The Comparison of Emergency Medical Service Responses to and Outcomes of Out-of-hospital Cardiac Arrest before and during the COVID-19 Pandemic in an Area of Korea

Background@#Since the declaration of the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 has affected the responses of emergency medical service (EMS) systems to cases of out-of-hospital cardiac arrest (OHCA). The purpose of this study was to identify the impact of the COVID-19 pandemic on EMS responses to and outcomes of adult OHCA in an area of South Korea. @*Methods@#This was a retrospective observational study of adult OHCA patients attended by EMS providers comparing the EMS responses to and outcomes of adult OHCA during the COVID-19 pandemic to those during the pre-COVID-19 period. Propensity score matching was used to compare the survival rates, and logistic regression analysis was used to assess the impact of the COVID-19 pandemic on the survival of OHCA patients. @*Results@#A total of 891 patients in the pre-COVID-19 group and 1,063 patients in the COVID-19 group were included in the final analysis. During the COVID-19 period, the EMS call time was shifted to a later time period (16:00–24:00, P < 0.001), and the presence of an initial shockable rhythm was increased (pre-COVID-19 vs. COVID-19, 7.97% vs. 11.95%, P = 0.004). The number of tracheal intubations decreased (5.27% vs. 1.22%, P < 0.001), and the use of mechanical chest compression devices (30.53% vs. 44.59%, P < 0.001) and EMS response time (median [quartile 1-quartile 3], 7 [5–10] vs. 8 [6–11], P < 0.001) increased. After propensity score matching, the survival at admission rate (22.52% vs. 18.24%, P = 0.025), survival to discharge rate (7.77% vs. 5.52%, P = 0.056), and favorable neurological outcome (5.97% vs. 3.49%, P < 0.001) decreased. In the propensity score matching analysis of the impact of COVID-19, odds ratios of 0.768 (95% confidence interval [CI], 0.592–0.995) for survival at admission and 0.693 (95% CI, 0.446–1.077) for survival to discharge were found. @*Conclusion@#During the COVID-19 period, there were significant changes in the EMS responses to OHCA. These changes are considered to be partly due to social distancing measures. As a result, the proportion of patients with an initial shockable rhythm in the COVID-19 period was greater than that in the pre-COVID-19 period, but the final survival rate and favorable neurological outcome were lower.

The Comparison of Emergency Medical Service Responses to and Outcomes of Out-of-hospital Cardiac Arrest before and during the COVID-19 Pandemic in an Area of Korea

Background@#Since the declaration of the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 has affected the responses of emergency medical service (EMS) systems to cases of out-of-hospital cardiac arrest (OHCA). The purpose of this study was to identify the impact of the COVID-19 pandemic on EMS responses to and outcomes of adult OHCA in an area of South Korea. @*Methods@#This was a retrospective observational study of adult OHCA patients attended by EMS providers comparing the EMS responses to and outcomes of adult OHCA during the COVID-19 pandemic to those during the pre-COVID-19 period. Propensity score matching was used to compare the survival rates, and logistic regression analysis was used to assess the impact of the COVID-19 pandemic on the survival of OHCA patients. @*Results@#A total of 891 patients in the pre-COVID-19 group and 1,063 patients in the COVID-19 group were included in the final analysis. During the COVID-19 period, the EMS call time was shifted to a later time period (16:00–24:00, P < 0.001), and the presence of an initial shockable rhythm was increased (pre-COVID-19 vs. COVID-19, 7.97% vs. 11.95%, P = 0.004). The number of tracheal intubations decreased (5.27% vs. 1.22%, P < 0.001), and the use of mechanical chest compression devices (30.53% vs. 44.59%, P < 0.001) and EMS response time (median [quartile 1-quartile 3], 7 [5–10] vs. 8 [6–11], P < 0.001) increased. After propensity score matching, the survival at admission rate (22.52% vs. 18.24%, P = 0.025), survival to discharge rate (7.77% vs. 5.52%, P = 0.056), and favorable neurological outcome (5.97% vs. 3.49%, P < 0.001) decreased. In the propensity score matching analysis of the impact of COVID-19, odds ratios of 0.768 (95% confidence interval [CI], 0.592–0.995) for survival at admission and 0.693 (95% CI, 0.446–1.077) for survival to discharge were found. @*Conclusion@#During the COVID-19 period, there were significant changes in the EMS responses to OHCA. These changes are considered to be partly due to social distancing measures. As a result, the proportion of patients with an initial shockable rhythm in the COVID-19 period was greater than that in the pre-COVID-19 period, but the final survival rate and favorable neurological outcome were lower.

