Preventive effect of aripiprazole once-monthly on relapse into mood episodes in bipolar disorder: A multicenter, one-year, retrospective, mirror image study.

BACKGROUND: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment. METHODS: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. RESULTS: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM. LIMITATIONS: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. CONCLUSION: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Effect of sputtering power on the physical properties of amorphous SiO2-doped InZnO transparent conductive oxide.

In order to control the optical and electrical properties of the transparent conductive oxide, the radio frequency (RF) sputtering power was changed from 30 to 40, 50, and 60 W. To optimize the power condition of the SiInZnO (SIZO) layer, we changed the sputtering power from 30 to 60 W, systematically. The chemical properties of the SIZO layer were analyzed using X-ray photoelectron spectroscopy (XPS). XPS proved that this change is dominant in thickness. In order to fabricate the SIZO transparent conducting oxide (TCO) with the optimized power of 50 W, the transmittance of 99.1% at 550 nm and the figure of merit of 12.4×10-3 Ω -1 were obtained.

Risk Factors and Trends in Adolescent's Suicide Attempt Rates Before and After the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Understanding adolescents' mental health during the coronavirus disease 2019 (COVID-19) pandemic and identifying those most at risk is an urgent public health challenge. This study explored the trend of suicide attempts and the association between loneliness, family financial stress, and suicide attempts during the COVID-19 pandemic among adolescents. METHODS: Data of the 2020 to 2022 Korea Youth Risk Behavior Surveys for adolescents aged 13-18 years were used. Multivariate logistic regression analyses were performed to examine the association between suicide attempts, family financial stress, and loneliness during the COVID-19 pandemic. RESULTS: The trend of suicide attempt rates was lowest in 2020 (1.9%, 1,034 out of 53,534) and it showed an increasing trend with rates of 2.2% (1,159 out of 53,445) in 2021 and 2.5% (1,271 out of 50,455) in 2022. The risk of suicide attempt was higher among adolescents who experienced financial stress (in 2020: adjusted odds ratio [AOR], 1.53, 95% confidence interval [CI], 1.26-1.88; in 2021: AOR, 1.63, 95% CI, 1.03-1.54) and felt lonely (in 2020: AOR, 2.19, 95% CI, 1.78-2.70; in 2021: AOR, 2.65, 95% CI, 2.16-3.26; in 2022: AOR, 1.3, 95% CI, 1.04-1.55) than those who did not. CONCLUSION: The COVID-19 pandemic affected the suicide attempts of adolescents, with financial stress and feelings of loneliness closely linked to this impact. Although the pandemic nears its end, the persistent risk of suicide attempts among adolescents remains a concern. Therefore, it is imperative to implement targeted screening and interventions to address adolescent suicide risk.

S-nitrosylation switches the Arabidopsis redox sensor protein, QSOX1, from an oxidoreductase to a molecular chaperone under heat stress.

The Arabidopsis quiescin sulfhydryl oxidase 1 (QSOX1) thiol-based redox sensor has been identified as a negative regulator of plant immunity. Here, we have found that small molecular weight proteins of QSOX1 were converted to high molecular weight (HMW) complexes upon exposure to heat stress and that this was accompanied by a switch in QSOX1 function from a thiol-reductase to a molecular chaperone. Plant treatment with S-nitrosoglutathione (GSNO), which causes nitrosylation of cysteine residues (S-nitrosylation), but not with H2O2, induced HMW QSOX1 complexes. Thus, functional switching of QSOX1 is induced by GSNO treatment. Accordingly, simultaneous treatment of plants with heat shock and GSNO led to a significant increase in QSOX1 chaperone activity by increasing its oligomerization. Consequently, transgenic Arabidopsis overexpressing QSOX1 (QSOX1OE) showed strong resistance to heat shock, whereas qsox1 knockout plants exhibited high sensitivity to heat stress. Plant treatment with GSNO under heat stress conditions increased their resistance to heat shock. We conclude that S-nitrosylation allows the thiol-based redox sensor, QSOX1, to respond to various external stresses in multiple ways.

Patient's Perspective on Psychiatric Drugs: A Multicenter Survey-Based Study.

