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Background: Recent studies have highlighted the significant role of inflammation in the development and progression of major depressive disorder (MDD). Elevated levels of proinflammatory cytokines have consistently been observed in MDD, and these markers are shown to be linked to disruptions in brain networks. Therefore, we aimed to explore the relationship between inflammatory markers and resting-state functional connectivity (RSFC) in patients with MDD., Methods: This study included 76 patients with MDD and 92 healthy controls (HCs). Seed-to-voxel RSFC analysis was performed using brain regions that have been identified in previous studies on the neural networks implicated in MDD. These regions served as key hubs in the default mode, salience, cognitive control, and frontostriatal networks and were used as seed regions., Results: Compared with HCs, patients with MDD exhibited elevated levels of interleukin (IL)-6 and IL-8. The MDD group showed significant alterations of the RSFC between the prefrontal cortex (PFC), anterior cingulate cortex, visual cortex, postcentral gyrus, and striatal regions compared to the HC group. Additionally, within the MDD group, a positive correlation was observed between tumor necrosis factor (TNF)-α levels and the RSFC of the right dorsolateral prefrontal cortex (dlPFC) and visual cortex. Conversely, in the HC group, TNF-α levels were negatively correlated with the RSFC between the right dlPFC and bilateral dorsomedial prefrontal cortex, while positive correlations were noted between the RSFC of the right dlPFC with occipital regions and the levels of both IL-8 and TNF-α., Conclusions: The present study confirmed that cytokine levels are linked to alterations in the RSFC, particularly in the prefrontal regions. Our findings suggest that systemic inflammation may contribute to functional disruptions in the brain networks involved in emotion regulation and cognitive control in MDD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kyu-Man Han reports financial support was provided by National Research Foundation of Korea. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Meniere's disease (MD) is a chronic inner ear disorder characterized by tinnitus, ear fullness, episodic vertigo, and fluctuating hearing loss, which significantly impacts quality of life and poses management challenges. Recent evidence suggests that upper respiratory infections (URIs) may contribute to MD's onset. This study examines the potential link between URIs and MD using data from the Korean National Health Insurance Service-National Sample Cohort (2002-2019). We analyzed 19,721 individuals with MD and 78,884 matched controls, adjusting for demographic factors and comorbidities using propensity score matching. Our results showed that individuals with a URI within one year prior to the index date exhibited a 2.01-fold greater likelihood of developing MD (95% confidence interval [CI] = 1.91-2.11, p < 0.001), while those with URIs within two years demonstrated a 1.54-fold higher probability (95% CI = 1.50-1.59, p < 0.001). Furthermore, we found that even remote URIs occurring up to two years before the index date significantly increased the risk of developing MD, underscoring the need for long-term patient follow-up. Overall, our study suggests that individuals with a history of URI may have an elevated risk of developing MD over multiple time frames, regardless of demographic or health profiles.

This study assesses the early effectiveness of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) 1 day after the first administration, as monitored through self-assessment via the mobile application, Esketamine Continuing Assessment for Relapse Prevention (EsCARe). In this multi-center, open-label, single-arm study, adults aged 18-65 years diagnosed with TRD after failing at least two antidepressant therapies were enrolled from five tertiary hospitals in South Korea. During the induction period, participants self-administered ESK twice weekly and used the EsCARe app daily to record mood, sleep, and somatic symptoms. Key clinical assessments, the Patient Health Questionnaire-9 (PHQ-9), the Hamilton Depression Rating Scale (HAMD), and the Generalized Anxiety Disorder Scale (GAD-7), were measured at baseline and at weeks 2 and 4. The reliability and validity of EsCARe was assessed. The treatment results indicated significant improvements in depressive and anxiety symptoms, with notable reductions in the PHQ-9 and the GAD-7 by week 2, and the HAMD by week 4. The EsCARe app reliably and validly monitored depressive symptoms and demonstrated a significant reduction in depressive symptoms 1 day after the first administration of ESK. Using ESK, complemented by mobile self-monitoring, effectively reduces the symptoms of TRD early in the treatment course. Integrating mobile health technology into the therapeutic regimen highlights a significant advancement in managing TRD, offering patients and clinicians immediate feedback on treatment efficacy.

Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case-control study within the Korean National Health Insurance Service-Health Screening Cohort (2002-2019) investigated this association using 38,957 migraine patients and 155,828 controls, considering migraine subtypes (with/without aura) and statin types (lipophilic vs. hydrophilic). Using propensity score matching and adjusting for confounders, statin use was linked to reduced migraine likelihood overall (odds ratio (OR) 0.93), particularly for migraines with aura (OR 0.75) and without aura (OR 0.94). Lipophilic statins were effective for both subtypes, while hydrophilic statins mainly reduced the likelihood of migraines without aura. Subgroup analyses showed consistent benefits across demographics, but varied effectiveness based on weight, smoking, alcohol use, hemoglobin levels, and dyslipidemia history. In summary, this nationwide cohort study suggests that statin use may reduce migraine likelihood among Korean adults across diverse demographics and clinical profiles, but varied effectiveness based on certain lifestyle and comorbidity factors underscores the importance of considering individual patient profiles when assessing the potential benefits of statin therapy for migraine prevention.

Background: Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD., Methods: A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci., Results: In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes ( EML6 , ZFP64 , CLSTN3 , KCNMA1 , TAOK2 , and NT5E )., Conclusion: Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.

Behavioral activation (BA) is a well-established method of evidence-based treatment for depression. There are clear links between the neural mechanisms underlying reward processing and BA treatment for depressive symptoms, including anhedonia; however, integrated interpretations of these two domains are lacking. Here we examine brain imaging studies involving BA treatments to investigate how changes in brain networks, including the reward networks, mediate the therapeutic effects of BA, and whether brain circuits are predictors of BA treatment responses. Increased activation of the prefrontal and subcortical regions associated with reward processing has been reported after BA treatment. Activation of these regions improves anhedonia. Conversely, some studies have found decreased activation of prefrontal regions after BA treatment in response to cognitive control stimuli in sad contexts, which indicates that the therapeutic mechanism of BA may involve disengagement from negative or sad contexts. Furthermore, the decrease in resting-state functional connectivity of the default-mode network after BA treatment appears to facilitate the ability to counteract depressive rumination, thereby promoting enjoyable and valuable activities. Conflicting results suggest that an intact neural response to rewards or defective reward functioning is predictive of the efficacy of BA treatments. Increasing the benefits of BA treatments requires identification of the unique individual characteristics determining which of these conflicting findings are relevant for the personalized treatment of each individual with depression., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Neurological Association.)

Gastric cancer (GC) survivors may be more likely to develop osteoporosis. However, few studies on the relationship between GC and osteoporosis have been conducted on large patient populations. We aimed to determine the incidence of osteoporosis and identify related factors by comparing patients with GC and matched controls using the Korean National Health Insurance Service-National Sample Cohort (KNHIS-NSC). This study included 9078 patients with GC and 36,312 controls (1:4 propensity score-matched for sex, age, residence, and income). The hazard ratio (HR) for osteoporosis was significantly greater for GC patients than for controls according to Charlson Comorbidity Index (CCI) score-adjusted models (adjusted HR = 1.13). Kaplan-Meier analysis revealed that the cumulative incidence of osteoporosis during the follow-up period commencing from the index date was significantly greater in GC patients than in the controls ( p = 0.0087). A positive correlation of osteoporosis with GC was detected for those aged < 65 years, males, and those with CCI scores = 0. In conclusion, the study findings suggest that men with GC aged < 65 years may be at an increased risk for osteoporosis. Research into additional risk factors and the optimal timing of interventions are needed to prevent fractures and minimize bone loss in GC survivors.

