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.

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.

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.

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.

Development of the clinical assessment scale in autoimmune encephalitis.

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.

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.

Altered Vascular Permeability in Migraine-associated Brain Regions: Evaluation with Dynamic Contrast-enhanced MRI.

Background Recent studies showed the possible association between inflammation-induced blood-brain barrier (BBB) structural changes followed by greater permeability of the BBB and chronic pain. Thus, measurement of BBB breakdown would be a valuable aid in the diagnosis in migraine. Dynamic contrast material-enhanced (DCE) MRI can determine perfusion and permeability properties related to the BBB. Purpose To evaluate the relationship between permeability of the BBB in migraine-associated brain regions by using DCE MRI. Materials and Methods In this prospective study, from September 2016 to December 2017, 56 study participants underwent DCE MRI after gadobutrol administration and were classified into migraine (n = 35) and healthy control (n = 21) groups. Automatic volumetric segmentation was performed on the pre-contrast-enhanced T1-weighted images by using FreeSurfer, and migraine-associated brain region masks were extracted by using the software NordicICE. The corresponding maps for pharmacokinetic parameters Ktrans (the volume transfer constant) and Vp (the fractional plasma volume) were coregistered with the region-of-interest masks, and their mean values of corresponding total volume of interest were calculated. For comparison analyses, the Mann-Whitney tests were used. Receiver operating characteristic curve analysis and Spearman rank correlation tests were used to identify correlations between clinical characteristics and the aforementioned perfusion parameters. Results Mean age was younger in the migraine group (mean ± standard deviation, 57 years ± 12) than in the healthy control group (mean, 71 years ± 8) (P < .001). In the migraine group, the mean value of Vp in the left amygdala (median, 0.27 mL/100 g) was lower than that in the healthy control group (median, 0.39 mL/100 g) (P = .04). The mean value of Vp in the left amygdala was correlated with the intensity of headache attack in participants with migraine (correlation coefficient, -0.34; P = .04). Conclusion Lower fractional plasma volume in the left amygdala was observed in participants with migraine than in healthy participants. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Carroll and Ginat in this issue.

Peripheral Blood Inflammatory Cytokines in Idiopathic REM Sleep Behavior Disorder.

BACKGROUND: Although previous research provides insight into the role of neuroinflammation in idiopathic REM sleep behavior disorder, the association of this disorder with peripheral blood inflammatory markers remains unclear. OBJECTIVE: To investigate inflammatory cytokines in plasma samples in patients with idiopathic rapid eye movement sleep behavior disorder and to explore whether these markers are associated with prodromal symptoms of α-synucleinopathies. METHODS: We collected plasma from patients with polysomnographically confirmed idiopathic rapid eye movement sleep behavior disorder without parkinsonism or dementia (n = 54) and from healthy controls (n = 56). The following cytokines were measured: interleukin-1ß, interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor-α. The idiopathic REM sleep behavior disorder patients underwent sleep, motor, cognitive, olfactory, and autonomic testing. RESULTS: The anti-inflammatory cytokine, interleukin-10, levels in the idiopathic rapid eye movement sleep behavior disorder group were significantly upregulated compared to the control group (P = 0.022), but this difference did not withstand Bonferroni correction. The other proinflammatory cytokine levels did not differ between the groups. No correlation was found between the cytokine levels and any clinical variable. CONCLUSIONS: Our data do not provide evidence supporting the role of peripheral inflammation in idiopathic rapid eye movement sleep behavior disorder. However, considering the limited statistical power because of the small sample size, further large-scale longitudinal studies with a broader spectrum of cytokines are needed to clarify this issue. © 2019 International Parkinson and Movement Disorder Society.

Anti-melanogenic activity of schaftoside in Rhizoma Arisaematis by increasing autophagy in B16F1 cells.