OBJECTIVE: We aimed to identify the expectations and preferences for medication and medical decision-making in patients with major psychiatric disorders. METHODS: A survey was conducted among patients with major psychiatric disorders who visited psychiatric outpatient clinics at 15 hospitals between 2016 and 2018 in Korea. The survey consisted of 12 questions about demographic variables and opinions on their expectations for medication, important medical decision-makers, and preferred drug type. The most preferred value in each category in the total population was identified, and differences in the preference ratio of each item among the disease groups were compared. RESULTS: A total of 707 participants were surveyed. In the total population, patients reported high efficacy (44.01%±21.44%) as the main wish for medication, themselves (37.39%±22.57%) and a doctor (35.27%±22.88%) as the main decision makers, and tablet/capsule (36.16%±30.69%) as the preferred type of drug. In the depressive disorders group, the preference ratio of high efficacy was significantly lower, and the preference ratio of a small amount was significantly higher than that of the psychotic disorder and bipolar disorder groups. The preference ratio of a doctor as an important decision maker in the bipolar disorder group was higher compared to the other groups. CONCLUSION: This study revealed the preference for medications and showed differences among patients with psychiatric disorders. Providing personalized medicine that considers a patient's preference for the drug may contribute to the improvement of drug compliance and outcomes.

Functional changes of OsTrxm from reductase to molecular chaperone under heat shock stress.

Ubiquitous disulfide reductases, thioredoxins (Trxs), function in the redox balance of all living organisms. Although the roles of the rice (Oryza sativa) Trx m-type isoform (OsTrxm) in chloroplast development have been already published, biochemical and molecular functions of OsTrxm remain to be elucidated for decades. The OsTrxm and its two conserved active cysteine mutant (OsTrxm C95S/C98S, referred to as OsTrxmC/S) proteins in Arabidopsis thaliana were overexpressed to characterize in vivo roles of active cysteines of OsTrxm. Interestingly, the OsTrxm overexpressed variant plants were resistant to heat shock treatment. Especially OsTrxmC/S with higher molecular weight (HMW) complexes showed higher heat tolerance than OsTrxm with lower molecular weight (LMW) structure in Arabidopsis thaliana. To confirm the importance of active cysteines on structural changes under heat stress, OsTrxm and OsTrxmC/S proteins were bacterially expressed and isolated. This study found that two proteins have various structures ranging from LMW to HMW complexes and have potential functions as a disulfide reductase and a molecular chaperone, which has never been reported anywhere. The function of molecular chaperone predominated in the HMW complexes, whereas the disulfide reductase function was observed in LMW forms. These results suggest that the active cysteines of OsTrxm play a critical role in protein structural change as well as heat tolerance in plants.

CK2 inhibitor CX4945 inhibits collagen degradation of HaCaT human keratinocyte cells via attenuation of MMP-1 secretion.

INTRODUCTION: During skin aging, the extracellular matrix (ECM) concomitantly breaks down. Out of the various protein components that comprise ECM, collagen is the most abundant one. Matrix metalloproteinase-1 (MMP-1) is a major collagenase that can degrade collagen. Therefore, the inhibition of MMP-1 may be critical for skin aging prevention. CX4945 is an inhibitor of casein kinase 2 and shows anticancer effects on various types of cancer cells. METHODS AND RESULTS: In this report, we investigated the MMP-1-inhibiting effect of CX4945 in HaCaT human keratinocyte cells. We performed zymography assays, Western blot analysis and immunoprecipitation assay to investigate the anti-MMP-1 effects of CX4945. CX4945 was found to inhibit collagen degradation via attenuation of the MMP-1 secretion out of HaCaT cells. This activity of CX4945 may be mediated by the induction of MMP-1 ubiquitylation via c-Jun N-terminal kinase (JNK) signaling. In wound healing cell migration assay, CX4945 also showed suppressive effect on the migration of HaCaT cells. This finding was closely related to the attenuation of CREB transcription factor via the downregulation of ERK mitogen-activated protein kinase as observed in Western blot analysis. CONCLUSION: Our report suggests that the inhibitory effects of CX4945 on MMP-1 in epidermal cells may offer a basis for further studying its therapeutic potential as an anti-wrinkle agent.

Nucleoredoxin gene SINRX1 negatively regulates tomato immunity by activating SA signaling pathway.