Colorants have been a staple in the cosmetics industry for a considerable time, although certain varieties have been banned owing to health risks. Detecting and confirming these banned colorants simultaneously poses several challenges when employing LC-MS/MS. Molecular networking is a promising analytical technology that can be used to predict the structure of components and the correlation between them using structural and MS/MS spectral similarities. Molecular networking entails assessing the number of fragmented ions and the cosine score (the closer it is to one, the higher the similarity). In this study, we developed and verified a method for the simultaneous quantitative analysis of the 26 banned colorants in cosmetics using LC-MS/MS. Additionally, we propose a novel approach that combines LC-Q-TOF-MS and molecular networking technology to detect banned colorants in cosmetics. For successful molecular networking, a minimum of six fragment ions with cosine scores exceeding 0.5 is required. We developed a screening method for characterizing banned colorants using molecular networking based on LC-TOF-MS results for 26 banned colorants. Furthermore, we demonstrated that our established method can be used for screening by analyzing actual cosmetics (eyebrow tattoo, lipstick tattoo, and hair tint) spiked with three non-targeted banned colorants with similar structures (m/z 267.116, 315.149, and 345.157) in cosmetics. The combination of molecular networking techniques and LC-MS/MS proves highly advantageous for the swift characterization and screening of non-targeted colorants in cosmetics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: It is well-known that suicide and excess mortality are high in patients with psychiatric illnesses and this has long been an important issue in the field of mental health. We aim to investigate suicide and other-cause deaths in patients with psychiatric illnesses., Methods: This retrospective, population-based cohort was based on the National Health Insurance claims data of the first admission with a principal diagnosis of major psychiatric disorder between 2010 and 2011, and followed up to 2020. A total of 95,855 participants were enrolled. Suicide and other-cause mortality were assessed through Log-rank test and Kaplan-Meier curve., Results: There were 95,855 patients, with an average age of 48.2 years. The number of suicide deaths and other-cause deaths was 2408 (288.1 per 100,000 person-years) and 15,192 (1817.6 per 100,000 person-years), respectively. The rate of healthcare utilization prior to suicide was 95.0 %, and the rate of utilization prior to one week before suicide was 43.5 %. The risk of suicide was highest in patients with depression, followed by alcohol use disorder, schizophrenia, and bipolar disorder., Conclusions: This study revealed various factors related to healthcare utilization associated with suicide and other-cause deaths in psychiatric patients. Educating frontline healthcare professionals, psychiatrists, emergency department personnel, and general practice doctors using such as Gatekeeper program is important to prevent suicides., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Growing research has proposed that rheumatoid arthritis (RA) and chronic periodontitis (CP) share similar pathophysiological mechanisms involving inflammation and tissue destruction. However, the potential correlation of CP as a contributing factor for the occurrence of RA warrants validation in the Korean population, where both diseases are prevalent, especially considering the increasingly aging demographic in Korea. This study examined 5139 RA cases and 509,727 matched controls from a Korean national cohort dataset (2002-2019) by carefully employing propensity score matching to ensure comparability between groups. Baseline characteristics were compared using standardized differences, and logistic regression was employed to estimate the impact of CP history on RA likelihood while controlling for covariates. We fully examined medical records documenting CP occurrences within the two-year period leading up to the index date, conducting comprehensive subgroup analyses. While a 1-year history of CP did not show a significant association with likelihood of RA, a 2-year history of CP increased RA likelihood by 12%, particularly among older adults, females, rural residents, and those with certain comorbidities such as hypercholesterolemia. Interestingly, this association persisted even among individuals with non-smoking habits, normal weight, and infrequent alcohol consumption. These findings suggest that chronic CP exposure for at least 2 years may independently elevate RA risk in Korean adults. The association in certain subgroups appears to suggest a predisposition toward genetic susceptibilities over lifestyle and environmental factors. Predicting RA in CP patients may be challenging, emphasizing the importance of regular RA screening, especially in high-risk subgroups.

Recent research suggests a potential relevance between chronic periodontitis (CP) and Parkinson's disease (PD), raising concerns about comorbid PD among elderly CP patients. However, the epidemiologic basis for this association remains unclear. Employing a nested case-control design, this study explored the association between CP and subsequent PD occurrences in Korean adults, leveraging a validated national population-based dataset covering the period from 2002 to 2019. It included 8794 PD patients and 35,176 matched control individuals, established through propensity score matching for age, sex, residential area, and income. Baseline characteristics were compared using standardized differences, and logistic regression was employed to assess the impact of CP histories on PD likelihood while controlling for covariates. We performed a thorough examination of CP events within both 1-year and 2-year intervals preceding the index date, incorporating subgroup analyses. Our analysis revealed no statistically significant association between CP history and PD development overall. However, subgroup analysis revealed a slightly increased likelihood of PD development among CP individuals with a high disease burden (Charlson Comorbidity Index score ≥ 2). In conclusion, although our study did not find a significant overall association between CP history and PD development, the elevated likelihood of PD in subgroups with high disease burden may suggest that comorbidities influence PD probability among certain CP patients. Considering comorbid conditions in PD screening for some individuals with CP may be also important.

While headaches frequently occur in individuals with chronic kidney disease (CKD), there are few statistical evaluations of their connection to migraines in population-based studies. In this nationwide longitudinal follow-up study of Korean health examination data (2002-2019), a total of 15,443 participants with CKD and 61,772 matched controls were enrolled. We applied overlap-weighted Cox proportional hazard regression models to assess hazard ratios, examining the correlation between CKD and the development of migraines. After accounting for various factors, we observed a modest reduction of approximately 11% in the likelihood of migraine occurrence among CKD patients (95% confidence intervals = 0.81-0.97) during the 16-year monitoring period. Subgroup analysis revealed a significant association among specific demographic and health conditions, including individuals aged 70 or older, females, overweight individuals, nonsmokers, and those without hypertension or diabetes. Our research may indicate a potential relationship between CKD and the onset of migraines in Korean adults, suggesting a slight reduction in the probability of the occurrence of migraines among those with CKD. These findings emphasize the need for attentive follow-up and preventive management in individuals without the identified protective factors, particularly in male CKD patients under the age of 70 with hypertension.

