Activation of ChAT+ neuron in dorsal motor vagus (DMV) increases blood glucose through the regulation of hepatic gene expression in mice.

The brain and peripheral organs communicate through hormones and neural connections. Proper communication is required to maintain normal whole-body energy homeostasis. In addition to endocrine system, from the perspective of neural connections for metabolic homeostasis, the role of the sympathetic nervous system has been extensively studied, but understanding of the parasympathetic nervous system is limited. The liver plays a central role in glucose and lipid metabolism. This study aimed to clarify the innervation of parasympathetic nervous system in the liver and its functional roles in metabolic homeostasis. The liver-specific parasympathetic nervous system innervation (PNS) was shown by tissue clearing, immunofluorescence and transgenic mice at the three-dimensional histological level. The parasympathetic efferent signals were manipulated using a chemogenetic technique and the activation of ChAT+ parasympathetic neurons in dorsal motor vagus (DMV) results in the increased blood glucose through the elevated hepatic gluconeogenic and lipogenic gene expression in the liver. Thus, our study showed the evidence of ChAT+ parasympathetic neurons in the liver and its role for hepatic parasympathetic nervous signaling in glucose homeostasis through the regulation of hepatic gene expression.

Oxidation capacity changes in the atmosphere of large urban areas in Europe: Modelling and experimental campaigns in atmospheric simulation chambers.

Air pollution is a major concern for human health and the environment. Consequently, environmental standards have become stricter to improve air quality. Thanks to this, the ambient levels of O3 precursors such as VOCs and NOX have decreased. However, O3 levels in Europe, especially during winter, have increased, potentially impacting on atmospheric oxidation capacity and the associated chemistry of tropospheric oxidants. In this work, we focus on recent changes in the oxidation capacity of urban atmospheres. The study is conducted with the results of the CMAQ modelling system with a regional resolution with 12 × 12 km2 across the entire European continent for the winter (January) and summer (July) of 2007 and 2015. The 2015 meteorological data is used for both years to emphasise emission changes during the studied period. We scrutinise the changes in ambient concentration levels of the main tropospheric oxidants (O3 and HOX radicals) in five representative cities, Valencia, Madrid, Milan, Berlin, and The Hague. The enhanced O3 formation in winter seems to be due to the low VOC/NOX ratio, while the opposite trend in summer may be related to a relatively high ratio. Additionally, photooxidation experiments are carried out in the EUPHORE chambers to study the effect of changes in NOX concentration and NO/NO2 ratio on the variation of the given oxidants at constant VOCs concentrations. For the baseline experiments, two scenarios are selected based on the model results of 2015: two representative winter and summer days of low and high pollution in Berlin and Madrid, respectively. The role of VOC/NOX and NO/NO2 ratios on atmospheric reactivity is discussed. As a result, it is first suggested that further decreases in ambient NOX levels are required to reduce ambient O3 levels. Moreover, additional factors should be considered when designing local-specific emission abatement strategies.

Targeting IKKß Activity to Limit Sterile Inflammation in Acetaminophen-Induced Hepatotoxicity in Mice.

The kinase activity of inhibitory κB kinase ß (IKKß) acts as a signal transducer in the activating pathway of nuclear factor-κB (NF-κB), a master regulator of inflammation and cell death in the development of numerous hepatocellular injuries. However, the importance of IKKß activity on acetaminophen (APAP)-induced hepatotoxicity remains to be defined. Here, a derivative of caffeic acid benzylamide (CABA) inhibited the kinase activity of IKKß, as did IMD-0354 and sulfasalazine which show therapeutic efficacy against inflammatory diseases through a common mechanism: inhibiting IKKß activity. To understand the importance of IKKß activity in sterile inflammation during hepatotoxicity, C57BL/6 mice were treated with CABA, IMD-0354, or sulfasalazine after APAP overdose. These small-molecule inhibitors of IKKß activity protected the APAP-challenged mice from necrotic injury around the centrilobular zone in the liver, and rescued the mice from hepatic damage-associated lethality. From a molecular perspective, IKKß inhibitors directly interrupted sterile inflammation in the Kupffer cells of APAP-challenged mice, such as damage-associated molecular pattern (DAMP)-induced activation of NF-κB activity via IKKß, and NF-κB-regulated expression of cytokines and chemokines. However, CABA did not affect the upstream pathogenic events, including oxidative stress with glutathione depletion in hepatocytes after APAP overdose. N-acetyl cysteine (NAC), the only FDA-approved antidote against APAP overdose, replenishes cellular levels of glutathione, but its limited efficacy is concerning in late-presenting patients who have already undergone oxidative stress in the liver. Taken together, we propose a novel hypothesis that chemical inhibition of IKKß activity in sterile inflammation could mitigate APAP-induced hepatotoxicity in mice, and have the potential to complement NAC treatment in APAP overdoses.

