Preventive and therapeutic effects of low-dose whole-body irradiation on collagen-induced rheumatoid arthritis in mice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation, resulting in cartilage destruction and bone erosion. It was reported that low-dose radiation modulates immune disease. Here, we investigated whether low-dose whole-body irradiation has preventive and therapeutic effects in collagen-induced RA (CIA) mouse models. Fractionated low-dose irradiation (0.05 Gy/fraction, total doses of 0.1, 0.5 or 0.8 Gy) was administered either concurrently with CIA induction by Type II collagen immunization (preventive) or after CIA development (therapeutic). The severity of CIA was monitored using two clinical parameters, paw swelling and redness. We also measured total Immunoglobulin G (IgG) and inflammatory cytokines (interleukine (IL)-6, IL-1ß and tumor necrosis factor-alpha (TNF-α)) in the serum by enzyme-linked immunosorbent assay, and we evaluated histological changes in the ankle joints by immunohistochemistry and hematoxylin and eosin staining. Low-dose irradiation reduced CIA clinical scores by up to 41% in the preventive model and by 28% in the therapeutic model, while irradiation in the preventive model reduced the typical CIA incidence rate from 82 to 56%. In addition, low-dose irradiation in the preventive model decreased total IgG by up to 23% and decreased IL-1ß and TNF-α by 69 and 67%, and in the therapeutic model, decreased total IgG by up to 35% and decreased IL-1ß and IL-6 by 59 and 42% with statistical significance (P < 0.01, 0.05 and 0.001). Our findings demonstrate that low-dose radiation has preventive and therapeutic anti-inflammatory effects against CIA by controlling the immune response, suggesting that low-dose radiation may represent an alternative therapy for RA, a chronic degenerative immune disease.

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.

The impact of COVID-19 on the patterns of emergency department visits among pediatric patients.

OBJECTIVES: This study aimed to investigate the patterns of pediatric patients visiting emergency departments (EDs) before and after the COVID-19 pandemic and evaluate the interactive effect between the COVID-19 outbreak and age groups. METHODS: We performed a cross-sectional study using the nationwide emergency patient database in Korea from January 2019 to December 2020. Pediatric patients (≤18 years) who visited all 402 nationwide EDs were included. The age- and sex-standardized incidence rates of pediatric ED visits per 1,000,000 person-days were calculated, and the incidence rate ratio (IRR) was calculated. The adjusted odds ratio (aOR) and 95% confidence interval (CI) of in-hospital mortality were calculated by a multivariable logistic regression. RESULTS: Among 2,808,756 patients, 1,835,045 (65.3%) patients visited before COVID-19, and 973,711 (34.7%) patients visited after the COVID-19 period. The standardized incidence rates of ED visits per 1,000,000 person-days were 589.3 in the before COVID-19 group and 326.9 in the after COVID-19 group (IRR (95% CI): 0.55 (0.53-0.58)). By diagnosis, the IRRs (95% CI) of mental health disorders (0.84 (0.42-1.65)) and self-harm or suicidal attempts (0.99 (0.38-2.59) were not significant, while the incidence rate of infectious disease was significantly decreased (0.48 (0.42-0.54)). The aOR (95% CI) of in-hospital mortality after COVID-19 was 1.58 (1.44-1.73) compared to that before COVID-19. CONCLUSIONS: During the COVID-19 pandemic, the incidence of pediatric ED visits decreased, and these effects differed by age group. Age-specific policies are needed to ensure that children receive the care they need at the right time.

Effects of Emergency Care-related Health Policies during the COVID-19 Pandemic in Korea: a Quasi-Experimental Study.

BACKGROUND: The purpose of this study was to review the nationwide emergency care-related health policies during the coronavirus disease 2019 (COVID-19) pandemic disaster in Korea and to analyze the effects of the policies on the safety of patients who visit emergency departments (EDs) during this period. METHODS: This study is a quasi-experiment study. The study population was patients who visited all 402 EDs in Korea between December 31, 2019 and May 13, 2020, using the National Emergency Department Information System (NEDIS) database. The study period was classified into 5 phases according to the level of national crisis warning of infectious disease and the implementation of emergency care-related health policies, and all study phases were 27 days. The primary outcome was in-hospital mortality, and the secondary outcome was length of stay (LOS) in the ED during the COVID-19 outbreak. RESULTS: The number of ED visits during the study period was 2,636,341, and the in-hospital mortality rate was 1.4%. The number of ED visits decreased from 803,160 in phase 1 to 496,619 in phase 5 during the study period. For in-hospital mortality, the adjusted odds ratio (OR) (95% confidence interval) was 0.77 (0.74-0.79) in phase 5 compared to phase 3. Additionally, by subgroup, the ORs were 0.69 (0.57-0.83) for the patients with acute myocardial infarction and 0.76 (0.67-0.87) for severe trauma in phase 5 compared to phase 3. The ED LOS increased while the number of ED visits decreased as the COVID-19 pandemic progressed, and the ED LOS declined after policy implementation (beta coefficient: -5.3 [-6.5 to -4.2] minutes in phase 5 compared to phase 3). CONCLUSION: Implementing appropriate emergency care policies in the COVID-19 pandemic would have contributed to improving the safety of all emergency patients and reducing in-hospital mortality by preventing excessive deaths.

