Chemically Driven Clearance of Amyloid Aggregates by Polyfunctionalized Furo[2,3-b:4,5-b']dipyridine-Chalcone Hybrids to Ameliorate Memory in an Alzheimer Mouse Model.

The aberrant assembly of amyloid-ß (Aß) is implicated in Alzheimer's disease (AD). Recent clinical outcomes of Aß-targeted immunotherapy reinforce the notion that clearing Aß burden is a potential therapeutic approach for AD. Herein, to develop drug candidates for chemically driven clearance of Aß aggregates, we synthesized 51 novel polyfunctionalized furo[2,3-b:4,5-b']dipyridine-chalcone hybrid compounds. After conducting two types of cell-free anti-Aß functional assays, Aß aggregation prevention and Aß aggregate clearance, we selected YIAD-0336, (E)-8-((1H-pyrrol-2-yl)methylene)-10-(4-chlorophenyl)-2,4-dimethyl-7,8-dihydropyrido[3',2':4,5]furo[3,2-b]quinolin-9(6H)-one, for further in vivo investigations. As YIAD-0336 exhibited a low blood-brain barrier penetration profile, it was injected along with aggregated Aß directly into the intracerebroventricular region of ICR mice and ameliorated spatial memory in Y-maze tests. Next, YIAD-0336 was orally administered to 5XFAD transgenic mice with intravenous injections of mannitol, and YIAD-0336 significantly removed Aß plaques from the brains of 5XFAD mice. Collectively, YIAD-0336 dissociated toxic aggregates in the mouse brain and hence alleviated cognitive deterioration. Our findings indicate that chemically driven clearance of Aß aggregates is a promising therapeutic approach for AD.

Factors Associated With Health-promoting Behaviors Among Nurses in South Korea: Systematic Review and Meta-analysis Based on Pender's Health Promotion Model.

PURPOSE: Although the importance of health promotion for nurses is increasing, there is a lack of meta-analyses targeting nurses in the world. This study aimed to identify the effect sizes between the health-promoting behaviors and related variables of nurses working in Korea. METHODS: Systematic review and meta-analysis were conducted according to the PRISMA and MOOSE guidelines. The literature included in this meta-analysis was published between 1994 and 2022 in core databases such as KMbase, KISS, KoreaMed, ScienceON, DBpia, NAL, RISS, CINAHL, CENTRAL, WoS, PubMed, and hand searched. In this study, the PICO-SD framework was applied with Participants being nurses actively working in various healthcare settings across Korea, and for a more comprehensive search, intervention and comparisons were not set. The outcomes measured were nurses' health-promoting behaviors, assessed using structured tools. The study design included observational studies. The Comprehensive Meta-Analysis and the R software program were used for meta-analysis. RESULTS: In total, 50 articles were selected for the systematic review and meta-analysis. The total effect size of the 50 articles was moderate (correlation effect size [ESr] = 0.30). The individual variables presented in the 50 articles were classified into nine sub-categories according to Pender's Health Promotion Model (HPM). Among them, situational influences demonstrated the largest effect size (ESr = 0.44, number of studies [k] = 2), followed by perceived self-efficacy (ESr = 0.39, k = 10) and activity-related affect (ESr = 0.32, k = 12). CONCLUSIONS: To achieve the optimal health status of nurses through health promotion intervention programs, these effective variables - situational influences, perceived self-efficacy, and activity-related affect - should be considered when developing the intervention program for nurses. REGISTRATION: CRD42022299907.

In Vitro Toxicity Screening of Fifty Complex Mixtures in HepG2 Cells.

