Imidazole propionate ameliorates atopic dermatitis-like skin lesions by inhibiting mitochondrial ROS and mTORC2.

Background: Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal inflammation and the development and progression of cardiovascular disease and diabetes. However, the anti-inflammatory activity of IMP has not been investigated. This study aimed to elucidate the role of IMP in treating atopic dermatitis (AD). Methods: To understand how IMP mediates immunosuppression in AD, IMP was intraperitoneally injected into a Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions mouse model. We also characterized the anti-inflammatory mechanism of IMP by inducing an AD response in keratinocytes through TNF-α/IFN-γ or IL-4 stimulation. Results: Contrary to the prevailing view that IMP is an unhealthy microbial metabolite, we found that IMP-treated AD-like skin lesions mice showed significant improvement in their clinical symptoms, including ear thickness, epidermal and dermal thickness, and IgE levels. Furthermore, IMP antagonized the expansion of myeloid (neutrophils, macrophages, eosinophils, and mast cells) and Th cells (Th1, Th2, and Th17) in mouse skin and prevented mitochondrial reactive oxygen species production by inhibiting mitochondrial energy production. Interestingly, we found that IMP inhibited AD by reducing glucose uptake in cells to suppress proinflammatory cytokines and chemokines in an AD-like in vitro model, sequentially downregulating the PI3K and mTORC2 signaling pathways centered on Akt, and upregulating DDIT4 and AMPK. Discussion: Our results suggest that IMP exerts anti-inflammatory effects through the metabolic reprogramming of skin inflammation, making it a promising therapeutic candidate for AD and related skin diseases.

Restless legs syndrome in patients with obstructive sleep apnea: Association between apnea severity and symptoms of depression, insomnia, and daytime sleepiness.

OBJECTIVE: To determine if the prevalence and severity of restless legs syndrome (RLS) varies with apnea severity and analyze differences between the sexes in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness in patients with obstructive sleep apnea (OSA). METHODS: Symptoms of depression, insomnia, and daytime sleepiness were defined as Patient Health Questionnaire-9 score ≥10, Insomnia Severity Index score ≥15, and Epworth Sleepiness Scale score ≥11. Multivariate logistic and linear regression analyses were conducted. RESULTS: In 707 adults with OSA (85.1% males), 16.1% (n = 114) had comorbid RLS. The prevalence of RLS was markedly lower in those with moderate and severe OSA than in those with mild OSA. Similarly, the odds of RLS significantly decreased with increasing apnea-hypopnea index. After controlling for age and sex, in patients with comorbid RLS, the International RLS Study Group Rating Scale scores were negatively correlated with apnea-hypopnea index and a nadir peripheral oxygen saturation during sleep. The presence of RLS was more likely to be associated with symptoms of depression, insomnia, and daytime sleepiness after controlling for confounding variables, but only in men. CONCLUSIONS: RLS is frequently noted in combination with OSA, with a female preponderance. The severities of OSA and RLS may be negatively associated. In patients with OSA, sex-related differences in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness warrant further investigations.

Attention-deficit hyperactivity disorder in adults with epilepsy: An indirect relationship with suicide risk.

PURPOSE: Studies on attention-deficit hyperactivity disorder (ADHD) are scarce in adults with epilepsy. This study aimed to investigate the risk factors for ADHD and determine whether ADHD is directly associated with the risk of suicide in adults with epilepsy. METHODS: ADHD was assessed using the Structured Clinical Interview for the DSM-5 Disorders Clinical Version. The Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0, Neurological Disorders Depression Inventory for Epilepsy (NDDIE), and Generalized Anxiety Disorder-7 (GAD-7) were also used. Suicide risk was defined as a MINI suicidality score of ≥ 1. Stepwise logistic regression and mediation analyses were conducted. RESULTS: Of the 157 adults with epilepsy, 19 (12.1 %) were diagnosed with ADHD, including inattentive (5.7 %), hyperactive (3.8 %), and combined (2.5 %) types. Thirty-two subjects (20.4 %) had a risk of suicide. ADHD was insignificantly associated with any epilepsy-related factors. The diagnosis of ADHD was not associated with suicide risk independent of NDDIE ≥ 14 and GAD-7 ≥ 7. Mediation effects of ADHD on suicidality using NDDIE ≥ 14 (odds ratio [OR] 2.850, 95 % confidence interval [CI] 1.398-5.811, p = 0.004) or GAD-7 ≥ 7 (OR 3.240, 95 % CI 1.537-6.828, p = 0.002) were statistically significant, with the proportion mediated being 84.5 % or 92.0 % of the total ADHD effect, respectively. These models were adjusted for age, sex, and composite epilepsy severity scores. CONCLUSIONS: ADHD was diagnosed in 12.1% of adults with epilepsy and was not associated with any epilepsy-related factors. ADHD was indirectly associated with the risk of suicide resulting from depression and anxiety in adults with epilepsy.