Analysis of emissions-driven changes in the oxidation capacity of the atmosphere in Europe.

Anthropogenic emissions in Europe have been gradually reduced thanks to a combination of factors, including restrictive regulation and policy implementation, fuel switching, technological developments, and improved energy efficiencies. Many measures have been specifically introduced to meet the annual and hourly limit value of NO2 for the protection of human health, mainly targeting traffic emissions. Due to NOX reduction policies in Europe, NO2 levels have generally declined, but O3 concentrations have been found to increase. This phenomenon would cause changes in the oxidant capacity of the atmosphere, altering the concentration of tropospheric oxidants in urban areas. The Community Multiscale Air Quality (CMAQ) modelling system has been used to study concentration changes of NO2, O3 and the main radicals in Europe between 2007 and 2015 for two months representatives of winter and summer conditions (January and July). In addition to describing the general situation in Europe, variations in pollutants along with NOX emission changes over 67 large European cities have been analysed by means of statistical methods. NOX emissions and NO2 concentrations decreased in both seasons during the period in all the selected cities. In most of them O3 concentrations increased in winter but decreased in summer. The concentration of the OH radical, the main oxidant during the daytime, shows an increase in winter. This is also the case for the main cities in summer although we found a general decrease in continent for this season. The NO3 radical, the main night-time oxidant, was found to increase in winter and decrease in summer. HNO3 shows a concentration decline in both seasons. The studied cities are classified in five groups by means of k-mean clustering procedure. We identified five groups with specific patterns, suggesting that the oxidant capacity of the European urban atmospheres has reacted differently to NOX emission abatement policies.

Video learning strategies affecting achievement, learning approach, and lifelong learning in a flipped periodontology course.

OBJECTIVE: To explore how video learning strategies influence students' Flipped learning (FL) achievement, deep approach to learning (DAL) and lifelong learning (LL) orientations and how DAL and LL can be promoted. METHODS: Data were collected from 65 dental students enrolled in a 21-week clinical periodontology course. Partial least squares structural equation modeling was conducted to investigate factors and pathways affecting FL achievement, DAL, and LL. RESULTS: FL achievement was predicted by repeated and in-advance video learning strategies. In-advance, meticulous, and expanded video learning strategies directly influenced DAL, and indirectly influenced LL via DAL. LL was not affected by any of the video learning strategies but by the DAL. CONCLUSION: This study implies that mere implementation of FL may not guarantee more developed DAL and enhanced LL. Redesigning a course with FL should entail revisiting and revising student assessment. LL is an inclusive approach that requires the long-term cultivation of meaning, experience, insight, learning, and practice.

Effective virtual patient simulators for medical communication training: A systematic review.

CONTEXT: Despite the growing use of virtual patients (VPs) in medical education, few studies have explored the features and effectiveness of VP-based medical communication skills training. We undertook a systematic review to summarise the design and evaluation of VP-based medical communication skills training systems in order to identify features of successful cases. METHODS: Following PRISMA guidelines, we searched four databases for studies published between 2006 and 2018. Using a refined classification scheme, we extracted data on instructional design (scenario and instructional intervention), technological design (modality and interaction), and evaluation (user experience, learning effectiveness and evaluator). We assessed the quality of studies using the Medical Education Research Study Quality Instrument (MERSQI) and the QualSyst standard assessment criteria. RESULTS: A total of 14 studies were included for review. Of these, 85.7% (n = 12) were quantitative and 71.4% (n = 10) involved undergraduate students. The most common VP training scenario was history taking followed by the delivery of bad news. Diverse instructional interventions, including tutorials, learning activities, and feedback, were embedded in the VPs. The first-person perspective animated within-screen size VP was a popular technological feature. Most evaluations concerned the reality of simulation (for user experience) and skill in expressing empathy (as a learning outcome). Of the eight comparative studies, half reported significant attitude or skill improvements in the VP group. The distinct features of VPs shown to be effective were well-designed instructional interventions (eg, a pre-activity with a protocol-informed tutorial), and post-activity (eg, debrief or reflection), scaffolding and human feedback, but not system feedback. CONCLUSIONS: Evidence-based VP training can enable students to gain communication skills in a safe and affordable learning environment. Elaborate technology alone cannot guarantee effective learning, but evidence-based instructional interventions can facilitate its optimal use and bring about better learning outcomes.