To develop the risk prediction technology for mixture toxicity, a reliable and extensive dataset of experimental results is required. However, most published literature only provides data on combinations containing two or three substances, resulting in a limited dataset for predicting the toxicity of complex mixtures. Complex mixtures may have different mode of actions (MoAs) due to their varied composition, posing difficulty in the prediction using conventional toxicity prediction models, such as the concentration addition (CA) and independent action (IA) models. The aim of this study was to generate an experimental dataset comprising complex mixtures. To identify the target complex mixtures, we referred to the findings of the HBM4EU project. We identified three groups of seven to ten components that were commonly detected together in human bodies, namely environmental phenols, perfluorinated compounds, and heavy metal compounds, assuming these chemicals to have different MoAs. In addition, a separate mixture was added consisting of seven organophosphate flame retardants (OPFRs), which may have similar chemical structures. All target substances were tested for cytotoxicity using HepG2 cell lines, and subsequently 50 different complex mixtures were randomly generated with equitoxic mixtures of EC10 levels. To determine the interaction effect, we calculated the model deviation ratio (MDR) by comparing the observed EC10 with the predicted EC10 from the CA model, then categorized three types of interactions: antagonism, additivity, and synergism. Dose-response curves and EC values were calculated for all complex mixtures. Out of 50 mixtures, none demonstrated synergism, while six mixtures exhibited an antagonistic effect. The remaining mixtures exhibited additivity with MDRs ranging from 0.50 to 1.34. Our experimental data have been formatted to and constructed for the database. They will be utilized for further research aimed at developing the combined CA/IA approaches to support mixture risk assessment.

Generation of tissues outside the field of view (FOV) of radiation therapy simulation imaging based on machine learning and patient body outline (PBO).

BACKGROUND: It is not unusual to see some parts of tissues are excluded in the field of view of CT simulation images. A typical mitigation is to avoid beams entering the missing body parts at the cost of sub-optimal planning. METHODS: This study is to solve the problem by developing 3 methods, (1) deep learning (DL) mechanism for missing tissue generation, (2) using patient body outline (PBO) based on surface imaging, and (3) hybrid method combining DL and PBO. The DL model was built upon a Globally and Locally Consistent Image Completion to learn features by Convolutional Neural Networks-based inpainting, based on Generative Adversarial Network. The database used comprised 10,005 CT training slices of 322 lung cancer patients and 166 CT evaluation test slices of 15 patients. CT images were from the publicly available database of the Cancer Imaging Archive. Since existing data were used PBOs were acquired from the CT images. For evaluation, Structural Similarity Index Metric (SSIM), Root Mean Square Error (RMSE) and Peak signal-to-noise ratio (PSNR) were evaluated. For dosimetric validation, dynamic conformal arc plans were made with the ground truth images and images generated by the proposed method. Gamma analysis was conducted at relatively strict criteria of 1%/1 mm (dose difference/distance to agreement) and 2%/2 mm under three dose thresholds of 1%, 10% and 50% of the maximum dose in the plans made on the ground truth image sets. RESULTS: The average SSIM in generation part only was 0.06 at epoch 100 but reached 0.86 at epoch 1500. Accordingly, the average SSIM in the whole image also improved from 0.86 to 0.97. At epoch 1500, the average values of RMSE and PSNR in the whole image were 7.4 and 30.9, respectively. Gamma analysis showed excellent agreement with the hybrid method (equal to or higher than 96.6% of the mean of pass rates for all scenarios). CONCLUSIONS: It was first demonstrated that missing tissues in simulation imaging could be generated with high similarity, and dosimetric limitation could be overcome. The benefit of this study can be significantly enlarged when MR-only simulation is considered.

Computational modeling approaches for developing a synergistic effect prediction model of estrogen agonistic activity.

