The Impact of the COVID-19 Outbreak on Emergency Medical Service: An Analysis of Patient Transportations and Time Intervals.

BACKGROUND: This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on the Emergency Medical Service (EMS) system in South Korea. The study focused on the differences in EMS time intervals following the COVID-19 outbreak, particularly for patients with fever. METHODS: A retrospective analysis of EMS patient transportation data from 2017 to 2022 was conducted using the national EMS database. RESULTS: Starting from the year 2020, coinciding with the COVID-19 outbreak, all EMS time intervals experienced an increase. For the years 2017 to 2022, the mean response time interval values were 8.6, 8.6, 8.6, 10.2, 12.8, and 11.4 minutes, and the mean scene time interval values were 7.1, 7.2, 7.4, 9.0, 9.8, and 10.9 minutes. The mean transport time interval (TTI) values were 12.1, 12.3, 12.4, 14.2, 16.9, and 16.2 minutes, and the mean turnaround time interval values were 27.6, 27.9, 28.7, 35.2, 42.0, and 43.1 minutes. Fever (≥ 37.5°C) patients experienced more pronounced prolongations in EMS time intervals compared to non-fever patients and had a higher probability of being non-transported. The mean differences in TTI between fever and non-fever patients were 0.8, 0.8, 0.8, 4.3, 4.8, and 3.2 minutes, respectively, from 2017 to 2022. Furthermore, the odds ratios for fever patients being transported to the emergency department were 2.7, 2.9, 2.8, 1.1, 0.8, and 0.7, respectively, from 2017 to 2022. CONCLUSION: The study findings highlight the significant impact of the COVID-19 outbreak on the EMS system and emphasize the importance of ongoing monitoring to evaluate the burden on the EMS system.

Investigating fatty liver disease-associated adverse outcome pathways of perfluorooctane sulfonate using a systems toxicology approach.

Adverse outcome pathway (AOP) frameworks help elucidate toxic mechanisms and support chemical regulation. AOPs link a molecular initiating event (MIE), key events (KEs), and an adverse outcome by key event relationships (KERs), which assess the biological plausibility, essentiality, and empirical evidence involved. Perfluorooctane sulfonate (PFOS), a hazardous poly-fluoroalkyl substance, demonstrates hepatotoxicity in rodents. PFOS may induce fatty liver disease (FLD) in humans; however, the underlying mechanism remains unclear. In this study, we evaluated the toxic mechanisms of PFOS-associated FLD by developing an AOP using publicly available data. We identified MIE and KEs by performing GO enrichment analysis on PFOS- and FLD-associated target genes collected from public databases. The MIEs and KEs were then prioritized by PFOS-gene-phenotype-FLD networks, AOP-helpFinder, and KEGG pathway analyses. Following a comprehensive literature review, an AOP was then developed. Finally, six KEs for the AOP of FLD were identified. This AOP indicated that toxicological processes initiated by SIRT1 inhibition led to SREBP-1c activation, de novo fatty acid synthesis, and fatty acid and triglyceride accumulation, culminating in liver steatosis. Our study provides insights into the toxic mechanism of PFOS-induced FLD and suggests approaches to assessing the risk of toxic chemicals.

Fibrinogen on extracellular vesicles derived from polyhexamethylene guanidine phosphate-exposed mice induces inflammatory effects via integrin ß.

Polyhexamethylene guanidine phosphate (PHMG-p), used as a humidifier disinfectant, causes interstitial lung disease, obliterative bronchiolitis, and lung fibrosis; however, little is known about its effect on intercellular interactions. Extracellular vesicles (EVs), which carry diverse compounds including proteins, RNA, and DNA to mediate cell-to-cell communication through their paracrine effects, have been highlighted as novel factors in lung fibrogenesis. This study aimed to identify the effect of proteins on small EVs (sEVs) from bronchoalveolar lavage fluid (BALF) of the recipient cells after PHMG-p exposure. A week after intratracheal administration of PHMG-p, sEVs were isolated from BALF of tissue showing overexpressed inflammatory and fibrosis markers. To investigate the role of sEVs in inflammation, naïve macrophages were cultured with sEVs, which induced their activation. To identify sEV proteins that are associated with these responses, proteomics analysis was performed. In the gene ontology analysis, coagulation, fibrinolysis, and hemostasis were associated with the upregulated proteins in sEVs. The highest increase was observed in fibrinogen levels, which was also related to those gene ontologies. We validated role of exosomal fibrinogen in inflammation using recombinant fibrinogen and an inhibitor of the integrin, which is the binding receptor for fibrinogen. Overall, we elucidated that increased fibrinogen levels in the early sEVs-PHMG activated inflammatory response during early fibrosis. These results suggest that sEVs from the BALF of PHMG-p-exposed mice could aggravate fibrogenesis by activating naïve macrophages via various proteins in the sEVs, Furthermore, this finding will be broadening the spectrum of communicating mediators.

