A prospective study on EEG default mode network associated with subsequent posttraumatic stress disorder following sexual assault.

This study aimed to explore the predictors of posttraumatic stress disorder (PTSD) in women who have recently experienced sexual assault, by examining psychological and neurophysiological factors using a prospective design with resting-state electroencephalogram (EEG) functional connectivity. The study enrolled 33 women who had been recently traumatized by sexual assault and conducted assessments within a month of the trauma. These survivors were evaluated for PTSD three months later and were classified into two groups: PTSD positive (n = 12) and PTSD negative (n = 21). They were compared to two control groups comprising women who had not experienced any extremely traumatic events: 25 with depression and 25 healthy controls. The evaluation focused on resting-state EEG functional connectivity within default mode network (DMN) using small-worldness (SW), based on graph theory. We also assessed self-reported levels of depression, anxiety, anger, and executive functions. The findings indicated that survivors who developed PTSD three months post-trauma exhibited higher anxiety levels and reduced DMN SW in the beta 3 frequency, compared to those who did not develop PTSD. Contrary to expectations, survivors without PTSD showed decreased executive functioning and lower prefrontal centrality compared to those with PTSD. This study underscores the importance of early assessment and intervention for sexual assault survivors at risk of developing PTSD.

Occurrence and risk assessment of okadaic acid, dinophysistoxin-1, dinophysistoxin-2, and dinophysistoxin-3 in seafood from South Korea.

The okadaic acid (OA)-group toxins, including OA, dinophysistoxin-1 (DTX1), dinophysistoxin-2 (DTX2), and dinophysistoxin-3 (DTX3), cause diarrheic shellfish poisoning in humans. To manage OA-group toxins more strictly, Korean regulations were recently revised to consider OA, DTX1, DTX2, and DTX3 combined. Thus, our study characterized the occurrence of OA, DTX1, DTX2, and DTX3 in seafood distributed across South Korea, and a risk assessment of seafood consumption was conducted. Two hundred and seventeen samples from 16 bivalve and 7 non-bivalve species collected from three representative coastal areas in 2021 were analyzed via liquid chromatography-tandem mass spectrometry. OA, DTX1, and DTX3 were detected in 2.3%, 4.1%, and 9.2% of the examined samples, with positive mean levels of 11.3, 16.4, and 40.9 µg/kg, respectively. DTX2 was not detected in any of the samples. At least one OA-group toxin was detected in the bivalve samples, including blood clams, pan shells, hard clams, mussels, and scallops, whereas none were detected in non-bivalves. The estimated acute exposure to OA-group toxins through the intake of seafood in the Korean population and consumer groups was low, ranging from 24.7 to 74.5% of the recommended acute reference dose (ARfD) of 0.33 µg OA equivalents/kg body weight. However, for the scallop consumers aged 7-12 years, acute exposure to OA-group toxins exceeded the ARfD, indicating a possible health risk. These results suggest that including DTX3 in the new regulatory limits is appropriate to protect Korean seafood consumers from exposure to OA-group toxins.

Lower cognitive function attenuates the convergence between self-ratings and observer ratings of depressive symptoms in late-life cognitive impairment.

OBJECTIVES: Assessment of depressive symptoms in older adults is challenging especially in the presence of risks in cognitive impairment. We aimed to examine whether the convergence between two measures of depressive symptoms (self-report and observer ratings) is affected by varying levels of cognitive function in older adults. METHODS: Self-reported scale of depression, informant-based rating of affective symptoms, and global cognitive function were assessed in 2533 older adults with no impairment, mild cognitive impairment, and Alzheimer's disease. The strength of rank-order correlation between the Geriatric Depression Scale (GDS) and behavioral ratings of the Neuropsychiatric Inventory (NPI) was examined as the metric of convergent validity. RESULTS: The results showed that the strength of convergence between the two measurements gradually decreased as a function of lowered cognitive function. Overall tendency showed that diagnoses of cognitive impairment and lower levels of cognitive function were associated with lower correspondence between the two depression measurements. The loss of convergent validity is especially evident in the behavioral symptom of apathy. CONCLUSIONS: Utilizing self-report scales of depression in older adults requires a cautious approach even with minimal or mild levels of cognitive impairment.