Stem Cell Factor-Inducible MITF-M Expression in Therapeutics for Acquired Skin Hyperpigmentation.

Rationale: Microphthalmia-associated transcription factor M (MITF-M) plays important roles in the pigment production, differentiation and survival of melanocytes. Stem cell factor (SCF) and its receptor KIT stimulate MITF-M activity via phosphorylation at the post-translation level. However, the phosphorylation shortens half-life of MITF-M protein over the course of minutes. Here, we investigated novel hypotheses of (i) whether SCF/KIT can regulate MITF-M activity through gene expression as the alternative process, and (ii) whether chemical inhibition of KIT activity can mitigate the acquired pigmentation in skin by targeting the expression of MITF-M. Methods: We employed melanocyte cultures in vitro and pigmented skin samples in vivo, and applied immunoblotting, RT-PCR, siRNA-based gene knockdown and confocal microscopy. Results: The protein and mRNA levels of MITF-M in epidermal melanocytes and the promoter activity of MITF-M in B16-F0 melanoma cells demonstrated that SCF/KIT could trigger the expression of MITF-M de novo, following the phosphorylation-dependent proteolysis of pre-existing MITF-M protein. SCF/KIT regulated the transcription abilities of cAMP-responsive element-binding protein (CREB), CREB-regulated co-activator 1 (CRTC1) and SRY-related HMG-box 10 (SOX10) but not ß-catenin at the MITF-M promoter. Meanwhile, chemical inhibition of KIT activity abolished SCF-induced melanin production in epidermal melanocyte cultures, as well as protected the skin from UV-B-induced hyperpigmentation in HRM2 mice or brownish guinea pigs, in which it down-regulated the expression of MITF-M de novo at the promoter level. Conclusion: We propose the targeting of SCF/KIT-inducible MITF-M expression as a strategy in the therapeutics for acquired pigmentary disorders.

Nuclear Entry of CRTC1 as Druggable Target of Acquired Pigmentary Disorder.

Rationale: SOX10 (SRY-related HMG-box 10) and MITF-M (microphthalmia-associated transcription factor M) restrict the expression of melanogenic genes, such as TYR (tyrosinase), in melanocytes. DACE (diacetylcaffeic acid cyclohexyl ester) inhibits melanin production in α-MSH (α-melanocyte stimulating hormone)-activated B16-F0 melanoma cells. In this study, we evaluated the antimelanogenic activity of DACE in vivo and elucidated the molecular basis of its action. Methods: We employed melanocyte cultures and hyperpigmented skin samples for pigmentation assays, and applied chromatin immunoprecipitation, immunoblotting, RT-PCR or siRNA-based knockdown for mechanistic analyses. Results: Topical treatment with DACE mitigated UV-B-induced hyperpigmentation in the skin with attenuated expression of MITF-M and TYR. DACE also inhibited melanin production in α-MSH- or ET-1 (endothelin 1)-activated melanocyte cultures. As a mechanism, DACE blocked the nuclear import of CRTC1 (CREB-regulated co-activator 1) in melanocytes. DACE resultantly inhibited SOX10 induction, and suppressed the transcriptional abilities of CREB/CRTC1 heterodimer and SOX10 at MITF-M promoter, thereby ameliorating facultative melanogenesis. Furthermore, this study unveiled new issues in melanocyte biology that i) KPNA1 (Impα5) escorted CRTC1 as a cargo across the nuclear envelope, ii) SOX10 was inducible in the melanogenic process, and iii) CRTC1 could direct SOX10 induction at the transcription level. Conclusion: We propose the targeting of CRTC1 as a unique strategy in the treatment of acquired pigmentary disorders.

Protective Role of Parenting Attitude on the Behavioral and Neurocognitive Development of the Children from Economically Disadvantaged Families.

