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Several studies have reported the pathogenic role of Malassezia in atopic dermatitis (AD); the significance of Malassezia’s influence on AD needs to be further investigated. Dupilumab, a monoclonal antibody to anti-Interleukin (IL) 4Rα, and ruxolitinib, a Janus kinase (JAK)1/2 inhibitor, are the first approved biologics and inhibitors widely used for AD treatment. In this study, we aimed to investigate how Malassezia Restricta (M. restricta) affects the skin barrier and inflammation in AD and interacts with the AD therapeutic agents ruxolitinib and anti-IL4Rα. To induce an in vitro AD model, a reconstructed human epidermis (RHE) was treated with IL-4 and IL-13. M. restricta was inoculated on the surface of RHE, and anti-IL4Rα or ruxolitinib was supplemented to model treated AD lesions. Histological and molecular analyses were performed. Skin barrier and ceramide-related molecules were downregulated by M. restricta and reverted by anti-IL4Rα and ruxolitinib. Antimicrobial peptides, VEGF, Th2-related, and JAK/STAT pathway molecules were upregulated by M. restricta and suppressed by anti-IL4Rα and ruxolitinib. These findings show that M. restricta aggravated skin barrier function and Th2 inflammation and decreased the efficacy of anti-IL4Rα and ruxolitinib.

Acute liver failure due to malignant melanoma is uncommon. We presents a case of acute liver failure secondary to hepatic infiltration of a malignant melanoma. An 86-year-old man was admitted with elevated liver enzymes and an increased lactate dehydrogenase level. His condition progressed to acute liver failure, but the etiology of liver failure was unclear. Esophagogastroduodenoscopy was performed to evaluate dyspepsia, which showed signs indicative of malignant melanoma. Based on the endoscopy findings and elevated liver enzyme levels, liver biopsy was performed to confirm the presence of malignant melanoma. Hepatic infiltration of malignant melanoma was observed histologically. However, massive and diffuse liver metastasis is very rare and difficult to identify on imaging studies. If the etiology of liver failure is unclear, diffuse metastatic melanoma infiltration should be considered as differential diagnosis. Early liver biopsy can help to clarify the diagnosis.

Purpose: This descriptive research study aimed to identify the factors that influence depression according to household type (older adults who live with a spouse, adult children, or alone).Methods: A total of 9,790 older adults were selected and analyzed using the 2020 National Older Koreans data. A Rao-Scott x2 test was conducted to evaluate the differences in the individual, health-behavior, and mental-health factors according to family structure. A complex samples logistic regression was used to analyze the factors that influence depression according to family structure.Results: Depression according to family structure was in the order of older adults who live alone, with adult children, or a spouse (p

Introduction Shift work is known to be associated with sleep disturbance and circadian misalignment and may contribute to alterations in the brain implicated in emotion dysregulation. In this study, we examined 1) neural correlates of emotion dysregulation, including emotional reactivity and regulation in shift workers and 2) relationships between neural correlates of emotion dysregulation, sleep disturbance, and circadian misalignment. Methods Fifty-six rotating shift workers (SW, 42 females, 30.80 ± 6.94 years old) who had non-standard shift schedules and 52 healthy controls (HC, 36 females, 31.69 ± 7.86 years old) who did not work as shift schedules participated in this study. Both SW and HC completed self-reported measures of sleep and mood problems, and wrote sleep diary and wore actigraphy to assess sleep quality and circadian rhythms. They also underwent one night polysomnography and were scanned while they were performing the emotion regulation task. We analyzed group differences in mood, sleep, circadian rhythms, and neural bases of emotional reactivity and regulation, and examined relationships between these variables. Results SW showed significant differences in actigraphy-estimated sleep (i.e., lower sleep efficiency) and circadian rhythms (e.g., greater motor activity [M10] and lower interdaily stability) compared to HC. SW also exhibited increased anterior insula (AI) activation in response to negative pictures, but reduced activation in the dorsomedial prefrontal cortex (dMPFC) and AI-dMPFC functional connectivity during emotion regulation compared to HC. AI activation and AI-dMPFC functional connectivity were significantly associated with sleep disturbance (i.e., sleep diary-estimated sleep onset latency) and circadian misalignment (e.g., M10 and interdaily stability). Furthermore, a mediation analysis revealed that shift work was associated with increased motor activity during the most active 10-hour period, which then contributed to increased AI activation in response to negative pictures. Conclusion Our findings suggest that shift work may contribute to sleep disturbance and circadian misalignment, and neural alterations associated with emotional reactivity and regulation. Furthermore, the mediation result suggests that increased motor activity along with misaligned circadian rhythm may serve as a pathway, through shift work contributes to heightened emotional reactivity to negative information. Support (if any) National Research Foundation (No. 2022R1A2C2008417, NRF-2022R1A2C1008209) and Korea Institute for Advancement of Technology (No. 20009210).