Efficacy of distance training program for cardiopulmonary resuscitation utilizing smartphone application and home delivery system.

AIM OF THE STUDY: Community cardiopulmonary resuscitation (CPR) education is important for laypersons. However, during the COVID-19 pandemic, with social distancing, conventional face-to-face CPR training was unavailable. We developed a distance learning CPR training course (HEROS-Remote) using a smartphone application that monitors real-time chest compression quality and a home delivery collection system for mannikins. This study aimed to evaluate the efficacy of the HEROS-Remote course by comparing chest compression quality with that of conventional CPR training. METHODS: We applied layperson CPR education with HEROS-Remote and conventional education in Seoul during the COVID-19 pandemic. Both groups underwent a 2-min post-training chest compression test, and we tested non-inferiority. Chest compression depth, rate, complete recoil, and composite chest compression score was measured. Trainees completed a satisfaction survey on CPR education and delivery. The primary outcome was the mean chest compression depth. RESULTS: A total of 180 trainees were enrolled, with 90 assigned to each training group. Chest compression depth of HEROS-Remote training showed non-inferiority to that of conventional training (67.4 vs. 67.8, p = 0.78), as well as composite chest compression score (92.7 vs. 95.5, p = 0.16). The proportions of adequate chest compression depth, chest compression rate, and chest compressions with complete chest recoil were similar in both training sessions. In the HEROS-Remote training, 90% of the trainees were satisfied with CPR training, and 96% were satisfied with the delivery and found it convenient. CONCLUSION: HEROS-Remote training was non-inferior to conventional CPR training in terms of chest compression quality. Distance learning CPR training using a smartphone application and mannikin delivery had high user satisfaction and was logistically feasible.

Polystyrene microplastic particles induce autophagic cell death in BEAS-2B human bronchial epithelial cells.

The detection of high levels of microplastics in indoor and outdoor air has increased concerns regarding its toxic effects on the respiratory system. They are not easily degradable and can be deposited deep in the lungs. Although several studies have reported inhalation toxicities of microplastics, they are still controversial due to a lack of evidence. Herein, we evaluated the inhalation toxicities of three differently charged polystyrene microplastics (PS-MPs), the most abundant microplastics in the air. Cytotoxicity and ROS generation were evaluated using WST-1 and DCF-DA assays, respectively. To evaluate the toxic effects on the lung, inflammatory responses were analyzed after repeated exposure to the PS-MPs through intratracheal instillation. To explore the mechanism of toxicity, autophagy and ER stress-associated proteins were analyzed. Only the positively charged PS-MPs (NH2 -PS-MPs) showed cytotoxicity and increased ROS generation in BEAS-2B cells. Similarly, only NH2 -PS-MPs significantly increased the expression and secretion of the pro-inflammatory cytokine IL-ß in the animal experiments. The expression of ER stress proteins indicated that NH2 -PS-MPs increased ER stress via PERK-EIF2α and ATF4-CHOP pathways. Moreover, accumulation of NH2 -PS-MPs in lysosomes and deformity of the nucleus were observed in BEAS-2B cells with autophagy induction. Taken together, our results demonstrated that NH2 -PS-MPs induced autophagic cell death in bronchial epithelial cells, leading to inflammatory responses in the lungs. These results suggest that repeated inhalation of microplastics can result in inflammatory responses in the lung through cellular damage of lung epithelial cells, and that inhalation microplastics should be monitored to reduce inhalation health risks.

Quality of chest compressions during prehospital resuscitation phase from scene arrival to ambulance transport in out-of-hospital cardiac arrest.