Rationale: The demand for weight loss products is increasing as slimness emerges as the new aesthetic standard and people's desire to achieve it increases. In addition, the distribution and sale of products containing illegal ingredients, pharmaceuticals, and chemicals for which safety is not guaranteed and that cannot be used as foods or dietary supplements are increasing. Thus, the development of an analytical method that could monitor these illegal products is required., Methods: A high-performance liquid chromatography-photodiode array method capable of rapid and reliable qualitative and quantitative analyses of 43 weight loss agents was established and validated., Results: The process involved dividing analytes into three groups for rapid analysis; when bisacodyl was mixed with chlorocyclopentylsibutramine, it decomposed into its metabolites: monoacetyl bisacodyl and bis-(p-hydroxypheny)-pyridyl-2-methane. This decomposition was due to NaOH that was used to prepare the chlorocyclopentylsibutramine standard solution. Bisacodyl did not degrade when mixed with neutralized chlorocyclopentylsibutramine, whereas when NaOH was added, it rapidly degraded. We identified the bisacodyl degradation products using liquid chromatography-quadrupole-Orbitrap/mass spectrometry. MS 2 spectra with proposed structures of fragment peaks were also obtained., Conclusions: The developed method could be used to regulate slimming products that threaten public health, and knowledge of bisacodyl degradation will be used as the basis for developing an analytic method., (© 2024 John Wiley & Sons Ltd.)

Major depressive disorder (MDD) is a common mental illness worldwide and is triggered by an intricate interplay between environmental and genetic factors. Although there are several studies on common variants in MDD, studies on rare variants are relatively limited. In addition, few studies have examined the genetic contributions to neurostructural alterations in MDD using whole-exome sequencing (WES). We performed WES in 367 patients with MDD and 161 healthy controls (HCs) to detect germline and copy number variations in the Korean population. Gene-based rare variants were analyzed to investigate the association between the genes and individuals, followed by neuroimaging-genetic analysis to explore the neural mechanisms underlying the genetic impact in 234 patients with MDD and 135 HCs using diffusion tensor imaging data. We identified 40 MDD-related genes and observed 95 recurrent regions of copy number variations. We also discovered a novel gene, FRMPD3, carrying rare variants that influence MDD. In addition, the single nucleotide polymorphism rs771995197 in the MUC6 gene was significantly associated with the integrity of widespread white matter tracts. Moreover, we identified 918 rare exonic missense variants in genes associated with MDD susceptibility. We postulate that rare variants of FRMPD3 may contribute significantly to MDD, with a mild penetration effect., (© 2024. The Author(s).)

Major depressive disorder (MDD) has consistently proven to be a multifactorial and highly comorbid disease. Despite recent depression-related research demonstrating causalities between MDD-related factors and a small number of variables, including brain structural changes, a high-statistical power analysis of the various factors is yet to be conducted. We retrospectively analyzed data from 155 participants (84 healthy controls and 71 patients with MDD). We used magnetic resonance imaging and diffusion tensor imaging data, scales assessing childhood trauma, depression severity, cognitive dysfunction, impulsivity, and suicidal ideation. To simultaneously evaluate the causalities between multivariable, we implemented two types of MDD-specified structural equation models (SEM), the behavioral and neurobehavioral models. Behavioral SEM showed significant results in the MDD group: Comparative Fit Index [CFI] = 1.000, Root Mean Square Error of Approximation [RMSEA]) = 0.000), with a strong correlation in the scales for childhood trauma, depression severity, suicidal ideation, impulsivity, and cognitive dysfunction. Based on behavioral SEM, we established neurobehavioral models showing the best-fit in MDD, especially including the right cingulate cortex, central to the posterior corpus callosum, right putamen, pallidum, whole brainstem, and ventral diencephalon, including the thalamus (CFI >0.96, RMSEA <0.05). Our MDD-specific model revealed that the limbic-associated regions are strongly connected with childhood trauma rather than depression severity, and that they independently affect suicidal ideation and cognitive dysfunction. Furthermore, cognitive dysfunction could affect impulsivity., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Major depressive disorder (MDD) is a prevalent mental health condition with significant societal impact. Owing to the intricate biological diversity of MDD, treatment efficacy remains limited. Immune biomarkers have emerged as potential predictors of treatment response, underscoring the interaction between the immune system and the brain. This study investigated the relationship between cytokine levels and cortical thickness in patients with MDD, focusing on the corticolimbic circuit, to elucidate the influence of neuroinflammation on structural brain changes and contribute to a deeper understanding of the pathophysiology of MDD., Method: A total of 114 patients with MDD and 101 healthy controls (HC) matched for age, sex, and body mass index (BMI) were recruited. All participants were assessed for depression severity using the Hamilton Depression Rating Scale (HDRS), and 3.0 T T1 weighted brain MRI data were acquired. Additionally, cytokine levels were measured using a highly sensitive bead-based multiplex immunosorbent assay., Results: Patients diagnosed with MDD exhibited notably elevated levels of interleukin-6 (p = 0.005) and interleukin-8 (p = 0.005), alongside significant cortical thinning in the left anterior cingulate gyrus and left superior frontal gyrus, with these findings maintaining significance even after applying Bonferroni correction. Furthermore, increased interleukin-6 and interleukin-8 levels in patients with MDD are associated with alterations in the left frontomarginal gyrus and right anterior cingulate cortex (ACC)., Conclusions: This suggests a potential influence of neuroinflammation on right ACC function in MDD patients, warranting longitudinal research to explore interleukin-6 and interleukin-8 mediated neurotoxicity in MDD vulnerability and brain morphology changes., Competing Interests: Declaration of competing interest The authors have no potential or actual conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Given the global significance of gout and gastric cancer (GC) as major health problems with interrelated impacts, we examined the development of GC in Korean patients with gout. We conducted a nested case-control study using data from 10,174 GC patients and 40,696 control patients from the Korean National Health Insurance Service-National Sample Cohort database. Propensity score matching (1:4) with propensity score overlap-weighted adjustment was used to reduce selection bias and estimate the odds ratio (OR) and 95% confidence intervals (CIs) for the association between gout and GC. An adjusted OR for GC was not significantly higher in patients with gout than in control patients (1.02; 95% CI, 0.93-1.12; p = 0.652). Additionally, no association between gout and GC was observed in subgroup analyses such as sex, age, level of income, region of residence, or Charlson Comorbidity Index score. In conclusion, these results suggest that gout is not a significant independent risk factor for GC among the Korean population. Additional investigation is required to establish a causal association between gout and GC, and to generalize these results to general populations.

Objective: This study investigated the association between white matter tract integrity and frontal executive function in adult non-geriatric patients with major depressive disorder (MDD) and healthy controls (HCs) using diffusion tensor imaging (DTI)., Methods: In total, 57 patients with MDD and 115 HCs participated in this study. We calculated the integrity of the white matter tracts using the Tracts Constrained by Underlying Anatomy tool (TRACULA) from FreeSurfer. We performed cognitive function tests. Oneway analysis of covariance was used to investigate the DTI parameters as dependent variables; diagnosis of MDD as an independent variable; and age, sex, and education level as covariates. For correlation analysis between the DTI parameters and cognitive function tests, Pearson's partial correlation analyses were performed in the MDD and HC groups., Results: The patients with MDD showed significantly decreased axial diffusivity (AD) in forceps major (FMajor), left corticospinal tract (CST), left superior longitudinal fasciculus-parietal bundle (SLFP), right anterior thalamic radiation (ATR), right CST, right inferior longitudinal fasciculus (ILF) and right superior longitudinal fasciculus-temporal bundle (SLFT) and mean diffusivity (MD) in the left CST, right CST, and right SLFT compared to HCs. We found that non-geriatric patients with MDD showed a significant negative correlation between the response time in the Stroop task and the AD value of the FMajor., Conclusion: Our findings suggest that impaired structural connectivity in the FMajor may be associated with cognitive dysfunction in non-geriatric patients with MDD.

