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Shiitake mushroom (Lentinula edodes) is commonly consumed worldwide and is cultivated in many farms in Korea using Chinese substrates owing to a lack of knowledge on how to prepare sawdust-based substrate blocks (bag cultivation). Consequently, issues related to the origin of the Korean or Chinese substrate used in shiitake mushrooms produced using bag cultivation have been reported. Here, we investigated differences in fatty acids (FAs) and stable isotope ratios (SIRs) in shiitake mushrooms cultivated using Korean and Chinese substrates under similar conditions (strain, temperature, humidity, etc.) and depending on the harvesting cycle. The total FA level decreased significantly by 5.49 mg∙g−1 as the harvesting cycle increased (p < 0.0001); however, no differences were found in FAs between shiitake mushrooms cultivated using Korean and Chinese substrates. Linoleic acid was the most abundant FA, accounting for 77–81% of the total FAs during four harvesting cycles. Moreover, the SIRs differed significantly between the Korean and Chinese substrates, and the harvesting cycles resulted in smaller maximum differences in SIR values compared to those of the cultivation substrate origins. Our findings contribute to the identification of the geographical origin of shiitake mushrooms and may have potential applications in international shiitake-mushroom markets.

Recent studies on osteosarcoma regimens have mainly focused on modifying the combination of antineoplastic agents rather than enhancing the therapeutic efficacy of each component. Here, an albumin nanocluster (NC)-assisted methotrexate (MTX), doxorubicin (DOX), and cisplatin (MAP) regimen with improved antitumor efficacy is presented. Human serum albumin (HSA) is decorated with thiamine pyrophosphate (TPP) to increase the affinity to the bone tumor microenvironment (TME). MTX or DOX (hydrophobic MAP components) is adsorbed to HSA-TPP via hydrophobic interactions. MTX- or DOX-adsorbed HSA-TPP NCs exhibit 20.8- and 1.64-fold higher binding affinity to hydroxyapatite, respectively, than corresponding HSA NCs, suggesting improved targeting ability to the bone TME via TPP decoration. A modified MAP regimen consisting of MTX- or DOX-adsorbed HSA-TPP NCs and free cisplatin displays a higher synergistic anticancer effect in HOS/MNNG human osteosarcoma cells than conventional MAP. TPP-decorated NCs show 1.53-fold higher tumor accumulation than unmodified NCs in an orthotopic osteosarcoma mouse model, indicating increased bone tumor distribution. As a result, the modified regimen more significantly suppresses tumor growth in vivo than solution-based conventional MAP, suggesting that HSA-TPP NC-assisted MAP may be a promising strategy for osteosarcoma treatment., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Objective: High-quality cardiopulmonary resuscitation with chest compression is important for good neurologic outcomes during out-of-hospital cardiac arrest (OHCA). Several types of mechanical chest compression devices have recently been implemented in Korean emergency medical services. This study aimed to identify the effect of prehospital mechanical chest compression device use on the outcomes of OHCA patients., Methods: We retrospectively analyzed data drawn from the regional cardiac arrest registry in Daegu, Korea. This registry prospectively collected data from January 2017 to December 2020. Patients aged 18 years or older who experienced cardiac arrest presumed to have a medical etiology were included. The exposure variable was the use of a prehospital mechanical device during transportation by emergency medical technicians. The outcomes measured were neurologic outcomes and survival to discharge. Logistic regression analysis was used., Results: Among 3,230 OHCA patients, 1,111 (34.4%) and 2,119 (65.6%) were managed with manual chest compression and with a mechanical chest compression device, respectively. The mechanical chest compression group showed poorer neurologic outcomes than the manual chest compression group (adjusted odds ratio, 0.12; 95% confidence interval, 0.04-0.33) and decreased survival to discharge (adjusted odds ratio, 0.39; 95% confidence interval, 0.19-0.82) after adjustment for confounding variables., Conclusion: Prehospital mechanical chest compression device use in OHCA was associated with poorer neurologic outcomes and survival to discharge compared to manual chest compression.