OBJECTIVE: Association between home environment and the behavioral and neurocognitive development of children from a community childcare center for low-income families was examined (aged 6 to 12 years, n=155). METHODS: The parents performed a questionnaire on home environment (K-HOME-Q) to assess home environment including parenting attitude and the Child Behavior Checklist (K-CBCL). The children performed the Wechsler Intelligence (IQ) Scale, Stroop interference test (Stroop), word fluency test (WF), and design fluency test (DF) to assess their neurocognitive development. RESULTS: 'Nurturing of Development' and 'Variety of Language Interaction' scores from the K-HOME-Q, were inversely associated with total behavior problems, externalization, rule-breaking, and aggressive behavior subscales of K-CBCL, and 'Emotional atmosphere' and 'Tolerance toward the child' scores showed inverse associations with the total behavior problems, rule-breaking, aggressive behavior, and withdrawn/depressed subscales. Despite economic hardship, the mean scores of the neurocognitive tests were comparable to the average level of Korean children's normative sample. However, 'Nurturing of Development' and 'Tolerance toward the Child' score of K-HOME-Q were associated with better executive function (IQ, WF, DF). CONCLUSION: These results suggest that parental stimulation of development and tolerant parenting attitude may offer protection against the negative effects of suboptimal economic environment on children's behavior and neurocognitive development.

Effects of wearing ankle weight on knee joint repositioning sense in the elderly.

[Purpose] To investigate the effects of different ankle weights on knee joint repositioning sense in elderly individuals. [Subjects and Methods] Twenty-one subjects were divided for assessment as follows: young (20-30 years, n=10) and elderly (60-70 years, n=11). Knee joint repositioning error was measured by asking the subjects to reposition the target angle of their knee joints while wearing different ankle weights (0%, 0.5%, 1%, and 1.5%) in an open kinetic chain. The Hawk Digital System (60 Hz; Motion Analysis, Santa Rosa, CA, USA) was used to measure knee joint repositioning error. Differences in knee joint repositioning error between the young and elderly groups according to ankle weight load were examined by using two-way mixed repeated-measures analysis of variance. [Results] The knee joint repositioning error was lower with than without ankle weights in both groups. The error value was lowest with the 1.0% weight, though not significantly. Knee joint repositioning error was significantly higher in the elderly under all the ankle weight conditions. [Conclusion] Knee joint repositioning sense can be improved in elderly individuals by wearing proper ankle weights. However, weights that are too heavy might disturb knee joint positioning sense.

Association of current phthalate exposure with neurobehavioral development in a national sample.

BACKGROUND: Previous studies have indicated that phthalate exposure may influence the development of children, but the current data are limited, and controversy remains regarding the sex-specific and age-specific effects of phthalate exposure. METHODS: We investigated the sex- and age-specific associations of current phthalate exposure with neurobehavioral development scores in a nationally representative sample of 6-18-year-olds participating in the Korean Environmental Health Survey in Children and Adolescents (KorEHS-C). Neurobehavioral development was assessed using the Korean Child Behavior Checklist (CBCL, N=1723) and the Korean Attention Deficit Hyperactivity Disorder Rating Scale (ARS, N=867). We measured the concentrations of phthalate metabolites in urine samples using high-performance liquid chromatography tandem mass spectrometry. The associations between urine phthalate metabolite concentrations and neurobehavioral development were examined by survey regression analysis for complex sampling and penalized regression splines using a generalized additive model. RESULTS: Survey regression analysis revealed that a higher mono-n-butyl phthalate (MnBP) level was associated with social (ß=0.60; 95% confidence interval=0.15-1.05), thought (0.55; 0.08-1.03), and attention (0.68; 0.21-1.14) problems on the CBCL. A significant association was found between the MnBP level and the ARS hyperactivity subscale score (0.42; 0.05-0.58). Higher levels of MnBP (0.87; 0.20-1.54), mono-2-ethyl-5-oxohexyl phthalate (MEOHP, 0.61; 0.11-1.11) and mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP, 0.51; 0.04-0.97) were associated with an increase in thought problems among the girls. Among the younger children aged 6-11 years, significant positive associations between the MnBP (0.71; 0.09-1.33), MECPP (0.74, 0.14-1.34), MEOHP (0.65; 0.10-1.20), and MEHHP (0.71; 0.21-1.21) levels and social problems and between the MnBP (1.11; 0.37-1.84), MEOHP (0.64; 0.13-1.15), and MEHHP (0.66; 0.18-1.14) levels and attention problems were observed. The penalized regression splines for the age-specific relationships between the urinary MnBP, MEOHP, and MEHHP levels and social and attention problems exhibited positive supralinear relationships with downward curvature in the 6-11 year age group. In contrast, the score for social problems exhibited nearly linear relationships with these levels in the 12-18 year age group. CONCLUSIONS: In this national sample, increased phthalate exposure exhibited supralinear associations with social, thought and attention problems in children aged 6-11 years, who showed greater vulnerability to phthalate exposure. The results highlight the need for the environmental regulation of phthalate exposure in younger children, even at low dosages.