Extracts of Grifola frondosa inhibit the MAPK signaling pathways involved in keratinocyte inflammation and ameliorate atopic dermatitis.

BACKGROUND/OBJECTIVES: Grifola frondosa, commonly referred to as the maitake mushroom, has been studied extensively to explore its potential health benefits. However, its anti-inflammatory effects in skin disorders have not been sufficiently elucidated. This study aimed to elucidate the anti-inflammatory role of the ethanol extract of G. frondosa in atopic dermatitis (AD) using in vivo and in vitro models. MATERIALS/METHODS: We investigated its impact on skin and spleen inflammatory responses in Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in a mouse model. Additionally, we determined the immunosuppressive response and mechanism of G. frondosa by inducing atopic-like immune reactions in keratinocytes through tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation. RESULTS: Our study revealed that G. frondosa ameliorates clinical symptoms in an AD-like mouse model. These effects contributed to the suppression of Th1, Th2, Th17, and Th22 immune responses in the skin and spleen, leading to protection against cutaneous inflammation. Furthermore, G. frondosa inhibited the production of antibodies immunoglobulin (Ig)E and IgG2a in the serum of AD mice. Importantly, the inhibitory effect of G. frondosa on inflammatory cytokines in TNF-α/IFN-γ-stimulated AD-like keratinocytes was associated with the suppression of MAPK (Mitogen Activated Protein Kinase) pathway activation. CONCLUSIONS: Collectively, these findings highlight the potential of G. frondosa as a novel therapeutic agent for AD treatment and prevention.

Perception of precocious puberty among school-aged children in South Korea with the experience of treatment for precocious puberty: a Q methodological approach.

PURPOSE: This study aimed to investigate the perceptions of precocious puberty and elucidate the distinct characteristics of each type of perception related to precocious puberty among school-aged children who had undergone treatment for the condition. METHODS: This study applied the Q methodology to identify and classify the perceptions of precocious puberty among school-aged children who had undergone treatment for the condition. The analysis involved 34 questions from the Q sample and data from 35 individuals in the P sample, using the PC-QUANL Program for analysis. RESULTS: The perceptions of precocious puberty among school-aged children who had undergone precocious puberty treatment were classified into the following four types: "shyness - passive self-management," "resentment - suppression," "anxiety - fear," and "adaptation - acceptance." CONCLUSION: This study investigated the experiences and perceptions of children who have undergone treatment for precocious puberty. Through the identification of four types of perceptions, we can see that there is a need to develop an intervention program for nursing that is tailored to the specific type of precocious puberty.

Sex differences in the relationship between aggression and symptoms of depression and anxiety in adults with refractory focal epilepsy.