The tomato (Solanum lycopersicum) is widely consumed globally and renowned for its health benefits, including the reduction of cardiovascular disease and prostate cancer risk. However, tomato production faces significant challenges, particularly due to various biotic stresses such as fungi, bacteria, and viruses. To address this challenges, we employed the CRISPR/Cas9 system to modify the tomato NUCLEOREDOXIN (SlNRX) genes (SlNRX1 and SlNRX2) belonging to the nucleocytoplasmic THIOREDOXIN subfamily. CRISPR/Cas9-mediated mutations in SlNRX1 (slnrx1) plants exhibited resistance against bacterial leaf pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326, as well as the fungal pathogen Alternaria brassicicola. However, the slnrx2 plants did not display resistance. Notably, the slnrx1 demonstrated elevated levels of endogenous salicylic acid (SA) and reduced levels of jasmonic acid after Psm infection, in comparison to both wild-type (WT) and slnrx2 plants. Furthermore, transcriptional analysis revealed that genes involved in SA biosynthesis, such as ISOCHORISMATE SYNTHASE 1 (SlICS1) and ENHANCED DISEASE SUSCEPTIBILITY 5 (SlEDS5), were upregulated in slnrx1 compared to WT plants. In addition, a key regulator of systemic acquired resistance, PATHOGENESIS-RELATED 1 (PR1), exhibited increased expression in slnrx1 compared to WT. These findings suggest that SlNRX1 acts as a negative regulator of plant immunity, facilitating infection by the Psm pathogen through interference with the phytohormone SA signaling pathway. Thus, targeted mutagenesis of SlNRX1 is a promising genetic means to enhance biotic stress resistance in crop breeding.

The physiological role of thiol-based redox sensors in plant defense signaling.

Plants have developed multilayered defense strategies to adapt and acclimate to the kaleidoscopic environmental changes that rapidly produce reactive oxygen species (ROS) and induce redox changes. Thiol-based redox sensors containing the redox-sensitive cysteine residues act as the central machinery in plant defense signaling. Here, we review recent research on thiol-based redox sensors in plants, which perceive the changes in intracellular H2 O2 levels and activate specific downstream defense signaling. The review mainly focuses on the molecular mechanism of how the thiol sensors recognize internal/external stresses and respond to them by demonstrating several instances, such as cold-, drought-, salinity-, and pathogen-resistant signaling pathways. Also, we introduce another novel complex system of thiol-based redox sensors operating through the liquid-liquid phase separation.

The Korean Version of Pandemic Stress Questionnaire: Validation in Korean Population.

Objective: The spread of Coronavirus disease 2019 (COVID-19) has acted as a significant stressor among individuals, causing a variety of psychological problems. The purpose of this study is to determine the level of stress caused by COVID-19 by translating and validating the Pandemic Stress Questionnaire (PSQ) in Korean, which measures stressful event caused by COVID-19. Methods: A statistical analysis was performed on 167 participants. The scale's internal consistency was verified using Cronbach's α. Furthermore, a correlation analysis was carried out to examine the relationships between Perceived Stress Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder Questionnaire-7, Patient Health Questionnaire-15, and World Health Organization Quality of Life Assessment Instrument Brief Form. Lastly, a multiple regression analysis was performed to determine the effect of pandemic-related stressful events on depression, anxiety, and somatic symptoms. Results: Cronbach's α for Korean version of PSQ (K-PSQ) Severity was 0.79, and that for K-PSQ Event was 0.78. The results of the multiple regression analysis revealed that pandemic stress events have an effect on anxiety and somatic symptoms. Conclusion: The K-PSQ is a tool in which individuals can simultaneously measure the occurrence of stressful events caused by COVID-19 and the severity of stress that is often experienced as a result. It is expected that this tool will be useful in the mental health field for measuring COVID-19-related stress.

Effects of 3D Postural Correction and Abdominal Muscle Contraction on the Symmetry of the Transverse Abdominis and Spinal Alignment in Patients with Idiopathic Scoliosis.