Hyperuricemia is caused by an imbalance of uric acid and is associated with many diseases. Although gout which is one of hyperuricemia-related diseases is curable with anti-hyperuricemic drugs some medications have side effects, such as hypersensitivity in patients with circulatory system disorders, flare reoccurrences, and increased cardiac risk. This study consisted of test tube (xanthine oxidase's inhibition) and animal study. Animal study using with ICR mice was composed of control, potassium oxonate-induced hyperuricemia, allopurinol, and 3 Korean red ginseng water extract (KRGWE) treatment groups (62.5; 125, and 500 mg/kg). We orally administered KRGWE once a day for 7 d to induce hyperuricemia and injected PO 2 h before the final KRGWE administration. We measured serum uric acid, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen, and creatinine and analyzed the genes such as organic anion transport (OAT)-1, OAT-3, and urate transport (URAT)-1. KRGWE dose-dependently controlled xanthine oxidase activity in the serum and completely inhibited serum uric acid. KRGWE affected both uric acid excretion-related and uric acid reabsorption-related gene expression. KRGWE stimulated uric acid excretion-related gene expressions, such as OAT-1 and OAT-3, but inhibited uric acid reabsorption-related gene expression, such as URAT-1. KRGWE improved liver and kidney functioning. KRGWE improved liver/kidney functioning and is promising anti-hyperuricemic agent which can control serum uric acid via downregulating URAT1 and upregulating OAT1 and OAT3.

Background: Early neurodevelopmental deviations, such as abnormal cortical folding patterns, are candidate biomarkers of major depressive disorder (MDD). We aimed to investigate the association of MDD with the local gyrification index (LGI) in each cortical region at the whole-brain level, and the association of the LGI with clinical characteristics of MDD., Methods: We obtained T1-weighted images from 234 patients with MDD and 215 healthy controls (HCs). The LGI values from 66 cortical regions in the bilateral hemispheres were automatically calculated according to the Desikan-Killiany atlas. We compared the LGI values between the MDD and HC groups using analysis of covariance, including age, sex, and years of education as covariates. The association between the clinical characteristics and LGI values was investigated in the MDD group., Results: Compared with HCs, patients with MDD showed significantly decreased LGI values in the cortical regions, including the bilateral ventrolateral and dorsolateral prefrontal cortices, medial and lateral orbitofrontal cortices, insula, right rostral anterior cingulate cortex, and several temporal and parietal regions, with the largest effect size in the left pars triangularis (Cohen's f 2 = 0.361; p = 1.78 × 10 -13 ). Regarding the association of clinical characteristics with LGIs within the MDD group, recurrence and longer illness duration were associated with increased gyrification in several occipital and temporal regions, which showed no significant difference in LGIs between the MDD and HC groups., Conclusions: These findings suggest that the LGI may be a relatively stable neuroimaging marker associated with MDD predisposition.

The potential connection between proton pump inhibitors (PPIs) and colorectal cancer (CRC) risk remains unclear, with specific ethnic genetic backgrounds playing a role in PPI-induced adverse effects. In this nested case-control study, we investigated the risk of CRC in relation to preceding PPI use and the duration of use using data from the Korean National Health Insurance Service-National Sample Cohort database, including 9374 incident CRC patients and 37,496 controls. To assess the impact of preceding PPI exposure (past vs. current) and use duration (days: <30, 30-90, and ≥90) on incident CRC, we conducted propensity score overlap-weighted multivariate logistic regression analyses, adjusted for confounding factors. Our findings revealed that past and current PPI users had an increased likelihood of developing CRC. Regardless of duration, individuals who used PPIs also had higher odds of developing CRC. Subgroup analyses revealed that CRC occurrence increased independent of history or duration of prior PPI use, consistent across various factors such as age, sex, income level, and residential area. These findings suggest that PPI use, regardless of past or present use and duration of use, may be related to an increased risk of developing CRC in the Korean population.

Considering the global importance of both gout and colorectal cancer (CRC) as significant health issues with mutual relevance, we aimed to examine the risk of colorectal cancer in Korean patients with gout. In this nested case-control study, we used data from 9920 CRC patients and 39,680 controls the Korean National Health Insurance Service-National Sample Cohort database. Propensity score overlap-weighted multivariate logistic regression analyses, adjusted for confounders, were used to assess the odds ratio (OR) and 95% confidence interval (CI) of the association between gout and CRC. Adjusted OR for CRC were similar between patients with gout and the control group (0.95; 95% CI, 0.86-1.04; p = 0.282). However, after adjustment, subgroup analysis revealed an 18% reduction in the probability of CRC among patients younger than 65 years with gout (95% CI, 0.70-0.95; p = 0.009). Conversely, absence of an association between gout and subsequent CRC persisted regardless of sex, income, residence, and Charlson Comorbidity Index score, even among individuals aged 65 years or older. These results imply that gout may not be a significant independent risk factor for CRC among the general population. However, in patients younger than 65 years with gout, a slightly reduced likelihood of CRC was observed. Further research is necessary to establish a causal relationship between gout and CRC and to generalize these findings to other populations.

Background: The coronavirus disease 2019 (COVID-19) pandemic has worsened mental health and reduced access to mental health services. During the pandemic, the demand for telemedicine has increased and related laws have been enacted. This study aimed to investigate telemedicine use for cases of major mental illnesses during the COVID-19 pandemic and to compare the characteristics of patients who received telemedicine service with those of patients who received in-person care., Methods: This population-based, cross-sectional, observational study was based on health insurance claims data, and included 2,749,872 patients who received outpatient treatment for mental illness from February 24, 2020 to June 30, 2022. Logistic regression was performed to assess the relationships between patient characteristics and telemedicine service use. Patients who received telemedicine services were analyzed in subgroups of each mental illness., Results: During the study period, 80,157 patients (2.9%), with an average age of 63 years, received at least one telemedicine treatment. There was a predominance of women and medical aid recipients. The lowest proportion of telemedicine treatments was for depression (2.1%), and the highest was for dementia (6.7%). The proportion of patients receiving telemedicine in long-term care hospitals was high (22.6%), with the highest odds ratio (OR) (5.84), compared with that in tertiary or general hospitals, followed by that in psychiatric hospitals and clinics. The proportions were high in the departments of internal medicine, neurology, and psychiatry. Patients aged > 80 years received most telemedicine treatment (OR: 1.23) across all diagnoses. Cases of dementia and other mental disorders had higher ORs (2.60 and 2.36, respectively) compared with cases of depression. Except for dementia and behavioral/emotional disorders, hospitalization increased the probability of telemedicine treatment. Comorbidities were positively associated with telemedicine treatment., Conclusions: Older people and people with other physical illnesses were more likely to use telemedicine treatments temporarily provided during the pandemic. Telemedicine maintained continuity of treatment for patients with dementia and severe mental illnesses. Telemedicine can be useful for filling the medical gaps for vulnerable populations other than those with mild mental illnesses. This aspect should be considered for the future establishment of telemedicine systems., (© 2023. BioMed Central Ltd., part of Springer Nature.)

