Guidelines for Packaging, Transport, and Storage of Source Cells for Organoids.

This paper presents guidelines for the systematic management of packaging, storage, transportation, and traceability of source cells used for organoid research. Given the important role of source cells in organoid studies, it is important to ensure the preservation of their quality and integrity throughout transportation and distribution processes. The proposed guidelines, therefore, call for a cohesive strategy through these stages to minimize the risks of contamination, deterioration, and loss-threats that significantly compromise the safety, efficacy, and efficiency of source cells. Central to these guidelines is the quality control measures that include roles and responsibilities across the entire supply chain, with recommendations specific to packaging materials, transportation facilities, and storage management. Furthermore, the need for an integrated management system is emphasized, spanning from source cell collection to the final application. This system is crucial for maintaining the traceability and accountability of source cells, facilitating the sharing, distribution, and utilization on a global scale, and supporting to advance organoid research and development.

Continuous TNF-α exposure in mammary epithelial cells promotes cancer phenotype acquisition via EGFR/TNFR2 activation.

Tumor necrosis factor alpha (TNF-α), an abundant inflammatory cytokine in the tumor microenvironment (TME), is linked to breast cancer growth and metastasis. In this study, we established MCF10A cell lines incubated with TNF-α to investigate the effects of continuous TNF-α exposure on the phenotypic change of normal mammary epithelial cells. The established MCF10A-LE cell line, through long-term exposure to TNF-α, displayed cancer-like features, including increased proliferation, migration, and sustained survival signaling even in the absence of TNF-α stimulation. Unlike the short-term exposed cell line MCF10A-SE, MCF10A-LE exhibited elevated levels of epidermal growth factor receptor (EGFR) and subsequent TNF receptor 2 (TNFR2), and silencing of EGFR or TNFR2 suppressed the cancer-like phenotype of MCF10A-LE. Notably, we demonstrated that the elevated levels of NAD(P)H oxidase 4 (NOX4) and the resulting increase in reactive oxygen species (ROS) were associated with EGFR/TNFR2 elevation in MCF10A-LE. Furthermore, mammosphere-forming capacity and the expression of cancer stem cell (CSC) markers increased in MCF10A-LE. Silencing of EGFR reversed these effects, indicating the acquisition of CSC-like properties via EGFR signaling. In conclusion, our results reveal that continuous TNF-α exposure activates the EGFR/TNFR2 signaling pathway via the NOX4/ROS axis, promoting neoplastic changes in mammary epithelial cells within the inflammatory TME.

Validating Well-Functioning Hepatic Organoids for Toxicity Evaluation.

"Organoids", three-dimensional self-organized organ-like miniature tissues, are proposed as intermediary models that bridge the gap between animal and human studies in drug development. Despite recent advancements in organoid model development, studies on toxicity using these models are limited. Therefore, in this study, we aimed to analyze the functionality and gene expression of pre- and post-differentiated human hepatic organoids derived from induced pluripotent stem cells and utilize them for toxicity assessment. First, we confirmed the functional similarity of this hepatic organoid model to the human liver through various functional assessments, such as glycogen storage, albumin and bile acid secretion, and cytochrome P450 (CYP) activity. Subsequently, utilizing these functionally validated hepatic organoids, we conducted toxicity evaluations with three hepatotoxic substances (ketoconazole, troglitazone, and tolcapone), which are well known for causing drug-induced liver injury, and three non-hepatotoxic substances (sucrose, ascorbic acid, and biotin). The organoids effectively distinguished between the toxicity levels of substances with and without hepatic toxicity. We demonstrated the potential of hepatic organoids with validated functionalities and genetic characteristics as promising models for toxicity evaluation by analyzing toxicological changes occurring in hepatoxic drug-treated organoids.

Essential Guidelines for Manufacturing and Application of Organoids.

