of [SP + 3H](3+), the results demonstrate that a compact dehydrated conformer population can be kinetically trapped on the time scale of several milliseconds, even when an extended gas phase conformation is energetically favorable.

Micro-Current Stimulation Can Modulate the Adipogenesis Process by Regulating the Insulin Signaling Pathway in 3T3-L1 Cells and ob/ob Mice.

Obesity is a disease in which fat is abnormally or excessively accumulated in the body, and many studies have been conducted to overcome it with various techniques. In this study, we evaluated whether micro-current stimulation (MCS) can be applied to prevent obesity by regulating the adipogenesis through 3T3-L1 cells and ob/ob mice. To specify the intensity of MCS, Oil Red O staining was conducted with various intensities of MCS. Based on these, subsequent experiments used 200 and 400 µA for the intensity of MCS. The expressions of insulin signaling pathway-related proteins, including phosphorylation of IGF-1 and IR, were decreased in all MCS groups, and in turn, downstream signals such as Akt and ERK were decreased. In addition, MCS reduced the nucleus translocation of PPAR-γ and decreased the protein expression of C/EBP-α. In the ob/ob mouse model, MCS reduced body weight gain and abdominal adipose tissue volume. In particular, the concentration of triglycerides in serum was also decreased. Taken together, our findings showed that MCS inhibited lipid accumulation by regulating insulin signaling in 3T3-L1, and it was effective at reducing body weight and adipose tissue volume in ob/ob mice. These suggest that MCS may be a useful treatment approach for obesity.

Disease progression and brain atrophy in NMDAR encephalitis: Associated factor & clinical implication.

OBJECTIVE: We investigated the longitudinal pattern, determining factors, and clinical implications of brain volume changes in N-methyl d-aspartate receptor-antibody (NMDAR) encephalitis. METHODS: Baseline clinical profiles, treatment profiles, and outcome measured using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) and modified Rankin scale (mRS) were obtained from a long-term clinical database documenting an NMDAR encephalitis cohort. In serial MRI, the change in the normalized volume of different brain regions from the baseline evaluation was measured. At each MRI evaluation time point, the cumulative disease burden (CASE score × months) and the cumulative duration of status epilepticus were also evaluated. RESULTS: Thirty-six patients were followed-up for 28.5 months (range 12-63 months). The volume ratio at last MRI to baseline was the lowest in the cerebellum (94.4 ± 5.7%, p < 0.001). Once developed, cerebellar volume reduction followed a progressive course until 2 years from disease onset. The degree of cerebellar volume reduction was positively correlated with mRS and total CASE scores (all, p < 0.001), and CASE scores in the domains of memory, language, and psychiatric problems, gait instability/ataxia, and weakness (all, p < 0.01). In linear mixed model analyses, the degree of cerebellar volume reduction was associated with cumulative disease burden up to 2 years (p < 0.001) and duration of status epilepticus (p < 0.001), and delayed removal of teratoma for ≥1 month (p = 0.006). INTERPRETATION: In NMDAR encephalitis, cerebellar volume reduction was progressive once developed. Cerebellar volume reduction might reflect disease burden and extent of progression and be associated with poor outcomes in multiple functional domains.

Designing of reverse vending machine to improve its sorting efficiency for recyclable materials for its application in convenience stores.

Plastics have multiple applications in disposable products, high-end technology parts, etc., owing to their functionality and manufacturing flexibility. However, their increased use has increased the global proportion of plastic wastes, which creates a serious environmental issue, thereby, creating a demand for plastic waste management techniques. Improving the efficiency of resource recovery by appropriate sorting and collection systems is necessary for successful plastic recycling. Therefore, this study proposed a three-step optimization process of a reverse vending machine (RVM), a small automatic recyclable waste sorter/collector system, for acquiring an optimal design and enhanced efficiency. The RVM system categorized recyclable wastes as plastics, glass, and cans using barcode, vision, and near infrared sensors. The average sorting efficiency of the designed RVM system was 94%, 95% for polyethylene terephthalate, and 98% for glass bottles. Therefore, the RVM system, with the average sorting efficiency of 95%, is suitable for application in on-site sorting in small-sized areas, such as convenience stores, which generate wastes on a small scale.Implications: This study proposed a three-step optimization process of a reverse vending machine (RVM), a small automatic recyclable waste sorter/collector system, for acquiring an optimal design and enhanced efficiency. The RVM system is suitable for application in on-site sorting in small-sized areas, such as convenience stores, which generate wastes on a small scale.