Polysomnography (PSG) is the gold-standard for sleep apnea and hypopnea syndrome (SAHS) diagnosis. Because the PSG system is not suitable for long-term continuous use owing to the high cost and discomfort caused by attached multi-channel sensors, alternative methods using a non-contact sensor have been investigated. However, the existing methods have limitations in that the radar-person distance is fixed, and the detected apnea hypopnea (AH) event cannot be provided in real-time. In this paper, therefore, we propose a novel approach for real-time AH event detection with impulse-radio ultra-wideband (IR-UWB) radar using a deep learning model. 36 PSG recordings and simultaneously measured IR-UWB radar data were used in the experiments. After the clutter was removed, IR-UWB radar images were segmented by sliding a 20-s window at 1-s shift, and categorized into two classes: AH and N. A hybrid model combining the convolutional neural networks and long short-term memory networks was trained with the data, which consisted of class-balanced segments. Time sequenced classified outputs were then fed to an event detector to identify valid AH events. Therefore, the proposed method showed a Cohen’s kappa coefficient of 0.728, sensitivity of 0.781, specificity of 0.956, and an accuracy of 0.930. According to the apnea-hypopnea index (AHI) estimation analysis, the Pearson’s correlation coefficient between the estimated AHI and reference AHI was 0.97. In addition, the average accuracy and kappa of SAHS diagnosis was 0.98 and 0.96, respectively, for AHI cutoffs of ≥ 5, 15, and 30 events/h. The proposed method achieved the state-of-the-art performance for classifying SAHS severity without any hand-engineered feature regardless of the user’s location. Our approach can be utilized for a cost-effective and reliable SAHS monitoring system in a home environment.

Background This study aimed to evaluate the heterogeneous association of depressive subtypes with cognitive function, according to age and sex. Methods This cross-sectional study utilized the baseline data from the Cardiovascular and Metabolic Disease Etiology Research Center cohort and included 5271 midlife participants. For identifying depressive subtypes of the Beck Depression Inventory Ⅱ items, factor analyses were utilized and yielded two factors —melancholic- and somatic-depressive subtypes. The information of Mini-Mental State Examination was used for screening cognitive function. The association between depressive subtypes and cognitive function was analysed using multiple regression after adjusting for all covariates. Results We observed heterogeneous association between depressive subtypes and cognitive dysfunction in midlife participants. The results of sex- and age- stratified analyses indicated that the somatic subtype was associated with dysfunction in cognitive ability. Among women, especially those aged over 60 years, MMSE scores decreased as the somatic depression scores increased. These results might suggest that the somatic subtype, rather than the melancholic subtype, has a greater association with cognitive assessment in a general midlife population, particularly older women. Limitations Although a confirmatory factor analysis was performed, depressive subtypes need validation and reliability tests. Conclusions Given this heterogeneity, characterisation of depressive subtypes according to sex and age may improve our understanding of how each depressive symptom is associated differently with cognitive dysfunction in midlife.

