Psychological Distress and Perceived Burden in Parents of Korean Children With IgE-Mediated Food Allergy.

BACKGROUND: Food allergy (FA) can have a profound effect on quality of life (QoL), stress, and anxiety in the family. We aimed to validate the Korean version of the Food Allergy Quality of Life-Parental Burden (FAQL-PB) and identify factors related to the parental psychosocial burden of caring for children with FAs. METHODS: Parents of children aged between 6 months and 17 years with immunoglobulin E (IgE)-mediated FAs from the Pediatric Allergy Department of five university hospitals in Korea were enrolled in the study. Parents were asked to complete the FAQL-PB, Food Allergy Independent Measure-Parent Form (FAIM-PF), Child Health Questionnaire-Parents Form 28 (CHQ-PF28), Beck's Anxiety Inventory, Connor-Davidson Resilience Scale, and Patient Health Questionnaire-9 for depression. Statistical analyses included internal consistency, test-retest reliability, concurrent validity, discriminative validity, and logistic regression analyses. RESULTS: A total of 190 parents were enrolled. Social activity limitation was the item with the highest FAQL-PB scores. The Cronbach's α for each item was higher than 0.8. The test-retest reliability was good (intra-class correlation coefficient, 0.716; 95% confidence interval [CI], 0.100-0.935). An increase in the FAQL-PB was significantly associated with an increase in the FAIM-PF (ß = 0.765, P < 0.001) (concurrent validity). There was a positive correlation between parental burden, anxiety, and depression, while resilience was inversely correlated with parental burden (all P < 0.001). The total FAQL-PB score in parents of children who had experienced anaphylaxis was significantly higher than that in parents of children who did not experience it (P = 0.008). When adjusting for age, sex, and underlying diseases, anaphylaxis (ß = 9.32; 95% CI, 2.97 to 15.68), cow's milk (CM) allergy (ß = 8.24; 95% CI, 2.04 to 14.44), soybean allergy (ß = 13.91; 95% CI, 1.62 to 26.20), higher anxiety (ß = 1.05; 95% CI, 0.07 to 1.41), higher depression (ß = 2.15; 95% CI, 1.61 to 2.69), and lower resilience (ß = -0.42; 95% CI, -0.61 to -0.2) were significantly associated with greater parental burden in children with IgE-mediated FAs. CONCLUSION: FAQL-PB is a reliable and valid tool for use in Korea. Anaphylaxis, CM or soybean allergies, more anxiety and depression symptoms, and lower resilience are associated with poorer QoL in parents of children with FAs.

Relationships Between Secondhand Smoke Incursion and Wheeze, Rhinitis, and Eczema Symptoms in Children Living in Homes Without Smokers in Multi-Unit Housing.

INTRODUCTION: Secondhand smoke (SHS) incursion can occur in units of multi-unit housing (MUH). The purpose of this study was to determine the relationship between SHS incursion and allergic symptoms in children living in MUH without smokers. METHODS: We conducted a cross-sectional study from May to September 2015 in Seoul, Korea. Children were recruited from elementary schools, kindergartens, and daycare centers. In total, 16676 children between 1 and 13 years of age living in MUH without smokers were included in the analysis. Allergic symptoms during the previous 12 months (current wheeze, rhinitis, and eczema) and home environmental factors, including the frequency of SHS incursion during the previous 12 months, were examined using a questionnaire filled out by the parents or guardians of the children. RESULTS: The prevalence of current allergic symptoms in children was 4.9% for wheeze, 42.0% for rhinitis, and 28.1% for eczema. The prevalence of SHS incursion into the children's homes was 61.6%. In a multivariable logistic regression analysis adjusted for demographic and home environmental factors, children living in homes with SHS incursion (either no more than once a month or more than once a month) were more likely to have current wheeze, rhinitis, and eczema than those with no SHS incursion. CONCLUSIONS: More than half of the children's homes in MUH without smokers had SHS incursion. SHS incursion into homes was associated with wheeze, rhinitis, and eczema symptoms in children. IMPLICATIONS: Children living in multi-unit housing (MUH) can be exposed to secondhand smoke (SHS) from smoke transferred from neighboring units with smokers. This study found that more than half of the children's homes without smokers in MUH had SHS incursion. Children living in homes with SHS incursion (either no more than once a month or more than once a month) were more likely to have current wheeze, rhinitis, and eczema than those with no SHS incursion. We confirmed that SHS incursion was associated with allergic symptoms in children.