Natural Occurrence of Alternaria Toxins in Agricultural Products and Processed Foods Marketed in South Korea by LC-MS/MS.

Alternaria mycotoxins including alternariol (AOH), alternariol monomethyl ether (AME), altenuene (ALT), altertoxin-I (ATX-I), tentoxin (TEN), and tenuazonic acid (TeA), are ubiquitous contaminants in agricultural products. A method for the simultaneous determination of these six toxins by ultrahigh performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) with solid phase extraction (SPE) was validated in rice, sesame, tomato, and apple juice matrices. The performance of the method was evaluated in terms of linearity (R2 > 0.999), the limit of detection (0.04-1.67 µg/kg), the limit of quantification (0.12-5.06 µg/kg), recovery (80.0-114.7%), and precision (<17.7%). The validated method was applied to monitor 152 marketed food samples in South Korea, as well as to investigate the co-occurrence and correlation between Alternaria toxins. The mean occurrence levels were 2.77 µg/kg for AOH, 4.36 µg/kg for AME, 0.14 µg/kg for ALT, 0.11 µg/kg for ATX-I, 0.43 µg/kg for TEN, and 104.56 µg/kg for TeA. Mean and extreme (95th percentile) daily dietary exposures of South Koreans to Alternaria toxins were estimated to be 22.93 ng/kg b.w./day and 86.07 ng/kg b.w./day, respectively.

Harm avoidance, daily stress, and problematic smartphone use in children and adolescents.

Objective: Temperament is close to susceptibility to stress and the increased level of stress may lead problematic smartphone use (PSU). In this study, the relationships between harm avoidance (HA) as a personality trait, daily traits, and PSU in children and adolescents were investigated. Methods: At baseline, all participants (184 children and adolescents, mean age 13.15 years) completed questionnaires on PSU using the Smartphone Addiction Scale-Short Version (SAS-SV) and the Korean Smartphone Addiction Proneness Scale (SAPS). The Daily Hassles Questionnaire (DHQ) and Junior Temperament and Character Inventory (JTCI) were also administered to evaluate stress levels and personality traits. SAS-SV, SAPS, and DHQ were reassessed at 3 and 6 months. Results: Among JTCI temperament, HA displayed robust positive correlations with SAS-SV, SAPS, and DHQ at all time points. Mediation effects of daily stress on the relationship between HA and PSU were observed at baseline, 3, and 6 months. Conclusion: The findings suggest that managing stress may important in PSU children and adolescents with high HA.

BK channel properties correlate with neurobehavioral severity in three KCNMA1-linked channelopathy mouse models.

KCNMA1 forms the pore of BK K+ channels, which regulate neuronal and muscle excitability. Recently, genetic screening identified heterozygous KCNMA1 variants in a subset of patients with debilitating paroxysmal non-kinesigenic dyskinesia, presenting with or without epilepsy (PNKD3). However, the relevance of KCNMA1 mutations and the basis for clinical heterogeneity in PNKD3 has not been established. Here, we evaluate the relative severity of three KCNMA1 patient variants in BK channels, neurons, and mice. In heterologous cells, BKN999S and BKD434G channels displayed gain-of-function (GOF) properties, whereas BKH444Q channels showed loss-of-function (LOF) properties. The relative degree of channel activity was BKN999S > BKD434G>WT > BKH444Q. BK currents and action potential firing were increased, and seizure thresholds decreased, in Kcnma1N999S/WT and Kcnma1D434G/WT transgenic mice but not Kcnma1H444Q/WT mice. In a novel behavioral test for paroxysmal dyskinesia, the more severely affected Kcnma1N999S/WT mice became immobile after stress. This was abrogated by acute dextroamphetamine treatment, consistent with PNKD3-affected individuals. Homozygous Kcnma1D434G/D434G mice showed similar immobility, but in contrast, homozygous Kcnma1H444Q/H444Q mice displayed hyperkinetic behavior. These data establish the relative pathogenic potential of patient alleles as N999S>D434G>H444Q and validate Kcnma1N999S/WT mice as a model for PNKD3 with increased seizure propensity.

