Enhancement of Exfoliating Effects through the Novel Cosmetic Ingredient Mandelic acid_Carnitine Ion-Pairing Complex.

PURPOSE: This study aimed to develop a novel exfoliating material with high efficacy and low irritation by synthesizing the Mandelic acid_Carnitine ion pairing complex (M_C complex) and evaluating its exfoliating properties. Additionally, the study assessed the skin improvement effects of the M_C complex through clinical evaluations. METHODS: The M_C complex was synthesized in a 1:1 molar ratio of Mandelic acid and Carnitine. Structural characterization was performed using dynamic light scattering and Fourier-transform infrared spectroscopy. Exfoliating efficacy was evaluated on porcine skin, and clinical assessments were conducted on human subjects to measure various skin improvement parameters. RESULTS: The formation of the M_C complex was confirmed through particle size analysis, zeta-potential measurements, and FT-IR spectroscopy. The M_C complex demonstrated superior exfoliating efficacy compared to Mandelic acid alone, especially at pH 4.5. Clinical evaluations showed significant improvements in blackheads, whiteheads, pore volume, depth, density, count, and affected area, as well as skin texture. No adverse reactions were observed. CONCLUSION: The M_C complex exhibits high exfoliating efficacy and minimal irritation, making it a promising cosmetic ingredient for improving skin health. These findings support its potential as a low-irritation exfoliating material under mildly acidic conditions, contributing to overall skin health enhancement.

Gut microbiome diversity in a febrile seizure mouse model.

Purpose: Febrile seizures at a young age can provoke late-onset temporal lobe epilepsy. Since recent evidence has suggested that the gut microbiome affects central nervous system pathology across the blood-brain barrier, we hypothesized that febrile seizures alter the composition of the gut microbiome to provoke epilepsy. Methods: Third-generation C57BL/6 mice were separated into two groups (n = 5 each), and hot air was applied to only one group to cause febrile seizures. After two weeks of heat challenge, the fecal pellets acquired from each group were analyzed. Results: The gut microbiota of fecal pellets from each group revealed five taxa at the genus level and eight taxa at the species level that were significantly different in proportion between the groups. Conclusion: Although there was no significant difference in the overall diversity of the gut microbiota between the two groups, the identified heterogeneity may imply the pathognomonic causative relevance of febrile seizures and the development of epilepsy.

Anti-acne activity of carnitine salicylate and magnolol through the regulation of exfoliation, lipogenesis, bacterial growth and inflammation.

BACKGROUND: Salicylic acid has been used as an anti-acne agent with its comedolytic property and antimicrobial activity. However, there is a limit to use for leave-on cosmetics because of the transient skin irritation and low efficacy at neutral pH condition. We prepared a salicylic acid-based ionic pair with L -carnitine (we named, IP-BHA) overcoming the limitation of salicylic acid. We examined the effect of IP-BHA as well as the combination effect with magnolol, a bioactive organic lignan, in order to clarify their efficacy as anti-acne agents. METHODS: After verifying the structure of IP-BHA, we confirmed anti-acne activities including the regulation of exfoliation, lipogenesis, bacterial growth, and inflammation with IP-BHA and/or magnolol. RESULTS: The antibacterial activity of IP-BHA and magnolol was evaluated by determining the minimum antibacterial inhibitory concentration. Magnolol showed strong activity against Cutibacterium acnes, which was better than a medical antibiotic acne drug, clindamycin. The combined application with IP-BHA was more effective in antibacterial activity by 2.5 times. It was confirmed that testosterone-induced lipogenesis was significantly inhibited by treatment with IP-BHA and magnolol, while single treatment had no significant inhibitory effect. Interestingly, MMP-1 and VEGF were induced by C. acnes lysate in human keratinocytes. We found that these inflammatory molecules were completely inhibited by combined application of IP-BHA and magnolol. Through ex vivo test, the dose-dependent exfoliation effect of IP-BHA was confirmed at pH 5.5, and the synergic exfoliation effect was shown in the combined application of IP-BHA and magnolol. When topically applied, the emulsion containing IP-BHA and magnolol relieved the sodium dodecyl sulfate-induced erythema and improved inflamed acne with papule and pustule. CONCLUSION: Our data demonstrate that the ionic paired salicylic acid with L -carnitine can overcome the limitations of salicylic acid at low concentration and natural skin pH. Based on the dual administration effects, we suggest that IP-BHA and magnolol may be the potential agent for acne by improving inflammatory skin condition.