AIM: Prehospital cardiopulmonary resuscitation is performed from scene arrival to hospital arrival. The diverse prehospital resuscitation phases can affect the quality of chest compressions. This study aimed to evaluate the dynamic changes in chest compression quality during prehospital resuscitation. METHODS: Adult out-of-hospital cardiac arrest patients treated without prehospital return of spontaneous circulation were included in Seoul between July 2020 and September 2021. The chest compressions quality was assessed using a real-time chest compression feedback device. The prehospital phase was divided by key events during the prehospital resuscitation timeline (phase 1: first 2 min after initiation of chest compression, phase 2: from the end of phase 1 to 1 min prior to ambulance departure; phase 3: from 1 min before to 1 min after ambulance departure; phase 4: from the end of phase 3 to hospital arrival). The main outcome was no-flow fraction. The no-flow fraction between prehospital phases was compared using repeated-measure analysis of variance. RESULTS: In total, 788 patients were included. Mean no-flow fraction was the highest in phase 3 (phase 1: 11.3% ± 13.8, phase 2: 19.3% ± 12.3, phase 3: 33.0% ± 34.9, phase 4: 18.7% ± 23.7, p < 0.001). The mean number of total no-flow events per minute was also the highest in phase 3. The minute-by-minute analysis showed that the no-flow fraction rapidly increased before ambulance departure and decreased during ambulance transport. CONCLUSION: Dynamic changes in chest compression quality were observed during prehospital resuscitation phase. The no-flow fraction was the highest from 1 min before to 1 min after ambulance departure.

Comparison of 3D airway models for the assessment of fibrogenic chemicals.

Lung epithelial cells and fibroblasts play key roles in pulmonary fibrosis and are involved in fibrotic signaling and production of the extracellular matrix (ECM), respectively. Recently, 3D airway models consisting of both cell types have been developed to evaluate the fibrotic responses while facilitating cell-cell crosstalk. This study aimed to evaluate the fibrotic responses in these models using different fibrogenic agents, which are known as key events in adverse outcome pathways of pulmonary fibrosis. We quantified cell injury and several sequential steps in fibrogenesis, including inflammation, the epithelial-mesenchymal transition (EMT), fibroblast activation, and ECM accumulation, using two different 3D airway models, the EpiAirway™-full thickness (Epi/FT) and MucilAir™-human fibroblast (Mucil/HF) models. In the Epi/FT model, fibrogenic agents induced the expression of inflammation and EMT-associated markers, while in the Mucil/HF model, they induced fibroblast activation and ECM accumulation. Using this information, we conducted gene ontology term network analysis. In the Epi/FT model, the terms associated with cell migration and response to stimulus made up a large part of the network. In the Mucil/HF model, the terms associated with ECM organization and cell differentiation and proliferation constituted a great part of the network. Collectively, our data suggest that polyhexamethyleneguanidine phosphate and bleomycin induce different responses in the two 3D airway models. While Epi/FT was associated with inflammatory/EMT-associated responses, Mucil/HF was associated with fibroblast-associated responses. This study will provide an important basis for selecting proper 3D airway models and fibrogenic agents to further research or screen chemicals causing inhalation toxicity.

Reprogrammed lung epithelial cells by decrease of miR-451a in extracellular vesicles contribute to aggravation of pulmonary fibrosis.