So far, only 70 patients around the world have been diagnosed with a newly identified rare syndrome known as KCNMA1-linked channelopathy. The condition is characterised by seizures and abnormal movements which include frequent 'drop attacks', a sudden and debilitating loss of muscle control that causes patients to fall without warning. The disease is associated with mutations in the gene for KCNMA1, a member of a class of proteins important for controlling nerve cell activity and brain function. However, due to the limited number of people affected by the condition, it is difficult to link a particular mutation to the observed symptoms; the basis for the drop attacks therefore remains unknown. Park et al. set out to 'model' KCNMA1-linked channelopathy in the laboratory, in order to determine which mutations in the KCNMA1 gene caused these symptoms. Three groups of mice were each genetically engineered to carry either one of the two most common mutations in the gene for KCNMA1, or a very rare mutation associated with the movement symptoms. Behavioural experiments and studies of nerve cell activity revealed that the mice carrying mutations that made the KCNMA1 protein more active developed seizures more easily and became immobilized, showing the mouse version of drop attacks. Giving these mice the drug dextroamphetamine, which works in some human patients, stopped the immobilizing attacks altogether. These results show for the first time which specific genetic changes cause the main symptoms of KCNMA1-linked channelopathy. Park et al. hope that this knowledge will deepen our understanding of this disease and help develop better treatments.

Clinical and biological subtypes of late-life depression.

BACKGROUND: Late-life depression (LDD) results from multiple psychosocial and neurobiological changes occurring in later life. The current study investigated how patterns of clinical symptoms and brain structural features are classified into LDD subtypes. METHOD: Self-report scale of depression, behavioral rating of affective symptoms, and brain structural imaging of white matter change and cortical thickness were assessed in 541 older adults with no cognitive impairment or mild cognitive impairment. Latent profile analysis was used to identify distinct subtypes of depression. RESULTS: The latent profile analysis identified four classes with mild to severe depressive symptoms and two classes with minimal symptoms. While the classes primarily differed in the overall severity, the combinatory patterns of clinical symptoms and neuropathological signature distinguished the classes with similar severity. The classes were distinguished in terms of whether or not neurodegenerative risk accompanied the corresponding depressive symptoms. The presence of the negative self-scheme and cortical thinning pattern notably characterized the subtypes of LDD. LIMITATIONS: The underlying etiologies of the biological subtypes are still speculative, and the current study lacks clinical history that differentiates late- and early-onset depression. CONCLUSIONS: Our finding provides insight in identifying heterogeneities of depressive disorder in later life and suggests that self-report and behavioral symptom profile in combination with white matter lesion and cortical thickness effectively characterizes distinct subtypes of LDD.

Utility of Machine Learning Approach with Neuropsychological Tests in Predicting Functional Impairment of Alzheimer's Disease.

