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This study aimed to investigate alterations in white matter (WM) microstructure in patients with psychotic and non-psychotic bipolar disorder (PBD and NPBD, respectively). We used 3T-magnetic resonance imaging to examine 29 PBD, 23 NPBD, and 65 healthy control (HC) subjects. Using tract-based spatial statistics for diffusion tensor imaging data, we compared fractional anisotropy (FA) and mean diffusion (MD) pairwise among the PBD, NPBD, and HC groups. We found several WM areas of decreased FA or increased MD in the PBD and NPBD groups compared to HC. PBD showed widespread FA decreases in the corpus callosum as well as the bilateral internal capsule and fornix. However, NPBD showed local FA decreases in a part of the corpus callosum body as well as in limited regions within the left cerebral hemisphere, including the anterior and posterior corona radiata and the cingulum. In addition, both PBD and NPBD shared widespread MD increases across the posterior corona radiata, cingulum, and sagittal stratum. These findings suggest that widespread WM microstructural alterations might be a common neuroanatomical characteristic of bipolar disorder, regardless of being psychotic or non-psychotic. Particularly, PBD might involve extensive inter-and intra-hemispheric WM connectivity disruptions.

We investigated the effect of the coronavirus disease-2019 (COVID-19) pandemic on suicide trends in Korea via a time-series analysis. We used Facebook Prophet to generate forecasting models based on the monthly numbers of suicide deaths in Korea between 1997 and 2018, validated the models by comparison with the 2019 numbers, and predicted the numbers of suicides in 2020. We compared the expected and observed numbers of suicides during the COVID-19 pandemic. The total numbers of suicides during the COVID-19 pandemic did not deviate from projections based on the pre-pandemic period. However, the number of suicides among women and those under the age of 34 years significantly exceeded the expected level. The COVID-19 pandemic did not increase the overall suicide rate significantly. However, suicides among women and young people increased, suggesting that the pandemic might drive more members of these groups to suicide. Further studies are needed to verify the long-term impact of the COVID-19 pandemic on suicide.

The dramatic changes in people’s daily lives caused by the 2019 coronavirus (COVID-19) pandemic have had a huge impact on their emotions and behaviors. This study aimed to examine psychosocial responses to COVID-19 using network analysis. A total of 1,500 urban residents of South Korea, selected from an online public panel, were surveyed using self-rating questionnaires addressing daily life changes, fear of infection, and distress related to COVID-19. Participants also completed a 10-item Perceived Stress Scale survey. We constructed regularized partial correlation networks, estimated global and local network metrics, tested network accuracy and stability, and compared the estimated networks between men and women. The network of the psychosocial responses consisted of 24 nodes that were classified into five groups: ‘fear of infection’, ‘difficulty with outside activities’, ‘economic loss’, ‘altered eating and sleeping’, and ‘adaptive stress’. The node centralities indicated that ‘distress in obtaining daily necessities’ and ‘concern about harming others’ were the most important issues in people’s responses to COVID-19. These nodes were connected by a negative edge, reflecting individual- and community-level issues, respectively. The overall level of perceived stress was linked to the network by the connection node ‘anger toward others or society’, which was associated with economic problems in men, but with distress from changes in daily activities in women. The results suggest that two contrasting feelings—personal insecurity regarding basic needs and a collectivistic orientation—play roles in the response to unusual experiences and distress due to COVID-19. This study also showed that public anger could arise from the psychological stress under the conditions imposed by COVID-19.