(1) Background: High-grade serous ovarian carcinoma (HGSOC) is an aggressive subtype of ovarian cancer. Recent advances have introduced prognostic markers and targeted therapies. Programmed cell death ligand 1 (PD-L1) has emerged as a potential biomarker for HGSOC, with implications for prognosis and targeted therapy eligibility; (2) Methods: A literature search was conducted on major databases, and extracted data were categorized and pooled. Subgroup analysis was performed for studies with high heterogeneity. (3) Results: Data from 18 eligible studies were categorized and pooled based on PD-L1 scoring methods, survival analysis types, and endpoints. The result showed an association between high PD-L1 expression and a favorable prognosis in progression-free survival (HR = 0.53, 95% CI = 0.35-0.78, p = 0.0015). Subgroup analyses showed similar associations in subgroups of neoadjuvant chemotherapy patients (HR = 0.6, 95% CI = 0.4-0.88, p = 0.009) and European studies (HR = 0.59, 95% CI = 0.42-0.82, p = 0.0017). In addition, subgroup analyses using data from studies using FDA-approved PD-L1 antibodies suggested a significant association between favorable prognosis and high PD-L1 expression in a subgroup including high and low stage data in overall survival data (HR = 0.46, 95% CI = 0.3-0.73, p = 0.0009). (4) Conclusions: This meta-analysis revealed a potential association between high PD-L1 expression and favorable prognosis. However, caution is warranted due to several limitations. Validation via large-scale studies, with mRNA analysis, whole tissue sections, and assessments using FDA-approved antibodies is needed.

A growing body of evidence suggests that immune-related genes play pivotal roles in the pathophysiology of depression. In the present study, we investigated a plausible connection between gene expression, DNA methylation, and brain structural changes in the pathophysiology of depression using a combined approach of murine and human studies. We ranked the immobility behaviors of 30 outbred Crl:CD1 (ICR) mice in the forced swim test (FST) and harvested their prefrontal cortices for RNA sequencing. Of the 24,532 analyzed genes, 141 showed significant correlations with FST immobility time, as determined through linear regression analysis with p ≤ 0.01. The identified genes were mostly involved in immune responses, especially interferon signaling pathways. Moreover, induction of virus-like neuroinflammation in the brains of two separate mouse cohorts (n = 30 each) using intracerebroventricular polyinosinic:polycytidylic acid injection resulted in increased immobility during FST and similar expression of top immobility-correlated genes. In human blood samples, candidate gene (top 5%) expression profiling using DNA methylation analysis found the interferon-related USP18 (cg25484698, p = 7.04 × 10 -11 , Δβ = 1.57 × 10 -2 ; cg02518889, p = 2.92 × 10 -3 , Δβ =  - 8.20 × 10 -3 ) and IFI44 (cg07107453, p = 3.76 × 10 -3 , Δβ =  - 4.94 × 10 -3 ) genes to be differentially methylated between patients with major depressive disorder (n = 350) and healthy controls (n = 161). Furthermore, cortical thickness analyses using T1-weighted images revealed that the DNA methylation scores for USP18 were negatively correlated with the thicknesses of several cortical regions, including the prefrontal cortex. Our results reveal the important role of the interferon pathway in depression and suggest USP18 as a potential candidate target. The results of the correlation analysis between transcriptomic data and animal behavior carried out in this study provide insights that could enhance our understanding of depression in humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Accumulating evidence from other countries indicates potential associations between gout and cardiovascular diseases; however, the associations of gout with cardiovascular diseases, particularly stroke, ischemic heart disease, and heart failure, remain ambiguous in the Korean population. We hypothesized that individuals with gout are at a higher likelihood of stroke, ischemic heart disease, or heart failure. This study expands upon previous research by ensuring a comparable baseline between patient and control groups and analyzing 16 years of data derived from an extensive healthcare database., Methods: We selected 22,480 patients with gout and 22,480 control individuals from the Korean National Health Insurance Service-Health Screening Cohort database (2002-2019), and matched them at a 1:1 ratio according to sex, age, income, and residence. A Cox proportional hazard model with weighted overlap was employed to examine the relationship between gout and the risk of stroke, ischemic heart disease, or heart failure after adjustment for several covariates., Results: The incidences of stroke, ischemic heart disease, or heart failure in participants with gout were slightly higher than those in controls (stroke: 9.84 vs. 8.41 per 1000 person-years; ischemic heart disease: 9.77 vs. 7.15 per 1000 person-years; heart failure: 2.47 vs. 1.46 per 1000 person-years). After adjustment, the gout group had an 11% (95% confidence interval [CI] = 1.04-1.19), 28% (95% CI = 1.19-1.37), or 64% (95% CI = 1.41-1.91) higher likelihood of experiencing stroke, ischemic heart disease, or heart failure, respectively, than the control group., Conclusion: The present findings suggest that individuals with gout in the Korean population, particularly those aged ≥ 60 years, were more likely to have stroke, ischemic heart disease, or heart failure., Competing Interests: Author HC was employed by the company M.D. Analytics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kang, Lee, Yoo, Han, Hong, Choi, Lim, Kim, Kim, Cho, Nam, Park, Kim, Baek, Lee and Kwon.)

Objective: The economic hardship brought by the coronavirus disease-2019 (COVID-2019) pandemic has caused mental health problems among people of different socioeconomic status (SES). As social support helps to buffer these problems, we investigated the association between job loss related to COVID-19 and depression, anxiety, and suicidal thoughts; the differences in the effects according to SES; and the mediating effects of social support., Methods: The effects of COVID-19-related job loss on depression, anxiety, and suicidal thoughts among 1,364 people were investigated through semi-structured and self-administered questionnaires: Patient Health Questionnaire-9, General Anxiety Disorder-7, and the Functional Social Support Questionnaire. Logistic regression and subgroup analyses were performed to assess the association between job loss and mental health status, and the moderating effects of income and educational levels. Moreover, the mediating effects of perceived social support on the association between job loss and depression, anxiety, and suicidal thoughts were analyzed., Results: COVID-19-related job loss increased the risk of depression and suicidal thoughts. Adults with lower income and education level were at higher risk of depression, anxiety, and suicidal thoughts; perceived social support level had significant mediating effects on the association between job loss and depression/anxiety; and income level had significant moderating effects on this mediating pathway., Conclusion: COVID-19-related job loss were likely to be significantly associated with negative mental health outcomes, especially among individuals with low income and education levels. As social support had buffering effects on such outcomes, related government policies in cooperation with the governance of communities and stakeholders must be prepared.