Exploration of shared features of B cell receptor and T cell receptor repertoires reveals distinct clonotype clusters.

Although B cells and T cells are integral players of the adaptive immune system and act in co-dependent ways to orchestrate immune responses, existing methods to study the immune repertoire have largely focused on separate analyses of B cell receptor (BCR) and T cell receptor (TCR) repertoires. Based on our hypothesis that the shared history of immune exposures and the shared cellular machinery for recombination result in similarities between BCR and TCR repertoires in an individual, we examine any commonalities and interrelationships between BCR and TCR repertoires. We find that the BCR and TCR repertoires have covarying clonal architecture and diversity, and that the pattern of correlations appears to be altered in immune-mediated diseases. Furthermore, hierarchical clustering of public B and T cell clonotypes in both health and disease based on correlation of clonal proportion revealed distinct clusters of B and T cell clonotypes that exhibit increased sequence similarity, share motifs, and have distinct amino acid characteristics. Our findings point to common principles governing memory formation, recombination, and clonal expansion to antigens in B and T cells within an individual. A significant proportion of public BCR and TCR repertoire can be clustered into nonoverlapping and correlated clusters, suggesting a novel way of grouping B and T cell clonotypes.

Improving and evaluating the adhesion and stability of make-up by enhancing the affinity between skin/make-up layer.

PURPOSE: Make-up clumps, bumps and collapses are the three factors that determine how well make-up has been performed. The purpose of this study is to reduce the three factors mentioned above by using amphiphilic substances to increase the affinity between the skin and the make-up layer. In addition, it aims to evaluate the improvement of the make-up layer by developing an objective make-up layer evaluation method. METHODS: Experiments were performed in an attempt to increase the affinity between the skin and the make-up layer by minimizing the difference in surface energy between the two. Multiple types of artificial skin (leather and bio-skin) were used and treated to form the liquid foundation layer. Qualitative evaluation of the make-up layer was conducted by analyzing the surface, cross-section, and fracture area of the make-up layer, using the evaluation method proposed in this study. RESULTS: After applying this method and taking measurements by 3D surface analysis, the surface roughness of the make-up layer reduced by 46%, and the maximum thickness of the make-up layer reduced by about 50% in comparison with the control group (method not applied). In the case of the make-up layer to which this method was applied, two-dimensional cross-sectional Scanning Electron Microscope (SEM) image analysis confirmed that agglomeration was reduced, and the thickness of the make-up layer was also reduced by an average of 54%. According to this result, the technique of increasing the affinity between the skin and the make-up layer reduces the level of aggregation of make-up and encourages the formation of a uniform and thin make-up layer. Also, the fracture area after motion simulation was reduced by 33%. These results indicate that the method of increasing the affinity between skin/make-up membranes positively affects the formation of a uniform make-up layer. CONCLUSION: Increasing the affinity by reducing the surface energy between the skin and the make-up layer plays an important role in forming a thin and uniform make-up layer by improving the problems of lifting, agglomeration, and collapse of the make-up. In addition, it has been confirmed that through this method, the quality of consumer experience related to make-up satisfaction can be improved. The results show that objective analyses of make-up help the understanding of the quality of consumer experience on make-up.

Safety and efficacy of dietary supplement (gintonin-enriched fraction from ginseng) in subjective memory impairment: A randomized placebo-controlled trial.

BACKGROUND: Gintonin inhibits ß-amyloid production, increases acetylcholine level in the brain, and promotes neurogenesis. We evaluated the efficacy of gintonin-enriched fraction (GEF) in improving the cognitive performance in subjective memory impairment. METHODS: In this 8-week, randomized, assessor and participant blinded, placebo-controlled study, participants with subjective memory impairment but preserved cognitive function (Korean Mini-Mental State Examination [K-MMSE] score ≥23) were assigned to GEF 300mg/day or placebo. K-MMSE, Korean versions of the Alzheimer's disease assessment scale, color-word stroop test (K-CWST), clinical dementia rating, and Beck depression inventory-II were evaluated along with the safety profiles. The primary outcome was set as the change in the K-MMSE. RESULTS: Seventy-six participants complete the study protocol. After 8 weeks, there was no inter-group difference in the primary or secondary outcome score changes. However, GEF group showed an improvement in the K-MMSE scores (P= 0.026), and in the number of correct answers in both word reading (P= 0.008) and color reading (P= 0.005) of K-CWST, although only the improvement in the K-CWST scores were higher than the minimum clinically important difference. The frequency of adverse events was comparable between the groups and all were of mild severity. CONCLUSION: GEF is safe but might not be effective in treating subjective memory impairment within the current study setting. However, GEF showed a trend of improving the global cognition and the frontal executive function. Further large-sized studies with longer follow-up period are warranted. CLINICAL TRIAL REGISTRATION: This clinical trial was registered at Clinical Research Information Service of Korea Centers for Disease Control and Prevention: KCT0004636.