The concerns regarding the potential health threats caused by estrogenic endocrine-disrupting chemicals (EDCs) and their mixtures manufactured by the chemical industry are increasing worldwide. Conventional experimental tests for understanding the estrogenic activity of mixtures are expensive and time-consuming. Although non-testing methods using computational modeling approaches have been developed to reduce the number of traditional tests, they are unsuitable for predicting synergistic effects because current prediction models consider only a single chemical. Thus, the development of predictive models is essential for predicting the mixture toxicity, including chemical interactions. However, selecting suitable computational modeling approaches to develop a high-performance prediction model requires considerable time and effort. In this study, we provide a suitable computational approach to develop a predictive model for the synergistic effects of estrogenic activity. We collected datasets on mixture toxicity based on the synergistic effect of estrogen agonistic activity in binary mixtures. Using the model deviation ratio approach, we classified the labels of the binary mixtures as synergistic or non-synergistic effects. We assessed five molecular descriptors, four machine learning-based algorithms, and a deep learning-based algorithm to provide a suitable computational modeling approach. Compared with other modeling approaches, the prediction model using the deep learning-based algorithm and chemical-protein network descriptors exhibited the best performance in predicting the synergistic effects. In conclusion, we developed a new high-performance binary classification model using a deep neural network and chemical-protein network-based descriptors. The developed model will be helpful for the preliminary screening of the synergistic effects of binary mixtures during the development process of chemical products.

Unmet Needs of Patients With Chronic Urticaria: A Survey in Korea.

Chronic urticaria (CU) is a common problem with a high disease burden that has a significant negative impact on quality of life. Many patients are undertreated, and awareness of management strategies is low among clinicians. The present study aimed to improve understanding of CU from the patients' perspective, including the disease burden and current healthcare system use. Adult patients who presented to our referral hospital for CU treatment completed self-report questionnaires about demographics, clinical characteristics of CU, the impact of CU on daily life, unmet needs, and the history of medical service usage. This self-report survey included 127 participants (females, 57.0%; mean age, 42.0 ± 13.6 years; mean CU duration, 1.8 ± 3.4 years); 51.6% reported frequent discomfort with CU in daily life, including 44.1% of those who reported a good response to medication. More than half of the respondents reported a depressed mood and anxiety. Although 46.4% of the respondents reported that urticaria completely disappeared while on medication, only 10% were satisfied with the CU management provided by primary care hospitals. The principal cause of dissatisfaction was that they did not know the cause of CU (68.4% of patients). In total, 55% of the patients visited 2 or more hospitals before presenting to our referral hospital and 6.3% had tried folk remedies. In conclusion, most patients report that CU is not adequately controlled. Therefore, in addition to appropriate medication, information on the cause of CU, long-term treatment plan, medication safety, and expected prognosis is required to meet patients' needs.

Disruption of IL-18 signaling via engineered IL-18BP biologics alleviates experimental cholestatic liver disease.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis around intrahepatic and extrahepatic bile ducts leading to severe hepatic cirrhosis and high mortality. Although there is an urgent clinical unmet need for PSC, no effective medical therapy has been developed to delay the disease progression until today. IL-18 binding protein (IL-18BP) is well-known to be a natural negative feedback regulator for IL-18, and we have developed a recombinant long-acting IL-18BP referred to as APB-R3 as a therapeutic agent to treat IL-18-related inflammatory diseases. Here, we aimed to study whether disrupted IL-18 signaling by APB-R3 treatment can inhibit PSC injuries in the experimental DDC diet-induced PSC rodent model. First, we found that the amounts of free IL-18 are augmented under PSC condition with increased expression of biliary IL-18 receptors. Administration of APB-R3 effectively attenuated key diagnostic parameters of PSC such as plasma ALP and GGT levels as well as bile acids levels. We also observed that blockade of IL-18 suppressed ductular reactive and proliferative phenotypes of cholangiocytes. Additionally, APB-R3 significantly ameliorated DDC diet-induced periductal fibrosis and transcriptional expressions of pro-fibrotic marker genes. Enhanced senescence associated secretory phenotype (SASP) markers in cholestatic liver disease were diminished by APB-R3 treatment. Our findings clearly demonstrate that the administration of IL-18BP biologics, APB-R3, effectively alleviates DDC diet-induced biliary injuries in rodent PSC model, implying APB-R3 can be a promising therapeutic reagent which warrants clinical human trials as new therapeutic options.