Teratoma Removal, Steroid, IVIG, Rituximab and Tocilizumab (T-SIRT) in Anti-NMDAR Encephalitis.

In anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, we analysed the efficacy of a combined immunotherapy protocol consisting of teratoma removal, steroid, intravenous immunoglobulin (IVIG), rituximab and tocilizumab (T-SIRT). This cohort study included seventy-eight consecutive patients treated for anti-NMDAR encephalitis between Jan 2014 and Oct 2019 in a national referral hospital. Detailed 2-year disease time course was analysed using Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at every 2 weeks for 12 weeks from baseline, every month for the next 3 months and then every 3 months. Treatment regimens at each time point were categorized as SI, SIR, or SIRT with/without teratoma removal (T). Adverse events were classified according to the Common Terminology Criteria for Adverse-Events (CTCAE v5.0), where a severe adverse event was defined as an adverse event with CATAE grade 4. In a linear mixed model analysis, using the SIRT regimen was more effective than SIR or SI regimens in lowering CASE scores (P < 0.001 and P = 0.001, respectively). The presence of teratoma (P = 0.001), refractory status epilepticus (P < 0.001) and a higher CASE score at baseline (P < 0.001) predicted a higher CASE score at each time point. Completion of the (T)-SIRT regimen within 1 month of onset resulted in better 1-year improvements in CASE score (P < 0.001) and modified Rankin scale scores (P = 0.001), compared to those of using other regimens within 1 month or delaying teratoma removal for more than 1 month. Pneumonia was a frequent adverse event (52/78, 66.7%) in the whole study population and neutropenia was frequent during SIRT (11/52, 21.2%), but the regimen was well tolerated in most patients. We concluded that the early application of combined immunotherapy consisting of T-SIRT had better efficacy than was found for delayed or partial application of this combination in anti-NMDAR encephalitis.

Efficacy of atomoxetine versus midodrine for neurogenic orthostatic hypotension.

OBJECTIVE: The efficacy and safety of 1-month atomoxetine and midodrine therapies were compared. Three-month atomoxetine and combination therapies were investigated for additional benefits. METHODS: This prospective open-label randomized trial included 50 patients with symptomatic neurogenic orthostatic hypotension (nOH). The patients received either atomoxetine 18 mg daily or midodrine 5 mg twice daily and were evaluated 1 and 3 months later. Those who still met the criteria for nOH at 1 month received both midodrine and atomoxetine for an additional 2 months, and if not, they continued their initial medication. The primary outcome was an improvement in orthostatic blood pressure (BP) drop (maximum BP change from supine to 3 min after standing) at 1 month. The secondary endpoints were symptom scores, percentage of patients with nOH at 1 and 3 months. RESULTS: Patients with midodrine or atomoxetine treatment showed comparative improvement in the orthostatic BP drop, and overall only 26.2% of the patients had nOH at 1 month, which was similar between the treatment groups. Only atomoxetine resulted in significant symptomatic improvements at 1 month. For those without nOH at 1 month, there was additional symptomatic improvement at 3 months with their initial medication. For those with nOH at 1 month, the combination treatment resulted in no additional improvement. Mild-to-moderate adverse events were reported by 11.6% of the patients. INTERPRETATION: One-month atomoxetine treatment was effective and safe in nOH patients. Atomoxetine improved orthostatic BP changes as much as midodrine and was better in terms of ameliorating nOH symptoms.