An organoid is a self-organized three-dimensional structure derived from stem cells that mimics the structure, cell composition, and functional characteristics of specific organs and tissues and is used for evaluating the safety and effectiveness of drugs and the toxicity of industrial chemicals. Organoid technology is a new methodology that could replace testing on animals testing and accelerate development of precision and regenerative medicine. However, large variations in production can occur between laboratories with low reproducibility of the production process and no internationally agreed standards for quality evaluation factors at endpoints. To overcome these barriers that hinder the regulatory acceptance and commercialization of organoids, Korea established the Organoid Standards Initiative in September 2023 with various stakeholders, including industry, academia, regulatory agencies, and standard development experts, through public and private partnerships. This developed general guidelines for organoid manufacturing and quality evaluation and for quality evaluation guidelines for organoid-specific manufacturing for the liver, intestines, and heart through extensive evidence analysis and consensus among experts. This report is based on the common standard guideline v1.0, which is a general organoid manufacturing and quality evaluation to promote the practical use of organoids. This guideline does not focus on specific organoids or specific contexts of use but provides guidance to organoid makers and users on materials, procedures, and essential quality assessment methods at end points that are essential for organoid production applicable at the current technology level.

Effects of an Electronic Medical Records-Linked Diabetes Self-Management System on Treatment Targets in Real Clinical Practice: Retrospective, Observational Cohort Study.

BACKGRUOUND: This study evaluated the effects of a mobile diabetes management program called "iCareD" (College of Medicine, The Catholic University of Korea) which was integrated into the hospital's electronic medical records system to minimize the workload of the healthcare team in the real clinical practice setting. METHODS: In this retrospective observational study, we recruited 308 patients. We categorized these patients based on their compliance regarding their use of the iCareD program at home; compliance was determined through self-monitored blood glucose inputs and message subscription rates. We analyzed changes in the ABC (hemoglobin A1c, blood pressure, and low-density lipoprotein cholesterol) levels from the baseline to 12 months thereafter, based on the patients' iCareD usage patterns. RESULTS: The patients comprised 92 (30%) non-users, 170 (55%) poor-compliance users, and 46 (15%) good-compliance users; the ABC target achievement rate showed prominent changes in good-compliance groups from baseline to 12 months (10.9% vs. 23.9%, P<0.05), whereas no significant changes were observed for poor-compliance users and non-users (13.5% vs. 18.8%, P=0.106; 20.7% vs. 14.1%, P=0.201; respectively). CONCLUSION: Implementing the iCareD can improve the ABC levels of patients with diabetes with minimal efforts of the healthcare team in real clinical settings. However, the improvement of patients' compliance concerning the use of the system without the vigorous intervention of the healthcare team needs to be solved in the future.

The Barriers to Recognizing and Reporting Child Physical Abuse by Emergency Physicians and Associated Factors.

BACKGROUND: Although the reporting rate of child abuse is increasing every year, the child abuse detection rate is 3.81% as of 2019 in Korea, which is significantly lower than that of developed countries for child rights. OBJECTIVE: We investigated the associated factors with barriers that emergency physicians face in recognizing and reporting cases of child abuse. METHODS: From May to July 2022, 240 emergency physicians working in the 15 emergency department were asked to participate in the survey via email. The questionnaire included the respondent's basic information, treatment experience for child abuse, reasons for reporting or not reporting, and opinions on measures to increase the reporting rate. We conducted a logistic regression analysis to discern the factors contributing to underreporting. RESULTS: Seventy-one individuals were included in the analysis, after excluding those who had never encountered suspected cases of child abuse. A multivariable logistic regression was performed with the above variables, and although it was not statistically significant, there was a tendency for workers to report well when working at a pediatric emergency department (odds ratio [95% confidence interval], 3.97 [0.98-16.09]). The primary reason for reporting suspected abuse was the pattern of damage suspected of abuse. The first reason for not reporting suspected abuse was because they were not sure it was child abuse. Respondents answered that to report better, a quick and appropriate response from the police and confidentiality of the reporter were needed. CONCLUSIONS: Physicians in pediatric emergency departments demonstrated a tendency for more proactive reporting suspected cases of child abuse.

The Association Between Inter-Hospital Transfers and the Prognosis of Pediatric Injury in the Emergency Department.

