Attitudes toward epilepsy and perceptions of epilepsy-related stigma in Korean evangelical Christians.

PURPOSE: The scriptural description of Jesus driving out an evil spirit from a boy with epilepsy supported the idea of the spiritual nature of epilepsy for centuries. Korea has a shorter history of Christianity than the Western world. We determined whether there are differences in attitudes toward epilepsy and perception of epilepsy-related stigma between people with and without belief in evangelical Christianity in Korea. METHODS: Data were collected from evangelical churches and theological colleges. People without religious beliefs were enrolled as a control group through convenience sampling. The Public Attitudes Toward Epilepsy (PATE) scale and the modified Stigma Scale for epilepsy were used. Familiarity with and knowledge of epilepsy were also assessed. Evangelical Christians were categorized as professional or nonprofessional depending on whether they had received professional education in Christian theology. RESULTS: A total of 227 evangelical Christians and 139 controls were included. The scores on the Stigma Scale and in the two PATE domains were significantly lower in the professional Christian group than in the controls or the nonprofessional group (p<0.05) but did not differ between the nonprofessional group and controls. After controlling for confounders, only the professional group was independently associated with lower scores on the Stigma Scale and in the PATE personal domain (p<0.05). The remaining associations lost their significance. CONCLUSIONS: We found no differences in attitudes toward epilepsy and perception of stigma between people with and without belief in evangelical Christianity in Korea.

Clinical features in patients with positional obstructive sleep apnea according to its subtypes.

PURPOSE: This study aimed to determine the prevalence of positional obstructive sleep apnea (OSA) and its subtypes in Korean adults with newly diagnosed OSA and document the clinical characteristics of positional OSA and its subtypes compared to non-positional OSA METHODS: In this cross-sectional study, we evaluated 1052 OSA adults. Positional OSA was defined as an overall apnea-hypopnea index (AHI) ≥5 and supine AHI to non-supine AHI ratio of ≥2. Positional OSA was subtyped depending on the degree of AHI while in the non-supine position: subtype I (a non-supine AHI <5/h), subtype II (a non-supine AHI ≥5/h and <15/h), and subtype III (a non-supine AHI ≥15/h). To compare clinical characteristics between patient groups depending on the positional tendency of OSA, statistical analyses were performed. RESULTS: The prevalence of positional OSA was 75.6 % with 39.9 % having AHI normalized <5/h while in non-supine position. Positional OSA patients had milder OSA, older age, and lower BMI than did non-positional OSA patients. However, having positional OSA did not influence daytime sleepiness, depressive symptoms, anxiety, and health-related quality of life. Unlike the subtype I and II positional OSAs, subtype III did not differ in clinical features from non-positional OSA. There were significant differences in supine sleep time depending on the positional tendency of OSA. Subtype III positional OSA had the shortest supine sleep time whereas subtype I positional OSA and non-positional OSA had the longest supine sleep time. CONCLUSIONS: Positional OSA subtypes have different clinical characteristics. Subtyping of positional OSA is helpful for developing specific treatment strategies according to positional tendency.

REM-related sleep-disordered breathing is associated with depressive symptoms in men but not in women.

PURPOSE: The purposes of the present study are to determine the prevalence and demographic features of rapid eye movement (REM)-related sleep-disordered breathing (SDB) in Korean adults with newly diagnosed obstructive sleep apnea (OSA) and determine if REM-related SDB is associated with depressive symptoms and health-related quality of life (HRQoL) in OSA patients. METHODS: In this cross-sectional study, we evaluated 1281 OSA adults who were consecutively recruited. REM-related SDB was defined as an overall apnea-hypopnea index (AHI) ≥5, an AHINREM <15, and AHIREM to AHINREM ratio of >2. The Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and Medical Outcomes Study Short-Form Health survey (SF-36) were used to evaluate all patients. Multiple regression analyses were performed to determine the associations between REM-related SDB and clinical outcomes. RESULTS: The prevalence of REM-related SDB was 18 % in this study. REM-related SDB was more commonly observed in patients with mild or moderate OSA (p < 0.001) and women (p < 0.001). The linear regression analysis showed that the presence of REM-related SDB was significantly associated with higher BDI scores, but only in men. AHIREM was positively associated with the BDI scores, but only in men with REM-related SDB. There were no differences in ESS and SF-36 scores between patients with and without REM-related SDB. CONCLUSIONS: Patients with REM-related SDB account for 18 % of Korean OSA adults. REM-related SDB was associated with depressive symptoms, but only in men. AHIREM is positively related to the degree of depressive symptoms in men with REM-related SDB.