The neurobiological substrates underlying the relationship of circadian rest-activity rhythm (RAR) alteration with accelerated late-life cognitive decline are not clearly understood. In the present study, the longitudinal relationship of objectively measured circadian RAR with in vivo Alzheimer's disease (AD) pathologies and cerebrovascular injury was investigated in non-demented older adults.The present study included 129 participants without dementia who participated in the Korean Brain Aging Study for Early DiagnosisPrediction of Alzheimer's Disease cohort. All participants underwent actigraphy at baseline and two consecutive [Delayed acrophase at baseline was significantly associated with greater annualized decline of AD-CM over a 2-year period, but not with that of other neuroimaging measures. In contrast, other circadian RAR parameters at baseline had no association with annualized change of any neuroimaging measures. Annualized decline of AD-CM was also significantly positively associated with the annual change in MMSE scores. Furthermore, a mediation analysis showed that greater reduction in AD-CM mediated the effect of delayed acrophase at baseline on faster decline of MMSE score.The findings indicates that delayed acrophase in late-life may cause or predict hypometabolism at AD-signature brain regions, which underlies cognitive decline in the near future. This article is protected by copyright. All rights reserved.

Background: This case study suggests the potential usefulness of Korean medicine treatment with herbal medicines for shoulder pain and improving the quality of life of patients with frozen shoulder.Case Summary: A patient had shoulder pain and decreased daily living function due to frozen shoulder. Korean medicine treatments, including herbal medicine; acupuncture at points TE14, HT1, BL11, SI10, and LI15; and pharma-acupuncture containing Sinbaro, were applied for 31 days. The Numeric Rating Scale scores for shoulder pain decreased from 7 to 4, and the Shoulder Pain and Disability Index scores decreased from 71.54 to 66.15, with an increase in range of motion from 30° flexion, 60° abduction, and 10° external rotation to around the normal range of motion.Conclusion: Korean medicine treatment can be considered an effective conservative management option for pain and decreased daily living function in patients with frozen shoulder.

Objective: This study addressed a case of central post-stroke pain described as right arm painful with coldness and left lateral medullary infarction.Methods: A patient, 71 years old female with medullary infarction, was treated with a Korean herbal medication (BackJun-pill). The improvement of symptoms was evaluated using the Numeral Rating Scale and reports of coldness and pain in the affected areas. We also measured the body temperature difference between the left and right arms using digital infrared thermographic imaging (DITI).Results: After six weeks of treatment with Korean medicine, the patient’s pain and sensation of coldness decreased.Conclusions: This clinical case study suggests that BackJun-pill may be effective for alleviating pain and coldness due to central post-stroke pain.

The present study examined the association between nightmare distress and alexithymia in traumatized North Korean (NK) refugees resettled in South Korea and the effects of clinical or subclinical psychiatric symptoms on this association.Thirty-eight NK refugees living in South Korea who had traumatic experiences (15 males, 23 females; 29.50 ± 13.11 years of age) were recruited. The Structured Clinical Interview for DSM-IV and the Clinician-Administered Post-Traumatic Stress Disorder (PTSD) Scale were conducted. All participants completed a series of questionnaires on the history of their previous traumatic experiences, the Beck Depression Inventory, the Nightmare Distress Questionnaire (NDQ), the Toronto Alexithymia Scale (TAS), and the Impact of Event Scale. In total, 18 refugees were classified as having nightmare distress based on NDQ scores, and 20 refugees were not.Refugees with nightmares reported significantly higher TAS total scores and Difficulty Identifying Feelings (DIF; a subscale of TAS) scores compared to those without nightmares. In addition, NDQ scores were positively correlated with TAS total scores (r = 0.43, p 0.01) and DIF scores (r = 0.49, p 0.01). These correlations remained significant after excluding refugees with current axis I psychiatric disorders or clinical or subclinical depressive symptoms. However, there was no significant correlation between nightmares and alexithymia after excluding refugees with clinical or subclinical trauma-related symptoms.Nightmares in traumatized refugees were associated with alexithymia even in the absence of current psychiatric disorders or depressive symptoms. Trauma-related symptoms might be a mediating factor between nightmares and alexithymia in traumatized refugees.