Extracellular vesicles (EVs) play novel roles in homeostasis through cell-to-cell communication in human airways via transferring miRNAs. However, the contribution of EV miRNAs to pulmonary phenotypic homeostasis is not clearly understood. Hence, the aim of this study was to elucidate the functional role of miRNAs obtained from epithelium-derived EVs in lung fibrogenesis. Pulmonary fibrosis was induced by exposure of polyhexamethylene guanidine phosphate (PHMG-p)-instilled mice. In histopathological changes, a clear phenotypic change was observed in bronchial epithelium. For figuring out the role of EVs derived from conditioned media of untreated cells (EV-Con) and PHMG-p-treated BEAS-2B (EV-PHMG), significant increase in EVs released from PHMG-p-treated BEAS-2B was detected. Functional analysis with targets of differentially expressed miRNAs in EVs was annotated to epithelial-mesenchymal transition (EMT). Especially, the most abundant miRNA, miR-451a, was downregulated in EV of PHMG-p-treated BEAS-2B cells. We found that odd-skipped related 1 (OSR1) was a putative target for miR-451a, which had been known as a transcription factor of several fibrosis-associated genes. Transfer of decreased miR-451a via EV-PHMG upregulated OSR1 and induced EMT compared to Con-EV-treated cells. In pulmonary fibrosis mice, miR-451a levels were significantly reduced in EV derived from bronchoalveolar lavage fluid and OSR1 expression was increased in lung tissues of mice with PHMG-p exposure. MiR-451a-transfected EVs markedly alleviated fibrogenesis in the PHMG-p-exposed lungs. Low level of miR-451a in EVs modulated EMT and fibrogenesis in recipient cells by increasing OSR1 levels in vitro and in vivo. Our results suggest that transferring EV miR-451a induces anti-fibrotic autocrine effect by downregulating its target, OSR1 maintaining pulmonary homeostasis disrupted by PHMG-p exposure, which can be a potential therapeutic target.

Anti-fibrotic effects of brevilin A in hepatic fibrosis via inhibiting the STAT3 signaling pathway.

Hepatic fibrosis is a chronic liver disease characterized by the accumulation of extracellular matrix (ECM). Activation of hepatic stellate cells (HSCs) after repetitive liver damage is a key event in hepatic fibrogenesis. As part of ongoing research projects to identify pharmacologically effective natural products, the phytochemical investigation of a MeOH extract of Centipeda minima led to the isolation of a sesquiterpene lactone, brevilin A, which was explored to elucidate potential anti-fibrotic effects by reversing HSC activation. First, we observed that transforming growth factor (TGF)-ß1 treatment significantly increased the expression levels of HSC activation marker, α-smooth muscle actin (α-SMA), and ECM protein such as collagen and fibronectin. Then, we demonstrated that brevilin A reversed the TGF-ß1-induced increase in protein and mRNA expression levels of α-SMA and collagen. To investigate the underlying molecular mechanism of brevilin A, we evaluated the effects of brevilin A on the STAT3 signaling pathway. STAT3 phosphorylation, increased by TGF-ß1 treatment, was strongly inhibited by brevilin A; the expression levels of fibronectin and connective tissue growth factor were also significantly decreased by brevilin A. The present study indicated that brevilin A has a preventive and therapeutic potential against hepatic fibrosis.

Prediction of cerebral perfusion pressure during CPR using electroencephalogram in a swine model of ventricular fibrillation.

BACKGROUND: Measuring the quality of cardiopulmonary resuscitation (CPR) is important for improving outcomes in cardiac arrest. Cerebral perfusion pressure (CePP) could represent cerebral circulation during CPR, but it is difficult to measure non-invasively. In this study, we developed the electroencephalogram (EEG) based brain index (EBRI) derived from EEG signals by machine learning techniques, which could estimate CePP accurately in a porcine cardiac arrest model. METHODS: We conducted a randomised crossover study using nine female pigs. After 1 min of untreated ventricular fibrillation, we performed CPR with 12 different 2-min tilting angle sessions, including two different head-up tilt (HUT) angles (30°, 15°) twice, horizontal angle (0°) four times and two different head-down tilt (HDT) angles (-15°, -30°) twice with the random order. We collected EEG signals using a single channel EEG electrode in real-time during CPR. We derived the EBRI models to predict the CePP classified by the 5 or 10 groups using three different machine learning algorithms, including the support vector machine (SVM), k-nearest neighbour (KNN) and random forest classification (RFC) method. We assessed the accuracy, sensitivity and specificity of each model. RESULTS: The accuracy of the EBRI model using an SVM algorithm in the 5-group CePP classification was 0.935 with a standard deviation (SD) from 0.923 to 0.946. The accuracy in the 10-group classification was 0.904 (SD: 0.896, 0.913). The accuracy of the EBRI using the KNN method in the 5-group classification was 0.927 (SD: 0.920, 0933) and in the 10-group was 0.894 (SD: 0.880, 0.907). The accuracy of the RFC algorithm was 0.947 (SD: 0.931, 0.963) in the 5-group classification and 0.920 (SD: 0.911, 0.929) in the 10-group classification. CONCLUSION: We developed the EBRI model using non-invasive acquisition of EEG signals to predict CePP during CPR. The accuracy the EBRI model was 0.935, 0.927 and 0.947 for each machine learning algorithm, and the EBRI could be used as a surrogate indicator for measuring cerebral perfusion during CPR.