Single-cell transcriptomics unveil profiles and interplay of immune subsets in rare autoimmune childhood Sjögren's disease.

Childhood Sjögren's disease represents critically unmet medical needs due to a complete lack of immunological and molecular characterizations. This study presents key immune cell subsets and their interactions in the periphery in childhood Sjögren's disease. Here we show that single-cell RNA sequencing identifies the subsets of IFN gene-enriched monocytes, CD4+ T effector memory, and XCL1+ NK cells as potential key players in childhood Sjögren's disease, and especially in those with recurrent parotitis, which is the chief symptom prompting clinical visits from young children. A unique cluster of monocytes with type I and II IFN-related genes is identified in childhood Sjögren's disease, compared to the age-matched control. In vitro regulatory T cell functional assay demonstrates intact functionality in childhood Sjögren's disease in contrast to reduced suppression in adult Sjögren's disease. Mapping this transcriptomic landscape and interplay of immune cell subsets will expedite the understanding of childhood Sjögren's disease pathogenesis and set the foundation for precision medicine.

Enhanced cognitive flexibility and phasic striatal dopamine dynamics in a mouse model of low striatal tonic dopamine.

The catecholamine neuromodulators dopamine and norepinephrine are implicated in motor function, motivation, and cognition. Although roles for striatal dopamine in these aspects of behavior are well established, the specific roles for cortical catecholamines in regulating striatal dopamine dynamics and behavior are less clear. We recently showed that elevating cortical dopamine but not norepinephrine suppresses hyperactivity in dopamine transporter knockout (DAT-KO) mice, which have elevated striatal dopamine levels. In contrast, norepinephrine transporter knockout (NET-KO) mice have a phenotype distinct from DAT-KO mice, as they show elevated extracellular cortical catecholamines but reduced baseline striatal dopamine levels. Here we evaluated the consequences of altered catecholamine levels in NET-KO mice on cognitive flexibility and striatal dopamine dynamics. In a probabilistic reversal learning task, NET-KO mice showed enhanced reversal learning, which was consistent with larger phasic dopamine transients (dLight) in the dorsomedial striatum (DMS) during reward delivery and reward omission, compared to WT controls. Selective depletion of dorsal medial prefrontal cortex (mPFC) norepinephrine in WT mice did not alter performance on the reversal learning task but reduced nestlet shredding. Surprisingly, NET-KO mice did not show altered breakpoints in a progressive ratio task, suggesting intact food motivation. Collectively, these studies show novel roles of cortical catecholamines in the regulation of tonic and phasic striatal dopamine dynamics and cognitive flexibility, updating our current views on dopamine regulation and informing future therapeutic strategies to counter multiple psychiatric disorders.

The inflammatory signature in monocytes of Sjögren's syndrome and systemic lupus erythematosus, revealed by the integrated Reactome and drug target analysis.

BACKGROUND: The innate immune regulation, especially by the type I IFN signature in the CD14+ monocytes, is known to be critical in the pathogenesis of autoimmune Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). OBJECTIVE: Since patients with one condition can be overlapped with another, this study is to identify shared differentially expressed genes (DEGs) in SjS and SLE compared to healthy controls (HCs) and refine transcriptomic profiles with the integrated Reactome and gene-drug network analysis for an anti-inflammation therapy. METHODS: CD14+ monocytes were purified from whole blood of SjS and SLE patients (females, ages from 32 to 62) and subject to bulk RNA-sequencing, followed by data analyses for comparison with HC monocytes (females, ages 30 and 33). Functional categorizations, using Gene Ontology (GO) and the Reactome pathway analysis, were performed and DEGs associated with therapeutic drugs were identified from the Drug Repurposing Hub (DHUB) database. RESULTS: The GO analysis revealed that DEGs in the inflammatory response and the cellular response to cytokine were highly enriched in both conditions. A propensity toward M1 macrophage differentiation appears to be prominent in SjS while the Response to Virus was significant in SLE monocytes. Through the Reactome pathway analysis, DEGs in the IFN signaling and the cytokine signaling in immune system were most significantly enriched in both. Upregulation of NGF-induced transcription activity in SjS and the complement cascade activity in SLE were also noted. Multiple anti-inflammatory drugs, such as prostaglandin-endoperoxide synthase and angiotensin-I-converting- enzyme were associated with the DEGs in these conditions. CONCLUSIONS: Taken together, our analysis indicates distinct inflammatory transcriptomic profiles shared in SjS and SLE monocytes. Comprehensive characterizations of the data from these conditions will ultimately allow differential diagnosis of each condition and identification of therapeutic targets.