본 연구는 한부모 가정 청소년과 양부모 가정 청소년의 성별에 따른 흡연 및 음주, 정신건강의 차이를 분석하기 위한 서술적 조사연구이다. 제 14차 청소년건강행태조사자료 중 연구목적에 적합한 54,133명을 대상으로 분석하였다. 가족구조와 성별에 따른 흡연요인, 음주요인, 정신건강요인의 차이는 Rao-Scott chi-square 검정을 하였으며, 가족구조 및 성별에 따른 흡연요인 및 음주요인, 정신건강요인의 영향요인은 복합표본 로지스틱 회귀분석을 실시하였다. 한부모 가정의 청소년(남학생, 여학생)은 양부모 가정의 청소년(남학생, 여학생)보다 흡연경험과 음주경험(p ＜.001), 스트레스(p ＜.001), 슬픔 및 절망감(p ＜.05), 자살생각(p ＜.001)의 경험이 많았다. 한부모 가정 남학생은 흡연경험(p ＜.001)과 음주경험(p ＜.001)이 많았고 여학생은 스트레스(p ＜.001), 슬픔 및 절망감(p ＜.001), 자살생각(p ＜.001)의 경험이 높았다. 이처럼 한부모 가정의 청소년은 성별에 따라 건강행태행위에 차이가 있기에 가정과 학교는 남학생은 금연ㆍ금주, 여학생은 정신건강 증진을 위한 차별화된 교육프로그램을 적용하여 효과를 확인해야 하겠다.

While previous studies have suggested that snoring may be associated with depressive symptoms and suicidality in adults and preschool children, there have been no investigations in non-clinical adolescent populations. This study aimed to demonstrate the association between snoring and depressive symptoms/suicidality in adolescents. This survey study recruited 8530 students (grades 7–11) and examined depressive symptoms, suicidality, snoring frequency, daytime sleepiness, sleep duration, and presence of insomnia by questionnaires. Correlation analyses, multiple linear regression analyses and mediation analyses were performed to determine the association between snoring frequency and depressive symptoms/suicidality. The study population included 8080 students (16.73 ± 1.09 years old). Snoring frequency was positively correlated with depressive symptoms and suicidality. Snoring frequency was associated with depressive symptoms and suicidality when adjusted for age and sex, and the association remained significant after additionally adjusting for sleep duration, insomnia, and daytime sleepiness. When depressive symptoms were included as a predictor of suicidality, snoring frequency showed no significant predictive value. Mediation analysis confirmed that depressive symptoms mediate the association between snoring frequency and suicidality. Our findings suggest that self-reported complaints of snoring are associated with increased depressive symptoms and suicidality in adolescents independently of sleep duration, insomnia, and daytime sleepiness, and the connection between snoring and suicidality is mediated by depressive symptoms. These data underscore the importance of identifying snorers among adolescents and screening for depression and suicidal ideation in this population.

Stearidonic acid (SDA) is a plant-based n-3 polyunsaturated fatty acid with multiple biological activities. The enrichment of SDA and synthesis of triacylglycerol (TAG) were carried out consecutively via two lipase-catalyzed reactions, hydrolysis, and esterification. First, SDA was enriched into a glyceride fraction from ahiflower seed oil by Candida rugosa lipase-catalyzed hydrolysis. Under the optimum conditions of 35°C, 0.1% lipase powder of Lipase OF, and 50% buffer solution (based on the weight of total substrate), SDA was enriched from 21.6 to 40.7 wt% in glyceride fraction. SDA-enriched TAG was then synthesized from the SDA-enriched glyceride and the SDA-enriched fatty acid via esterification using an in-house immobilized lipase as a biocatalyst. The SDA-enriched fatty acid was obtained from part of the SDA-enriched glyceride by saponification and the in-house immobilized lipase was prepared from Eversa