PURPOSE: To determine whether sex affects the relationship between aggression and symptoms of depression and anxiety in adults with refractory focal epilepsy. METHODS: This cross-sectional study was conducted in 85 adults with refractory focal seizures, which are defined as one or more seizures recurring per month even when the patient is treated with two or more antiseizure medications. We used the Buss-Perry Aggression Questionnaire (AQ) and the Hospital Anxiety and Depression Scale (HADS) to evaluate aggression and symptoms of depression and anxiety, respectively. We performed multivariate linear regression and analysis of covariance with interaction terms. HADS-depression and HADS-anxiety scores were separately evaluated to avoid multicollinearity between both of them. RESULTS: The HADS-depression and HADS-anxiety scores, male sex, an antiseizure medication load of ≥3, and the use of pregabalin were independently correlated with at least one of the AQ total and subscale scores. These models for depressive and anxiety symptoms explained 34.2% and 32.5%, respectively, of the variance of the AQ total score. Although the AQ total scores did not differ between the sexes, sex significantly affected the relationships between aggression and symptoms of depression and anxiety. Specifically, HADS-depression and HADS-anxiety scores were positively associated with the AQ total scores, especially scores of verbal aggression and anger subtypes, in men but not in women. CONCLUSIONS: These findings support the importance of including anger management and other strategies targeted toward aggression in the development of psychological interventions to reduce anxiety and depression in adults with refractory focal epilepsy. Tailoring those interventions to the needs of males and females will be important to consider. .

Comparisons of impulsivity among patients with different subtypes of epilepsy.

PURPOSE: This study assessed whether patients with epilepsy have a higher level of impulsivity than healthy controls, and compared impulsivity among patients with different subtypes of epilepsy. METHODS: The multicenter study included 108 subjects with epilepsy and 56 healthy volunteers. Subjects were evaluated by the Barratt Impulsiveness Scale-11 (BIS-11) and Patient Health Questionnaire-9, with BIS-11 scores analyzed as both dichotomized and continuous variables. High impulsivity was defined as a total BIS-11 score ≥ 67. RESULTS: Of the 108 subjects with epilepsy, 36 had idiopathic generalized epilepsy (IGE), 47 had temporal lobe epilepsy (TLE), and 25 had frontal lobe epilepsy (FLE). A significantly higher percentage of subjects with epilepsy (22.2%) than controls (1.8%) had BIS-11 scores ≥ 67 (p = 0.001), although mean BIS-11 scores were similar in subjects with epilepsy (59.5 ± 10.0) and controls (58.8 ± 4.6). Higher percentages of subjects with IGE and FLE had BIS-11 scores ≥ 67 than subjects with TLE and controls. Mean total BIS-11 scores did not differ between controls and subjects with IGE and FLE, but were lower in subjects with TLE than in controls. Differences in impulsivity among controls and subjects with epilepsy subtypes varied depending on BIS-11 subscale. CONCLUSIONS: Patients with epilepsy, particularly IGE and FLE, were more likely to have high impulsivity scores, defined by a certain cutoff on the BIS-11, than controls and subjects with TLE. However, mean impulsivity scores did not differ among controls and subjects with IGE and FLE. Dichotomizing BIS-11 scores may be necessary to avoid false negative results in subjects with epilepsy.

Dual burdens of felt stigma and depressive symptoms in patients with epilepsy: Their association with social anxiety, marriage, and employment.

PURPOSE: The present study evaluated whether patients with epilepsy with dual conditions of felt stigma and depressive symptoms are more strongly associated with social anxiety, being unmarried, and being unemployed than those with depressive symptoms or felt stigma alone. METHODS: This multicenter, cross-sectional study evaluated subjects using the Stigma Scale-Revised, the Patient Health Questionnaire-9, and the six-item versions of the Social Interaction Anxiety Scale, and the companion Social Phobia Scale. Subjects were grouped by depressive symptoms and felt stigma into four groups. Multivariate logistic regression analyses were performed. RESULTS: The 298 subjects included 173 men and 125 women. Of these subjects, 35 (11.7%) had depressive symptoms alone, 33 (11.1%) had stigma alone, and 27 (9.1%) had both depressive symptoms and felt stigma. Multivariate logistic regression analyses showed that, compared with the control group having neither depressive symptoms nor felt stigma, the odds ratios (ORs) for social interaction anxiety and social phobia were highest in the group of dual conditions (OR 18.7 and 13.5, respectively), followed by the depression-alone (OR 7.7 and 4.6, respectively) and stigma-alone (OR 5.0 and 2.8, respectively) groups. Similarly, the ORs for being unmarried (OR 29.2) and unemployed (OR 3.1) were significant only in the group of dual conditions. In addition, male sex and younger age were independently associated with being unmarried whereas seizures recurring ≥1 per month were independently associated with being unemployed. CONCLUSIONS: Dual conditions of felt stigma and depressive symptoms may be more strongly associated with social anxiety, being unmarried, and being unemployed than depressive symptoms or felt stigma alone in patients with epilepsy.