Oncogenic Ras downregulates mdr1b expression through generation of reactive oxygen species

In the present study, we investigated the effect of oncogenic H-Ras on rat mdr1b expression in NIH3T3 cells. The constitutive expression of H-RasV12 was found to downregulate the mdr1b promoter activity and mdr1b mRNA expression. The doxorubicin-induced mdr1b promoter activity of the H-RasV12 expressing NIH3T3 cells was markedly lower than that of control NIH3T3 cells. Additionally, there is a positive correlation between the level of H-RasV12 expression and a sensitivity to doxorubicin toxicity. To examine the detailed mechanism of H-RasV12-mediated down-regulation of mdr1b expression, antioxidant N-acetylcysteine (NAC) and NADPH oxidase inhibitor diphenylene iodonium (DPI) were used. Pretreating cells with either NAC or DPI significantly enhanced the oncogenic H-Ras-mediated down-regulation of mdr1b expression and markedly prevented doxorubicin-induced cell death. Moreover, NAC and DPI treatment led to a decrease in ERK activity, and the ERK inhibitors PD98059 or U0126 enhanced the mdr1b-Luc activity of H-RasV12-NIH3T3 and reduced doxorubicin-induced apoptosis. These data suggest that RasV12 expression could downregulate mdr1b expression through intracellular reactive oxygen species (ROS) production, and ERK activation induced by ROS, is at least in part, contributed to the downregulation of mdr1b expression.

Oncogenic Ras downregulates mdr1b expression through generation of reactive oxygen species

In the present study, we investigated the effect of oncogenic H-Ras on rat mdr1b expression in NIH3T3 cells. The constitutive expression of H-RasV12 was found to downregulate the mdr1b promoter activity and mdr1b mRNA expression. The doxorubicin-induced mdr1b promoter activity of the H-RasV12 expressing NIH3T3 cells was markedly lower than that of control NIH3T3 cells. Additionally, there is a positive correlation between the level of H-RasV12 expression and a sensitivity to doxorubicin toxicity. To examine the detailed mechanism of H-RasV12-mediated down-regulation of mdr1b expression, antioxidant N-acetylcysteine (NAC) and NADPH oxidase inhibitor diphenylene iodonium (DPI) were used. Pretreating cells with either NAC or DPI significantly enhanced the oncogenic H-Ras-mediated down-regulation of mdr1b expression and markedly prevented doxorubicin-induced cell death. Moreover, NAC and DPI treatment led to a decrease in ERK activity, and the ERK inhibitors PD98059 or U0126 enhanced the mdr1b-Luc activity of H-RasV12-NIH3T3 and reduced doxorubicin-induced apoptosis. These data suggest that RasV12 expression could downregulate mdr1b expression through intracellular reactive oxygen species (ROS) production, and ERK activation induced by ROS, is at least in part, contributed to the downregulation of mdr1b expression.