BACKGROUND: In assessing the levels of clinical impairment in dementia, a summary index of neuropsychological batteries has been widely used in describing the overall functional status. OBJECTIVE: It remains unexamined how complex patterns of the test performances can be utilized to have specific predictive meaning when the machine learning approach is applied. METHODS: In this study, the neuropsychological battery (CERAD-K) and assessment of functioning level (Clinical Dementia Rating scale and Instrumental Activities of Daily Living) were administered to 2,642 older adults with no impairment (n = 285), mild cognitive impairment (n = 1,057), and Alzheimer's disease (n = 1,300). Predictive accuracy on functional impairment level with the linear models of the single total score or multiple subtest scores (Model 1, 2) and support vector regression with low or high complexity (Model 3, 4) were compared across different sample sizes. RESULTS: The linear models (Model 1, 2) showed superior performance with relatively smaller sample size, while nonlinear models with low and high complexity (Model 3, 4) showed an improved accuracy with a larger dataset. Unlike linear models, the nonlinear models showed a gradual increase in the predictive accuracy with a larger sample size (n > 500), especially when the model training is allowed to exploit complex patterns of the dataset. CONCLUSION: Our finding suggests that nonlinear models can predict levels of functional impairment with a sufficient dataset. The summary index of the neuropsychological battery can be augmented for specific purposes, especially in estimating the functional status of dementia.

Multiple Cognitive and Behavioral Factors Link Association Between Brain Structure and Functional Impairment of Daily Instrumental Activities in Older Adults.

OBJECTIVE: Functional impairment in daily activity is a cornerstone in distinguishing the clinical progression of dementia. Multiple indicators based on neuroimaging and neuropsychological instruments are used to assess the levels of impairment and disease severity; however, it remains unclear how multivariate patterns of predictors uniquely predict the functional ability and how the relative importance of various predictors differs. METHOD: In this study, 881 older adults with subjective cognitive complaints, mild cognitive impairment (MCI), and dementia with Alzheimer's type completed brain structural magnetic resonance imaging (MRI), neuropsychological assessment, and a survey of instrumental activities of daily living (IADL). We utilized the partial least square (PLS) method to identify latent components that are predictive of IADL. RESULTS: The result showed distinct brain components (gray matter density of cerebellar, medial temporal, subcortical, limbic, and default network regions) and cognitive-behavioral components (general cognitive abilities, processing speed, and executive function, episodic memory, and neuropsychiatric symptoms) were predictive of IADL. Subsequent path analysis showed that the effect of brain structural components on IADL was largely mediated by cognitive and behavioral components. When comparing hierarchical regression models, the brain structural measures minimally added the explanatory power of cognitive and behavioral measures on IADL. CONCLUSION: Our finding suggests that cerebellar structure and orbitofrontal cortex, alongside with medial temporal lobe, play an important role in the maintenance of functional status in older adults with or without dementia. Moreover, the significance of brain structural volume affects real-life functional activities via disruptions in multiple cognitive and behavioral functions.

Identification of Major Psychiatric Disorders From Resting-State Electroencephalography Using a Machine Learning Approach.

We aimed to develop a machine learning (ML) classifier to detect and compare major psychiatric disorders using electroencephalography (EEG). We retrospectively collected data from medical records, intelligence quotient (IQ) scores from psychological assessments, and quantitative EEG (QEEG) at resting-state assessments from 945 subjects [850 patients with major psychiatric disorders (six large-categorical and nine specific disorders) and 95 healthy controls (HCs)]. A combination of QEEG parameters including power spectrum density (PSD) and functional connectivity (FC) at frequency bands was used to establish models for the binary classification between patients with each disorder and HCs. The support vector machine, random forest, and elastic net ML methods were applied, and prediction performances were compared. The elastic net model with IQ adjustment showed the highest accuracy. The best feature combinations and classification accuracies for discrimination between patients and HCs with adjusted IQ were as follows: schizophrenia = alpha PSD, 93.83%; trauma and stress-related disorders = beta FC, 91.21%; anxiety disorders = whole band PSD, 91.03%; mood disorders = theta FC, 89.26%; addictive disorders = theta PSD, 85.66%; and obsessive-compulsive disorder = gamma FC, 74.52%. Our findings suggest that ML in EEG may predict major psychiatric disorders and provide an objective index of psychiatric disorders.