Skin pigmentation involves multiple processes, including melanin synthesis, transport, and melanosome release. Melanin content determines skin color and protects against UV radiation-induced damage. Autophagy is a cooperative process between autophagosomes and lysosomes that degrades cellular components and organelles. In the present study, B16F1 cells were treated with Rhizoma Arisaematis extract (RA) and assessed for pigmentation and autophagy regulation. RA treatment suppressed the α-MSH-stimulated increase of melanogenesis and down-regulated the expression of tyrosinase and TRP1 proteins in B16F1 cells. In addition, autophagy was activated in RA-treated cells. Inhibition of autophagy reduced the anti-melanogenic activity of RA in α-MSH-treated B16F1 cells. We identified schaftoside as an effector molecule by LC-MS analysis of RA. Consistently, treatment of schaftoside showed anti-melanogenic effect and induced autophagy activation in B16F1 cells. Inhibition of autophagy by 3 MA treatment reduced the anti-melanogenic effect of the schaftoside and recovered expression level of melanogenesis regulators in α-MSH-treated B16F1 cells. Taken together, our results suggest that schaftoside from RA inhibits skin pigmentation through modulation of autophagy.

A New ELISA to Overcome the Pitfalls in Quantification of Recombinant Human Monoclonal Anti-HBs, GC1102, by Commercial Immunoassays.

Several methods for the quantification of human anti-HBs, an antibody to hepatitis B surface antigen (HBsAg), have been developed based on enzyme reaction, chemiluminescence, fluorescence, and radioactivity for application to human serum or plasma. Commercial anti-HBs immunoassay kits use a sandwich method in which a bridge is formed by the anti-HBs between a HBsAg immobilized solid matrix and the labeled HBsAg. However, this direct sandwich enzyme-linked immunosorbent assay (ELISA) is insufficient to accurately evaluate the activity of the human monoclonal anti-HBs, GC1102. As an alternative, we developed an indirect anti-HBs ELISA (anti-HBs qELISA_v.1) that improved detection of anti-HBs. In this current study, we further optimized this indirect method to minimize nonspecific binding of human serum, by employing incubation buffers containing animal serum, Tween 20, skim milk, and a low pH washing buffer. This new and improved method, termed anti-HBs qELISA_v.2, showed accurate quantification of plasma-derived hepatitis B immune globulin (HBIG) and was comparable to results obtained with commercial ELISA (r = 0.93) and RIA (r = 0.85) kits. Further, the GC1102 in human serum could be precisely measured using the anti-HBs qELISA_v.2 without limitations of nonspecific binding.

Anti-LGI1 encephalitis is associated with unique HLA subtypes.

OBJECTIVE: Autoimmune encephalitis (AE), represented by anti-leucine-rich glioma-inactivated 1 (anti-LGI1) and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, has increasing clinical significance based on recent discoveries of neuronal autoantibodies. However, its immunopathogenesis is not fully understood. Here, we investigated whether AE is associated with the human leukocyte antigen (HLA) subtypes. METHODS: We compared the HLA genotypes of 11 anti-LGI1 and 17 anti-NMDAR encephalitis patients to the control groups, which consisted of 210 epilepsy patients and 485 healthy Koreans. RESULTS: Anti-LGI1 encephalitis was associated with the DRB1*07:01-DQB1*02:02 haplotype (10 patients; 91%) in HLA class II genes, as well as with B*44:03 (8 patients; 73%) and C*07:06 (7 patients; 64%) in the HLA class I region. The prevalence of these alleles in anti-LGI1 encephalitis was significantly higher than that in the epilepsy controls or healthy controls. By contrast, anti-NMDAR encephalitis was not associated with HLA genotypes. Additional analysis using HLA-peptide binding prediction algorithms and computational docking underpinned the close relationship. INTERPRETATION: This finding suggests that most anti-LGI1 encephalitis develops in a population with specific HLA subtypes, providing insight into a novel disease mechanism. Ann Neurol 2017;81:183-192.

Increased adverse events associated with antiepileptic drugs in anti-leucine-rich glioma-inactivated protein 1 encephalitis.

Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis is a rare autoimmune condition presenting mainly as altered mental state, cognitive dysfunction, and seizure. Antiepileptic drugs (AEDs) are usually initiated to control seizures despite their limited efficacy; however, accumulating clinical experience suggests a high incidence of adverse reactions to AEDs in anti-LGI1 encephalitis. We reviewed the medical records of patients who were diagnosed with anti-LGI1 encephalitis to analyze the adverse effects of AEDs in these patients. Among the 20 patients who were treated with AEDs, 10 (50%) changed their AEDs due to adverse cutaneous drug reaction. Eight of them presented with maculopapular eruption, one with drug rash with eosinophilia and systemic symptoms syndrome, and one with eczema. Causative agents mostly consisted of aromatic AEDs. Oxcarbazepine was discontinued in two additional patients due to hyponatremia. Six patients (30%) discontinued their dose of levetiracetam because of psychiatric manifestations including irritability/aggressive behavior (four patients), insomnia (one patient), and depressive mood (one patient). Clinicians should consider adverse cutaneous drug reaction, psychiatric adverse events, and hyponatremia when selecting AEDs for the treatment of anti-LGI1 encephalitis.

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.

Site-Specific Relationship Between Intracranial Aneurysm and Aortic Aneurysm.

BACKGROUND AND PURPOSE: The high prevalence of intracranial aneurysms (IAs) in patients with a bicuspid aortic valve or coarctation of the aorta suggests a link between IA and aortic pathology. However, studies reporting this link do not sufficiently address the heterogeneity of IAs arising from different anatomic locations. This study aimed to explore whether a location-specific relationship exists between the 2 kinds of aneurysms. METHODS: Retrospective institutional analysis of patients aged ≥18 years with both IA and an aortic aneurysm (AA) was performed from 2005 to 2014. IAs were categorized based on their locations: internal carotid artery, other anterior circulation, and posterior arteries. AAs were classified as ascending, descending, infrarenal, or multiple. We analyzed the clinical characteristics and the distribution of IA in each AA group. RESULTS: Of 2375 patients, 660 with available intracranial angiography were screened for IA. We identified 71 patients with 97 IAs. The frequency of both anterior circulation-IAs and internal carotid artery-IAs differed significantly among the AA groups (P=0.001 and P=0.01, respectively). Anterior circulation-IAs were most frequently observed in ascending AA group and least frequently in infrarenal AA group. In contrast, internal carotid artery-IAs were found mostly in infrarenal AA group, least in ascending AA group. Proportions of patients having anterior circulation-IA and internal carotid artery-IA were also highest in ascending AA group and infrarenal AA group, respectively. The number of posterior arteries-IAs was too small to characterize. CONCLUSIONS: The differing distribution patterns of IA among AA groups suggest a site-specific sharing of pathomechanism between the 2 types of aneurysms.

Seasonal Variation, Cranial Autonomic Symptoms, and Functional Disability in Migraine: A Questionnaire-Based Study in Tertiary Care.

OBJECTIVE/BACKGROUND: Seasonal variation of migraine attack frequency has been described as a phenomenon. We aimed to compare functional disability and the occurrence of cranial autonomic symptoms (CASs) in patients who reported a seasonal variation in their migraine attack frequency with those who did not. METHODS: We conducted a questionnaire-based observational study on patients with migraine without aura who visited our institution from January 2005 to December 2013. Patient demographics, headache characteristics, and accompanying symptoms were recorded, and functional disability was evaluated by Migraine Disability Assessment (MIDAS) Questionnaire. RESULTS: Of 4423 patients screened, 769 were eligible for analysis, and 104 (13.5%) of them reported seasonal variation. Several CAS features such as conjunctival injection (25.0% vs 14.0%), lacrimation (20.2% vs 10.8%), eyelid edema (20.2% vs 10.2%), forehead and facial sweating (22.1% vs 11.4%), and ptosis (23.1% vs 11.4%) were more prominent in this subset of patients. They showed higher MIDAS scores (15.4 ± 23.5) than the other migraineurs (10.4 ± 16.9), with a 1.77-fold increased risk (95% confidence interval 1.06-2.96) of severe functional disability (MIDAS score ≥21) after adjustment for age group, sex, headache frequency, intensity, and duration. The higher the number of CASs, the greater also was the proportion of patients with severe functional disability. CONCLUSIONS: Patients who reported seasonal variation in migraine also reported more CASs and had more severe functional disability. The profound functional disability in the migraineurs reporting seasonal variation or CAS also provides direction for proactive clinical management in these patients.

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.

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.

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.

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.