Evaluating the effect of the COVID-19 pandemic on hypertension and diabetes care in South Korea: an interrupted time series analysis.

BACKGROUND: Access to healthcare services is important, especially for patients with chronic diseases. We evaluated the effect of the COVID-19 pandemic on outpatient visits and medication for patients with hypertension and diabetes in South Korea. METHODS: Nationwide claims data were extracted for patients with hypertension and diabetes from January 2019 to July 2020. We used an interrupted time series (ITS) analysis to evaluate the pandemic's impact on outpatient care using the number of outpatient visits and days of medication supplied per visit. We identified the change in the continuity of care in medication, a consequence of the change in outpatient care, using the Medication Possession Ratio (MPR). RESULTS: The number of outpatient visits for diabetes significantly declined in February 2020, when community transmission began. However, when high-intensity social distancing was relaxed in April 2020, outpatient visits for hypertension and diabetes rebounded significantly. Moreover, when the outpatient visits declined, the number of days of medication supplied per visit increased. Consequently, the average MPRs significantly increased compared to 2019, increasing the ratio of patients with appropriate medication supply (MPR ≥ 0.8). CONCLUSIONS: Outpatient visits decreased immediately when COVID-19 spread to local communities. However, the number of days of medication supplied per visit increased to compensate for the longer intervals between visits. Rather, the change in the continuity of care in medication improved; thus, the temporary decrease in outpatient visits might have had a limited negative impact on health outcomes.

Urinary concentrations of organophosphate esters and associated health outcomes in Korean firefighters.

Although firefighters are at an increased risk of occupational exposure to chemicals, such as flame retardants, research on the exposure of Korean firefighters to organophosphate esters (OPEs)-a group of emerging flame retardants-remains limited. Therefore, in the present study, OPE metabolite concentrations in the urine samples of 149 former and current Korean firefighters were measured. Based on the data obtained, the estimated daily intakes (EDIs) of OPEs were calculated. Subsequently, the association between the urinary concentrations of OPE metabolites and the potential determinants of OPE exposure and health outcomes (e.g., obesity and serum lipids) was investigated. We found that bis(1-chloro-2-propyl) phosphate (BCIPP) and bis(2-chloroethyl) phosphate (BCEP) were the most prevalent urinary OPE metabolites, with median concentrations of 2.33 and 1.80 ng/mL, respectively; these concentrations were higher than those reported previously in other countries, such as the USA and China. Moreover, their parent compounds-tris(1-chloro-2-propyl) phosphate (TCIPP) and tris(2-chloroethyl) phosphate (TCEP)-exhibited EDIs of 126 and 94.8 ng/kg bw/day, respectively. Unlike the high detection rate of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) in other populations, its detection rate in this study was low (6.7%), suggesting regional differences in the exposure pattern of OPEs among countries. Furthermore, occupational characteristics, such as recent participation in firefighting activity, were identified as determinants of the urinary concentrations of OPE metabolites. Total OPE metabolites were inversely associated with body mass index and positively associated with high-density lipoprotein cholesterol. Overall, our findings demonstrate that Korean firefighters are highly exposed to several occupation-related OPEs. Further prospective studies will help elucidate the potential health implications of occupational exposure to OPEs among firefighters.

Association between environmental chemical exposure and albumin-to-creatinine ratio is modified by hypertension status in women of reproductive age.