Mismatches Between the Number of Installed Automated External Defibrillators and the Annual Rate of Automated External Defibrillator Use Among Places.

AIM: In South Korea, the law concerning automated external defibrillators (AEDs) states that they should be installed in specific places including apartment complexes. This study was conducted to investigate the current status and effectiveness of installation and usage of AEDs in South Korea. METHODS: Installation and usage of AEDs in South Korea is registered in the National Emergency Medical Center (NEMC) database. Compared were the installed number, usage, and annual rate of AED use according to places of installation. All data were obtained from the NEMC database. RESULTS: After excluding AEDs installed in ambulances or fire engines (n = 2,003), 36,498 AEDs were registered in South Korea from 1998 through 2018. A higher number of AEDs were installed in places required by the law compared with those not required by the law (20,678 [56.7%] vs. 15,820 [43.3%]; P <.001). Among them, 11,318 (31.0%) AEDs were installed in apartment complexes. The overall annual rate of AED use was 0.38% (95% CI, 0.33-0.44). The annual rate of AED use was significantly higher in places not required by the law (0.62% [95% CI, 0.52-0.72] versus 0.21% [95% CI, 0.16-0.25]; P <.001). The annual rate of AED use in apartment complexes was 0.13% (95% CI, 0.08-0.17). CONCLUSION: There were significant mismatches between the number of installed AEDs and the annual rate of AED use among places. To optimize the benefit of AEDs in South Korea, changes in the policy for selecting AED placement are needed.

Low-dose ionizing radiation attenuates mast cell migration through suppression of monocyte chemoattractant protein-1 (MCP-1) expression by Nr4a2.

Purpose: The aim of this study was to investigate whether low-dose ionizing radiation attenuates mast cell migration by modulating migration-associated signaling pathways and the expression of chemotactic cytokines.Materials and methods: IgE-sensitized RBL-2H3 mast cells were exposed with ionizing radiation at 0.01, 0.05, 0.1, or 0.5 Gy using a 137Cs γ-irradiator and stimulated with 2,4-dinitrophenol-human serum albumin. Cell migration was determined using a transwell assay system, F-actin distribution using Alex Fluor 488-conjugated phalloidin, expression of various signaling proteins by Western blotting, mRNA expression by RT-PCR.Results: Low-dose ionizing radiation significantly suppressed mast cell migration induced by IgE-mediated mast cell activation. Furthermore, low-dose ionizing radiation altered cell morphology, as reflected by changes in F-actin distribution, and inhibited the activation of PI3K, Btk, Rac1, and Cdc42. These effects were mediated by Nr4a2, an immune-modulating factor. Knockdown of Nr4a2 reduced mast cell migration, inhibited the PI3K and Btk signaling pathways, and reduced expression of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). We further demonstrated that direct blockade of MCP-1 using neutralizing antibodies inhibits mast cell migration.Conclusion: Low-dose ionizing radiation inhibits mast cell migration through the regulation production of MCP-1 by Nr4a2 in the activated mast cell system.

Production of kaempferol 3-O-rhamnoside from glucose using engineered Escherichia coli.

Flavonoids are ubiquitous phenolic compounds and at least 9,000 have been isolated from plants. Most flavonoids have been isolated and assessed in terms of their biological activities. Microorganisms such as Escherichia coli and Saccharomyces cerevisiae are efficient systems for the synthesis of flavonoids. Kaempferol 3-O-rhamnoside has notable biological activities such as the inhibition of the proliferation of breast cancer cells, the absorption of glucose in the intestines, and the inhibition of the self-assembly of beta amyloids. We attempted to synthesize kaempferol 3-O-rhamnoside from glucose in E. coli. Five flavonoid biosynthetic genes [tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), chalcone synthase (CHS), flavonol synthase (FLS), and flavonol 3-O-rhamnosyltransferase (UGT78D1)] from tyrosine were introduced into E. coli that was engineered to increase tyrosine production. By using this approach, the production of kaempferol 3-O-rhamnoside increased to 57 mg/L.

Synthesis of flavonoid O-pentosides by Escherichia coli through engineering of nucleotide sugar pathways and glycosyltransferase.

Plants produce two flavonoid O-pentoses, flavonoid O-xyloside and flavonoid O-arabinoside. However, analyzing their biological properties is difficult because flavonoids are not naturally produced in sufficient quantities. In this study, Escherichia coli was used to synthesize the plant-specific flavonoid O-pentosides quercetin 3-O-xyloside and quercetin 3-O-arabinoside. Two strategies were used. First, E. coli was engineered to express components of the biosynthetic pathways for UDP-xylose and UDP-arabinose. For UDP-xylose biosynthesis, two genes, UXS (UDP-xylose synthase) from Arabidopsis thaliana and ugd (UDP-glucose dehydrogenase) from E. coli, were overexpressed. In addition, the gene encoding ArnA (UDP-l-Ara4N formyltransferase/UDP-GlcA C-4″-decarboxylase), which competes with UXS for UDP-glucuronic acid, was deleted. For UDP-arabinose biosynthesis, UXE (UDP-xylose epimerase) was overexpressed. Next, we engineered UDP-dependent glycosyltransferases (UGTs) to ensure specificity for UDP-xylose and UDP-arabinose. The E. coli strains thus obtained synthesized approximately 160 mg/liter of quercetin 3-O-xyloside and quercetin 3-O-arabinoside.