Alopecia areata (AA) is an autoimmune condition related to the collapse of the immune privilege of hair follicles. Certain AA populations present severe clinical manifestations, such as total scalp hair or body hair loss and a treatment refractory property. The aim of this study was to assess the effects of allogenic human mesenchymal stem cells (hMSCs) from healthy donors on the peripheral blood mononuclear cells (PBMCs) of severe AA patients, with a focus on the change in the cell fraction of Th1, Th17, and Treg cells and immunomodulatory functions. PBMCs of 10 AA patients and eight healthy controls were collected. Levels of Th17, Th1, and Treg subsets were determined via flow cytometry at baseline, activation status, and after co-culturing with hMSCs. All participants were severe AA patients with SALT > 50 and with a long disease duration. While the baseline Th1 and Treg levels of AA patients were comparable to those of healthy controls, their Th17 levels were significantly lower than those of the controls. When stimulated, the levels of CD4+IFN-γ+ T cells of the AA patients rose sharply compared to the baseline, which was not the case in those of healthy controls. The cell fraction of CD4+Foxp3+ regulatory T cells also abruptly increased in AA patients only. Co-culturing with allogenic hMSCs in activated AA PBMCs slightly suppressed the activation levels of CD4+INF-γ+ T cells, whereas it significantly induced the differentiation of CD4+Foxp3+ regulatory T cells. However, these changes were not prominent in the PBMCs of health controls. To examine the pathomechanisms, PBMCs of healthy donors were treated with IFN-γ to induce AA-like environment and then treated with allogenic grants and compared with ruxolitinib as a positive treatment control. hMSC treatment was shown to significantly inhibit the mRNA levels of proinflammatory cytokines, such as IFN-γ, TNF-α, IL-1α, IL-2R, IL-15, and IL-18, and chemokines, such as CCR7 and CCR10, in IFN-treated PBMCs. Interestingly, hMSCs suppressed the activation of JAK/STAT signaling by IFN in PBMCs with an effect that was comparable to that of ruxolitinib. Furthermore, the hMSC treatment showed stronger efficacy in inducing Foxp3, IL-10, and TGF-β mRNA transcription than ruxolitinib in IFN-treated PBMCs. This study suggests that allogenic hMSC treatments have therapeutic potential to induce immune tolerance and anti-inflammatory effects in severe AA patients.

Hyperoxia is frequently used for treating acute respiratory failure, but it can cause acute lung injury. Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1) is localized in mitochondria and related to reactive oxygen species production, inflammation, and apoptosis, which are the features of hyperoxic acute lung injury (HALI). However, the contribution of NLRX1 in HALI has not been addressed, so we designed to demonstrate the role of NLRX1 in hyperoxia. A murine model of HALI was generated in wild-type mice (WT) and NLRX1−/− mice by exposing them to over 95% oxygen for 72 h. As a result, NLRX1 expression was elevated in mice exposed to hyperoxia. In acute lung injury, levels of inflammatory cells, protein leakage, cell cytotoxicity, and pro-inflammatory cytokines were diminished in NLRX1−/− mice compared to WT mice. In survival test, NLRX1−/− mice showed alleviated mortality under hyperoxic conditions, and apoptotic cell death and caspase expression and activity were reduced in NLRX1−/− mice. Furthermore, levels of MAPK signaling proteins ERK 1/2, JNK, and p38 were decreased in NLRX1-deficient mice than in WT mice exposed to hyperoxia. This study reveals that the genetic deficiency of NLRX1 dampens hyperoxia-induced apoptosis, suggesting NLRX1 acts as a pivotal regulator of HALI.

Metastasis, in which cancer cells migrate to other tissues and form new tumors, is a major cause of both cancer death and treatment failure. In a previous study, benproperine (Benp) was identified as a cancer cell migration inhibitor and an inhibitor of actin-related protein 2/3 complex subunit 2 (ARPC2). However, Benp is a racemic mixture, and which stereoisomer is the active isomer remains unclear. In this study, we found that S-Benp is an active isomer and inhibits the migration and invasion of cancer cells much more strongly than R-Benp, with no effect on normal cells. The metastasis inhibitory effect of S-Benp was also verified in an animal model. Validating that inhibitors bind to their targets in cells and tissues has been a very challenging task in drug discovery. The direct interactions between ARPC2 and S-Benp were verified by surface plasmon resonance analysis (SPR), a cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS). In the mutant study with ARPC2F225A cells, S-Benp did not bind to ARPC2F225A according to CETSA and DARTS. Furthermore, we validated that S-Benp colocalized with ARPC2 in cancer cells and directly bound to ARPC2 in tumor tissues using Cy3-conjugated S-Benp according to CETSA. Finally, actin polymerization assays and immunocytochemistry showed that S-Benp suppressed actin remodeling such as lamellipodium formation. Taken together, our data suggest that S-Benp is an active stereoisomer of Benp and a potential metastasis inhibitor via ARPC2 binding.