BACKGROUND: Inter-hospital transfers of severely injured patients are inevitable due to limited resources. We investigated the association between inter-hospital transfer and the prognosis of pediatric injury using the Korean multi-institutional injury registry. METHODS: This retrospective observational study was conducted from January 2013 to December 2017; data for hospitalized subjects aged < 18 years were extracted from the Emergency Department-based Injury in Depth Surveillance database, in which 22 hospitals are participating as of 2022. The survival rates of the direct transfer group and the inter-hospital transfer group were compared, and risk factors affecting 30-day mortality and 72- hour mortality were analyzed. RESULTS: The total number of study subjects was 18,518, and the transfer rate between hospitals was 14.5%. The overall mortality rate was 2.3% (n = 422), the 72-hour mortality was 1.7% (n = 315) and the 30-day mortality rate was 2.2% (n = 407). The Kaplan-Meier survival curve revealed a lower survival rate in the inter-hospital transfer group than in the direct visit group (log-rank, P < 0.001). Cox proportional hazards regression analysis showed that inter-hospital transfer group had a higher 30-day mortality rate and 72-hour mortality (hazard ratio [HR], 1.681; 95% confidence interval [CI], 1.232-2.294 and HR, 1.951; 95% CI, 1.299-2.930) than direct visit group when adjusting for age, sex, injury severity, and head injury. CONCLUSION: Among the pediatric injured patients requiring hospitalization, inter-hospital transfer in the emergency department was associated with the 30-day mortality rate and 72-hour mortality rate in Korea.

Low Molecular Weight Collagen Peptide (LMWCP) Promotes Hair Growth by Activating the Wnt/GSK-3ß/ß-Catenin Signaling Pathway.

Low molecular weight collagen peptide (LMWCP) is a collagen hydrolysate derived from fish. We investigated the effects of LMWCP on hair growth using human dermal papilla cells (hDPCs), human hair follicles (hHFs), patch assay, and telogenic C57BL/6 mice, while also examining the underlying mechanisms of its action. LMWCP promoted proliferation and mitochondrial potential, and the secretion of hair growth-related factors, such as EGF, HB-EGF, FGF-4, and FGF-6 in hDPCs. Patch assay showed that LMWCP increased the neogeneration of new HFs in a dose-dependent manner. This result correlated with an increase in the expression of dermal papilla (DP) signature genes such as, ALPL, SHH, FGF7, and BMP-2. LMWCP upregulated phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and nuclear translocation of ß-catenin, and it increased the expression of Wnt3a, LEF1, VEGF, ALP, and ß-catenin. LMWCP promoted the growth of hHFs and increased the expression of ß-catenin and VEGF. Oral administration of LMWCP to mice significantly stimulated hair growth. The expression of Wnt3a, ß-catenin, PCNA, Cyclin D1, and VEGF was also elevated in the back skin of the mice. Furthermore, LMWCP increased the expression of cytokeratin and Keratin Type I and II. Collectively, these findings demonstrate that LMWCP has the potential to increase hair growth via activating the Wnt/ß-catenin signaling pathway.

In Vitro and In Vivo Bone-Forming Effect of a Low-Molecular-Weight Collagen Peptide.

This study reveals that low-molecular-weight collagen peptide (LMWCP) can stimulate the differentiation and the mineralization of MC3T3-E1 cells in vitro and attenuate the bone remodeling process in ovariectomized (OVX) Sprague-Dawley rats in vivo. Moreover, the assessed LMWCP increased the activity of alkaline phosphatase (ALP), synthesis of collagen, and mineralization in MC3T3-E1 cells. Additionally, mRNA levels of bone metabolism-related factors such as the collagen type I alpha 1 chain, osteocalcin (OCN), osterix, bone sialoprotein, and the Runt family-associated transcription factor 2 were increased in cells treated with 1,000 µg/ml of LMWCP. Furthermore, we demonstrated that critical bone morphometric parameters exhibited significant differences between the LMWCP (400 mg/kg)-receiving and vehicle-treated rat groups. Moreover, the expression of type I collagen and the activity of ALP were found to be higher in both the femur and lumbar vertebrae of OVX rats treated with LMWCP. Finally, the administration of LMWCP managed to alleviate osteogenic parameters such as the ALP activity and the levels of the bone alkaline phosphatase, the OCN, and the procollagen type 1 N-terminal propeptide in OVX rats. Thus, our findings suggest that LMWCP is a promising candidate for the development of food-based prevention strategies against osteoporosis.

Comparison of age-adjusted shock indices as predictors of injury severity in paediatric trauma patients immediately after emergency department triage: A report from the Korean multicentre registry.