Neuroprotective effects of urolithin A on H₂O₂-induced oxidative stress-mediated apoptosis in SK-N-MC cells

Neuregulin 1/ErbB4 signaling attenuates neuronal cell damage under oxygen-glucose deprivation in primary hippocampal neurons / 대한해부학회지

Neuregulin-1 Protects Neuronal Cells Against Damage due to CoCl2-Induced Hypoxia by Suppressing Hypoxia-Inducible Factor-1α and P53 in SH-SY5Y Cells / 대한배뇨장애요실금학회지

PURPOSE@#Hypoxia-mediated neurotoxicity contributes to various neurodegenerative disorders, including Alzheimer disease. Neuregulin-1 (NRG1) plays an important role in the development and plasticity of the brain. The aim of the present study was to investigate the neuroprotective effect and the regulating hypoxic inducible factor of NRG1 in cobalt chloride (CoCl₂) induced hypoxia.@*METHODS@#Hypoxia was induced in SH-SY5Y cells by CoCl₂ treatment. SH-SY5Y cells were pretreated with NRG1 and then treated with CoCl₂. Western blotting, immunocytochemistry, and lactate dehydrogenase (LDH) release assays were performed to examine neuroprotective properties of NRG1 in SH-SY5Y cells.@*RESULTS@#Our data showed that CoCl₂ induced cytotoxicity and changes of hypoxia-inducible factor-1α (HIF-1α) and p53 expression in SH-SY5Y cells. However, pretreatment with NRG1 inhibited CoCl₂-induced accumulation of HIF-1α and p53 stability. In addition, NRG1 significantly attenuated cell death of SH-SY5Y induced by CoCl₂.@*CONCLUSIONS@#NRG1 can regulate HIF-1α and p53 to protect neurons against hypoxic damage.

Classify the Acute Drug Intoxication Patients with Poisoning Severity Score(PSS) and Calculate the Optimal Cutoff Value of PSS, PSSsum to Predict Poor Prognosis

PURPOSE: This study examined the Poisoning Severity Score (PSS) from acute poisoning patients, to determine the relationships among the PSS, PSSsum, the primary outcome (prolonged stay at the ER over 24 hours, general ward and ICU admission and the application of intubation and mechanical ventilator, and the administration of inotropes). METHODS: A retrospective study was conducted through the EMR for 15 months. The PSS grade was classified according to the evidence of symptoms and signs. The differences in the primary outcomes between the PSS of when a single organ was damaged, and the PSS, PSSsum combined with the grade of when multiple organs were damaged, were studied. The cutoff value was calculated using the receiving operating characteristics (ROC) curve. RESULTS: Of the 284 patients; 85 (29.9%) were men with a mean age of 48.8 years, and their average arrival time to the ER was 4.4±6.7 hours. The most frequently used drug was hypnotics. The number of patients with PSS grade 0, 1, 2, 3, and 4 was 17, 129, 122, 24, and one, respectively. No ICU admissions, application of intubation and mechanical ventilators, administration of inotropes were observed among the patients with PSS grades 0 and 1 but only on patients with PSS grades 2 to 4. At PSS, when separating the patients according to the number of damaged organs, 17 had no symptoms, 133 had one organ damaged, 75 had two organs damaged, 36 had three organs damaged, and 23 had four organs damaged. Significant differences were observed between increasing number of damaged organs and the primary outcome. CONCLUSION: Among the acute poisoning patients, the PSS was higher in severity when the grade was higher. The number of damaged organs and the primary outcome showed meaningful statistical differences. This study confirmed that when the patients' PSS>2 and PSSsum>5, the frequency of ICU admission was higher, and they were considered to be severe with an increased prescription risk of application of intubation and mechanical ventilator, and the administration of inotropes.

Temporal and subcellular distributions of Cy5.5-labeled hyaluronic acid nanoparticles in mouse organs during 28 days as a drug carrier