Felt stigma may potentiate the relationship between perceived stress and depressive symptoms in persons with epilepsy.

PURPOSE: This study assessed the strengths of association among perceived stress, felt stigma, and depression in adults with epilepsy, and evaluated whether felt stigma altered the association between perceived stress and depression. METHODS: This multicenter, cross-sectional study included adults with epilepsy. Depression was assessed using the Beck Depression Inventory (BDI), and perceived stress was evaluated using the 10-item Perceived Stress Scale. Felt stigma was determined using the three-item Stigma Scale for Epilepsy, with individuals categorized as positive for felt stigma if they answered "yes" to at least one of these items. A hierarchical linear regression analysis and an analysis of covariance with interaction terms were performed. RESULTS: The 316 adults with epilepsy included 171 men and 145 women; of these, 109 (34.5%) reported felt stigma. A hierarchical linear regression analysis showed that perceived stress was the most important correlate of depressive symptoms, followed by felt stigma, being unemployed, recurrence of generalized or focal to bilateral tonic-clonic seizures, and being married. The model explained 54.0% of the variance of BDI scores. Significant interactions between felt stigma and perceived stress on BDI scores was identified in both crude and adjusted models (p < 0.05 each). Specifically, in an adjusted model, BDI scores were more strongly associated with perceived stress in persons with (p < 0.001, partial eta2 = 0.225) than without (p < 0.001, partial eta2 = 0.205) felt stigma. CONCLUSIONS: Perceived stress was the most significant correlate of depressive symptoms in adults with epilepsy, followed by felt stigma. The interaction between perceived stress and felt stigma on depressive symptoms was significant. These findings may help in developing cognitive behavioral therapy for stigma and stress management in persons with epilepsy.

Endogenous pannexin1 channels form functional intercellular cell-cell channels with characteristic voltage-dependent properties.

The occurrence of intercellular channels formed by pannexin1 has been challenged for more than a decade. Here, we provide an electrophysiological characterization of exogenous human pannexin1 (hPanx1) cell­cell channels expressed in HeLa cells knocked out for connexin45. The observed hPanx1 cell­cell channels show two phenotypes: O-state and S-state. The former displayed low transjunctional voltage (Vj) sensitivity and single-channel conductance of ∼175 pS, with a substate of ∼35 pS; the latter showed a peculiar dynamic asymmetry in Vj dependence and single-channel conductance identical to the substate conductance of the O-state. S-state hPanx1 cell­cell channels were also identified between TC620 cells, a human oligodendroglioma cell line that endogenously expresses hPanx1. In these cells, dye and electrical coupling increased with temperature and were strongly reduced after hPanx1 expression was knocked down by small interfering RNA or inhibited with Panx1 mimetic inhibitory peptide. Moreover, cell­cell coupling was augmented when hPanx1 levels were increased with a doxycycline-inducible expression system. Application of octanol, a connexin gap junction (GJ) channel inhibitor, was not sufficient to block electrical coupling between HeLa KO Cx45-hPanx1 or TC620 cell pairs. In silico studies suggest that several arginine residues inside the channel pore may be neutralized by hydrophobic interactions, allowing the passage of DAPI, consistent with dye coupling observed between TC620 cells. These findings demonstrate that endogenously expressed hPanx1 forms intercellular cell­cell channels and their unique properties resemble those described in innexin-based GJ channels. Since Panx1 is ubiquitously expressed, finding conditions to recognize Panx1 cell­cell channels in different cell types might require special attention.

Concealment behaviors in Korean adults with epilepsy: Their relationships to social anxiety and seizure severity independent of felt stigma.