INTRODUCTION: Shock index paediatric-adjusted (SIPA) was presented for early prediction of mortality and trauma team activation in paediatric trauma patients. However, the derived cut-offs of normal vital signs were based on old references. We established alternative SIPAs based on the other commonly used references and compared their predictive values. METHODS: We performed a retrospective review of all paediatric trauma patients aged 1-15 years in the Emergency Department (ED)-based Injury In-depth Surveillance (EDIIS) database from January 1, 2011 to December 31, 2019. A total of 4 types of SIPA values were obtained based on the references as follows: uSIPA based on the Nelson textbook of paediatrics 21st ed., SIATLS based on the ATLS 10th guideline, SIPALS based on the PALS 2020 guideline, and SIPA. In each SIPA group, the cut-off was established by dividing the group into 4 subgroups: toddler (age 1-3), preschooler (age 4-6), schooler (age 7-12), and teenager (age 13-15). We performed an ROC analysis and calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to compare the predicted values of each SIPA in mortality, ICU admission, and emergent surgery or intervention. RESULTS: A total of 332,271 patients were included. The proportion of patients with an elevated shock index was 14.9 % (n = 49,347) in SIPA, 22.8 % (n = 75,850) in uSIPA, 0.3 % (n = 1058) in SIATLS, and 4.3 % (n = 14,168) in SIPALS. For mortality, uSIPA achieved the highest sensitivity (57.0 %; 95 % confidence interval 56.9 %-57.2 %) compared to SIPA (49.4 %, 95 % CI 49.2 %-49.5 %), SIATLS (25.5 %, 95 % CI 25.4 %-25.7 %), and SIPALS (43.8 %, 95 % CI 43.7 %-44.0 %), but there were no significant differences in the negative predictive value (NPV) or area under the curve (AUC). The positive predictive value (PPV) was highest in SIATLS (5.7 %, 95 % CI 5.6 %-5.8 %) compared to SIPA (0.2 %, 95 % CI 0.2 %-0.3 %), uSIPA (0.2 %, 95 % CI 0.2 %-0.2 %), and SIPALS (0.7 %, 95 % CI 0.7 %-0.8 %). The same findings were presented in ICU admission and emergent operation or intervention. CONCLUSION: The ATLS-based shock index achieved the highest PPV and specificity compared to SIPA, uSIPA, and SIPALS for adverse outcomes in paediatric trauma.

γ-Ray Irradiation Enables Annealing- and Light-Soaking-Free Solution Processable SnO2 Electron Transport Layer for Inverted Organic Solar Cells.

The electrode buffer layer is crucial for high-performance and stable OSCs, optimizing charge transport and energy level alignment at the interface between the polymer active layer and electrode. Recently, SnO2 has emerged as a promising material for the cathode buffer layer due to its desirable properties, such as high electron mobility, transparency, and stability. Typically, SnO2 nanoparticle layers require a postannealing treatment above 150°C in an air environment to remove the surfactant ligands and obtain high-quality thin films. However, this poses challenges for flexible electronics as flexible substrates can't tolerate temperatures exceeding 100°C. This study presents solution-processable and annealing-free SnO2 nanoparticles by employing y-ray irradiation to disrupt the bonding between surfactant ligands and SnO2 nanoparticles. The SnO2 layer treated with y-ray irradiation is used as an electron transport layer in OSCs based on PTB7-Th:IEICO-4F. Compared to the conventional SnO2 nanoparticles that required high-temperature annealing, the y-SnO2 nanoparticle-based devices exhibit an 11% comparable efficiency without postannealing at a high temperature. Additionally, y-ray treatment has been observed to eliminate the light-soaking effect of SnO2 . By eliminating the high-temperature postannealing and light-soaking effect, y-SnO2 nanoparticles offer a promising, cost-effective solution for future flexible solar cells fabricated using roll-to-roll mass processing.

[Pulmonary Artery Intimal Sarcoma Involving the Peripheral Pulmonary Artery, Initially Misdiagnosed as Pulmonary Artery Thromboembolism and Vasculitis: A Case Report]. / 폐동맥 í˜ˆì „ìƒ‰ì „ì¦ê³¼ 혈관염으로 오진된 주변부 폐동맥에서 발생한 폐동맥 ë‚´ë§‰ìœ¡ì¢ : 증례 ë³´ê³ .