Efficacy of a new dispatcher-assisted cardiopulmonary resuscitation protocol with audio call-to-video call transition.

BACKGROUND: Video call based dispatcher-assisted cardiopulmonary resuscitation (V-DACPR) has been suggested to improve the quality of bystander cardiopulmonary resuscitation. In the current system, dispatchers must convert the audio calls to video calls to provide V-DACPR. We aimed to develop new audio call-to-video call transition protocols and test its efficacy and safety compared to conventional DACPR(C-DACPR). METHODS: This was a randomized controlled simulation trial that compared the quality of bystander chest compression that was performed under three different DACPR protocols: C-DACPR, V-DACPR with rapid transition, and V-DACPR with delayed transition. Adult volunteers excluding healthcare providers were recruited for the trial. The primary outcome of the study was the mean proportion of adequate hand positioning during chest compression. RESULTS: Simulation results of 131 volunteers were analyzed. The mean proportion of adequate hand positioning was highest in V-DACPR with rapid transition (V-DACPR with rapid transition vs. C-DACPR: 92.7% vs. 82.4%, p = 0.03). The mean chest compression depth was deeper in both V-DACPR groups than in the C-DACPR group (V-DACPR with rapid transition vs. C-DACPR: 40.7 mm vs. 35.9 mm, p = 0.01, V-DACPR with delayed transition vs. C- DACPR: 40.9 mm vs. 35.9 mm, p = 0.01). Improvement in the proportion of adequate hand positioning was observed in the V-DACPR groups (r = 0.25, p < 0.01 for rapid transition and r = 0.19, p < 0.01 for delayed transition). CONCLUSION: Participants in the V-DACPR groups performed higher quality chest compression with higher appropriate hand positioning and deeper compression depth compared to the C-DACPR group.

Dendropanoxide, a Triterpenoid from Dendropanax morbifera, Ameliorates Hepatic Fibrosis by Inhibiting Activation of Hepatic Stellate Cells through Autophagy Inhibition.

Hepatic fibrosis results from chronic liver damage and is characterized by excessive accumulation of extracellular matrix (ECM). In this study, we showed that dendropanoxide (DPX), isolated from Dendropanax morbifera, had anti-fibrotic effects on hepatic fibrosis by inhibiting hepatic stellate cell (HSC) activation. DPX suppressed mRNA and protein expression of α-SMA, fibronectin, and collagen in activated HSCs. Moreover, DPX (40 mg/kg) treatment significantly lowered levels of liver injury markers (aspartate aminotransferase and alanine transaminase), expression of fibrotic markers, and deposition of ECM in a carbon tetrachloride-induced mouse model. Anti-fibrotic effects of DPX were comparable to those of silymarin in a hepatic fibrosis mouse model. As a possible mechanism of anti-fibrotic effects, we showed that DPX inhibited autophagosome formation (LC3B-II) and degradation of p62, which have important roles in HSC activation. These findings suggest that DPX inhibits HSC activation by inhibiting autophagy and can be utilized in hepatic fibrosis therapy.

Hepatoprotective Potency of Chrysophanol 8-O-Glucoside from Rheum palmatum L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway.