The effects of ankle loads on balance ability during one-leg stance.

[Purpose] The purpose of this study was to evaluate the effects of ankle loads on balance ability and to suggest an appropriate load amount. [Subjects and Methods] The 31 healthy subjects randomly put 0%, 1%, and 2% body weight loads on their ankles using a strap, and limit of stability was measured using a Biorescue system. Limits of stability were measured for 10 seconds using their dominant leg in the left, right, forward, and backward directions. [Results] All values for limit of stability increased significantly with the 1% load compared with the 0% load during a one-leg stance. However, all values except for the backward limit of stability showed a significant decrease with the 2% load compared with the 1% load. There was a significant difference between the 0% and 2% loads. [Conclusion] Application of loads on the ankles can be used as a training method for improving balance ability, and to increase efficiency, it is appropriate to apply 1% of the subject's body weight.

Effect of the application of local vibration in scaption on joint stability.

[Purpose] The aim of this study was to determine the initial effect of local vibration on the stability of the shoulder joints by applying local vibration to the shoulder joints. [Subjects and Methods] For the test, the subjects held a FlexBar with one hand, at about 10 cm from one end, and performed the oscillation movement with the shoulder at 90° flexion and the elbow in the full-extension position in scaption; the vibration stimulus was set to 5 Hz. Then, the subjects underwent the Upper Quarter Y Balance Test to evaluate the stability of the shoulder joints. [Results] The moving distances in the left, right, and upper directions after the oscillation movement were increased significantly compared with the results before the oscillation movement. [Conclusion] A vibration stimulus is effective as an exercise method to increase the stability of the shoulder joints.

The effects of shoulder joint abduction angles on the muscle activity of the serratus anterior muscle and the upper trapezius muscle while vibrations are applied.

[Purpose] The purpose of this study was to examine the ratio between the upper trapezius and the serratus anterior muscles during diverse shoulder abduction exercises applied with vibrations in order to determine the appropriate exercise methods for recovery of scapular muscle balance. [Subjects and Methods] Twenty-four subjects voluntarily participated in this study. The subjects performed shoulder abduction at various shoulder joint abduction angles (90°, 120°, 150°, 180°) with oscillation movements. [Results] At 120°, all the subjects showed significant increases in the muscle activity of the serratus anterior muscle in comparison with the upper trapezius muscle. However, no significant difference was found at angles other than 120°. [Conclusion] To selectively strengthen the serratus anterior, applying vibration stimuli at the 120° shoulder abduction position is considered to be appropriate.

Comparison of Muscle Activities Using a Pressure Biofeedback Unit during Abdominal Muscle Training Performed by Normal Adults in the Standing and Supine Positions.

[Purpose] The purpose of this study was to assess the effects of draw-in exercise on abdominal muscle activity in the standing and supine positions. [Methods] Twenty healthy women participated in this study. The subjects were required to complete two draw-in exercises (standing and supine positions) using a biofeedback pressure unit. The root mean square (RMS) values of the EMG data were expressed as a percentage of the resting contraction. The data were analyzed using the independent t-test. [Results] According to the changes in the activities of the abdominal muscles, the draw-in exercise in the standing position produced the most significant increase in the activities of the rectus abdominis, the transverse abdominis, the internal oblique, and the external oblique muscles. [Conclusion] The activities of the trunk stability muscles (rectus abdominis, transverse abdominis, internal oblique, and external oblique) increased more in the standing than in the supine position, enabling the subjects to overcome gravity. Therefore, to strengthen the activation of the abdominal muscles, a standing position seems to be more effective than a supine position for draw-in exercises.