Pulmonary artery sarcomas are rare, high-grade malignancies, primarily affecting the proximal elastic pulmonary artery and usually manifesting as tumoral impaction on imaging. Due to similar clinical and imaging findings, pulmonary artery sarcomas are frequently misdiagnosed as pulmonary thromboembolism or, occasionally, as vasculitis. Herein, we reported a case of pulmonary artery intimal sarcoma initially misdiagnosed as pulmonary thromboembolism and vasculitis due to its relatively atypical location and morphology, along with a literature review.

Impact of an Emergency Department Isolation Policy for Patients With Suspected COVID-19 on Door-to-Electrocardiography Time and Clinical Outcomes in Patients With Acute Myocardial Infarction.

BACKGROUND: Rapid electrocardiography diagnosis within 10 minutes of presentation is critical for acute myocardial infarction (AMI) patients in the emergency department (ED). However, the coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the emergency care system. Screening for COVID-19 symptoms and implementing isolation policies in EDs may delay the door-to-electrocardiography (DTE) time. METHODS: We conducted a cross-sectional study of 1,458 AMI patients who presented to a single ED in South Korea from January 2019 to December 2021. We used multivariate logistic regression analysis to assess the impact of COVID-19 pandemic and ED isolation policies on DTE time and clinical outcomes. RESULTS: We found that the mean DTE time increased significantly from 5.5 to 11.9 minutes (P < 0.01) in ST segment elevation myocardial infarction (STEMI) patients and 22.3 to 26.7 minutes (P < 0.01) in non-ST segment elevation myocardial infarction (NSTEMI) patients. Isolated patients had a longer mean DTE time compared to non-isolated patients in both STEMI (9.2 vs. 24.4 minutes) and NSTEMI (22.4 vs. 61.7 minutes) groups (P < 0.01). The adjusted odds ratio (aOR) for the effect of COVID-19 duration on DTE ≥ 10 minutes was 1.93 (95% confidence interval [CI], 1.51-2.47), and the aOR for isolation status was 5.62 (95% CI, 3.54-8.93) in all patients. We did not find a significant association between in-hospital mortality and the duration of COVID-19 (aOR, 0.9; 95% CI, 0.52-1.56) or isolation status (aOR, 1.62; 95% CI, 0.71-3.68). CONCLUSION: Our study showed that ED screening or isolation policies in response to the COVID-19 pandemic could lead to delays in DTE time. Timely evaluation and treatment of emergency patients during pandemics are essential to prevent potential delays that may impact their clinical outcomes.

Human Probiotic Lactobacillus paracasei-Derived Extracellular Vesicles Improve Tumor Necrosis Factor-α-Induced Inflammatory Phenotypes in Human Skin.

Lactic acid bacteria (LAB), a probiotic, provide various health benefits. We recently isolated a new Lactobacillus paracasei strain with strong anti-inflammatory effects under lipopolysaccharide-induced conditions and proposed a new mode of action-augmenting the endoplasmic reticulum stress pathway for anti-inflammatory functions in host cells. The beneficial effects of the L. paracasei strains on the skin have been described; however, the effects of L. paracasei-derived extracellular vesicles (LpEVs) on the skin are poorly understood. Herein, we investigated whether LpEVs can improve inflammation-mediated skin phenotypes by determining their effects on primary human skin cells and a three-dimensional (3D) full-thickness human skin equivalent under tumor necrosis factor (TNF)-α-challenged inflammatory conditions. LpEVs were efficiently taken up by the human skin cells and were much less cytotoxic to host cells than bacterial lysates. Furthermore, low LpEV concentrations efficiently restored TNF-α-induced cellular phenotypes, resulting in increased cell proliferation and collagen synthesis, but decreased inflammatory factor levels (matrix metalloproteinase 1, interleukin 6, and interleukin 8) in the human dermal fibroblasts, which was comparable to that of retinoic acid, a representative antiaging compound. The beneficial effects of LpEVs were validated in a 3D full-thickness human skin equivalent model. LpEV treatment remarkably restored the TNF-α-induced epidermal malformation, abnormal proliferation of keratinocytes in the basal layer, and reduction in dermal collagen synthesis. Additionally, LpEVs penetrated and reached the deepest dermal layer within 24 h when overlaid on top of a 3D full-thickness human skin equivalent. Furthermore, they possessed superior antioxidant capacity compared with the human cell-derived EVs. Taken together, the anti-inflammatory probiotic LpEVs can be attractive antiaging and antioxidant substances for improving inflammation-induced skin phenotypes and disorders.