Temporal and subcellular distributions of hyaluronic acid (HA) as a degradable nanoparticle (NP) in animals were investigated to determine if HA-NP could be utilized as an appropriate drug delivery system. After mice were intravenously injected with 5 mg/kg of Cy5.5-labeled HA-NP sized 350–400 nm or larger HA-polymers, the fluorescence intensity was measured in all homogenized organs from 0.5 h to 28 days. HA-NP was greatly detected in spleen, liver and kidney until day 28, while it was maintained at low levels in other organs. HA-polymer was observed at low levels in all organs. HA-NP quantities in spleen and liver were reduced until day 3, but increased sharply between days 3 and 7, then decreased again, while their HA-polymers were maintained at low levels until day 28. In kidneys, both HA-NP and HA-polymer showed high levels after 0.5 h of administration, but steadily decreased until day 28. According to ultrastructural analyses, HA-NP was engulfed in Kupffer cells of liver and macrophages of spleen and kidney at day 1 and was accumulated in the cytoplasm of kidney tubular cells at day 7. Overall, these findings suggest that HA-NP could be considered a desirable drug carrier in the liver, kidney, or spleen.

Neuroprotective effects of Momordica charantia extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SK-N-MC cells / 한국영양학회지

PURPOSE: Many studies have suggested that neuronal cells protect against oxidative stress-induced apoptotic cell death by polyphenolic compounds. We investigated the neuroprotective effects and the mechanism of action of Momordica charantia ethanol extract (MCE) against H₂O₂-induced cell death of human neuroblastoma SK-N-MC cells. METHODS: The antioxidant activity of MCE was measured by the quantity of total phenolic acid compounds (TPC), quantity of total flavonoid compounds (TFC), and 2,2-Diphenyl-1-pycrylhydrazyl (DPPH) radical scavenging activity. Cytotoxicity and cell viability were determined by CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Antioxidant enzyme (SOD-1,2 and GPx-1) expression was determined by real-time PCR. Mitogen-activated protein kinases (MAPK) pathway and apoptosis signal expression was measured by Western blotting. RESULTS: The TPC and TFC quantities of MCE were 28.51 mg gallic acid equivalents/extract g and 3.95 mg catechin equivalents/extract g, respectively. The IC₅₀ value for DPPH radical scavenging activity was 506.95 µg/ml for MCE. Pre-treatment with MCE showed protective effects against H₂O₂-induced cell death and inhibited ROS generation by oxidative stress. SOD-1,2 and GPx-1 mRNA expression was recovered by pre-treatment with MCE compared with the presence of H₂O₂. Pre-treatment with MCE inhibited phosphorylation of p38 and the JNK pathway and down-regulated cleaved caspase-3 and cleaved PARP by H₂O₂. CONCLUSION: The neuroprotective effects of MCE in terms of recovery of antioxidant enzyme gene expression, down-regulation of MAPK pathways, and inhibition apoptosis is associated with reduced oxidative stress in SK-N-MC cells.

Prevalence of bovine tuberculosis, brucellosis and Q fever in Korean black goats

As the meat of black goats has become popular as a healthy food, domestic goat meat-related industries are steadily growing. However, previous studies are scarce of informations about the zoonotic disease originated from the black goat in Korea. In this study, we investigated Korean black goat's infectious diseases representing bovine tuberculosis, brucellosis, and Q fever. One hundred and eighty samples were collected from a local slaughter house located in Jeollanam-do. Three typical zoonotic diseases were separately examined by carrying out enzyme linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). Histopathological test was additionally performed in tuberculosis. In case of tuberculosis, results of the PCR and histopathological test were negative but the ELISA results were positive in eight samples. In case of brucellosis, one out of the total samples was shown to be positive in the ELISA and none in the PCR. In case of Q fever, there were forty one positive in the ELISA and twenty positive in the real-time PCR. Those results indicate that the Korean black goat could be a natural reservoir in the possible chain-infections among human, cows and goats. Thus, further study needs in order to improve productivity as well as to prevent the zoonosis spreading and circulation of other livestock with the black goat in this country.