Introduction: Trichilemmal cysts (TCs) are common benign cysts that form from the hair follicles in the skin. Proliferating trichilemmal cysts (PTCs) are rare types of TCs characterized by rapid cellular proliferation. Malignant transformation of PTC (MPTC) is a rare adnexal tumor that account for <0.1% of all skin cancers. TCs and PTCs are benign tumors; however, MPTCs grow rapidly and are prone to metastasis., Case Presentation: A 77-year-old man was referred to our hospital with a solitary pinkish mass on his left elbow. Trichilemmal carcinoma arising from a PTC was confirmed through excisional biopsy, and wide excision was performed. One month postoperatively, a cystic mass was observed and was suspected to have local recurrence; however, bursitis was confirmed after excisional biopsy. After 1 year of follow-up, the patient maintained an improvement without recurrence or any other surgical complications., Conclusions: In addition to being a very rare disease, MTPC occurred in the elbow of a man who does not fit the general etiology; therefore, it is considered an interesting case, and we report this case for academic contribution., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Early life stress of childhood adversity (CA) may result in major depressive disorder (MDD) by sensitizing individuals to proximal stressors in life events. The neurobiological changes that underlie adult depression may result from the absence of proper care and supervision of caregivers. We aimed to find both gray and white matter abnormalities in MDD patients, who reported the experiences of CA., Methods: The present study examined cortical alterations in 54 patients with MDD and 167 healthy controls (HCs) using voxel-based morphology and fractional anisotropy (FA) tract-based spatial statistics (TBSS). Both patients and HCs were administered the self-questionnaire clinical scale (the Korean translation of the Childhood Trauma Questionnaire CTQK). Pearson's correlation analysis was performed to find the associations between FA and CTQK., Results: The MDD group showed a significant decrease in gray matter (GM) in the left rectus at both the cluster and peak levels after family-wise error correction. The TBSS results showed significantly reduced FA in widespread regions, including the corpus callosum (CC), superior corona radiata, cingulate gyrus, and superior longitudinal fasciculus. The CA was negatively correlated with the FA in CC and crossing pontine tract., Conclusion: Our findings demonstrated GM atrophy and white matter (WM) connectivity changes in patients with MDD. The major findings of the widespread FA reduction in WM provided the evidence of brain alterations in MDD. We further propose that the WM would be vulnerable to emotional, physical, and sexual abuse in early childhood during the brain development., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Although psychological interventions for stress relief, such as cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR), have been developed, they have not been widely used in treating depression. The use of mobile devices can increase the possibility of actual use by integrating interventions and reducing the difficulty and cost burden of treatment application. This study aims to determine whether "inMind," an integrated mobile application for stress reduction, developed for the general population, decreases stress for patients with mild to moderate major depressive disorder during the pharmacological treatment period., Methods: This study is a single-blind, multicenter, randomized, controlled crossover trial. The App, developed in Republic of Korea, provides integrated interventions for stress reduction for the general population through three modules based on mindfulness-based stress reduction, cognitive behavior therapy, and relaxation sounds that are known to be effective in stress reduction ("meditation," "cognitive approach," and "relaxation sounds," respectively). Participants ( n = 215) recruited via medical practitioner referral will be randomized to an App first group (fAPP) or a wait list crossover group (dAPP). The study will be conducted over 8 weeks; the fAPP group will use the App for the first 4 weeks and the dAPP group for the next 4 weeks. During all study periods, participants will receive their usual pharmacological treatment. The Depression Anxiety Stress Scale-21 is the primary outcome measure. The analysis will employ repeated measurements using a mixed-model approach., Discussion: The App can potentially be an important addition to depression treatment because of its applicability and the comprehensive nature of the interventions that covers diverse stress-relieving models., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05312203, identifier 2021GR0585., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Shin, Han, Lee, Jeong, Pae, Patkar, Masand and Han.)

Objective: A growing body of evidence reports on the effect of different types of childhood abuse on the structural and functional architecture of the brain. In the present study, we aimed to investigate the differences in cortical thickness according to specific types of childhood abuse between patients with major depressive disorder (MDD) and healthy controls (HCs)., Methods: A total of 61 patients with MDD and 98 HCs were included in this study. All participants underwent T1-weighted magnetic resonance imaging, and the occurrence of childhood abuse was assessed using the Childhood Trauma Questionnaire. We investigated the association between whole-brain cortical thickness and exposure to any type of childhood abuse and specific type of childhood abuse in the total sample using the FreeSurfer software., Results: No significant difference was reported in the cortical thickness between the MDD and HC groups nor between the "any abuse" and "no abuse" groups. Compared to no exposure to childhood sexual abuse (CSA), exposure to CSA was significantly associated with cortical thinning in the left rostral middle frontal gyrus (p=0.00020), left (p=0.00240), right fusiform gyri (p=0.00599), and right supramarginal gyrus (p=0.00679)., Conclusion: Exposure to CSA may lead to cortical thinning of the dorsolateral prefrontal cortex, which is deeply involved in emotion regulation, to a greater extent than other types of childhood abuse.

Childhood abuse is associated with brain structural alterations; however, few studies have investigated the association between specific types of childhood abuse and cortical volume in patients with major depressive disorder (MDD). We aimed to investigate the association between specific types of childhood abuse and gray matter volumes in patients with MDD. Seventy-five participants with MDD and 97 healthy controls (HCs) aged 19-64 years were included. Cortical gray matter volumes were compared between MDD and HC groups, and also compared according to exposure to each type of specific childhood abuse. Emotional, sexual, and physical childhood abuse were assessed using the 28-item Childhood Trauma Questionnaire. Patients with MDD showed a significantly decreased gray matter volume in the right anterior cingulate gyrus (ACG). Childhood sexual abuse (CSA) was associated with significantly decreased gray matter volume in the right middle occipital gyrus (MOG). In the post-hoc comparison of volumes of the right ACG and MOG, MDD patients with CSA had significantly smaller volumes in the right MOG than did MDD patients without CSA or HCs. The right MOG volume decrease could be a neuroimaging marker associated with CSA and morphological changes in the brain may be involved in the pathophysiology of MDD., Competing Interests: Declaration of Competing Interest The authors have no potential or actual conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: The present study examined the impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health service utilization through a comparative analysis of nationwide data regarding inpatient care users, outpatient visits, emergency department (ED) visits, and admissions via the ED before and during the pandemic., Methods: Data from approximately 350,000 Koreans diagnosed with mental illness were analyzed in terms of hospitalization, outpatient visits, and ED visits between January 2018 and June 2021. An interrupted time series analysis was conducted to determine the significance of changes in mental health service utilization indicators., Results: The number of hospital admissions per patient decreased by 1.2% at the start of the pandemic and 0.7% afterward. The length of hospital stay increased by 1.8% at the outbreak of the pandemic, and then decreased by 20.2%. Although the number of outpatients increased, the number of outpatient visits per patient decreased; the number of outpatient visits for schizophrenia (3.4%) and bipolar disorder (3.5%) significantly decreased immediately post-outbreak. The number of ED visits per patient decreased both immediately post-outbreak and afterward, and ED visits for schizophrenia (19.2%), bipolar disorder (22.3%), and depression (17.4%) decreased significantly immediately post-outbreak. Admissions via the ED did not show a significant change immediately post-outbreak., Conclusions: Mental health service utilization increased during the pandemic, but medical service use decreased overall, with a particularly significant decrease in ED utilization. As the pandemic worsened, the decline in outpatient visits became more pronounced among those with severe mental illness.