Epidemiologic trends of patients who visited nationwide emergency departments: a report from the National Emergency Department Information System (NEDIS) of Korea, 2018-2022.

OBJECTIVE: : This study analyzed trends in emergency department (ED) visits in South Korea using the National Emergency Department Information System (NEDIS) data from 2018 to 2022. METHODS: : This was a retrospective observational study using data from the NEDIS database from 2018 to 2022. Age- and sex-standardized ED visits per 100,000 population, as well as age- and sex-standardized rates for mortality, admission, and transfer, were calculated. RESULTS: : The standardized ED visits per 100,000 population was approximately 20,000 from 2018 to 2019 and decreased to about 18,000 in 2022. The standardized mortality rate ranged from 1.4% to 1.7%. The admission rate (18.4%-19.4%) and the transfer rates (1.6%-1.8%) were similar during the study period. Approximately 5.5% of patients were triaged as Korean Triage and Acuity Scale score 1 or 2. About 91% of patients visited the ED directly and 21.7% of patients visited the ED with an ambulance. The ED length of stay was less than 6 hours in 90.3% of patients and the ED mortality rate was 0.6%. Acute gastroenteritis was the most common diagnosis. Respiratory virus symptoms, such as fever and sore throat, were also common chief complaints. CONCLUSION: : ED visits decreased during the 5-year period, while admission, transfer, and death rates remained relatively stable.

Asymmetric TMO-Metal-TMO Structure for Enhanced Efficiency and Long-Term Stability of Si-Based Heterojunction Solar Cells.

In this study, we fabricated Si-based heterojunction solar cells (HSCs) with an asymmetric TMO-metal-TMO (TMT) structure using both MoO3 and V2O5 as the hole-selective contacts. Our HSCs offer enhanced long-term stability and effective passivation for crystal defects on the Si sur-face. We analyzed the oxygen vacancy state and surface morphology of the MoO3- and V2O5-TMO thin films using X-ray photoelectron spectroscopy and atomic force microscopy to investigate their passivation characteristics for Si surface defects. From the measured minority carrier lifetime, V2O5 revealed a highly improved lifetime (590 µs) compared to that of MoO3 (122.3 µs). In addition, we evaluated the long-term stability of each TMO thin film to improve the operation stability of the HSCs. We deposited different types of TMOs as the top- and bottom-TMO layers and assessed the effect of the thickness of each TMO layer. The fabricated asymmetric TMT/Si HSCs showed noticeable improvements in efficiency (7.57%) compared to 6.29% for the conventional symmetric structure which used the same TMO material for both the top and bottom layers. Furthermore, in terms of long-term stability, the asymmetric TMT/Si HSCs demonstrated an efficiency that was 250% higher than that of symmetric TMT/Si HSCs, as determined via power conversion efficiency degradation over 2000 h which is mainly attributed by the lower oxygen vacancy of the top-TMO, V2O5. These results suggest that the asymmetric TMT structure is a promising approach for the fabrication of low-cost and high-efficiency Si-based HSCs with enhanced long-term stability.

Predictors of Caregiver Satisfaction With Pediatric Laceration Repair in the Pediatric Emergency Department.

OBJECTIVES: The objective of this study was to define the care factors that are important to caregivers' satisfaction with pediatric laceration repair and the overall emergency department (ED) experience. METHODS: This was a cross-sectional observation study performed in an urban tertiary hospital. The caregivers of patients younger than 18 years who presented to the ED for laceration repair completed a survey. Demographic data were analyzed. Univariate and multivariate logistic regressions were used to determine the factors related to satisfaction with the laceration repair and the overall ED experience. RESULTS: Fifty-five caregivers were enrolled. Most of the children had facial lacerations (n = 44, 80%). The median length of ED stay was 181 minutes (interquartile range [IQR], 157-208 minutes). The children's median age was 41.8 months (IQR, 23-91 months); the caregivers' median age was 37 years (IQR, 35-41 years). Most lacerations were repaired by plastic surgeons (81.8%). In the multivariate regression analysis, preparation before the procedure, mid-income family, caring attitude of the nurse, cosmetic outcome, and measures to control the patient's anxiety were significantly related to the caregiver's satisfaction with laceration repair (P < 0.05), whereas preparation before the procedure and ED environment were significantly related to the caregiver's satisfaction with the overall ED experience (P < 0.05). CONCLUSIONS: Preparation before the procedure was significantly related to the caregiver's satisfaction with both pediatric laceration repair and the overall PED experience. The strongest predictors were cosmetic outcome for laceration repair and preparation for the procedure for the overall PED experience. Our findings suggest that improvements in various aspects will increase parent satisfaction.