High-Dose Diazepam Controls Severe Dyskinesia in Anti-NMDA Receptor Encephalitis.

OBJECTIVE: Because there is no standard treatment to control dyskinesia in anti-NMDA receptor (NMDAR) encephalitis, we analyzed the therapeutic efficacy of high-dose diazepam in dyskinesia associated with NMDAR encephalitis. METHODS: We reviewed patients with NMDAR encephalitis with dyskinesia who were admitted to Seoul National University Hospital between November 2012 and July 2018. High-dose diazepam was administered orally or via a nasogastric tube 3-6 times a day. We assessed the treatment effect by comparing dyskinesia severity between the first day of the highest dose of diazepam and one week after the treatment. RESULTS: Among 68 patients with NMDAR encephalitis during the study period, 33 patients were treated with enteral diazepam (ranging from 6 to 180 mg) to control dyskinesia, along with immunotherapy. The severity of dyskinesia improved from average grade 2.4 ± 0.6 to 1.1 ± 0.7 after 1 week of the highest dose of diazepam (mean severity change -1.4 ± 0.6, 95% confidence interval -1.2 to -1.6; p < 0.001). No patients had serious adverse events except for mild sedation. CONCLUSIONS: Dyskinesia in NMDAR encephalitis improved after treatment with enteral diazepam without significant side effects. This study suggests that enteral diazepam could be a treatment option for control dyskinesia in NMDAR encephalitis. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with dyskinesias associated with NMDAR encephalitis, enteral diazepam is effective and safe in dyskinesia control.

A new rapid titration protocol for lamotrigine that reduces the risk of skin rash.

OBJECTIVE: Lamotrigine is one of the most widely used antiepileptic drugs, but it has a critical issue of a skin rash if the starting dose is too high or the escalation rate is too rapid. We investigated the efficacy and safety of a novel and rapid titration protocol for lamotrigine that takes only 11 days to reach a daily dose of 200 mg. METHODS: We prospectively enrolled 33 adult patients (age 18-85) who were diagnosed with epilepsy and started lamotrigine administration for the first time at a single tertiary hospital. Our new protocol starts with a subthreshold dose of the drug and then administers a stepwise-incremental dose until reaching the full therapeutic dose within 11 days. RESULTS: Of 29 patients analyzed, only two (6.9%) experienced idiosyncratic skin rash before the first follow-up visit at 2 weeks (±3 days). In addition, a therapeutic concentration was reached in more than 75% of studied patients after 2 weeks of lamotrigine administration. SIGNIFICANCE: These findings demonstrate the value of the novel tolerance induction protocol for lamotrigine, which could widen the available application of lamotrigine in various situations. However, this study is a preliminary study limited by a small number of patients and its nonrandomized and open-label design, so the current protocol needs more rigorous clinical evaluations before the application to the real clinical setting.

Cognitive improvement effect of gintonin might be associated with blood-brain barrier permeability enhancement: dynamic contrast-enhanced MRI pilot study.