Genetic influences on hallux valgus in Koreans: the healthy twin study.

Hallux valgus (HV) is a common foot deformity of multifactorial etiology, but knowledge about the relative importance of genetics and environments on HV has been limited. In order to estimate genetic influences on HV, 1,265 adults, including 175 monozygotic twin (MZ) pairs, 31 dizygotic twin (DZ) pairs, and 853 first-degree singleton family members of the twins were included from the Healthy Twin study, a population-based twin-family cohort in Korea. All participants underwent foot examination and weight-bearing radiographic assessment (anterior-posterior and lateral) in addition to a general health survey. Of the subjects, 208 (16.4%) were classified as HV (as HV angle >20°). The genetic influence on HV was estimated to be substantial; the heritability of HV was 0.51 (95% CI 0.42-0.59) and the heritability of HV angle was 0.47 (0.38-0.56), while contributions from shared environmental effects were negligible. These findings suggest that genetic factors play an important role in determining HV deformity.

The realities and associated factors of palliative chemotherapy near the end of life in the patients enrolled in palliative care unit.

BACKGROUND: It is important to know and decide when to end regimen for the quality of life of the patients. However, there is currently no clear agreement on when to terminate palliative chemotherapy. We investigated the duration between the last chemotherapy and death, and associated factors affecting patients receiving palliative care after the last chemotherapy. METHODS: We studied 242 patients who were put into palliative care ward after receiving chemotherapy and died during hospitalization from 2008 to 2009. Electronic medical records were used to gather information on demographic characteristics, types of primary cancer, and palliative chemotherapy. Then we analyzed the relationship between the clinical characteristics of patients and interval between last chemotherapy and death. RESULTS: The average survival time of patients after referral to palliative care was 17.5 days; survival time after discontinuation of chemotherapy was 103 days. Also, 104 (43.0%) patients died within 3 months and 14 (5.8%) patients died within 1 month of persistent palliative chemotherapy. Chemotherapy on patients within 3 months from their death was not associated with the social characteristics of the population. CONCLUSION: The patients who were referred to palliative care were found to have continued to receive chemotherapy within 3 months before death. However, only a small number of patients received chemotherapy within 1 month before death, which confirms that futile chemotherapy that extends to the end of life was less frequent. Doctors should be able to recognize the implications of excessive and aggressive use of chemotherapy and should actively communicate with patients about therapeutic choices.

A case of Hashimoto's encephalopathy presenting with seizures and psychosis.

Hashimoto's encephalopathy (HE) is a rare, poorly understood, autoimmune disease characterized by symptoms of acute or subacute encephalopathy associated with increased anti-thyroid antibody levels. Here, we report a case of a 14-year-old girl with HE and briefly review the literature. The patient presented with acute mental changes and seizures, but no evidence of infectious encephalitis. In the acute stage, the seizures did not respond to conventional antiepileptic drugs, including valproic acid, phenytoin, and topiramate. The clinical course was complicated by the development of acute psychosis, including bipolar mood, insomnia, agitation, and hallucinations. The diagnosis of HE was supported by positive results for antithyroperoxidase and antithyroglobulin antibodies. Treatment with methylprednisolone was effective; her psychosis improved and the number of seizures decreased. HE is a serious but curable, condition, which might be underdiagnosed if not suspected. Anti-thyroid antibodies must be measured for the diagnosis. HE should be considered in patients with diverse neuropsychiatric manifestations.

Topiramate on the quality of life in childhood epilepsy.

This study evaluated the effect of topiramate (TPM) on the quality of life (QOL) in childhood epilepsy, using the Korean quality of life in childhood epilepsy (K-QOLCE) questionnaire. An open label, prospective, observational study of the families of 664 children with epilepsy from 41 centers was conducted. The parents completed the K-QOLCE at the baseline visit and again 6months after starting TPM treatment. The parents reported the seizure frequency at both assessment dates. Statistically significant improvements in all K-QOLCE domains except social functioning were found at 6months after starting TPM treatment from the baseline-scores (P<0.05). However, improved QOL scores were not dependent on the reduction in seizure frequency. TPM significantly improved QOL in children with epilepsy, suggesting its potential clinical benefits.