Clinical and Psychological Characteristics of Young Men with Military Adaptation Issues Referred for a Psychiatric Evaluation in South Korea: Latent Profile Analysis of Minnesota Multiphasic Personality Inventory-2 and Temperament and Character Inventory.

OBJECTIVE: To investigate clinical and psychological characteristics of young men referred for a psychiatric evaluation due to expected unsuitability for military service and identify their heterogeneous subgroups based on the profiles of MMPI-2 and TCI. METHODS: We conducted a latent profile analysis of 348 men using MMPI-2 and TCI and then a comparative analysis of four latent classes in relation to sociodemographic, clinical, and IQ variables. RESULTS: We identified four classes with distinct clinical and psychological features: Class 1 (nonclinical: n=68), Class 2 (internalized: n=129), Class 3 (externalized: n=60), Class 4 (confused: n=91). Class 1 showed no significant psychiatric symptoms and relatively adaptive temperament and characteristics. Class 2 showed relatively higher harm avoidance and introverted traits indicating vulnerability to internalizing disorder. Class 3 was related to higher novelty seeking, impulsivity, and bipolarity. Class 4 showed the most severe clinical symptoms including psychotic experiences with extremely unstable temperament and immature personality. In total, 50-70% participants reported clinically significant depression, anxiety, and suicidal idea. Participants showed lower processing speed index (M=85.9, SD=16.6) than the general population. CONCLUSION: The results suggest that clinical conceptualization and therapeutic intervention considering distinctive features of young men with adaptive problems related to military service are needed.

Status Dystonicus, Oculogyric Crisis and Paroxysmal Dyskinesia in a 25 Year-Old Woman with a Novel KCNMA1 Variant, K457E.

The diagnosis of a paroxysmal dyskinesia is difficult and status dystonicus is a rare life threatening movement disorder characterised by severe, frequent or continuous episodes of dystonic spasms. A 25 year old woman with chronic ataxia and paroxysmal dyskinesia presented with facial twitching, writhing of arms, oculogyric crisis and visual and auditory hallucinations. She developed respiratory failure and was ventilated. No cause was found so whole exome sequencing was performed and this revealed a novel, non-synonymous heterozygous variant in exon 11 of the KCNMA1 gene, K457E (c 1369A>G) in the patient but not her parents. This variant has not been previously reported in gnomAD or ClinVar. The finding of a de novo variant in a potassium channel gene guided a trial of the potassium channel antagonist 3,4 diaminopyridine resulting in significant improvement, discharge from the intensive care unit and ultimately home.

Respiratory sinus arrhythmia biofeedback alters heart rate variability and default mode network connectivity in major depressive disorder: A preliminary study.

Traditional major depressive disorder (MDD) interventions do not improve heart rate variability (HRV), despite symptom reduction. We investigated whether respiratory sinus arrhythmia (RSA)-biofeedback (BFB) effectively changed HRV, psychological symptoms, and functional connectivity of the default mode network (DMN), which is known to increase in MDD. Thirty MDD patients were randomly assigned to two groups (RSA-BFB with treatment as usual [TAU] with medication [BFB + TAU; n = 16] and TAU [n = 14]). Six RSA-BFB sessions were performed over 4 weeks. We assessed psychological symptoms (including depression, anxiety, and hopelessness), high frequency (HF; an index of HRV during rest and stress), and DMN functional connectivity, as measured by source-level coherence of 19-channel electroencephalography using standardized weighted low-resolution brain electromagnetic tomography. Large-scale DMN was represented by small-worldness based on graph theory. The BFB + TAU group showed greater reductions in depression (especially psychic anxiety and vegetative symptoms) compared to the TAU group. Significant group by session interactions were found in resting HF-HRV, stress-reactive HF-HRV, and beta DMN small-worldness. During the post-intervention session, the BFB + TAU group showed higher resting HF-HRV and stress-reactive HF-HRV (d = 1.41 for the resting stage and d = 1.99 for the Stroop test, P < .005). Compared to baseline, the BFB + TAU group showed increased HF-HRV reactivity and decreased DMN small-worldness in the beta band, implying decreased global DMN functional connectivity. Conversely, the TAU group showed decreased HF-HRV during stress and no DMN alterations. This study was limited by small sample size and open-label design. These preliminary findings suggest that brief RSA-BFB may improve autonomic nervous system and DMN functions in MDD.