Chemicals have been identified as a potential risk factor of renal dysfunction. However, studies that consider both multiple chemicals and non-chemical risk factors, such as hypertension, are rare. In this study, we assessed the associations between exposure to several chemicals, including major metals, phthalates, and phenolic compounds, and the albumin-to-creatinine ratio (ACR). A group of Korean adult women in reproductive age (n = 438, aged between 20 and 49 years), who had previously been studied for association of several organic chemicals, was chosen for this purpose. We constructed multivariable linear regression models for individual chemicals and weighted-quantile sum (WQS) mixtures, by hypertension status. Among the study population, approximately 8.5% of the participants exhibited micro/macro-albuminuria (ACR ≥30 mg/g), and 18.5% and 3.9% exhibited prehypertension and hypertension, respectively. Blood cadmium and lead levels showed a stronger association with ACR only among women with prehypertension or hypertension. Among organic chemicals, depending on the statistial model, benzophenone-1 (BP-1) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) showed a significant association regardless of hypertension status, but most associations disappeared in the (pre)hypertensive group. These findings clearly indicate that hypertension status can modify and may potentiate the association of environmental chemicals with ACR. Our observations suggest that low-level environmental pollutant exposure may have potential adverse effects on kidney function among general adult women. Considering the prevalence of prehypertension in the general population, efforts to reduce exposure to cadmium and lead are necessary among adult women to minimize the risk of adverse kidney function.

Comprehensive Analysis of Epstein-Barr Virus LMP2A-Specific CD8+ and CD4+ T Cell Responses Restricted to Each HLA Class I and II Allotype Within an Individual.

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8+ and CD4+ T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8+ T cell responses were significantly higher than CD4+ T cell responses. CD8+ T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4+ T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×105 CD8+ or CD4+ T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.

Assessing Quality of Life in Patients With Chronic Urticaria Through Comparisons With Patients Having Other Common Chronic Diseases.

BACKGROUND: Chronic urticaria (CU) is a common chronic inflammatory disease, but the burden on quality of life (QOL) has been underestimated. OBJECTIVE: To compare QOL among patients with CU and those with other chronic diseases. METHODS: Adult patients who visited a referral hospital for CU were enrolled. Patients completed self-reported questionnaires including clinical characteristics of chronic urticaria and the short form 36 health survey. As a comparative group, patients with rheumatoid arthritis, patients with diabetes treated with insulin, patients on maintenance hemodialysis, and healthy controls were enrolled and completed the short form 36 health survey. RESULTS: In all, 119 patients with CU were enrolled and their short form 36 scores were not significantly different from those of healthy controls. However, patients with CU with poor responses to treatment showed impaired QOL to a degree similar to that of patients with rheumatoid arthritis or insulin-treated diabetes. The patients with CU showed various clinical characteristics with respect to treatment response, accompanying symptoms, and aggravating factors. Among these factors, pain at the urticarial lesion and symptom aggravation during exercise and after the consumption of certain foods were related with lower QOL. CONCLUSIONS: Patients with CU with an incomplete response to treatment had significantly low QOL, comparable to that of patients with rheumatoid arthritis or insulin-treated diabetes. To minimize this effect, clinicians should aim to control symptoms and aggravating factors.

Development of a cryogenic passive-scattering-type near-field optical microscopy system.

Passive scattering-type, scanning near-field optical microscopy (s-SNOM) has been employed to study localized, long-wavelength infrared (LWIR) surface waves without external illumination. Here, we develop a cryogenic passive s-SNOM instrument in a vacuum chamber with 4 K liquid-helium cooling. Notably, the extremely low-temperature environment inside the chamber enables the realization of passive near-field detection with low background thermal noise. The technique mainly utilizes a highly sensitive LWIR confocal optical system and a tuning fork-based atomic force microscope, and the near-field detection was performed at a wavelength of 10.2 ± 0.9 µm. In this paper, we discuss the cryogenic s-SNOM implementation in detail and report the investigation of thermally excited surface electromagnetic fields on a self-heated NiCr wire deposited on SiO2 at a temperature of 5 K. The origin of the surface electromagnetic fields was established to be the thermally excited fluctuating charges of the conduction electrons. The cryogenic s-SNOM method presented herein shows significant promise for application in a variety of spheres, including hot-carrier dissipation in ballistic conductors.

Aryloxypropanolamine targets amyloid aggregates and reverses Alzheimer-like phenotypes in Alzheimer mouse models.