Identification of potent, selective, CNS-targeted inverse agonists of the ghrelin receptor.

The optimization for selectivity and central receptor occupancy for a series of spirocyclic azetidine-piperidine inverse agonists of the ghrelin receptor is described. Decreased mAChR muscarinic M2 binding was achieved by use of a chiral indane in place of a substituted benzylic group. Compounds with desirable balance of human in vitro clearance and ex vivo central receptor occupancy were discovered by incorporation of heterocycles. Specifically, heteroaryl rings with nitrogen(s) vicinal to the indane linkage provided the most attractive overall properties.

Novel oxidative modifications in redox-active cysteine residues.

Redox-active cysteine, a highly reactive sulfhydryl, is one of the major targets of ROS. Formation of disulfide bonds and other oxidative derivatives of cysteine including sulfenic, sulfinic, and sulfonic acids, regulates the biological function of various proteins. We identified novel low-abundant cysteine modifications in cellular GAPDH purified on 2-dimensional gel electrophoresis (2D-PAGE) by employing selectively excluded mass screening analysis for nano ultraperformance liquid chromatography-electrospray-quadrupole-time of flight tandem mass spectrometry, in conjunction with MODi and MODmap algorithm. We observed unexpected mass shifts (Δm=-16, -34, +64, +87, and +103 Da) at redox-active cysteine residue in cellular GAPDH purified on 2D-PAGE, in oxidized NDP kinase A, peroxiredoxin 6, and in various mitochondrial proteins. Mass differences of -16, -34, and +64 Da are presumed to reflect the conversion of cysteine to serine, dehydroalanine (DHA), and Cys-SO2-SH respectively. To determine the plausible pathways to the formation of these products, we prepared model compounds and examined the hydrolysis and hydration of thiosulfonate (Cys-S-SO2-Cys) either to DHA (Δm=-34 Da) or serine along with Cys-SO2-SH (Δm=+64 Da). We also detected acrylamide adducts of sulfenic and sulfinic acids (+87 and +103 Da). These findings suggest that oxidations take place at redox-active cysteine residues in cellular proteins, with the formation of thiosulfonate, Cys-SO2-SH, and DHA, and conversion of cysteine to serine, in addition to sulfenic, sulfinic and sulfonic acids of reactive cysteine.

Risk factors associated with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission, outbreak duration, and mortality in acute-care settings.

BACKGROUND: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute-care settings affects patients, healthcare workers, and the healthcare system. We conducted an analysis of risk factors associated with outbreak severity to inform prevention strategies. METHODS: This cross-sectional analysis of COVID-19 outbreaks was conducted at Fraser Health acute-care sites between March 2020 and March 2021. Outbreak severity measures included COVID-19 attack rate, outbreak duration, and 30-day case mortality. Generalized linear models with generalized estimating equations were used for all outcome measures. A P value of 0.05 indicated statistical significance. Analyses were performed using SAS version 3.8 software, R version 4.1.0 software, and Stata version 16.0 software. RESULTS: Between March 2020 and March 2021, 54 COVID-19 outbreaks were declared in Fraser Health acute-care sites. Overall, a 10% increase in the hand hygiene rate during the outbreak resulted in an 18% decrease in the attack rate (P < .01), 1 fewer death (P = .03), and shorter outbreaks (P < .01). A 10-year increase in unit age was associated with 2.2 additional days of outbreak (P < 0.01) and increases in the attack rate (P < .05) and the number of deaths (P < .01). DISCUSSION: We observed an inverse relationship between increased hand hygiene compliance during outbreaks and all 3 severity measures. Increased unit age was also associated with increases in each of the severity measures. CONCLUSION: This study highlights the importance of hand hygiene practices during an outbreak and the difficulties faced by older facilities, many of which have infrastructural challenges. The latter reinforces the need to incorporate infection control standards into healthcare planning and construction.