Study Objectives This study investigated the altered neural function involved in emotional interference and its role in linking sleep disturbance and depressive/anxiety symptoms in rotating shift workers. Methods Sixty rotating shift workers and 61 controls performed the emotional Stroop task in three blocks (emotional-related, sleep-related, and neutral words) during functional magnetic resonance imaging (fMRI) assessments. Sleep disturbance and depressive/anxiety symptoms were assessed using self-report measures and sleep diaries. Actigraphy was used to assess the sleep and circadian variables. fMRI scans were performed to compare brain activation during the emotional Stroop task. The proposed moderating models were tested using the PROCESS macro in SPSS software. Results A significant condition effect on reaction time was detected. Regardless of the group, reaction times were longer in the negative emotional word and sleep-related conditions than in the neutral word condition. Whole-brain analysis revealed that rotating shift workers show greater neural activation in the left dorsolateral prefrontal cortex (DLPFC) compared with controls while performing the emotional Stroop task with negative emotional words. Sleep disturbance was more strongly associated with depressive symptoms when activation of the left DLPFC was higher during the emotional Stroop task with negative words. Conclusions The left DLPFC may play important roles in increased sensitivity to emotional information, possibly due to circadian misalignment, and has moderating effects on the association between sleep disturbance and depressive symptoms in rotating shift workers. These findings will help to identify possible brain regions where interventions can be performed to correct sleep and mood problems in rotating shift workers.

Yunjee Hwang,1 Kyung Hwa Lee,2,3 Nambeom Kim,4 Jooyoung Lee,5 Ha Young Lee,2 Jeong Eun Jeon,2 Yu Jin Lee,2 Seog Ju Kim5 1Department of Brain and Cognitive Engineering, Korea University, Seoul, Republic of Korea; 2Department of Psychiatry and Center for Sleep and Chronobiology, Seoul National University, College of Medicine and Hospital, Seoul, Republic of Korea; 3Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea; 4Department of Biomedical Engineering Research Center, Gachon University, Incheon, Republic of Korea; 5Department of Psychiatry, Sungkyunkwan University College of Medicine, Samsung Medical Center, Seoul, Republic of KoreaCorrespondence: Yu Jin Lee, Department of Psychiatry and Center for Sleep and Chronobiology, Seoul National University, College of Medicine and Hospital, Seoul, Republic of Korea, Email ewpsyche@snu.ac.kr Seog Ju Kim, Department of Psychiatry, Sungkyunkwan University College of Medicine, Samsung Medical Center, Seoul, Republic of Korea, Email ksj7126@skku.eduPurpose: Sounds play important roles in promoting and disrupting sleep. How our brain processes sleep-related sounds and individual differences in processing sleep-related sounds must be determined to understand the role of sound in sleep. We investigated neural responses to sleep-related sounds and their associations with cognitive appraisals of sleep.Participants and Methods: Forty-four healthy adults heard sleep-related and neutral sounds during functional magnetic resonance imaging using a 3T scanner. They also completed the Dysfunctional Beliefs and Attitudes about Sleep (DBAS) questionnaire, which was used to assess cognitive appraisals of sleep. We conducted a voxel-wise whole-brain analysis to compare brain activation in response to sleep-related and neutral sounds. We also examined the association between the DBAS score and brain activity in response to sleep-related sounds (vs neutral sounds) using region of interest (ROI) and whole-brain correlation analyses. The ROIs included the anterior cingulate cortex (ACC), anterior insula (AI), and amygdala.Results: The whole-brain analysis revealed increased activation in the temporal regions and decreased activation in the ACC in response to sleep-related sounds compared to neutral sounds. The ROI and whole-brain correlation analyses showed that higher DBAS scores, indicating a negative appraisal of sleep, were significantly correlated with increased activation of the ACC, right medial prefrontal cortex, and brainstem in response to sleep-related sounds.Conclusion: These results indicate that the temporal cortex and ACC, which are implicated in affective sound processing, may play important roles in the processing of sleep-related sounds. The positive association between the neural responses to sleep-related sounds and DBAS scores suggest that negative and dysfunctional appraisals of sleep may be an important factor in individual differences in the processing of sleep-related sounds.Keywords: anterior cingulate cortex, appraisal, functional magnetic resonance imaging, sleep-related sounds