Since ancient times, plants have been a good source of natural antioxidants. Plants remove active oxygen through antioxidants and contain various active ingredients. These active ingredients of plants are used to alleviate skin aging and chronic diseases. Ajuga spectabilis Nakai (AS) is a perennial plant, is endemic to Korea, and has the characteristics of alpine plants. The aim of this study was to assure the possibility of using AS as a functional natural and cosmetic material. For this, we carried out biologically activated material characteristic evaluations about antioxidant, wrinkle reduction, and anti-inflammatory effects using AS extract. To carry out this experiment, we extracted AS extract from AS water extract (AS-W) and AS 70% ethanol extract (AS-E). AS-E showed the highest DPPH activity and tyrosinase inhibitory activity. After, the measurement of metalloprotease (MMP)-1 inhibition effect showed the AS-W and AS-E activation at the concentration of 100 µg/mL. In addition, at the same concentration, from the result of the measurement of the biosynthesis quantity of pro-collagen type-1 we knew that its excellent effect appeared in AS-E (CCD-986sk). The inhibition of NO production in AS-W and AS-E was confirmed in LPS-induced mouse macrophage RAW264.7 cells. On cell viability, it was judged that AS-E had no toxicity because it showed a high cell viability at a high concentration, and it was used for the anti-inflammatory activity. Inhibition of NO production worked only in AS-E; inflammatory cytokine TNF-α and IL-6 were suppressed in a concentration-dependent manner in AS-E. AS is believed to be used as a natural cosmetic material because it has been proven to have antioxidant, whitening, wrinkle-improving, and anti-inflammatory effects. Therefore, the results indicate that AS extract can play an important role as a functional natural material and a cosmetic material for whitening, wrinkle reduction, and anti-inflammatory effect.

Alexithymia is characterized by impairments in the processing of emotions. Although the disruptions in the white matter (WM) integrity in Major depressive disorder (MDD) has frequently been reported, the underlying relationship with alexithymia remains unclear. In the present study, we investigated WM tracts with Tracts Constrained by UnderLying Anatomy approach to discover potential associations between alexithymia and WM integrity to identify the neural basis of impaired emotional self-awareness in MDD. 101 patients with MDD and 99 healthy sex- and age-matched individuals underwent diffusion-weighted imaging. All participants were assessed with the 20-item Toronto Alexithymia Scale (TAS). TAS scores were significantly higher in MDD patients than in controls. Patients with MDD exhibited significantly lower FA values in the left inferior longitudinal fasciculus and it also showed negative associations with TAS. These results contribute to the neurobiological evidence on the association between MDD and alexithymia. Additionally, they suggest that reduced white matter integrity in the regions constitutes a principal pathophysiology underlying impaired emotional recognition and description in MDD.

Major depressive disorder (MDD) is one of the most common psychiatric disorders, and present various symptoms such as the dysregulation of mood, cognition, and behavior. The purpose of the present study was to investigate the morphometric change in MDD patients by voxel-based morphometry (VBM) and sulcal depth analyses. Forty-six MDD patients (mean age, SD; 36.07±14.34), and 23 age- and sex-matched normal controls (NML) (mean age, SD; 36.78±14.42) were included. Coronal 3D T1 magnetic resonance imaging (MRI) was obtained with the resolution of isotropic 1.0 mm. To check morphological changes of brain, T1 MRIs were objectively processed by VBM and sulcal depth methods. In sulcal depth analysis, depressed patients showed reduced sulcal depth in the areas of left posterior ramus of the lateral sulcus, superior frontal sulcus, supramarginal gyrus, central sulcus (Rolando's fissure), and Heschl's gyrus. And right posterior ramus of the lateral sulcus, temporal plane of the superior temporal gyrus, anterior transverse collateral sulcus, and central sulcus (Rolando's fissure) were also reduced compared to NML. But, VBM analyses did not showed significant finding. Reduced sulcal depth in the motor and emotion related areas were found in patients with MDD. Especially reduced sulcal depth in bilateral central sulci which are connecting between primary motor cortex and primary sensory cortex seems to be related with social and physical anhedonia in MDD.

Lac dye is a natural colorant derived mainly from the insect Kerria lacca (Kerr) and has been used in food and beverage as a red-coloring additive. Despite its increasing use for human consumption as an alternative for allergy-associated cochineal, its toxicity profile remained incomplete to sufficiently assess its safety for the intended use. In this study, we evaluated systemic and genetic toxicity by performing acute and subacute oral toxicity studies in Sprague-Dawley (SD) rats using highly purified lac dye (LD) formulated in water and a battery of genotoxicity tests, respectively. To assess antigenic potentials, we carried out an in vivo passive cutaneous anaphylaxis test. A single dose of LD did not cause mortality at 5000 mg/kg body weight (BW), setting oral LD 50 of >5000 mg/kg BW in SD rats. In the 90-day study, transient salivation without accompanying histopathological lesions in the salivary glands in 200 and 500 mg/kg BW groups and red-purple pigmentation on the surface of femora and skulls in 500 mg/kg groups were observed as nonadverse effects associated with LD, and no adverse effect was detected in all of the parameters examined, establishing a 500 mg/kg BW as no-observed-adverse-effect-level (NOAEL). Furthermore, LD was not mutagenic nor clastogenic in the genotoxicity tests. When tested for antigenicity, LD did not induce anaphylactic skin responses as opposed to the positive reaction by ovalbumin, suggesting a lack of antigenicity. Taken together, these findings provide extended toxicity information on LD with direct evidence supporting the lack of antigenicity, providing essential guidance for its safe use in humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Kim, Kim, Kwon, Lim, Han, Choi, Jung and Kang.)

Background: Despite the growing number of refugees and their mental health issues, neurobiological mechanisms to explain clinical symptoms resulting from traumatic events, such as post-traumatic stress disorder (PTSD) or major depressive disorder (MDD), have not been extensively investigated. Research on the mental health of North Korean refugees (NKRs) who defected to South Korea for resettlement is still at an early stage but commonly reports structural and functional abnormalities in brain regions related to reward and motivational processing. The nucleus accumbens (NAc) and ventral pallidum (VP) are the major sites in subcortical structures that play key roles in reward and motivation., Methods: The present study examined subcortical structural abnormalities of 28 NKRs and age-, sex- matched South Korean Controls (SKCs) using shape analysis at the vertex level., Results: Among the 28 NKRs, 18 had psychiatric disorders, including PTSD and MDD. The NKRs showed significantly reduced volumes in the right NAc and bilateral VP compared to the SKRs. The volume of the right VP showed a significant negative correlation with current PTSD severity in the NKR group., Conclusions: Our findings demonstrated that structural alterations of the NAc and VP may explain PTSD and MDD observed in the refugees and further suggest that the aftereffect of trauma, manifested as anhedonia and anxiety, may show chronically., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022. Published by Elsevier B.V.)