Discovery and evaluation of spirocyclic derivatives as antagonists of the neuropeptide Y5 receptor.

A novel series of spirocyclic derivatives was synthesized and evaluated as NPY Y5R antagonists for the treatment of obesity. Cis and trans analogs 7a and 8a were equipotent in a Y5R binding assay (K(i)'s ≤ 1 nM) and displayed good stability in human and rat liver microsome preparations. Compound 7a failed to demonstrate weight loss activity in a diet-induced obese (DIO) rat model at unbound drug levels in the brain that exceeded the Y5R K(i) value by 25-fold over a 24-h time-period.

The Association between Unstable Employment and Suicidal Behavior in Young-Adult Precarious Workers.

OBJECTIVE: Precarious workers have increased over the past two decades in South Korea. Employment instability, especially among young adults, is considered a serious social problem. The unstable employment status of precarious workers has negative impacts on their mental health, such as suicidal behavior. This study aims to identify the effect of the unstable employment conditions on the suicidal behavior of precarious workers. METHODS: An online survey was conducted with a panel sample of South Korean adults (n=797) who were precarious workers aged between 25-34 years. We applied Model 6 of SPSS PROCESS MACRO 3.5 to examine the multiple mediation effects of depression and anger in the relationship between employment instability and suicide. RESULTS: Unstable employment had no direct effect on suicidal behavior. The path of unstable employment to suicidal behavior via depression and anger had a significant indirect effect. However, employment and anger were negatively related. The indirect effect of depression and anger on the relation between unstable employment and suicidal behavior was statistically significant. CONCLUSION: This study suggests an association between unstable employment and suicidal behavior, mediated by depression and anger. Specifically, a high level of unstable employment status increased depression. In contrast, a low level of unstable employment status increased anger, which ultimately led to an increase in suicidal behavior. These contrasting findings are likely to reflect the heterogeneity of precarious workers. Further longitudinal studies are necessary to identify the causality between precarious employment and suicidal behavior over time.

Reciprocal Prediction between Impulsivity and Problematic Internet Use among North Korean Refugee Youths in South Korea by Gender and Adverse Childhood Experience.

OBJECTIVE: North Korean refugee youths are at higher risk of developing a wide array of psychosocial sequelae, including increased impulsivity and problematic internet use. We aimed to identify reciprocal temporal relationships by performing autoregressive cross-lagged modeling and to examine how these relations differ by gender and adverse childhood experience. METHODS: We used the follow-up data of 108 North Korean refugee youths in South Korea over a 1-year period. The Barratt Impulsivity Scale-Brief and Young's Internet Addiction Test were used to assess impulsivity and problematic internet use, respectively. RESULTS: Autoregressive effects were significant across all groups, indicating that impulsivity and problematic internet use were stable across time; however, prospective prediction of problematic internet use from impulsivity was not significant across all groups. Problematic internet use at baseline positively predicted impulsivity at after 1 year of follow up in only males and individuals with adverse childhood experience. CONCLUSION: Our findings suggest that the negative effect of problematic internet use (i.e., increased impulsivity) among North Korean refugee youths may be more profound in males and those with adverse childhood experience. We present possible explanations for these findings and discuss the implications for targeted interventions.

Design and synthesis of orally-active and selective azaindane 5HT2c agonist for the treatment of obesity.

Based on our original pyrazine hit, CP-0809101, novel conformationally-restricted 5HT2c receptor agonists with 2-piperazin-azaindane scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the selectivity against 5HT2a and 5HT2b receptors with excellent 2c potency. Orally-active and selective compounds were identified with dose-responsive in vivo efficacy in our pre-clinical food intake model.

Orally active and brain permeable proline amides as highly selective 5HT2c agonists for the treatment of obesity.