Introduction Obstructive sleep apnea (OSA), which is associated with a high mortality, is a heterogeneous disease that is affected by various pathophysiology. Although the severity of OSA is divided based on apnea-hypopnea index (AHI), AHI alone did not sufficiently represent these pathologies. The objective of this study is to categorize OSA using PSG data and compare the characteristics of each group including mortality. Methods 7,247 subjects were recruited at the Center for Sleep and Chronobiology, Seoul National University Hospital from June 2004 to December 2021. Demographic data, polysomnography, Sleep scale including Epworth sleepiness scale, Pittsburgh sleep quality index, Beck depression inventory, and Beck anxiety inventory were performed. After categorizing OSA using K-mean cluster analysis, Kaplan-Meir survival analysis and Cox proportional hazard regression analysis were used to evaluate all-cause mortality and hazard ratios. Results Three clusters were identified; Cluster 1 was associated with moderate OSA (mean AHI=19.28/h), high sleep efficiency and low arousal, Cluster 2 with moderate OSA (mean AHI=24.81/h), low sleep efficiency and high arousal, Cluster 3 with the most severe OSA (mean AHI=64.76/h), obese, and decreased O2 saturation. Conventional classification of OSA showed no difference in mortality between group, whereas Cluster 1 and Cluster 3 showed significant higher all-cause mortality compared to not-OSA group (Cluster 1, Log rank p=0.008; Cluster 3 Log rank p< 0.001). The risk of mortality was also significantly increased in cluster 1 (HR 2.048, 95% CI 1.265-3.317, p=0.004) and cluster 3 (HR 3.686, 95% CI 1.871-7.262, p< 0.001). These results were also observed after adjustment for sex, age, BMI and comorbid disease (Cluster 1, HR 2.053, 95% CI 1.197-3.518, p=0.009; Cluster 4, HR 2.640, 95% CI 1.230-5.666, p=0.012). Conclusion Phenotyping of OSA considered multiple variables is more appropriate to predict mortality than conventional classification based on AHI. In addition to evaluate patient with severe OSA, patients with moderate OSA who shows relatively good sleep and low arousal should be cautiously evaluated and monitored. Support (if any) This study was supported by the Technology Innovation Infrastructure program through the Korea Institute for Advancement of Technology funded by the Ministry of Trade, Industry and Energy.(study no.: P0014279, 20009210, Dr. Yu Jin Lee)

Introduction Physiological hyperarousal is suggested as a core feature of insomnia and resting-state functional magnetic resonance imaging (rs-fMRI) studies have examined the neurobiological basis of the hyperarousal theory. However, few have investigated the associations between rs-fMRI and the biomarkers of physiological hyperarousal. We aimed to investigate (1) the differences in the resting-state functional connectivity (RSFC) between chronic insomnia disorder (CID) patients and good sleepers (GS), and (2) the relationships between altered RSFC and the hyperarousal biomarkers including electroencephalogram (EEG) and heart rate variability (HRV). Methods Fifty CID patients (37 females, 45.8±12.7 years old) and 52 GS (32 females, 37.0±13.2 years old) completed self-report questionnaires, and underwent nocturnal polysomnography and rs-fMRI. We analyzed RSFC in the amygdala (AMYG) and anterior insula (AI), which were core regions of the salience network probably associated with hyperarousal. We also analyzed EEG relative beta power at central derivations and frequency domain HRV parameters (e.g., low frequency and high frequency) in ECG lead ll during sleep. We then tested differences in the RSFC between CID and GS and examined the correlations between RSFC, EEG beta power, and HRV. Results Compared with GS, CID showed more negative RSFC between the right AMYG and left supramarginal gyrus (SMG), but less positive RSFC between the left AI and bilateral lateral prefrontal cortex (LPFC). The right AMYG-left SMG RSFC was positively correlated with EEG beta power in non-rapid eye movement (NREM) stage 3 sleep measured on central regions (C3: r=-0.336, p=0.012; C4: r=-0.314, p=0.024). We did not find any significant correlations between RSFC and HRV parameters. Conclusion Decreased RSFC between the AMYG and SMG in insomnia patients may reflect a difficulty in the cortical top-down regulation of the amygdala, indicating hyperarousal during daytime. We also found a significant correlation between the AMYG-SMG RSFC and EEG beta power. This result suggests that altered AMYG connectivity during daytime is associated with cortical hyperarousal during sleep. Overall, our study may provide neurobiological evidence for the 24-hour hyperarousal theory of insomnia. Support (if any) The Korea Institute for Advancement of Technology funded by the Ministry of Trade, Industry and Energy (study no.: P0014279, 20009210).