PURPOSE: This study assessed whether seizure severity and social anxiety were related to self-disclosure or concealment behaviors independent of felt stigma in Korean adults with epilepsy. METHODS: This multicenter, cross-sectional study used the Disclosure Management Scale (DMS), the short forms of the Social Phobia Scale (SPS-6) and Social Interaction Anxiety Scale (SIAS-6), and the Stigma Scale-Revised to evaluate Korean adults with epilepsy. Seizure severity was measured as a composite variable, and multivariate linear regression analyses were performed to assess whether seizure severity and social anxiety were related to concealment behaviors. RESULTS: The 315 subjects included 132 (41.9%) women and 183 (58.1%) men. Of these subjects, 212 (67.3%) reported rarely or never talking to others about their epilepsy, whereas only 98 (31.1%) stated that they rarely or never kept their epilepsy secret from others. Linear regression analyses showed that concealment behaviors were positively correlated with degree of social anxiety (on separate models using the SIAS-6 and SPS-6) and felt stigma, and negatively associated with level of seizure severity. Both models accounted for about 14% of the variance in DMS scores. CONCLUSIONS: The majority of Korean adults with epilepsy choose concealment and selective disclosure strategies. Social anxiety and seizure severity along with felt stigma play significant roles in deciding whether to disclose or conceal a diagnosis of epilepsy. The explanatory power of these models was weak.

Aggression is more strongly associated with suicidality, independent of depression, than emotional instability and impulsivity in people with epilepsy.

PURPOSE: We evaluated the relative contributions of emotional instability, impulsivity, and aggression to the presence of suicide risk in people with epilepsy after adjusting for depressive symptoms. METHODS: This was a cross-sectional study that used the short form of the Affective Lability Scale (ALS-18), the Barratt Impulsiveness Scale Version 11 (BIS-11), the Brief Aggression Questionnaire (BAQ), and the Patient Health Questionnaire-9 (PHQ-9). Suicidality was assessed using the Mini International Neuropsychiatric Interview (MINI), and the presence of suicide risk was defined as a MINI suicidality score ≥1. Stepwise logistic regression and mediation analyses using a two-stage regression method were performed. RESULTS: Of the 171 subjects (63.2% men) included, suicide risk was present in 38 subjects (22.2%). The stepwise logistic regression analysis identified four variables that were independently associated with suicide risk: higher PHQ-9 score, higher BAQ score, longer duration of epilepsy, and unemployment. The univariate analysis showed that ALS-18 and BIS-11 scores were significantly associated with suicide risk; however, they were backward eliminated from the logistic model according to the criterion of p > 0.1. The mediating effects of ALS-18 and BIS-11 scores on suicide risk via PHQ-9 scores (but not BAQ scores) were significant, with the proportion mediated 61.5% and 54.0% of the total effect, respectively. CONCLUSIONS: Alongside depressive symptoms, aggression may be a more useful concept than emotional instability and impulsivity for identifying suicidal risk in people with epilepsy.

7-desacetoxy-6,7-dehydrogedunin discovered by high-throughput screening system suppresses melanogenesis through ATP-P2X7 signaling inhibition.