Rhubarb is a well-known herb worldwide and includes approximately 60 species of the Rheum genus. One of the representative plants is Rheum palmatum, which is prescribed as official rhubarb due to its pharmacological potential in the Korean and Chinese pharmacopoeia. In our bioactive screening, we found out that the EtOH extract of R. palmatum inhibited hepatic stellate cell (HSC) activation by transforming growth factor ß1 (TGF-ß1). Chemical investigation of the EtOH extract led to the isolation of chrysophanol 8-O-glucoside, which was determined by structural analysis using NMR spectroscopic techniques and electrospray ionization mass spectrometry (ESIMS). To elucidate the effects of chrysophanol 8-O-glucoside on HSC activation, activated LX-2 cells were treated for 48 h with chrysophanol 8-O-glucoside, and α-SMA and collagen, HSC activation markers, were measured by comparative quantitative real-time PCR (qPCR) and western blotting analysis. Chrysophanol 8-O-glucoside significantly inhibited the protein and mRNA expression of α-SMA and collagen compared with that in TGF-ß1-treated LX-2 cells. Next, the expression of phosphorylated SMAD2 (p-SMAD2) and p-STAT3 was measured and the translocation of p-STAT3 to the nucleus was analyzed by western blotting analysis. The expression of p-SMAD2 and p-STAT3 showed that chrysophanol 8-O-glucoside strongly downregulated STAT3 phosphorylation by inhibiting the nuclear translocation of p-STAT3, which is an important mechanism in HSC activation. Moreover, chrysophanol 8-O-glucoside suppressed the expression of p-p38, not that of p-JNK or p-Erk, which can activate STAT3 phosphorylation and inhibit MMP2 expression, the downstream target of STAT3 signaling. These findings provided experimental evidence concerning the hepatoprotective effects of chrysophanol 8-O-glucoside against liver damage and revealed the molecular basis underlying its anti-fibrotic effects through the blocking of HSC activation.

Tyrosine kinase inhibitor neratinib attenuates liver fibrosis by targeting activated hepatic stellate cells.

Liver fibrosis, a common outcome of chronic liver disease characterized by excessive accumulation of extracellular matrix (ECM), is a leading cause of mortality worldwide. The tyrosine kinase inhibitor neratinib is a human epidermal growth factor receptor 2 (HER2) inhibitor approved by the FDA for HER2-positive breast cancer treatment; however, it has not yet been evaluated for liver fibrosis treatment. We elucidated the anti-fibrotic effects of neratinib in hepatic stellate cells (HSCs) and in vivo models of CCl4-induced liver fibrosis. HSC activation is a key step in liver fibrogenesis and has a crucial role in collagen deposition, as it is primarily responsible for excessive ECM production. The effect of neratinib on HSC was evaluated in transforming growth factor (TGF-ß)-incubated LX-2 cells and culture-activated primary human HSCs. In vivo study results indicated that neratinib inhibited the inflammatory response, HSC differentiation, and collagen accumulation induced by CCl4. Moreover, the anti-fibrotic effects of neratinib were not associated with the HER2 signaling pathways. Neratinib inhibited FGF2 expression in activated HSCs and serum FGF2 level in the model, suggesting that neratinib possessed therapeutic potency against liver fibrosis and the potential for application against other fibrotic diseases.

Emergency Department Triage Early Warning Score (TREWS) predicts in-hospital mortality in the emergency department.

AIM: The purpose is to assess the adequacy of the National Early Warning Score (NEWS) in the emergency department (ED) and the usefulness of the Triage in Emergency Department Early Warning Score (TREWS) that has been developed using the NEWS in the ED. METHODS: In this retrospective observational cohort study, we performed univariable and multivariable regression analyses with 81,520 consecutive ED patients to develop a new scoring system, the TREWS. The primary outcome was in-hospital mortality within 24 h, and secondary outcomes were in-hospital mortality within 48 h, 7 days, and 30 days. The prognostic properties of the TREWS were compared with those of the NEWS, Modified Early Warning Score (MEWS), and Rapid Emergency Medicine Score (REMS) using the area under the receiver operating characteristic curve (AUC) technique. RESULTS: The AUC of the TREWS for in-hospital mortality within 24 h was 0.906 (95% CI, 0.903-0.908), those of the NEWS, MEWS, and REMS were 0.878 (95% CI, 0.875-0.881), 0.857 (95% CI, 0.854-0.860), and 0.834 (95% CI, 0.831-0.837), respectively. Differences in the AUC between the TREWS and NEWS, the TREWS and MEWS, and the TREWS and REMS were 0.028 (95% CI, 0.022-0.033; p < .001), 0.049 (95% CI, 0.041-0.057; p < .001), and 0.072 (95% CI, 0.063-0.080; p < .001), respectively. The TREWS showed significantly superior performance in predicting secondary outcomes. CONCLUSION: The TREWS predicts in-hospital mortality within 24 h, 48 h, 7 days, and 30 days better than the NEWS, MEWS, and REMS for patients arriving at the ED.