This study aimed to investigate the effectiveness of 3D postural correction (3DPC) using corrective cushions (CCs) and abdominal muscle contraction (AMC) on the thickness symmetry of the transversus abdominis (TrA) and spinal alignment in patients with idiopathic scoliosis (IS). In the first experiment, ultrasound measurements were taken of the TrA thickness on both the convex and concave sides of the lumbar curve in the supine position during AMC and non-AMC without 3DPC, and during AMC and non-AMC with 3DPC using CCs, in 11 IS patients. In the second experiment, 37 IS patients participated in a four-week 3DPC exercise program that aimed to maintain TrA thickness symmetry based on the results of the first experiment. The study found that TrA thickness symmetry significantly increased after 3DPC using CCs and combined with AMC (p < 0.05). Additionally, the Cobb angles and trunk rotation angles showed significant decreases, and trunk expansion showed a significant increase (p < 0.05). These results indicate that the simultaneous application of 3DPC and AMC is the most effective way to achieve TrA thickness symmetry in IS patients. Therefore, 3DPC and AMC should be considered as crucial elements in exercise interventions for IS patients.

MARS2 drives metabolic switch of non-small-cell lung cancer cells via interaction with MCU.

Mitochondrial methionyl-tRNA synthetase (MARS2) canonically mediates the formation of fMet-tRNAifMet for mitochondrial translation initiation. Mitochondrial calcium uniporter (MCU) is a major gate of Ca2+ flux from cytosol into the mitochondrial matrix. We found that MARS2 interacts with MCU and stimulates mitochondrial Ca2+ influx. Methionine binding to MARS2 would act as a molecular switch that regulates MARS2-MCU interaction. Endogenous knockdown of MARS2 attenuates mitochondrial Ca2+ influx and induces p53 upregulation through the Ca2+-dependent CaMKII/CREB signaling. Subsequently, metabolic rewiring from glycolysis into pentose phosphate pathway is triggered and cellular reactive oxygen species level decreases. This metabolic switch induces inhibition of epithelial-mesenchymal transition (EMT) via cellular redox regulation. Expression of MARS2 is regulated by ZEB1 transcription factor in response to Wnt signaling. Our results suggest the mechanisms of mitochondrial Ca2+ uptake and metabolic control of cancer that are exerted by the key factors of the mitochondrial translational machinery and Ca2+ homeostasis.

Ursonic acid inhibits migration and invasion of human osteosarcoma cells through the suppression of mitogen-activated protein kinases and matrix metalloproteinases.

INTRODUCTION: Osteosarcoma (OS) is the most common form of bone malignancy. Although contemporary chemotherapy and surgery have improved the prognosis of those with OS, developing new OS therapies has proven difficult for some time. The activation of the matrix metalloproteinase (MMP) and mitogen-activated protein kinase (MAPK) signaling pathways can induce metastasis, which is an obstacle to OS treatment. Ursonic acid (UNA) is a phytochemical with the potential to cure a variety of human ailments, including cancer. METHODS AND RESULTS: In this study, we investigated the anti-tumor properties of UNA in MG63 cells. We conducted colony formation assay, wound healing assay, and Boyden chamber assays to investigate the anti-OS effects of UNA. UNA was found to significantly inhibit the proliferative, migratory, and invasive abilities of MG63 cells. This bioactivity of UNA was mediated by the inhibition of extracellular signal-regulated kinase (ERK) and p38 and reduction of MMP-2 transcriptional expression as observed in western blot analysis, gelatin zymography and RT-PCR. Anti-OS activities of UNA were also observed in Saos2 and U2OS cells, indicating that its anti-cancer properties are not specific to cell types. CONCLUSION: Our findings suggest that UNA has the potential for use in anti-metastatic drugs in the treatment of OS.

A study on skin mobility according to joint movement: Variations in mobility according to joint motion range and correlation and influence with hydrica composition.