ObjectiveTo investigate the frequency distribution of various craniofacial skeletal patterns in a large Korean adult obstructive sleep apnea (OSA) population, and to find a relationship between craniofacial risks and respiratory and sleep characteristics.MethodsA total of 1226 OSA patients (mean age of 44.9±13.3 years) were included in this retrospective cross-sectional study. All subjects were evaluated for gender and age using fourteen polysomnographic, five cephalometric, two comorbid variables, and three self-reported indexes. Frequency analysis was used to screen the distribution of main skeletal patterns and subtypes. Intergroup comparisons were performed using independent t-test, chi-square test or analysis of variance. Univariable regression analysis was done to find a relationship between skeletal risks and OSA characteristics.ResultsThe frequency distribution of skeletal patterns was as follows: sagittally 57.2%, 32.3%, and 10.5% of Class II, Class I, and Cass III; vertically 54.0%, 26.7%, and 19.3% of hyperdivergent, normodivergent, and hypodivergent type, respectively. Polysomnographic, symptomatic, and comorbid variables showed no differences among patients with different skeletal patterns. Conversely, skeletal variables showed no differences according to OSA severity. The prevalence of highly risky skeletal pattern of hyperdivergent Class II was more likely to be females (OR 4.52, P < .01) and less obese (OR 3.21, P < .01), irrelevant to OSA and sleep characteristics.ConclusionCharacteristic frequency distributions of skeletal patterns and subtypes were observed in adult OSA patients however, no statistical association was found between the skeletal patterns and OSA characteristics due to the large interindividual variation.

α-Klotho is a type 1 transmembrane protein that exhibits aging suppression function. The large amino-terminal extracellular domain of α-klotho is shed as soluble klotho (sKlotho) and functions as a circulating cardioprotective hormone. Diacylglycerol (DAG)-activated calcium-permeable TRPC6 channel plays a critical role in stress-induced cardiac remodeling. DAG activates TRPC6 by acting directly on the channel to increase its activity and by stimulation of channel exocytosis. sKlotho protects the heart by inhibiting DAG stimulation of TRPC6 exocytosis. How DAG stimulates TRPC6 exocytosis and thereby inhibition by sKlotho are unknown. Using a compound that directly activates TRPC6 without affecting channel exocytosis, we validate that sKlotho selectively blocks DAG stimulation of channel exocytosis. We further show that DAG stimulates exocytosis of TRPC6-containing vesicles pre-docked to the plasma membrane. Mnuc13 family proteins play important roles in the proper assembly of SNARE proteins and priming the vesicle competent for fusion. We show that DAG stimulates TRPC6 exocytosis by targeting to the C1 domain of Munc13-2. The results provide fresh insights into the molecular mechanism by which DAG regulates vesicle fusion and how sKlotho protects the heart against injury.

BackgroundThe prognostic role of BDNF val66met polymorphism on long-term cardiac outcomes in acute coronary syndrome (ACS) has been unclear. Environmental factors may modify the association, but these have not been investigated to date. This study aimed to investigate the potential interactive effects of BDNF val66met polymorphism and personality traits, one of the main environmental prognostic factors of ACS, on major adverse cardiac events (MACEs) in patients with ACS.MethodsA total of 611 patients with recent ACS were recruited at a university hospital in Korea. Baseline evaluations from 2007 to 2012 assessed BDNF val66met polymorphism and personality using the Big Five Inventory, which yielded two personality clusters (resilient and vulnerable) and five dimensions (extraversion, agreeableness, conscientiousness, neuroticism, and openness). Over a 5~12 year follow-up after the index ACS, times to MACE were investigated using Cox regression models after adjustment for a range of covariates.ResultsThe BDNF val66met polymorphism modified the associations between vulnerable personality type and worse long-term cardiac outcomes in ACS patients with significant interaction terms, in that the associations were statistically significant in the presence met allele. Similar findings were observed for the individual personality dimensions of agreeableness and neuroticism.ConclusionsGene (BDNF val66met polymorphism) x environment (personality traits) interactions on long-term cardiac outcomes were found in ACS.