Daytime Neurophysiological Hyperarousal in Chronic Insomnia: A Study of qEEG.

BACKGROUND: The hyperarousal model demonstrates that instability of sleep-wake regulation leads to insomnia symptoms and various neurophysiological hyperarousal states. Previous studies have shown that hyperarousal states that appear in chronic insomnia patients are not limited to sleep at nighttime but are stable characteristics that extend into the daytime. However, this phenomenon is mainly measured at bedtime, so it hard to determine whether it is maintained throughout a 24 h cycle or if it just appears at bedtime. METHODS: We examined the resting state qEEG (quantitative electroencephalogram) and ECG (electrocardiogram) of chronic insomnia patients (n = 24) compared to good sleepers (n = 22) during the daytime. RESULTS: As compared with controls, participants with insomnia showed a clearly high beta band activity in eyes closed condition at all brain areas. They showed a low frequency band at the frontal area; high frequency bands at the central and parietal areas were found in eyes open condition. Significantly higher heart rates were also found in the chronic insomnia group. CONCLUSION: These findings suggest that chronic insomnia patients were in a state of neurophysiological hyperarousal during the middle of the day due to abnormal arousal regulation.

Conservative management of traumatic acute intramural hematoma of duodenal 2nd and 3rd portion: A case report and review of literature.

Traumatic intramural duodenal hematoma (IMDH) is a rare disease occurring usually in children. The treatment modality of traumatic IMDH varies according to clinical manifestations. We had a case of a young man who had traumatic IMDH and treated nonoperatively. He had 3 weeks of conservative care and has been discharged, with follow up abdominal CT scan showing complete resolution of the hematoma. In conclusion, patient with traumatic acute intramural hematoma of duodenal 2nd and 3rd portion have excellent clinical outcomes with conservative therapy.

Maladaptive neurovisceral interactions in patients with Internet gaming disorder: A study of heart rate variability and functional neural connectivity using the graph theory approach.

Heart rate variability (HRV) can be used to represent the regulatory adaptive system and is a proxy for neurovisceral integration. Consistent with the view that, like other addictions, Internet gaming disorder (IGD) involves disrupted regulatory function, the present study hypothesized that IGD patients would show (a) decreased HRV, (b) ineffective functional neural connectivity, and (c) differential patterns of association between HRV and functional neural connectivity relative to healthy controls (HCs). The present study included 111 young adults (53 IGD patients and 58 age- and sex-matched HCs) who underwent simultaneous recordings with an electrocardiogram and electroencephalogram during a resting state. Heart rate (HR), HRV, and functional neural connectivity were calculated using the graph theory approach. Compared with the HCs, the IGD patients exhibited elevated HR and decreased HRV based on the high frequency (HF), which reflects suppression of parasympathetic and/or vagal tone. The IGD patients also exhibited a heightened theta band characteristic path length (CPL) compared with HCs, indicating decreased efficacy of the functional network. Furthermore, IGD patients exhibited negative correlations between the standard deviation of the normal-to-normal interval index (SDNNi) and theta and delta CPL values, which were not observed in HCs. In conclusion, the present findings suggest that IGD patients might have maladaptive brain-body integration features involving disruptions of the autonomic nervous system and brain function.

Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer.

BACKGROUND: Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. METHODS: The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. RESULTS: TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. CONCLUSION: Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer.

KCNMA1-linked channelopathy.