Autophagy Regulates Formation of Primary Cilia in Mefloquine-Treated Cells

Primary cilia have critical roles in coordinating multiple cellular signaling pathways. Dysregulation of primary cilia is implicated in various ciliopathies. To identify specific regulators of autophagy, we screened chemical libraries and identified mefloquine, an anti-malaria medicine, as a potent regulator of primary cilia in human retinal pigmented epithelial (RPE) cells. Not only ciliated cells but also primary cilium length was increased in mefloquine-treated RPE cells. Treatment with mefloquine strongly induced the elongation of primary cilia by blocking disassembly of primary cilium. In addition, we found that autophagy was increased in mefloquine-treated cells by enhancing autophagic flux. Both chemical and genetic inhibition of autophagy suppressed ciliogenesis in mefloquine-treated RPE cells. Taken together, these results suggest that autophagy induced by mefloquine positively regulates the elongation of primary cilia in RPE cells.

Primary Repair of Spontaneous Intramural Esophageal Dissection: A Case Report

Intramural esophageal dissection (IED) is a laceration between the mucosal and submucosal layers without perforation. Spontaneous IED is relatively common in elderly female patients on anticoagulation medication, while secondary IED is associated with endoscopic procedures or foreign body impaction. Although conservative management is regarded as the primary treatment for IED, there are several reported cases treated by endoscopic intervention or esophagectomy. We experienced rare spontaneous IED in a young male patient who was treated exclusively with primary repair of the esophagus. To the best of our knowledge, this is the first case report in which the patient recovered completely with only primary repair.

Two Cases of Hypophosphatemic Osteomalacia After Long-term Low Dose Adefovir Therapy in Chronic Hepatitis B and Literature Review

Adefovir dipivoxil (ADV) is a nucleotide used as long-term therapy of chronic hepatitis B. Many published reports have shown that long-term high-dose therapy with adefovir can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemia, renal insufficiency and osteomalacia. We have encountered two patients who developed evidence of hypophosphatemic osteomalacia while on long-term low-dose adefovir therapy for chronic hepatitis B. We report on its clinical features and its potential resolution with cessation of the drug and supplementation with phosphate. We also reviewed the other published cases associated with hypophosphatemic osteomalacia after low-dose adefovir therapy. The symptoms and the hypophosphatemia improved after cessation of the drug and supplementation with phosphate in most cases. Patients taking adefovir long-term should receive regular investigation of the phosphate level and renal function.

Anti-obesity effect of EGCG and glucosamine-6-phosphate through decreased expression of genes related to adipogenesis and cell cycle arrest in 3T3-L1 adipocytes / 한국영양학회지

PURPOSE: Several studies have proven that EGCG, the primary green tea catechin, and glucosamine-6-phosphate (PGlc) reduce triglyceride contents in 3T3-L1 adipocytes. The objective of this study is to evaluate the combination effect of EGCG and PGlc on decline of accumulated fat in differentiated 3T3-L1 adipocytes. METHODS: EGCG and PGlc were administered for 6 day for differentiation of 3T3-L1 adipocytes. Cell viability was measured using the CCK assay kit. In addition, TG accumulation in culture 3T3-L1 adipocytes was investigated by Oil Red O staining. We examined the expression level of several genes and proteins associated with adipogenesis and lipolysis using real-time RT-PCR and Western blot analysis. A flow cytometer Calibar was used to assess the effect of EGCG and PGluco on cell-cycle progression of differentiating 3T3-L1 cells. RESULTS: Intracelluar lipid accumulation was significantly decreased by combination treatment with EGCG 60 microM and PGlc 200 microg/m compared with control and EGCG treatment alone. In addition, use of combination treatment resulted in directly decreased expression of PPARgamma, C/EBPalpha, and SREBP1. In addition, it inhibited adipocyte differentiation and adipogenesis through downstream regulation of adipogenic target genes such as FAS, ACSL1, and LPL, and the inhibitory action of EGCG and PGlc was found to inhibit the mitotic clonal expansion (MCE) process as evidenced by impaired cell cycle entry into S phase and the S to G2/M phase transition of confluent cells and levels of cell cycle regulating proteins such as cyclin A and CDK2. CONCLUSION: Combination treatment of EGCG and PGlc inhibit-ed adipocyte differentiation through decreased expression of genes related to adipogenesis and adipogenic and cell cycle arrest in early stage of adipocyte differentiation.