BACKGROUND: Aggregated amyloid-ß (Aß) is considered a pathogenic initiator of Alzheimer's disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal of amyloid burden from AD patient brains by antibodies has shown therapeutic potential, the development of small molecule drugs inducing chemical dissociation and clearance of Aß is compelling as a therapeutic strategy. In this study, we synthesized and screened aryloxypropanolamine derivatives and identified 1-(3-(2,4-di-tert-pentylphenoxy)-2-hydroxypropyl)pyrrolidin-1-ium chloride, YIAD002, as a strong dissociator of Aß aggregates. METHODS: The dissociative activity of aryloxypropanolamine derivatives against Aß aggregates were evaluated through in vitro assays. Immunohistochemical staining, immunoblot assays, and the Morris water maze were used to assess the anti-Alzheimer potential in YIAD002-treated 5XFAD and transgenic APP/PS1 mice. Target-ligand interaction mechanism was characterized via a combination of peptide mapping, fluorescence dissociation assays, and constrained docking simulations. RESULTS: Among 11 aryloxypropanolamine derivatives, YIAD002 exerted strongest dissociative activity against ß-sheet-rich Aß aggregates. Upon oral administration, YIAD002 substantially reduced amyloid burden and accordingly, improved cognitive performance in the Morris water maze and attenuated major pathological hallmarks of AD including tauopathy, neuroinflammation, and synaptic protein loss. Mechanism studies suggest that YIAD002 interferes with intermolecular ß-sheet fibrillation by directly interacting with KLVFFA and IGLMVG domains of Aß. In addition, YIAD002 was found to possess dissociative activity against aggregates of pyroglutamate-modified Aß and tau. CONCLUSIONS: Collectively, our results evince the potential of chemical-driven dissociation of Aß aggregates by aryloxypropanolamines as a therapeutic modality of the amyloid clearance approach.

Comprehensive analysis of mycobacterium tuberculosis antigen-specific CD4+ T cell responses restricted by single HLA class II allotype in an individual.

Mycobacterium tuberculosis infection is generally asymptomatic as latent tuberculosis, but it is still known as the world's leading bacterial cause of death. The diagnosis of latent tuberculosis infection relies on the evidence of cellular immunity to mycobacterial antigens. Since the association between HLA class II and tuberculosis infection has been reported in several population groups, a detailed study on the CD4+ T cell response to major tuberculosis antigens is needed. To elucidate which HLA class II allotypes in an individual are preferentially used in tuberculosis, CD4+ T cells specific to TB10.4, Ag85b, ESAT-6, and CFP-10 of Mycobacterium tuberculosis antigens were analyzed comprehensively. A total of 33 healthy donors were analyzed by ex vivo and cultured ELISPOT using panels of artificial antigen-presenting cells expressing a single HLA class II allotype. The CD4+ T cell responses were increased by an average of 39-fold in cultured ELISPOT compared with ex vivo ELISPOT. In ex vivo and cultured ELISPOT, CD4+ T cell responses showed significantly higher by HLA-DR than those of HLA-DQ and HLA-DP locus. In cultured ELISPOT, 9 HLA-DR allotypes, 4 HLA-DQ allotypes, and 3 HLA-DP allotypes showed positive CD4+ T cell responses. Among ten donors with positive CD4+ T cell responses when tested for mixed Mycobacterium tuberculosis antigens, seven donors were positive for only a single allotype, and three were positive for two allotypes in an individual. However, only one allotype was used for a single antigen-specific response when a single tuberculosis antigen was used individually. These results on the distribution of HLA class II allotypes showing high CD4+ T-cell responses to Mycobacterium tuberculosis antigens and the intra-individual allotype dominance will provide valuable information for understanding the immunobiology and immunogenetics of tuberculosis, which can contribute to the development of more effective vaccines.