BACKGROUND: Hyperpigmented skin disorders such as melasma and lentigo are common photoaging diseases that cause cosmetic problems. The pigmentation is usually exacerbated by ultraviolet (UV) radiation, and various factors and pathways are involved in UV-mediated melanogenesis. Adenosine 5'-triphosphate (ATP), a well-known molecular unit of intracellular energy, is also regarded as a mediator of UV-mediated melanogenesis via the P2X7 purinergic receptor. OBJECTIVE: To discover natural substances with an anti-melanogenic effect through inhibition of ATP-P2X7 axis by high-throughput screening (HTS). METHODS: Among natural compounds provided by the Korea Chemical Bank, chemical compounds with a P2X7 inhibiting effect were screened through an HTS system. Then the selected compounds were verified for their anti-melanogenic effect after treating primary human epidermal melanocytes (PHEMs) with and without ATP. The expression of MITF, tyrosinase, and PMEL/gp100 was analyzed by Western blot, and melanin content was measured as 405 nm absorbance. RESULTS: Among 962 natural compounds, 58 showed greater than 80% suppression of YO-PRO-1 fluorescence, representing P2X7 activity. Among them, considering cell viability, chemical stability, and availability, 7-desaxacetoxy-6,7-dehydrogedunin (7DG), a limonoid natural compound, was selected. The expression of MITF, tyrosinase, and PMEL/gp100; tyrosinase enzyme activity; and melanin content, which were increased by ATP treatment were abrogated by 7DG. Even when 7DG was treated in PHEMs without addition of ATP, tyrosinase expression and melanin content were significantly decreased. Hypopigmenting effect of 7DG was confirmed in ex vivo culture of human skins. CONCLUSIONS: 7DG has an anti-melanogenic effect through ATP-P2X7 pathway inhibition and could be a potential skin whitening material.

Immunomodulatory and anti-inflammatory efficacy of hederagenin-coated maghemite (γ-Fe2O3) nanoparticles in an atopic dermatitis model.

We investigated the immunomodulatory and anti-inflammatory efficacy of hederagenin coating on maghemite (γ-Fe2O3) nanoparticles (HM) in atopic dermatitis (AD), as well as the physical and optical properties of maghemite nanoparticles (MP) using SEM, XRD spectroscopy, UV-vis spectra, Raman spectra, and FTIR spectroscopy. Dose-dependent treatment with HM (10, 50, 100, 200 µg/mL) inhibited the expression of Interleukin-2 (IL-2) and Tumor necrosis factor- α (TNF-α) in inflammatory induced HaCaT and Jurkat cells with inflammation caused by TNF/IFN-γ and PMA/A23187. AD model was induced by performing topical application of 2,4-dinitrochlorobenzene (DNCB) and dermatophagoides farinae extract (DFE) for a 31-day period on 8-week-old BALB/c mice. The HM treatments efficiently diminished the AD-like cutaneous lesion induced by DNCB-DFE sensitization in mice. Compared to the AD-only groups, HM treatment considerably attenuated mast cell infiltration and lowered epidermal, and dermal thickness of mice ears skin. In addition, HM treatment prominently alleviated the enlarged size and weight of lymph nodes. Furthermore, HM treatment resulted in a notable reduction in the mRNA expression of Th1 cytokines (TNF-α and IFN-γ), Th2 cytokines (IL-4 and IL-6), Th17 (IL-17), and TSLP. Our data showed that HM provides better AD attenuation compared to MP. Additionally, HM had synergistic effect and act as anti-inflammatory and immunomodulatory agent. Thus, HM shows great potential in AD medication and as a substitution of non-steroid-based medication.

Impulsivity in persons with epilepsy: Association with seizure severity and suicide risk.

PURPOSE: Clinical research regarding impulsivity in patients with epilepsy is limited. The present study investigated the associations between impulsivity and seizure-related factors or suicidality in patients with epilepsy, independent of depression and anxiety. METHODS: The multicenter study included 146 subjects (63% men). We utilized the Barratt Impulsiveness Scale-11 (BIS-11), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and suicidality module of the Mini International Neuropsychiatric Interview (MINI). Stepwise regression analyses and an analysis of covariance with interaction terms were performed. RESULTS: The mean BIS-11 score was 59.3 (SD = 10.7). Psychiatric pathologies, including suicidality, were reported in relatively large proportions of patients, including PHQ-9 score ≥ 10 in 29 (19.9%) patients, GAD-7 score ≥ 7 in 35 (24.0%) patients, and MINI suicidality score ≥ 6 in 15 (10.3%) patients. Stepwise linear regression revealed that BIS-11 score was positively associated with the PHQ-9 scores (p < 0.001), antiseizure medication polytherapy (p < 0.001), use of lamotrigine (p = 0.009), and recurrence of generalized or focal to bilateral tonic clonic seizures (p = 0.010). The coefficient of determination for the model was 0.397. Generalized or focal to bilateral tonic clonic seizure recurrence tended to be positively associated with total BIS-11 scores in men but not in women. In subscale analyses, somewhat different variables were associated with different BIS-11subscales. A trend for a positive association between BIS-11 score and suicidality was found (p = 0.066). CONCLUSIONS: This study identified a positive association between clinical seizure severity and impulsivity, and found that this association tended to be sex-specific, occurring only in males. Impulsivity could potentially be weakly associated with suicidality in patients with epilepsy.