Background When evaluating hearing disability in medicolegal cases, an average of thresholds at several frequencies is calculated using pure tone audiometry. Occasionally, there are instances in which thresholds at certain frequencies are omitted. One typical example is the threshold at 3 kHz (H3k). The American Academy of Otolaryngology–Head and Neck Surgery Committee on Hearing and Equilibrium (1995) suggested that the average of thresholds at 2 kHz and 4 kHz (H24k) could replace H3k for a comparison of results between studies. However, to the best of our knowledge, there is no report in the literature that compares H3k and H24k. Objective This study aimed to investigate the agreement between H3k and H24k. Methods This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2012, which was conducted by the Korean government. A total of 18,472 participants (unweighted) who represented 39,357,497 Koreans (weighted) were included. To verify the agreement of H3k and H24k, a paired t-test, Cohen’s d, Pearson’s correlation, Cronbach’s coefficient, intraclass correlation coefficient (ICC), a Bland–Altman plot, and linear regression analysis were used. Results The means of H3k and H24k were 16.2 dBHL and 16.6 dBHL, respectively. They were significantly different in a paired t-test (p

Allergic diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis are attractive research areas. Tyrosol (2-(4-hydroxyphenyl)ethanol) is a polyphenolic compound with diverse biological activities. In this study, we investigated whether tyrosol has anti-allergic inflammatory effects. Ovalbumin-induced active systemic anaphylaxis and immunoglobulin E-mediated passive cutaneous anaphylaxis models were used for the immediate-type allergic responses. Oral administration of tyrosol reduced the allergic symptoms of hypothermia and pigmentation in both animal models. Mast cells that secrete allergic mediators are key regulators on allergic inflammation. Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines. Intracellular calcium levels and activation of inhibitor of kappa B kinase (IKK) regulate cytokine expression and degranulation. Tyrosol blocked calcium influx and phosphorylation of the IKK complex. To define the molecular target for tyrosol, various signaling proteins involved in mast cell activation such as Lyn, Syk, phosphoinositide 3-kinase (PI3K), and Akt were examined. Our results showed that PI3K could be a molecular target for tyrosol in mast cells. Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K. Therefore, we expect tyrosol become a potential therapeutic candidate for allergic inflammatory disorders.

Background/Objective There have been several operative techniques for adenoidectomy and their efficacy and morbidity are different according to the technique. This prospective multicenter study was aimed to compare the efficacy and morbidity of coblation adenoidectomy (CA) with those of power-assisted adenoidectomy. Study Design Prospective multi-institutional study. Methods Children who underwent CA, power-assisted adenoidectomy with cauterization (PAA+C) or without cauterization (PAA-C) due to adenoid hypertrophy were enrolled from 13 hospitals between July 2013 and June 2014. Mean operation time, degree of intraoperative bleeding and postoperative bleeding rate were evaluated. Results A total of 388 children (mean age ± standard deviation = 6.6 ± 2.5 years; 245 males and 143 females) were included. According to the adenoidectomy technique, the children were classified into 3 groups: (1) CA (n = 116); (2) PAA+C (n = 153); and (3) PAA-C (n = 119). Significant differences were not found in age and sex among three groups. In the CA group, mean operation time was significantly shorter (P < 0.001) and degree of intraoperative bleeding was significantly less (P < 0.001) compared to PAA+C or PAA-C group. Delayed postoperative bleeding rate of PAA-C group was significantly higher than that of CA or PAA+C group (P = 0.016). Conclusions This prospective multicenter study showed that CA was superior to PAA in terms of mean operation time and degree of intraoperative bleeding.

Background: Brain derived neurotrophic factor (BDNF) has been shown to play an important role in poststroke recovery. BDNF secretion is influenced by genetic and epigenetic profiles. This study aimed to investigate whether BDNF val66met polymorphism and promoter methylation status were associated with outcomes at two weeks and one year after stroke. Methods and Findings: A total of 286 patients were evaluated at the time of admission and two weeks after stroke, and 222 (78%) were followed one year later in order to evaluate consequences of stroke at both acute and chronic stages. Stroke outcomes were dichotomised into good and poor by the modified Rankin Scale. Stroke severity (National Institutes of Health Stroke Scale), physical disability (Barthel Index), and cognitive function (Mini-Mental State Examination) were measured. Associations of BDNF genotype and methylation status on stroke outcomes and assessment scale scores were investigated using logistic regression, repeated measures ANOVA and partial correlation tests. BDNF val66met polymorphism was independently associated with poor outcome at 2 weeks and at 1 year, and with worsening physical disability and cognitive function over that period. Higher BDNF promoter methylation status was independently associated with worse outcomes at 1 year, and with the worsening of physical disability and cognitive function. No significant genotype-methylation interactions were found. Conclusions: A role for BDNF in poststroke recovery was supported, and clinical utility of BDNF genetic and epigenetic profile as prognostic biomarkers and a target for drug development was suggested.

Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies.

This study investigated the relationship between erythrocyte membrane fatty acid (FA) levels and the severity of symptoms of individuals at ultra-high risk (UHR) for psychosis. Subjects of the present study consisted of 80 neuroleptic-naïve UHR patients. Partial correlation coefficients were calculated between baseline erythrocyte membrane FA levels, measured by gas chromatography, and scores on the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning Scale, and Montgomery-Asberg Depression Rating Scale (MADRS) after controlling for age, sex, smoking and cannabis use. Subjects were divided into three groups according to the predominance of positive or negative symptoms based on PANSS subscale scores; membrane FA levels in the three groups were then compared. More severe negative symptoms measured by PANSS were negatively correlated with two saturated FAs (myristic and margaric acids), one ω-9 monounsaturated FA (MUFA; nervonic acid), and one ω-3 polyunsaturated FA (PUFA; docosapentaenoic acid), and were positively correlated with two ω-9 MUFAs (eicosenoic and erucic acids) and two ω-6 PUFAs (γ-linolenic and docosadienoic acids). More severe positive symptoms measured by PANSS were correlated only with nervonic acid. No associations were observed between FAs and MADRS scores. In subjects with predominant negative symptoms, the sum of the ω-9 MUFAs and the ω-6:ω-3 FA ratio were both significantly higher than in those with predominant positive symptoms, whereas the sum of ω-3 PUFAs was significantly lower. In conclusion, abnormalities in FA metabolism may contribute to the neurobiology of psychopathology in UHR individuals. In particular, membrane FA alterations may play a role in negative symptoms, which are primary psychopathological manifestations of schizophrenia-related disability.

Background In evaluating hearing disability in medicolegal work, the apportionment of age- and gender-related sensorineural hearing loss should be considered as a prior factor, especially for the elderly. However, in the literature written in the English language no studies have reported on the age- and gender-related mean hearing threshold for the South Korean population. Objective This study aimed to identify the mean hearing thresholds in the South Korean population to establish reference data and to identify the age- and gender-related characteristics. Methods This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2012, which was conducted by the Korean government, the data of which was disclosed to the public. A total of 15,606 participants (unweighted) representing 33,011,778 Koreans (weighted) with normal tympanic membrane and no history of regular or occupational noise exposure were selected and analyzed in this study. The relationship between the hearing threshold level and frequency, age, and gender was investigated and analyzed in a highly-screened population by considering the sample weights of a complex survey design. Results A gender ratio difference was found between the unweighted and the weighted designs: male:female, 41.0%: 59.0% (unweighted, participants) vs. 47.2%:52.8% (weighted, representing population). As age increased, the hearing threshold increased for all frequencies. Hearing thresholds of 3 kHz, 4 kHz, and 6 kHz showed a statistical difference between both genders for people older than 30, with the 4 kHz frequency showing the largest difference. This paper presents details about the mean hearing threshold based on age and gender. Conclusions The data from KNHANES 2010–2012 showed gender differences at hearing thresholds of 3 kHz, 4 kHz, and 6 kHz in a highly-screened population. The most significant gender difference in relation to hearing threshold was observed at 4 kHz. The hearing thresholds at all of the tested frequencies worsened with increasing age. The mean hearing thresholds suggested in this study will be useful for the formulation of healthcare-related hearing policies and used as reference data for disability ratings for hearing loss due to various causes.