BACKGROUND: Skin structures arranged in an advantageous structure for skin stretching to facilitate movement of the human body, and have structural functions to help the movement of the joints by changing the position of the skin, such as the stretch that occurs incidentally. Proper movement of the skin is required to be efficient owing to the nature of the skin that covers the entire human body with a single connected tissue layer. AIMS: The purpose of this study was to quantify the skin mobility that occurs during joint motion and to identify the correlation and influence with hydrica composition. MATERIALS & METHODS: The subjects of this study were healthy people in their 20s-50s (20 male, 20 female), The movement of the skin marker attached to the skin was measured using X-ray, and the hydrica composition was measured using Inbody S10. RESULTS: Experiments showed that the skin on the side at which the joint bends and wrinkles form moved away from the moving joint, while the skin on the side where the wrinkles spread out moved toward the moving joint. As the range of joint motion increases, the skin became more mobile (OR: 18.95 ± 5.91 mm, MR: 34.09 ± 7.87 mm, IR: 51.14 ± 8.73 mm, FF: 78.76 ± 12.24) (p < 0.05). As a result of regression analysis between the total amount of skin mobility and the factors of hydrica composition, it was found that the ABW (arm body water) affected skin mobility as B = 7.430 (p < 0.05, adjusted R2  = 0.119). CONCLUSION: Based on the results of this study, it was revealed that directional movement of the skin appeared according to joint movement, and it was affected by body water.

Effects of Psychosocial Interventions for Patients with Breast Cancer: A Meta-analysis.

Objective: This study involved a meta-analysis of South Korean studies regarding psychosocial interventions for patients with breast cancer to provide basic data to support the development of an integrated healthcare service model. Methods: Randomized controlled studies with a pretest-posttest design were selected, and those presenting means, standard deviations, and standardized mean differences were included. For quality evaluation and heterogeneity testing, the Jadad scale and the Q-value and I2 were used. To estimate the effect size of each study, Hedge's g was used. Publication bias was analyzed with the Funnel plot and Egger's regression test. Results: Of the 28 studies selected for the, meta-analysis was performed on eight. The total number of datasets included in the meta-analysis was 33. The evaluation based on the Jadad scale revealed no significant inter-rater variation (p = 0.35). The mean number of sessions was 7.93 and the mean intervention time was 13.2 hours. The interventions were mostly administered in a group structure (94%) and, regarding the type, they were categorized as integrated (36.4%), cognitive (30.3%), and meditation (24.2%). The mean effect size was 1.21 against no treatment group. Conclusion: The analyzed studies showed heterogeneity, with a corresponding asymmetry found on the Funnel plot. Despite the heterogeneity and publication bias, the mean effect size was significantly large. Cognitive interventions, meditation, and psychological education programs are expected to assist in reducing negative emotions and enhancing quality of life in patients with breast cancer.

Psychometric Properties of the Korean Version of Functioning Assessment Short Test in Bipolar Disorder.

Objective: The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST). Methods: A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted. Results: The internal consistency (Cronbach's alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p < 0.001). The K-FAST exhibited significant correlations with GAF (r = -0.771), WHOQOL-BREF (r = -0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078). Conclusion: The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.

S-acylated and nucleus-localized SALT OVERLY SENSITIVE3/CALCINEURIN B-LIKE4 stabilizes GIGANTEA to regulate Arabidopsis flowering time under salt stress.

The precise timing of flowering in adverse environments is critical for plants to secure reproductive success. We report a mechanism in Arabidopsis (Arabidopsis thaliana) controlling the time of flowering by which the S-acylation-dependent nuclear import of the protein SALT OVERLY SENSITIVE3/CALCINEURIN B-LIKE4 (SOS3/CBL4), a Ca2+-signaling intermediary in the plant response to salinity, results in the selective stabilization of the flowering time regulator GIGANTEA inside the nucleus under salt stress, while degradation of GIGANTEA in the cytosol releases the protein kinase SOS2 to achieve salt tolerance. S-acylation of SOS3 was critical for its nuclear localization and the promotion of flowering, but partly dispensable for salt tolerance. SOS3 interacted with the photoperiodic flowering components GIGANTEA and FLAVIN-BINDING, KELCH REPEAT, F-BOX1 and participated in the transcriptional complex that regulates CONSTANS to sustain the transcription of CO and FLOWERING LOCUS T under salinity. Thus, the SOS3 protein acts as a Ca2+- and S-acylation-dependent versatile regulator that fine-tunes flowering time in a saline environment through the shared spatial separation and selective stabilization of GIGANTEA, thereby connecting two signaling networks to co-regulate the stress response and the time of flowering.

Correction: Lee et al. Demyristoylation of the Cytoplasmic Redox Protein Trx-h2 Is Critical for Inducing a Rapid Cold Stress Response in Plants. Antioxidants 2021, 10, 1287.

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