Insomnia moderates the association between recurrent seizures and emotional instability in persons with epilepsy.

PURPOSE: We investigated the moderating effect of sleep disturbance on the association between seizure recurrence and emotional instability in patients with epilepsy, independent of psychological distress. METHODS: This was a cross-sectional study. Patients completed the short form of the Affective Lability Scale (ALS-18), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7). A stepwise linear regression analysis and an analysis of covariance with an interaction term were performed. RESULTS: A total of 171 subjects (63.2% men) were included. The mean ALS-18 score was 15.6 ±â€¯11.3. An ISI ≥ 15, PHQ-9 ≥ 10, and GAD-7 ≥ 7 were noted in 20.5%, 18.1%, and 23.4% of subjects, respectively. A stepwise linear regression analysis found that recurrent seizures in the last year, an ISI ≥ 15, a GAD-7 ≥ 7, and use of levetiracetam were significant and independent factors that were positively associated with higher ALS-18 scores. The coefficient of determination for the model was 0.331. The interaction between recurrent seizures and an ISI ≥ 15 had a significant effect on the ALS-18 scores (F = 6.812, p = 0.010, partial eta2 = 0.040). An ISI ≥ 15 was associated with ALS-18 scores in patients without seizure recurrence (p < 0.001). This association almost reached significance (p = 0.084) in those with recurrent seizures. In contrast, the presence of recurrent seizures was associated with ALS-18 scores in patients with an ISI < 15 (p < 0.001), but not in those with an ISI ≥ 15 (p = 0.360). CONCLUSIONS: The significant interaction between insomnia and seizure status may have an effect on emotional instability. These findings have clinical implications in the development of potential interventions for emotional instability in patients with epilepsy.

Disaster Healthcare Workers' Experience of Using the Psychological First Aid Mobile App During Disaster Simulation Training.

OBJECTIVE: The study aimed to examine the experience of disaster healthcare workers with simulation training using the Psychological First Aid (PFA) mobile app. METHODS: This study was designed using qualitative research methodology with focus group interviews. The participants were 19 disaster healthcare workers from community mental health service centers who attended disaster simulation training in flood, fire, or leakage of hazardous chemicals. Before the simulation, participants were provided the PFA mobile app and allowed to practice the PFA techniques to apply them during the simulation. Data were collected through focus group interviews and qualitatively analyzed using the content analysis method. RESULTS: The findings were divided into 6 categories: experience in realistic disaster situations, satisfaction with education methods using a mobile app, effectiveness of the PFA app in disaster relief, confidence in disaster relief by integrating experience and knowledge of the PFA app, self-reflection as a disaster healthcare worker, and identifying limitations and making developmental suggestions. CONCLUSIONS: Based on the participants' developmental proposals in this study, the disaster simulation training, incorporating improvements in the disaster simulation training and the PFA app features, will serve as a new framework for disaster support education and systematic mental health services to survivors by disaster healthcare workers.

Phospholipase D2 is a positive regulator of sirtuin 1 and modulates p53-mediated apoptosis via sirtuin 1.