Background: An aberrant neural connectivity has been known to be associated with bipolar disorder (BD). Local gyrification may reflect the early neural development of cortical connectivity and has been studied as a possible endophenotype of psychiatric disorders. This study aimed to investigate differences in the local gyrification index (LGI) in each cortical region between patients with BD and healthy controls (HCs)., Methods: LGI values, as measured using FreeSurfer software, were compared between 61 patients with BD and 183 HCs. The values were also compared between patients with BD type I and type II as a sub-group analysis. Furthermore, we evaluated whether there was a correlation between LGI values and illness duration or depressive symptom severity in patients with BD., Results: Patients with BD showed significant hypogyria in various cortical regions, including the left inferior frontal gyrus (pars opercularis), precentral gyrus, postcentral gyrus, superior temporal cortex, insula, right entorhinal cortex, and both transverse temporal cortices, compared to HCs after the Bonferroni correction ( p < 0.05/66, 0.000758). LGI was not associated with clinical factors such as illness duration, depressive symptom severity, and lithium treatment. No significant differences in cortical gyrification according to the BD subtype were found., Conclusions: BD appears to be characterized by a significant regionally localized hypogyria, in various cortical areas. This abnormality may be a structural and developmental endophenotype marking the risk for BD, and it might help to clarify the etiology of BD.

Objective: Considerable evidence suggests that neuroinflammation plays an important role in the pathophysiology of major depressive disorder (MDD). However, the relationship between serum C4 binding protein (C4BP) and white matter (WM) tract integrity in MDD has not been investigated., Methods: We obtained diffusion tensor images of 44 patients with MDD and 44 healthy controls and performed TRActs Constrained by UnderLying Anatomy (TRACULA) analysis to assess WM tract integrity. Serum C4-binding protein alpha chain (C4BPA) and C4- binding protein beta chain (C4BPB) levels were measured and in-between group comparisons were obtained. The correlation between serum C4BP levels and WM tract integrity was examined., Results: In comparison to healthy controls, both serum C4BPA and C4BPB were higher in MDD. Also, fractional anisotropy (FA) was increased in the left cingulum-angular bundle (CAB) in MDD, but not healthy controls (HCs). A significant correlation was found between serum C4BP and FA levels in the right cingulum-cingulate gyrus bundle (CCG) in MDD., Conclusion: This study is the first to investigate the correlation between serum C4BP levels and WM tract integrity in MDD. We identified an increase in WM integrity in the left CAB region in MDD. Furthermore, serum C4BP levels were higher in MDD, and this finding correlated with increased WM integrity in the right CCG region.

Work-family conflict (WFC), an inter-role conflict between work and family, negatively affects mental health. Using a nationally representative systematic sample, this study aimed to investigate the association between WFC, depressive symptoms, and potential moderators in the association of adult female workers. Data of 4714 female workers (aged ≥19 years) were obtained cross-sectionally from the 2018 nationwide Korean Longitudinal Survey of Women and Families (KLoWF). WFC was assessed using a 7-item questionnaire, based on which scores were classified into high (>75th percentile score) and low (≤75th percentile score) levels of WFC. Significant depressive symptoms were defined as a score of ≥10 on the 10-item version of the Center for Epidemiologic Studies for Depression Scale. Female workers with high WFC levels were more likely to have depressive symptoms than those with low WFC levels (odds ratio = 2.29, 95% confidence interval = 1.91-2.74). In stratified analyses, high WFC levels were associated with the highest odds of depressive symptoms in the following groups: young adults (19-39 years), those with a college degree or above or with high income, never-married individuals, those with a family size of three or a single child, nonstandard workers, and pink-collar workers. This study replicated and extended previous findings on the association between WFC and depressive symptoms. The association was moderated by age, education and income levels, marital status, family size, number of children, and job conditions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Workplace gender discrimination (WGD) may have long-term negative impacts on female workers' mental health. We aimed to investigate the association between WGD and the prevalence of depressive symptoms using a nationally representative sample of female employees in South Korea., Methods: Data of 3190 adult female employees were obtained from the 2018 nationwide Korean Longitudinal Survey of Women and Families. Women's perception of WGD was assessed using a 6-item questionnaire. Respondents were classified into high, medium, and low levels of WGD according to the 25th and 75th percentile scores. A score of ≥10 on the 10-item version of the Center for Epidemiologic Studies for Depression Scale was defined as having significant depressive symptoms., Results: A high level of WGD was significantly associated with a higher odds ratio (OR) for depressive symptoms compared to the low level (OR = 1.87, 95% confidence interval = 1.45-2.41). In the subgroup analyses, high WGD levels were associated with the highest OR for depressive symptoms in the following subgroups: younger age (19-39 years), those with a college degree, non-standard workers, pink collar workers, those with a workplace size of 10-29 employees, those with high levels of job autonomy, or low levels of emotional labor., Limitations: Causal interpretation is limited owing to the study's cross-sectional design., Conclusions: A high level of perceived WGD was associated with depressive symptoms among female employees. Certain groups of female employees may be particularly vulnerable to the detrimental effects of WGD on depression., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The Nod-like receptor pyrin containing 3 (NLRP3) inflammasome has been reported to be a convergent point linking the peripheral immune response induced by psychological stress and neuroinflammatory processes in the brain. We aimed to identify differences in the methylation profiles of the NLRP3 gene between major depressive disorder (MDD) patients and healthy controls (HCs). We also investigated the correlation of the methylation score of loci in NLRP3 with cortical thickness in the MDD group using magnetic resonance imaging (MRI) data. A total of 220 patients with MDD and 82 HCs were included in the study, and genome-wide DNA methylation profiling of the NLRP3 gene was performed. Among the total sample, 88 patients with MDD and 74 HCs underwent T1-weighted structural MRI and were included in the neuroimaging-methylation analysis. We identified five significant differentially methylated positions (DMPs) in NLRP3 . In the MDD group, the methylation scores of cg18793688 and cg09418290 showed significant positive or negative correlations with cortical thickness in the occipital, parietal, temporal, and frontal regions, which showed significant differences in cortical thickness between the MDD and HC groups. Our findings suggest that NLRP3 DNA methylation may predispose to depression-related brain structural changes by increasing NLRP3 inflammasome-related neuroinflammatory processes in MDD.

Trait impulsivity is a known risk factor for suicidality, and the prefrontal cortex plays a key role in impulsivity and its regulation. However, the relationship between trait impulsivity, neural basis, and suicidality has been inconsistent. Therefore, this study aimed to explore the relationship between impulsivity and its structural correlates (prefrontal gray matter volume), suicidal ideation, and actual suicide attempts. A total of 87 individuals with major depressive disorder participated in study, and the gray matter volume of the prefrontal regions was extracted from T1 images based on region of interest masks. The variables for the mediation models were selected based on correlation analysis and tested for their ability to predict suicide attempts, with impulsivity and suicidal ideation as the mediation variables and gray matter volume as the independent variable. A significant correlation was observed between suicidal ideation and the left dorsolateral prefrontal cortex and right dorsomedial prefrontal cortex. The dual-mediation model revealed a significant indirect relationship between gray matter volume in both regions and suicide attempts mediated by motor impulsivity and suicidal ideation. The counterintuitive positive relationship between gray matter volume and suicidality was also discussed.

Bupleurum latissimum Nakai is a rare endemic species native to Ulleung-do in South Korea. This study aimed to report on the rhizosphere soil microbial diversity of B. latissimum. Proteobacteria , Actinobacteria , and Verrucomicrobia were identified in relative abundances of 27.77%, 21.70%, and 15.27%, respectively.