Brain-penetrable proline amides were developed as 5HT2c agonists with more than 1000-fold binding selectivity against 5HT2b receptor. After medicinal chemistry optimization and SAR studies, orally active proline amides with robust efficacy in a rodent food intake inhibition model were uncovered.

Repeated aerosol delivery of carboxyl-terminal modulator protein suppresses tumor in the lungs of K-rasLA1 mice.

RATIONALE: Difficulties in achieving long-term survival of patients with lung cancer treated with conventional therapies suggest that novel approaches are required. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer. OBJECTIVES: To investigate the repeated effect of carboxyl-terminal modulator protein (CTMP) on multistage lung tumorigenesis. In this study, we addressed this question by studying the effects of lentivirus-based CTMP in the lungs of 9- and 13-week-old K-ras(LA1) mice, a model of lung cancer. METHODS: An aerosol of lentivirus-based CTMP was delivered into 9- and 13-week-old K-ras(LA1) mice, a model of lung cancer, through a nose-only inhalation system twice a week for 4 weeks. The effects of CTMP on lung cancer progression and Akt-related signals were evaluated. MEASUREMENTS AND MAIN RESULTS: Long-term repeated delivery of CTMP effectively reduced tumor progression in the lungs at different stages of development. Lentiviral-CTMP inhibited protein synthesis and cell cycle and altered Akt signaling pathway in the lungs of 9-week-old K-ras(LA1) mice, and increased apoptosis was observed in the lungs of 13-week-old K-ras(LA1) mice. CONCLUSIONS: Long-term repeated viral delivery of CTMP may provide a useful tool for designing lung tumor treatment.

The effect of early trauma on North Korean refugee youths' mental health: Moderating effect of emotional regulation strategies.

Research shows that North Korean refugee youths are exposed to early traumatic events and are, therefore, vulnerable to mental health problems. We investigated the relationship between early trauma and emotion regulation strategies with symptoms of depression and attention-deficit hyperactivity disorder (ADHD) among North Korean refugee youths. In 2017-2018, we surveyed youths attending alternative schools for North Korean refugees in Seoul. One hundred and fifty-seven students (54 boys, 103 girls; 18.66 ± 2.82 years) completed questionnaires assessing early trauma experiences, emotion regulation strategies, depressive symptoms, and ADHD symptoms. Descriptive, correlation, and moderation analyses were conducted. Early trauma experience directly and negatively affected both the depressive and ADHD symptoms of North Korean refugee youths. The use of expressive suppression strategy significantly aggravated these effects of early trauma on both depressive and ADHD symptoms, indicating that it might be a risk factor for mental health problems among them. Contrarily, cognitive reappraisal seemed to buffer the effect of the expressive suppression strategy on depressive symptoms. A tailored intervention promoting emotion regulation strategies to prevent depressive and ADHD symptoms among this group is necessary.

Associations among Employment Status, Health Behaviors, and Mental Health in a Representative Sample of South Koreans.

The purpose of the present study was to compare the health behaviors, general health, and mental health of South Korean employees according to their employment status, and to examine how these associations vary across genders using the latest Korean National Examination Health and Nutrition Survey data. Logistic regression analyses were performed using employment status-permanent job, temporary job, and unemployed-as predictor variables and health-related variables as the outcome variables. Results indicated that temporary workers and the unemployed have higher odds of poor mental health regardless of gender. On the other hand, only male permanent workers were found to have a higher risk of problematic drinking compared to precarious workers and the unemployed. Meanwhile, only women showed a higher risk of current smoking in the temporary job and unemployed groups compared with permanent employees. Regarding general health, women, not men, in the temporary job group reported poorer general health (i.e., low health-related quality of life and higher self-perceived poor health) than those in other groups. These findings suggest that the development and implementation of intervention services, as well as organizational actions, need to consider differential impacts of unfavorable employment status on health issues according to gender.

Nanostructured lipid carriers-mediated brain delivery of carbamazepine for improved in vivo anticonvulsant and anxiolytic activity.