Effects of emergency department boarding on mortality in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: Patients with ST-segment elevation myocardial infarction (STEMI) are sometimes boarded in the emergency department (ED) after percutaneous coronary intervention (PCI). We evaluated the effects of direct and indirect admission to the CCU on mortality and the effect on length of stay (LOS) in patients with STEMI. METHOD: This was a retrospective observational study of patients with STEMI between Jan 2014 and Nov 2017. The patients were divided into the direct admission (DA) group, who were admitted into the CCU immediately after PCI, and the indirect admission (IA) group, who were admitted after boarding in the ED. The primary endpoint was in-hospital mortality. Secondary endpoints were 3-month mortality, LOS in CCU and hospital, and LOS under intensive care. RESULTS: During the study period, 780 patients were enrolled and analyzed. The in-hospital mortality rate and 3-month mortality rate were 5.9% (46 patients) and 8.5% (66 patients). The DA group and IA group had similar in-hospital and 3-month mortality rates (P = .50, P = .28). The median CCU LOS and hospital LOS was similar for both groups (P = .28, P = .46). However, LOS under in intensive care for the IA group was significantly longer than that of the DA group (DA, 31.9 h; IA, 38.7 h; P < .001). CONCLUSION: This study suggests that direct admission after PCI and indirect admission was not associated with mortality in patients with STEMI. In addition, the stay in ED also appears to be associated with the duration of stay under critical care.

(-)-Catechin-7-O-ß-d-Apiofuranoside Inhibits Hepatic Stellate Cell Activation by Suppressing the STAT3 Signaling Pathway.

Hepatic fibrosis is characterized by the abnormal deposition of extracellular matrix (ECM) proteins. During hepatic fibrogenesis, hepatic stellate cell (HSC) activation followed by chronic injuries is considered a key event in fibrogenesis, and activated HSCs are known to comprise approximately 90% of ECM-producing myofibroblasts. Here, we demonstrated that (-)-catechin-7-O-ß-d-apiofuranoside (C7A) significantly inhibited HSC activation via blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This is the first study to show the hepatic protective effects of C7A with possible mechanisms in vitro and in vivo. In our bioactivity screening, we figured out that the EtOH extract of Ulmusdavidiana var. japonica root barks, which have been used as a Korean traditional medicine, inhibited collagen synthesis in HSCs. Four catechins isolated from the EtOAc fraction of the EtOH extract were compared with each other in terms of reduction in collagen, which is considered as a marker of hepatic protective effects, and C7A showed the strongest inhibitory effects on HSC activation in protein and qPCR analyses. As a possible mechanism, we investigated the effects of C7A on the STAT3 signaling pathway, which is known to activate HSCs. We found that C7A inhibited phosphorylation of STAT3 and translocation of STAT3 to nucleus. C7A also inhibited expressions of MMP-2 and MMP-9, which are downstream genes of STAT3 signaling. Anti-fibrotic effects of C7A were evaluated in a thioacetamide (TAA)-induced liver fibrosis model, which indicated that C7A significantly inhibited ECM deposition through inhibiting STAT3 signaling. C7A decreased serum levels of aspartate amino transferase and alanine transaminase, which were markedly increased by TAA injection. Moreover, ECM-associated proteins and mRNA expression were strongly suppressed by C7A. Our study provides the experimental evidence that C7A has inhibitory effects on HSC activation after live injury and has preventive and therapeutic potentials for the management of hepatic fibrosis.

Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons.