Urinary paraben concentrations of adult women by fasting status: Comparison between Korea and the United States.

Personal care products (PCPs) are considered as a major source of paraben exposure; however, the dietary contribution is not well known. We compared the urinary levels of methyl-, ethyl-, and propyl-paraben (MeP, EtP, and PrP), and investigated their associations with fasting status and contacts with other potential exposure sources among Korea and the US adult women. A group of fasting, non-pregnant adult women (n = 469) was recruited from Seoul, Ansan/Incheon, and Jeju, Korea in 2015-2016, and their urine was measured for parabens. Non-fasting Korean women of matching age (25-45 years) were chosen from the Korean National Environmental Health Survey (KoNEHS) Cycle 3 (n = 579). For the US women, both fasting (n = 154) and non-fasting (n = 201) females were chosen from the NHANES 2015-2016 participants. In fasting Korean women, the urinary MeP, EtP, and PrP concentrations (median) were measured at 47.30, 17.90, and 2.30 ng/mL, respectively. Urinary EtP and PrP levels in fasting Korean women were significantly lower than those in non-fasting women (EtP and PrP median of 26.40 and 3.57 ng/mL). On average, the difference in urinary EtP levels by fasting status was greater among the highly exposed groups. In the US population, EtP levels were significantly lower (median ranged 1.55-1.80 ng/mL depending on fasting status), but MeP levels were higher (67.90-84.35 ng/mL) than those of the Korean population. When only fasting women were considered, the median EtP levels of Korean women were 11.5-fold greater than those of US women, suggesting that the non-dietary contributions of EtP exposure could not be ignored among Korean women. Regardless of fasting status, MeP and PrP were significantly correlated, and their urinary levels in fasting Korean women were correlated with the use of several personal care products. The major dietary and non-dietary sources that may explain EtP exposure in Korean women warrant further investigation.

Depressive Symptoms Feature-Based Machine Learning Approach to Predicting Depression Using Smartphone.

With the impact of the COVID-19 pandemic, the number of patients suffering from depression is rising around the world. It is important to diagnose depression early so that it may be treated as soon as possible. The self-response questionnaire, which has been used to diagnose depression in hospitals, is impractical since it requires active patient engagement. Therefore, it is vital to have a system that predicts depression automatically and recommends treatment. In this paper, we propose a smartphone-based depression prediction system. In addition, we propose depressive features based on multimodal sensor data for predicting depressive mood. The multimodal depressive features were designed based on depression symptoms defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The proposed system comprises a "Mental Health Protector" application that collects data from smartphones and a big data-based cloud platform that processes large amounts of data. We recruited 106 mental patients and collected smartphone sensor data and self-reported questionnaires from their smartphones using the proposed system. Finally, we evaluated the performance of the proposed system's prediction of depression. As the test dataset, 27 out of 106 participants were selected randomly. The proposed system showed 76.92% on an f1-score for 16 patients with depression disease, and in particular, 15 patients, 93.75%, were successfully predicted. Unlike previous studies, the proposed method has high adaptability in that it uses only smartphones and has a distinction of evaluating prediction accuracy based on the diagnosis.

Concentrations of blood and urinary arsenic species and their characteristics in general Korean population.