The limited brain delivery of carbamezapine (CBZ) presents a major hurdle in the successful epilepsy treatment. The potential of carbamezapine-loaded nanostructured lipid carriers (CBZ-NLCs) for improved brain delivery is investigated in the current study. CBZ-NLCs were prepared by using binary mixture of trilaurin and oleic acid as a lipid core stabilized with Poloxamer 188, Tween 80 and Span 80. CBZ-NLCs were evaluated for physicochemical properties, in vitro release, in vivo brain kinetics, anticonvulsant and anxiolytic activities. The optimized CBZ-NLCs demonstrated nanometric particle size (97.7 nm), surface charge of -22 mV and high drug incorporation (85%). CBZ-NLCs displayed biphasic release pattern with initial fast followed by sustained drug release. CBZ-NLCs significantly enhanced the AUC of CBZ (520.4 µg·h/mL) in brain compared with CBZ dispersion (244.9 µg·h/mL). In vivo anticonvulsant activity of CBZ-NLCs in PTZ-induced seizure model showed a significant increase in the onset time (143.0 sec) and reduction in duration (17.2 sec) of tonic-clonic seizures compared with CBZ dispersion (75.4 and 37.2 sec). The anxiolytic activity in light-dark box and elevated-plus maze models also demonstrated superiority of CBZ-NLCs to CBZ dispersion. From the results, CBZ-NLCs presents a promising strategy to improve brain delivery and therapeutic outcomes of CBZ in epilepsy.

Design, synthesis, and pharmacology of fluorescently labeled analogs of serotonin: application to screening of the 5-HT2C receptor.

Novel fluorescent derivatives of serotonin have been synthesized and used as tracers for the development of a 5-HT2C fluorescence polarization assay. Serotonin analogs that feature a fluorescent probe attached through an ether linkage at the tryptamine 5-position have high affinity for the 5-HT2C receptor, and affinity is dependent on both linker length and pendent dye. These variables have been optimized to generate Cy3B derivative 5a, which has 10-fold higher 5-HT2C affinity relative to serotonin (Kd=0.23 nM). In receptor activation experiments, 5a acts as a full agonist of 5-HT2C. Upon binding to 5-HT2C cell membranes, 5a shows a robust increase in fluorescence polarization (FP) signal. In an FP binding assay using 5a as a tracer ligand, Ki values for known 5-HT2C agonists and antagonists showed excellent agreement with Ki values from radioligand binding (r2=0.93). The FP ligand assay is suitable for high-throughput drug screening applications with respect to speed of analysis, displaceable signal, precision, and sensitivity to various reagents. A 384-well-based high-throughput assay that is rapid, economical, and predictive of test compounds' ability to bind to the 5-HT2C receptor has been compiled and validated.

Efficient gene delivery with osmotically active and hyperbranched poly(ester amine)s.

Degradable and hyperbranched poly (ester amine)s (PEAs) were successfully synthesized by Michael addition reaction between hydrophilic glycerol triacrylate (GTA) and low-molecular-weight polyethylenimine (LMW-PEI) and evaluated as nonviral gene carriers. PEAs effectively condensed DNA with particle sizes below 200 nm and suitable surface charges (15-45 mV), suitable for intracellular delivery. PEAs degraded in a controlled fashion showing half-lives of more than 12 days and were essentially nontoxic in three different cell lines. Elevated transfection levels by luciferase assay revealed the superiority of PEAs over PEI 25K and Lipofectamine. PEAs synthesized using 1:4 mol ratio of GTA to PEI [GTA/PEI-1.2(1:4)] showed highest transfection efficiency in HepG2 cells. PEAs showed significant gene expression in vitro as well as in vivo through aerosol administration. Reduction in packed cell volume (PCV) of cells when treated with polyplexes supported the hyperosmotic effect of PEAs. Effect of bafilomycin A1 on transfection efficiency of PEAs on 293T cells indicated its endosomal buffering capacity. High transfection efficiency was attributed to the synergism from hyperosmotic glycerol backbone in the PEAs and endosomal buffering capacity of PEI amine groups. Therefore, this convergence of osmotically active biodegradable PEAs suggests their potential as a safe and efficient gene delivery vector.