In our ongoing research to discover natural products with neuroprotective effects, hyperoside (quercetin 3-O-galactoside) was isolated from Acer tegmentosum, which has been used in Korean traditional medicine to treat liver-related disorders. Here, we demonstrated that hyperoside protects cultured dopaminergic neurons from death via reactive oxygen species (ROS)-dependent mechanisms, although other relevant mechanisms of hyperoside activity remain largely uncharacterized. For the first time, we investigated the neuroprotective effects of hyperoside on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in neurons, and the possible underlying mechanisms. Hyperoside significantly ameliorated the loss of neuronal cell viability, lactate dehydrogenase release, excessive ROS accumulation and mitochondrial membrane potential dysfunction associated with 6-OHDA-induced neurotoxicity. Furthermore, hyperoside treatment activated the nuclear erythroid 2-related factor 2 (Nrf2), an upstream molecule of heme oxygenase-1 (HO-1). Hyperoside also induced the expression of HO-1, an antioxidant response gene. Remarkably, we found that the neuroprotective effects of hyperoside were weakened by an Nrf2 small interfering RNA, which blocked the ability of hyperoside to inhibit neuronal death, indicating the vital role of HO-1. Overall, we show that hyperoside, via the induction of Nrf2-dependent HO-1 activation, suppresses neuronal death caused by 6-OHDA-induced oxidative stress. Moreover, Nrf2-dependent HO-1 signaling activation represents a potential preventive and therapeutic target in Parkinson's disease management.

Worsened survival in the head-up tilt position cardiopulmonary resuscitation in a porcine cardiac arrest model.

OBJECTIVE: Head elevation at an angle of 30° during cardiopulmonary resuscitation (CPR) was hemodynamically beneficial compared to supine position in a previous porcine cardiac arrest experimental study. However, survival benefit of head-up elevation during CPR has not been clarified. This study aimed to assess the effect of head-up tilt position during CPR on 24-hour survival in a porcine cardiac arrest experimental model. METHODS: This was a randomized experimental trial using female farm pigs (n=18, 42±3 kg) sedated, intubated, and paralyzed on a tilting surgical table. After surgical preparation, 15 minutes of untreated ventricular fibrillation was induced. Then, 6 minutes of basic life support was performed in a position randomly assigned to either head-up tilt at 30° or supine with a mechanical CPR device, LUCAS-2, and an impedance threshold device, followed by 20 minutes of advanced cardiac life support in the same position. Primary outcome was 24-hour survival, analyzed by Fisher exact test. RESULTS: In the 8 pigs from the head-up tilt position group, one showed return of spontaneous circulation (ROSC); all eight pigs expired within 24 hours. In the eight pigs from the supine position group, six had the ROSC; six pigs survived for 24 hours and two expired. The head-up position group showed lower 24-hour survival rate and lower ROSC rate than supine position group (P<0.01). CONCLUSION: The use of head-up tilt position with 30 degrees during CPR showed lower 24-hour survival than the supine position.

Effects of ß-Sitosterol from Corn Silk on TGF-ß1-Induced Epithelial-Mesenchymal Transition in Lung Alveolar Epithelial Cells.

Pulmonary fibrosis is a chronic lung disease characterized by abnormal accumulation of the extracellular matrix (ECM). Chronic damage of the alveolar epithelium leads to a process called "epithelial-mesenchymal transition" (EMT) and increases synthesis and deposition of ECM proteins. Therefore, inhibition of EMT might be a promising therapeutic approach for the treatment of pulmonary fibrosis. ß-Sitosterol is one of the most abundant phytosterols in the plant kingdom and the major constituent in corn silk, which is derived from the stigma and style of maize (Zea mays). In this study, we elucidated that ß-sitosterol inhibited transforming growth factor-ß1 (TGF-ß1)-induced EMT and consequently had an antifibrotic effect. ß-Sitosterol (1-10 µg/mL) significantly downregulated the TGF-ß1-induced fibrotic proteins, such as collagen, fibronectin, and α-smooth muscle actin in human alveolar epithelial cells (p < 0.01). After 24 h, relative wound density (RWD) was increased in TGF-ß1 treated group (82.16 ± 5.70) compare to the control group (64.63 ± 2.21), but RWD was decreased in ß-sitosterol cotreated group (10 µg/mL: 71.54 ± 7.39; 20 µg/mL: 65.69 ± 6.42). In addition, the changes of the TGF-ß1-induced morphological shape and protein expression of EMT markers, N-cadherin, vimentin, and E-cadherin, were significantly blocked by ß-sitosterol treatment (p < 0.01). The effects of ß-sitosterol on EMT were found to be associated with the TGF-ß1/Snail pathway, which is regulated by Smad and non-Smad signaling pathways. Taken together, these findings suggest that ß-sitosterol can be used to attenuate pulmonary fibrosis through suppression of EMT by inhibiting the TGF-ß1/Snail pathway.