Along with the multiple neuroprotective effect, recent studies suggest that gintonin might increase the blood brain barrier permeability. We evaluated the effect of gintonin on the vascular permeability changes in different brain segments, using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). In this 8-week, randomized, open label pilot study, ten participants with subjective memory impairment but preserved cognitive function assigned to gintonin-enriched fraction (GEF) 300 mg/day or placebo groups. Korean versions of the Alzheimer's disease assessment scale (ADAS-K) and DCE-MRI parameters including Ktrans and Vp in different brain segments were evaluated at baseline and at 8 weeks after treatment. Nine participants completed the study protocol. No adverse events occurred during the observation period for 8 weeks in both groups. Following gintonin administration, increment trends of the brain permeability that did not reach a statistical significance were observed in the left hippocampus (Ktrans and Vp, both, p = 0.062), left thalamus and in left putamen (Ktrans, p = 0.062), and left insula and right amygdala (Vp, p = 0.062), but not in the control placebo group. The increment of the Ktrans value in the left thalamus from the baseline was highly correlated with the change of the ADAS scores (r = -0.900, p = 0.037). Gintonin might enhance the blood-brain barrier (BBB) permeability in the brain structures involved in cognitive functions. Further efficacy exploration for the synergistic effect of gintonin's BBB permeability enhancement to its other cognitive enhancing mechanisms are warranted. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003418.

Effects of perampanel on cognition and quantitative electroencephalography in patients with epilepsy.

Antiepileptic drugs are well known for their effects on cognition and electrophysiologic changes. However, perampanel is yet to be evaluated for its effects on cognitive function and electroencephalography (EEG). The purpose of the present study was to identify the effect of perampanel on neuropsychological (NP) tests and quantitative EEG (QEEG) and their relationship with the level of the drug in blood. Seventeen patients with epilepsy were enrolled in the study. Electroencephalographic recordings were obtained, and NP tests were conducted before perampanel intake and 6 months after treatment. The relative frequency band power, peak alpha frequency, and NP test scores were compared before and after drug administration. The serum concentration of perampanel was correlated with the QEEG changes. Delayed recall of the Rey Complex Figure showed significant improvement (20.03 vs. 22.94; P = 0.004) following perampanel administration. Other cognitive function tests showed no significant differences before and after drug administration. Theta frequency band power increased in all brain regions (P = 0.001-0.01), and alpha frequency power decreased in all brain regions (P = 0.006-0.03). The theta/alpha ratio, which represents background EEG slowing, increased in all brain areas (P = 0.003-0.02). The peak frequency of the alpha rhythm decreased after perampanel intake (t = 2.45, P = 0.03). Difference of relative alpha power in the central region positively correlated with the blood level of perampanel (r = 0.53, P = 0.03). Perampanel induced electrophysiological slowing, but cognitive decline was not observed. Because the controls were not compared in the study, the results of cognitive function tests should be interpreted conservatively. Background EEG slowing correlated with the serum concentration of perampanel. Our results show the effect of perampanel on cognitive function and background EEG in adult 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.

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.

Understanding new-onset refractory status epilepticus from an immunological point of view.

New-onset refractory status epilepticus (NORSE) is unexpected onset of refractory status epilepticus in individuals with no preexisting relevant neurologic condition. The etiologies remain largely cryptogenic; treatment is challenging after failure to control seizures despite use of multiple antiepileptic drugs and anesthetic agents. Frequent fever and other infectious prodromes, elevated proinflammatory cytokine/chemokine levels, and limbic or multifocal brain lesions indicate active inflammation in NORSE. Among identified causes, autoimmune encephalitis is the most common and accounts for more than one-third of all known NORSE cases, followed by infection-related etiologies. Although more evidence is needed, anti-cytokine therapies with tocilizumab and anakinra along with other immunotherapeutic agents used in autoimmune encephalitis can aid in alleviating or hindering the inflammatory cascade and controlling seizures.

Initial cerebrospinal fluid-restricted oligoclonal bands associate with anti-N-methyl-D-aspartate receptor encephalitis severity: a pilot study.

Purpose: Intrathecal antibody production is thought to underly the pathogenesis and symptomatology of N-methyl-D-aspartate receptor encephalitis (NMDARE). In the present study, the clinical correlation of cerebrospinal fluid (CSF) restricted oligoclonal bands (OCBs), as a measure of intrathecal antibody synthesis, was examined in confirmed NMDARE cases. Methods: The present study included patients with a confirmed diagnosis of NMDARE who underwent initial CSF evaluation and were followed up for a minimum of 12 months. Disease severity was assessed at baseline and 1, 3, 6, 9, and 12 months. Data regarding duration of hospitalization and intensive care unit (ICU) stay, the presence of uncontrolled seizures, and antiepileptic drug requirement were obtained for each patient. Results: Among the 14 confirmed NMDARE patients, seven had CSF-OCBs. The presence of CSF-OCBs was associated with a more severe disease at baseline (p = 0.004), worse final outcome (p = 0.005), and longer hospitalization (median, 19 vs. 173 days; p < 0.001) and ICU stay (median, 0 vs. 29 days; p = 0.006). CSF-OCB positivity was closely associated with treatment refractoriness within 4 weeks (p = 0.029). Conclusion: The presence of CSF-OCBs at the onset of disease in NMDARE patients was associated with initial treatment refractoriness and a more severe disease course leading to longer hospitalization, ICU admission, intractable seizures, and a poorer outcome. The results indicate that CSF-OCBs may be useful for prognostication. Furthermore, severe disease in NMDARE may be accompanied by oligoclonal expansion antibody-producing B cells.