Arsenic (As) exposure has been extensively studied by investigating As species (e.g., inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)) in urine, yet recent research suggests that blood could be a possible biomarker of As exposure. These investigations, however, were conducted on iAs-contaminated areas, and evidence on populations exposed to low levels of iAs is limited. This study aimed to describe the levels and distributions of As species in urine and blood, as well as to estimate methylation efficiency and related factors in the Korean population. Biological samples were obtained by the Korean Ministry of Food and Drug Safety. A total of 2025 urine samples and 598 blood samples were utilized in this study. Six As species were measured using ultra-high-performance liquid chromatography with inductively coupled plasma mass spectrometry (UPLC-ICP-MS): As(V), As(III), MMA, DMA, arsenobetaine (AsB), and arsenocholine (AsC). Multiple linear regression models were used to examine the relationship between As species (concentrations and proportions) and covariates. AsB was the most prevalent species in urine and blood. The relative composition of iAs, MMA, DMA, and AsC in urine and blood differed significantly. Consumption of blue-backed fish was linked to higher levels of AsB in urine and blood. Type of drinking water and multigrain rice consumption were associated with increased iAs concentration in urine. Except for iAs, every species had correlations in urine and blood in both univariate and multivariate analyses. Adolescents and smokers presented a lower methylation efficiency (higher %MMA and lower %DMA in urine) and females presented a higher methylation efficiency (lower %iAs, %MMA, and higher %DMA in urine). In conclusion, blood iAs concentration cannot represent urinary iAs; nonetheless, different compositions of urine and blood might reflect distinct information about iAs exposure. Further investigations on exposure factors and health are needed using low-exposure groups.

The cost- effectiveness of early dental visit in infants and toddlers focused on regional deprivation in South Korea: A retrospective cohort study.

BACKGROUND: The aims of this study are to evaluate the cost-effectiveness of early dental visits (EDVs) and to investigate how regional deprivation impacts the economic evaluation. METHODS: This study used the South Korea National Health Insurance database, which included medical claim data and voluntary-based oral examination data. The subjects of this study included whole participants for oral examinations for infants and toddlers of the National Health Insurance Corporation. A retrospective cohort study was designed and measured all oral treatments, costs, and number of visits for 208,969 children (experimental group, 101,768; non- experimental group, 107,201) who underwent oral examination for infants and toddlers from 2007 to 2014. The cost-effectiveness was measured using the incremental cost-effectiveness ratio, and the T-health index was used as the measurement for effectiveness. In addition, the difference in the effect according to the level of regional deprivation was confirmed. RESULTS: The findings of this study showed that EDVs were cost-effective and that children who participated in EDVs had better oral health (T-health-2 index difference 0.32 point in most deprived regions) and needed 5 USD less costly dental treatments than those who did not have EDVs. The cost-effectiveness of EDVs varied according to the level of regional deprivation and was the highest in the most deprived regions. CONCLUSIONS: The study findings suggested that the provision of oral examination for infants and toddlers was a cost-effective dental policy. Additionally, EDVs were more effective in children who resided in the most deprived regions, a finding that will lead to the development of policy intervention to improve dental care despite spatial inequality for disadvantaged population groups. Regarding the distribution of dental hospitals/clinics, incentive based dental polices for either dental providers or patients are needed that will assure the delivery of dental care despite spatial inequality.

Nurses' ethical leadership and related outcome variables: Systematic review and meta-analysis.

AIM: To investigate the outcomes and the effect sizes of ethical leadership in nursing practice. BACKGROUND: Many meta-analysis of ethical leadership have been conducted in other fields, but there are none for the effects of ethical leadership of nurse leaders and should be investigated. EVALUATION: For a systematic literature review, we searched PubMed, EMBASE, the Cochrane Library, CINAHL, OVID, Web of Science and Korean databases for studies published in Korean or English. We used Comprehensive Meta-Analysis (CMA) 2.0 and R 3.6.2 for the meta-analysis. KEY ISSUES: We divided the outcomes of ethical leadership into three categories and investigated the effect sizes: subordinates' perceptions of their leaders (ES = 0.65), subordinates' ethical behaviours (ES = 0.04) and job or organisational outcomes (ES = 0.45). In addition, we identified 14 outcome variables, and transformational leadership showed the greatest effect size (ES = 0.77) among them. CONCLUSION: This study confirmed the positive effects of ethical nursing leadership on individual nurses' perceptions about their leaders, their jobs and organisations. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing organisations and nurse administrators should make efforts to highlight ethical leadership of nurse leaders to improve outcomes of organisational performance including individual nurses' perceptions about their leaders, their jobs and organisations.