KCNMA1 encodes the pore-forming α subunit of the "Big K+" (BK) large conductance calcium and voltage-activated K+ channel. BK channels are widely distributed across tissues, including both excitable and nonexcitable cells. Expression levels are highest in brain and muscle, where BK channels are critical regulators of neuronal excitability and muscle contractility. A global deletion in mouse (KCNMA1-/- ) is viable but exhibits pathophysiology in many organ systems. Yet despite the important roles in animal models, the consequences of dysfunctional BK channels in humans are not well characterized. Here, we summarize 16 rare KCNMA1 mutations identified in 37 patients dating back to 2005, with an array of clinically defined pathological phenotypes collectively referred to as "KCNMA1-linked channelopathy." These mutations encompass gain-of-function (GOF) and loss-of-function (LOF) alterations in BK channel activity, as well as several variants of unknown significance (VUS). Human KCNMA1 mutations are primarily associated with neurological conditions, including seizures, movement disorders, developmental delay, and intellectual disability. Due to the recent identification of additional patients, the spectrum of symptoms associated with KCNMA1 mutations has expanded but remains primarily defined by brain and muscle dysfunction. Emerging evidence suggests the functional BK channel alterations produced by different KCNMA1 alleles may associate with semi-distinct patient symptoms, such as paroxysmal nonkinesigenic dyskinesia (PNKD) with GOF and ataxia with LOF. However, due to the de novo origins for the majority of KCNMA1 mutations identified to date and the phenotypic variability exhibited by patients, additional evidence is required to establish causality in most cases. The symptomatic picture developing from patients with KCNMA1-linked channelopathy highlights the importance of better understanding the roles BK channels play in regulating cell excitability. Establishing causality between KCNMA1-linked BK channel dysfunction and specific patient symptoms may reveal new treatment approaches with the potential to increase therapeutic efficacy over current standard regimens.

A Second Derivative Fourier-Transform Infrared Spectroscopy Method to Discriminate Perilla Oil Authenticity.

The aim of this study was to discriminate the authenticity of perilla oils distributed in Korea using their Fourier-Transform infrared spectroscopy (FT-IR) spectra with attenuated total reflectance accessory. By using orthogonal projections for latent structures discriminant analysis (OPLS-DA) technique, the =C-H cis-double bond, -C-H asymmetric and -C-H symmetric stretching are determined to be the best variables for discriminating the perilla oil authenticity. Comparing the integral and the second derivative methods between authentic and adulterated perilla oil samples, the most obvious and significant differences among the three variables is =C-H cis-double bond stretching. The procedure for applying the second derivative range of variables found in authentic perilla oil samples correctly discriminated between the adulterated samples of perilla oils with soybean oils and/or corn oils added at concentrations of ≥ 5 vol%. These results showed that the second derivative FT-IR analysis can be used as a simple and alternative method for discriminating the authenticity of perilla oil.

Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3.

Altered neuronal connectivity has been implicated in the pathophysiology of Autism Spectrum Disorder (ASD). SLIT/ROBO signaling plays an important role in developmental processes of neuronal connectivity, including axon guidance, neuronal migration, and axonal and dendritic branching. Genetic evidence supports that SLIT3, one of the genes encoding SLITs, is associated with ASD. Yet the causal link between SLIT3 mutation and autism symptoms has not been examined. Here we assessed ASD-associated behaviors in Slit3 knockout (KO) mice. Our data showed that Slit3-KO mice exhibited reduced marble burying behaviors but normal social behaviors. In addition, Slit3-KO mice displayed hypolocomotion in the open field test and impaired motor coordination in the rotarod test. Anxiety-like behaviors were mainly observed in female KO mice assessed by three types of behavioral tests, namely, the open field test, elevated plus maze test, and light/dark box test. No differences were observed between KO and wildtype mice in recognition memory in the novel object recognition test or depression-like behavior in the tail suspension test. Taken together, loss of Slit3 may result in disrupted neural circuits related to motor function and increased anxiety-like states, which are co-occurring symptoms in ASD.