Sleep hygiene and its association with daytime sleepiness, depressive symptoms, and quality of life in patients with mild obstructive sleep apnea.

PURPOSE: To investigate the direct and indirect associations of sleep hygiene with daytime sleepiness, depressive symptoms, and quality of life (QoL), in newly diagnosed, untreated patients with mild obstructive sleep apnea (OSA). METHODS: Data were collected from adults with mild OSA. The Sleep Hygiene Index (SHI), Sleep Problems Index-1 (SPI-1) of the Medical Outcomes Study-Sleep Scale, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and Medical Outcomes Study Short-Form Health survey (SF-36) were used to evaluate patients. To determine the indirect and direct associations between SHI and disease outcomes, the Sobel test and multiple linear regression analyses were used, respectively. When we evaluated the direct associations, we excluded 3 items of the original SHI which were more reflective of general health rather than sleep-specific habits and environments. RESULTS: In total, 260 patients with mild OSA participated in this study. The average age, AHI, and SHI scores were 49.1 years (SD 12.5), 9.3/h (SD 2.9), and 24.7 (SD 6.0), respectively. Here, ≥ 10% of participants indicated poor sleep hygiene behaviors on 7 of 13 items. Young age and men were associated with higher SHI scores (both p<0.01). The 13-item SHI scores were indirectly related to ESS, BDI, and SF-36 scores via SPI-1 (all p<0.05). The 10-item SHI scores were related to ESS (p=0.049) and SF-36 (p=0.001), but not to BDI, independently of SPI-1 or other confounding factors in mild OSA patients. Age, sex, AHI, and body mass index were not related to ESS, BDI, or total SF-36 scores. CONCLUSIONS: Sleep hygiene is indirectly related to daytime sleepiness, depressive symptoms, QoL via sleep quality and also related to daytime sleepiness and QoL independent of sleep quality in mild OSA patients.

The utility of a Korean version of the REM sleep behavior disorder screening questionnaire in patients with obstructive sleep apnea.

PURPOSE: To explore the utility of a Korean version of the rapid eye movement sleep behavior disorder screening questionnaire (RBDSQ-K) to discriminate patients with idiopathic REM sleep behavior disorder (iRBD) from patients with obstructive sleep apnea (OSA) and healthy subjects. METHODS: Participants with iRBD (n=47) and OSA (n=213) were diagnosed by polysomnography. In healthy subjects (n=58), RBD was excluded by medical history without polysomnography. Receiver operating characteristic curve analysis was used to identify the optimal cutoff value of the RBDSQ-K for iRBD. RESULTS: RBDSQ-K score was higher in iRBD subjects than in OSA subjects and healthy subjects (both p<0.001). The optimal cutoff was 6.5 to distinguish iRBD subjects from OSA subjects and 4.5 to distinguish iRBD subjects from healthy subjects. The corresponding sensitivity and specificity was high for detecting iRBD from OSA and healthy subjects. The percentages of individuals with RBDSQ-K scores ≥5 and ≥7 were higher in OSA subjects with daytime sleepiness (36.1% and 13.8%, respectively) than in OSA subjects without daytime sleepiness (12.0% and 3.1%, respectively). Apnea-hypopnea index had no influence on RBDSQ-K score. Cronbach's alpha for the RBDSQ-K was 0.768, indicating a high degree of internal consistency. CONCLUSIONS: The RBDSQ-K had acceptable sensitivity and specificity for screening persons with probable RBD from healthy subjects and OSA subjects when the cutoff score was 4.5 and 6.5 points, respectively. However, attention must be paid to the possibility of false positives when using this scale, especially in OSA subjects with daytime sleepiness.