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent histone deacetylase that plays diverse physiological roles. However, little is known about the regulation of SIRT1 activity. Here, we show that phospholipase D2 (PLD2), but not PLD1, selectively interacts with SIRT1 and increases the deacetylase activity of SIRT1. PLD2 does not interact with the other isozymes of SIRT (SIRT2-7). Two leucine residues in the LXXLL motif (L173 and L174) in the phox domain of PLD2 interact with the region essential for SIRT1 activity. PLD2 stimulates the SIRT1-mediated deacetylation of p53 independent of its lipase activity. In our study, mutagenesis of the LXXLL motif suppressed the interaction of PLD2 with SIRT1 and inhibited SIRT1-mediated p53 deacetylation and p53-induced transactivation of proapoptotic genes. Ultimately, overexpression of wild-type PLD2 but not that of LXXLL-mutant PLD2 protected cells against etoposide-induced apoptosis. Moreover, PLD2 did not protect against apoptosis induced by SIRT1 depletion under genotoxic stress. Collectively, our results suggest that PLD2 is a positive regulator of SIRT1 and modulates p53-mediated apoptosis via SIRT1.

The Korean version of the Virtual Patient Learning System Evaluation Tool: Assessment of reliability and validity.

BACKGROUND: Due to the recent spread of coronavirus disease 2019, Korean nursing colleges are increasingly using virtual patient simulation to make up for a lack of available clinical practice in medical institutions. Therefore, an instrument is required to evaluate the effects of the virtual patient learning system in South Korea. OBJECTIVE: To assess the validity and reliability of the Korean version of the Virtual Patient Learning System Evaluation Tool (K-VPLSET). DESIGN: This is a methodological study. SETTINGS: This study was conducted via an online survey for Korean nursing students. PARTICIPANTS: The present study included 373 participants who were 3rd and 4th year Korean nursing students. METHODS: After translating the English version of VPLSET into Korean, a pilot test with a cognitive interview was undertaken to ensure that the meaning of original instrument and appropriateness for Korean nursing students had been retained. The content validity of the K-VPLSET was examined by a panel of six experts. Convenience sampling was used to recruit 3rd and 4th year Korean nursing students, among whom 170 were recruited for exploratory factor analysis (EFA) and 203 for confirmatory factor analysis (CFA). SPSS version 26.0 was used for EFA, whereas AMOS version 22.0 was used for CFA. RESULTS: From the 32 initial items, the final version of the K-VPLSET ultimately included 20 items, with a Cronbach's α of 0.89. EFA identified four factors ("Nursing Knowledge Improvement," "Clinical Competency Development," "Confidence in Nursing Performance," and "Nursing Care Plan Application") that explained 56.9% of the total variance. CFA confirmed the validity of the instrument. CONCLUSIONS: Our findings confirmed that the K-VPLSET is a valid and reliable instrument for assessing the effects of the virtual patient learning system, through which the quality of e-learning for Korea nursing students can be determined.

Factors associated with alexithymia in adults with epilepsy.

PURPOSE: The relationship between epilepsy and alexithymia, characterized by the inability to feel or express emotion, remains incompletely understood. We investigated alexithymia and its association with epilepsy-related factors in patients with epilepsy (PWE). METHODS: In this cross-sectional study, PWE and healthy control subjects were recruited. Alexithymia was assessed using the Toronto Alexithymia Scale-20 (TAS-20). The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) were also administered to assess depression and anxiety, respectively. Mediation analysis was conducted using a two-stage regression method. RESULTS: Ninety adult PWE and 161 healthy control subjects were included in the study. PWE had significantly higher TAS-20 scores (B = 2.445, p = 0.014) than controls, but the prevalence of alexithymia, defined as TAS-20≥61, did not differ between PWE and control subjects after controlling for confounders (15.6% vs. 6.2%, respectively; p = 0.873). Uncontrolled seizures significantly increased alexithymia through depression (B = 3.536, p = 0.006), and this effect was responsible for 61.2% of the total effect on alexithymia. The direct effects of uncontrolled seizures on alexithymia were not significant. In contrast, AED polytherapy had significant direct effects on alexithymia (B = 4.489, p = 0.037) independent of depression. The indirect effects of AED polytherapy via depression did not reach statistical significance (B = 2.371, p = 0.066). CONCLUSIONS: Alexithymia was more severe, but not more prevalent, in PWE than in healthy controls. AED polytherapy was directly associated with alexithymia, while uncontrolled seizures were indirectly related to alexithymia through depressive symptoms.