Patterns of Change in Employment Status and Their Association with Self-Rated Health, Perceived Daily Stress, and Sleep among Young Adults in South Korea.

We identified distinct trajectories of temporal changes in employment status and investigated their association with self-rated health, perceived stress, and sleep. Data pertaining to 1228 respondents (age: 17-31 years) were extracted from the Korea Youth Panel (YP2007) survey (3rd-9th wave) datasets. Participants were either paid employees (permanent or precarious) or currently unemployed but seeking a job at baseline. Latent class growth analyses were employed to extract different classes based on the annual change in employment status (permanent/precarious/unemployed). Logistic regression analyses were performed using extracted classes as predictor variables and health-related variables at the final time-point as outcome variables. Five trajectories of employment status change were identified: stability sustained; gradually deteriorated; swiftly alleviated; gradually alleviated; instability sustained. Compared with the stability sustained group, the gradually deteriorated and gradually alleviated groups showed higher odds of perceived stress. The gradually deteriorated, instability sustained, and gradually alleviated groups showed significantly higher odds of shorter sleep than the stabilized group. We highlight the adverse health effects of prolonged unstable employment and the need for interventions to mitigate these effects.

Factors Related to Change in Depression among North Korean Refugee Youths in South Korea.

This study investigated change in depression and revealed factors related to change using one-year follow-up data. A sample of 108 North Korean Refugee Youths (NKRYs) aged 13 to 26 years (66 females) was recruited from two alternative schools for NKRYs in South Korea. Based on the Center for Epidemiologic Studies Depression Scale cut-off score of 16, respondents were grouped based on change in depression score after one year as stable low, alleviated, deteriorated, or prolonged. Multinomial logistic regression assessed the influence of baseline psychological scores (resilience, emotional regulation strategy, and self-esteem), and reported social support (psychological/practical) on the odds of group classification. With the stable low group as the reference category, those with alleviated depression at Time 2 had significantly higher odds of expressive suppression and tended to have lower self-esteem at Time 1. The deteriorated depression group was more likely than the stable low group to have lower resilience and cognitive appraisal scores. Those with prolonged high depression were more likely than the stable low group to have lower resilience, less practical social support, and lower self-esteem. Psychological interventions, particularly those focused on increasing self-esteem and resilience, could be helpful for NKRYs with potential risk of depression. In addition, practical support should be provided on an as-needed basis to prevent chronic depression among NKRYs.

Serum immunoglobulin fused interferon-alpha inhibited tumor growth in athymic mice bearing colon 26 adenocarcinoma cells.

Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 x : 30 microg/kg and 50 x : 150 microg/kg). A slight anti-tumoral effect was observed in all 10 x groups compared to the control. In the 50 x groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-beta. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition.

Major Stressors among Korean Adolescents According to Gender, Educational Level, Residential Area, and Socioeconomic Status.

Adolescents are exposed to many stressors which have been associated with poor mental health. Using data from the 2015 Korea Youth Risk Behavior Web-based Survey, we identified the major stressors among Korean adolescents based on gender, current educational level, residential area, and socioeconomic status (SES). The major stressors among girls were relationship- and appraisal-related factors, whereas boys more often reported health- and conflict-related factors. High school students more often reported academic performance and family circumstances as major stressors, whereas middle school students tended to report conflict-related factors. Urban adolescents reported academic performance and conflicts with parents as major stressors while rural adolescents reported conflicts with teachers and peer relationship problems. Finally, adolescents of lower SES reported multiple factors, including relational and family problems, as major stressors; contrarily, among those of higher SES, the primary stressor was uniquely related to academic performance. This result is significant in that adolescents' stress levels, as well as the types of major stressors, vary depending on individual factors. It could also be beneficial for developing and implementing individualized and thus more efficient stress-management strategies.