Maclurin [(3,4-dihydroxyphenyl)-(2,4,6-trihydroxyphenyl) methanone] is a natural compound that can be extracted from white mulberry(Morus alba) and purple mangosteen(Garcinia mangostana). Maclurin is known for its dual-sided effect on reactive oxygen species (ROS). Osteosarcoma is a primary malignant tumor of the bone and is one of the most aggressive cancers. It is common especially in children and young adults and can progress into highly metastatic cancer. In this study, we investigated the anti-cancer effects of maclurin on U2OS human osteosarcoma cells. The results indicated that maclurin exerts prooxidative effects and induces apoptosis via capase-3-independent PARP regulation in U2OS human osteosarcoma cells. Maclurin also inhibits the migration of U2OS human osteosarcoma cells. Maclurin modulates two of the three major mitogen-activated protein kinases that are closely linked with cancer metastasis; that is, it activates p38 and inactivates Extracellular signal-regulated kinase. The apoptosis-inducing effects of maclurin on U2OS osteosarcoma cells were diminished by additional treatment with antioxidant N-acetyl cysteine (NAC), but the migration-inhibiting effect was not affected by NAC treatment. This further suggested the only apoptosis-inducing effect of maclurin may be strongly related to its prooxidative activity. Taken together, these results suggested that maclurin may be a strong candidate molecule as an anti-osteosarcoma agent. This article is protected by copyright. All rights reserved.

STUDY OBJECTIVES: To assess the seasonality of restless legs syndrome (RLS) using data from the Korean national health insurance database. METHODS: We retrospectively reviewed a randomly selected sample representing 3% of the national health insurance claims database in South Korea. From this sample, we obtained the monthly numbers of patients with RLS and diagnoses from 2009 to 2016, along with prescriptions for monthly dopamine agonists and clonazepam for patients with RLS from 2009 to 2013. Total dopamine agonist and clonazepam doses were converted to levodopa-equivalent doses, and the monthly cumulative prescription dose was calculated. Cosinor analysis was used to evaluate the seasonal pattern of each variable. RESULTS: This study included 11,466 patients with RLS and their diagnoses and 4,887 prescriptions for dopamine agonists and clonazepam. There were significant seasonal patterns in the numbers of patients with RLS (P < .001) and diagnoses (P < .001), both of which peaked in August. The magnitude of the greatest difference in the number of patients with RLS between August (highest) and February (lowest) was 29.96% (95% confidence interval, 24.03–100.80), and that of the number of RLS diagnoses was 39.56% (95% confidence interval, 31.24–47.89). The cumulative prescription dose of medication showed no significant seasonality. CONCLUSIONS: Our findings suggest that the prevalence of RLS is seasonally affected, with an increase during summer. CITATION: Oh SM, Son K-L, Choi S-J, Lee MH, Yoon SY, Lee YJ. The seasonal pattern of restless legs syndrome in a sample from the Korean health insurance review and assessment service national database. J Clin Sleep Med. 2021;17(5):1051–1056.