Trends in emergency department visits for suicide attempts before and during the COVID-19 pandemic in Korea: A nationwide study, 2016-2021.

BACKGROUND: There is increasing concern that the effects of the COVID-19 pandemic will result in excess suicides by increasing known risk factors, such as suicide attempts. However, evidence on the long-term impacts of COVID-19 on suicide attempts is lacking. We aimed to assess the short- and long-term effects of the COVID-19 pandemic on patients with suicide attempts in emergency departments (EDs) and to evaluate age- and sex-specific differences. METHOD: We conducted nationwide cross-sectional study among patients with suicide attempts in the ED from 2016 to 2021. The trend test were used to determine whether study subjects were affected by changes in ED visits for suicide attempts. We estimated the average annual percentage change (APC) stratified by sex and age groups. RESULTS: The number of ED visits related to suicide attempts increased from 27,581 in 2016 to 37,719 in 2021. In particular, it decreased immediately after the COVID-19 pandemic but increased again in 2021. We identified that the average APC increased by 6.8 % overall, 1.6 % among males, and 10.8 % among females. Moreover, the APC of trend sharply increased in patients aged 10s and 20s. The in-hospital mortality was 3.6 % for females, compared to 9.5 % for males, which showed sex differences. LIMITATIONS: This study was limited to confirming causal relationship based on a descriptive study. CONCLUSIONS: The incidence of suicide attempts in ED has increased in Korea. In particular, there was a sharp increase among women, adolescents and young adults. Patient-tailored treatment and preventive medical system for suicide attempts is important.

Association of NRF2 with HIF-2α-induced cancer stem cell phenotypes in chronic hypoxic condition.

The acquisition of the cancer stem cell (CSC) properties is often mediated by the surrounding microenvironment, and tumor hypoxia is considered an important factor for CSC phenotype development. High levels of NRF2 (Nuclear Factor Erythroid 2-Like 2; NFE2L2), a transcription factor that maintains cellular redox balance, have been associated with facilitated tumor growth and therapy resistance. In this study, we investigated the role of NRF2 in hypoxia-induced CSC phenotypes in colorectal cancer cells. Chronic hypoxia for 72 h resulted in CSC phenotypes, including elevation of krupple-like factor 4 (KLF4) and octamer-binding transcription factor 4 (OCT4), and an increase in cancer migration and spheroid growth with concomitant hypoxia-inducible factor 2α (HIF-2α) accumulation. All these chronic hypoxia-induced CSC properties were attenuated following HIF-2α-specific silencing. In this chronic hypoxia model, NRF2 inhibition by shRNA-based silencing or brusatol treatment blocked HIF-2α accumulation, which consequently resulted in decreased CSC marker expression and inhibition of CSC properties such as spheroid growth. In contrast, NRF2 overactivation by genetic or chemical approach enhanced the chronic hypoxia-induced HIF-2α accumulation and cancer migration. As a molecular mechanism of the NRF2-inhibition-mediated HIF-2α dysregulation, we demonstrated that miR-181a-2-3p, whose expression is elevated in NRF2-silenced cells, targeted the HIF-2α 3'UTR and subsequently suppressed the chronic hypoxia-induced HIF-2α and CSC phenotypes. The miR-181a-2-3p inhibitor treatment in NRF2-silenced cells could restore the levels of HIF-2α and CSC markers, and increased cancer migration and sphere formation under chronic hypoxia. In line with this, the miR-181a-2-3p inhibitor transfection could increase tumorigenicity of NRF2-silenced colorectal cancer cells. Collectively, our study suggests the involvement of NRF2/miR181a-2-3p signaling in the development of HIF-2α-mediated CSC phenotypes in sustained hypoxic environments.