Effect of desalted Salicornia europaea L. ethanol extract (PM-EE) on the subjects complaining memory dysfunction without dementia: a 12 week, randomized, double-blind, placebo-controlled clinical trial.

Desalted Salicornia europaea L. (SE) inhibits acetylcholine esterase, attenuates oxidative stress and inflammatory cytokines, and activates neurotrophic pathway. We performed 12-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy of PhytoMeal(a desalted SE)-ethanol extract (PM-EE), in improving the cognitive performance in patients with subjective memory impairment. 63 participants complaining memory dysfunction without dementia (Korean Mini-Mental State Examination [K-MMSE] score ≥ 23) were assigned to PM-EE 600 mg/day or placebo. The cognitive domain of the Alzheimer's disease assessment scale-Korean version (ADAS-K) was set as the primary outcome. After 12 weeks, there was no differences in the changes in the primary outcome or the frequency of adverse events between the groups. In the subgroup analysis for the 30 subjects with mild cognitive impairment (MCI, baseline K-MMSE scores ≤ 28), PM-EE significantly improved the color-reading score of the Korean color-word stroop test (8.2 ± 25.0 vs. - 4.7 ± 13.2, P = 0.018). Our findings suggest that PM-EE is safe but might not be effective in this setting of this study. However, PM-EE may improve the frontal executive function in the patients with MCI. Further large-sized studies with longer follow-up period is warranted (trial registration number KCT0003418).

HLA-B27 association of autoimmune encephalitis induced by PD-L1 inhibitor.

OBJECTIVE: While immune checkpoint inhibitors are increasingly used for various cancers, unpredictable immune-related adverse events (irAEs) such as autoimmune encephalitis is life-threatening. Here, we report an association between human leukocyte antigen (HLA) and atezolizumab-induced encephalitis. METHODS: From an institutional prospective cohort for encephalitis, we identified patients with autoimmune encephalitis after the use of atezolizumab, a PD-L1 (programmed death-ligand 1) inhibitor, from August 2016 to September 2019 and analyzed their HLA genotypes. RESULTS: A total of 290 patients received atezolizumab, and seven patients developed autoimmune encephalitis, and five of whom were enrolled for the analysis. The patients presented altered mentality, seizures, or myelitis. Three patients had the HLA-B*27:05 genotype in common (60%), which is significantly frequent given its low frequency in the general population (2.5%). After Bonferroni correction, HLA-B*27:05 was significantly associated with autoimmune encephalitis by atezolizumab (corrected P < 0.001, odds ratio 59, 95% CI = 9.0 ~ 386.9). INTERPRETATION: Here we found that three in five patients with autoimmune encephalitis associated with atezolizumab had the rare HLA-B*27:05 genotype. Further systematic analyses in larger cohorts are necessary to investigate the value of HLA screening to prevent the life-threatening adverse events.

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.

Distinct immunoreactivity pattern to Bacillus mannanilyticus in a subgroup of anti-NMDA receptor encephalitis.

Over half of anti-NMDA receptor encephalitis (NMDARE) is unrelated to etiologies such as teratomas or herpes simplex encephalitis. Bacillus mannanilyticus nonribosomal peptide synthetase (NRPS) shares a protein sequence with GluN1. After confirming the anti-NRPS antibody immunoreactivity in an index patient by liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 24/57 (42%) patients with similar immunoreactivity patterns by western blotting. These patients mostly (20/24 [83%]) did not have ovarian teratomas, had fewer medial temporal (2/24 [8%]) and any (5/24 [21%]) brain lesions and less pleocytosis (13/24 [54%]). These results identified an anti-NMDARE subgroup with a distinct immunoreactivity pattern, which needs further investigation.