In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades the lung via ACE2 receptors and causes severe pneumonia. Similarly, recent reports have shown the association of COVID-19 with decreased 25-hydroxycholesterol (25-HC) and increased cytokine levels. This mechanism, which involves the activation of inflammatory NF-κB- and SREBP2-mediated inflammasome signaling pathways, is believed to play a crucial role in COVID-19 pathogenesis, inducing acute respiratory distress syndrome (ARDS) and sepsis. To resolve those clinical conditions observed in severe SARS-CoV-2 patients, we report 25-HC and didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) as a COVID-19 drug candidate for the restoration of intracellular cholesterol level and suppression of cytokine storm. Our data demonstrate that 25-HC@DDAB can selectively accumulate the lung tissues and effectively downregulate NF-κB and SREBP2 signaling pathways in COVID-19 patient-derived PBMCs, reducing inflammatory cytokine levels. Altogether, our findings suggest that 25-HC@DDAB is a promising candidate for the treatment of symptoms associated with severe COVID-19 patients, such as decreased cholesterol level and cytokine storm., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Timely treatment is important for patients with acute ischemic stroke (AIS). However, the coronavirus disease 2019 (COVID-19) outbreak may have caused delays in patient management. Therefore, we analyzed the prognosis and the time spent at the prehospital and hospital stages in managing patients diagnosed with AIS during the COVID-19 outbreak., Methods: This retrospective study evaluated patients diagnosed with AIS in the emergency department (ED) at five medical centers in Daegu city between February 18 and April 17 each year from 2018 to 2020. Data on the patients' clinical features and time spent on management were collected and compared according to COVID-19 and pre-COVID-19 summaries., Results: From a total of 533 patients diagnosed with AIS, 399 patients visited the ED before COVID-19 and 134 during the COVID-19 outbreak. During the COVID-19 outbreak, compared with pre-COVID-19, AIS patients had poor National Institute of Health Stroke Scale scores at the initial hospital visit (6 vs. 4, p =0.013) and discharge (3 vs. 2, p =0.001). During the COVID-19 outbreak, the proportion of direct visits to hospitals through public emergency medical services (EMS) increased, and the onset of symptoms-to-ED door time via the public EMS was delayed (87 min vs. 68 min, p =0.006)., Conclusions: The prognosis of AIS patients during the COVID-19 outbreak was worse than that of pre-COVID-19 patients with delays at the prehospital stage, despite the need for timely care., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 Sang-Hun Lee et al.)

Background: Futile resuscitation for out-of-hospital cardiac arrest (OHCA) patients in the coronavirus disease (COVID)-19 era can lead to risk of disease transmission and unnecessary transport. Various existing basic or advanced life support (BLS or ALS, respectively) rules for the termination of resuscitation (TOR) have been derived and validated in North America and Asian countries. This study aimed to evaluate the external validation of these rules in predicting the survival outcomes of OHCA patients in the COVID-19 era., Methods: This was a multicenter observational study using the WinCOVID-19 Daegu registry data collected during February 18-March 31, 2020. The subjects were patients who showed cardiac arrest of presumed cardiac etiology. The outcomes of each rule were compared to the actual patient survival outcomes. The sensitivity, specificity, false positive value (FPV), and positive predictive value (PPV) of each TOR rule were evaluated., Results: In total, 170 of the 184 OHCA patients were eligible and evaluated. TOR was recommended for 122 patients based on the international basic life support termination of resuscitation (BLS-TOR) rule, which showed 85% specificity, 74% sensitivity, 0.8% FPV, and 99% PPV for predicting unfavorable survival outcomes. When the traditional BLS-TOR rules and KoCARC TOR rule II were applied to our registry, one patient met the TOR criteria but survived at hospital discharge. With regard to the FPV (upper limit of 95% confidence interval < 5%), specificity (100%), and PPV (> 99%) criteria, only the KoCARC TOR rule I, which included a combination of three factors including not being witnessed by emergency medical technicians, presenting with an asystole at the scene, and not experiencing prehospital shock delivery or return of spontaneous circulation, was found to be superior to all other TOR rules., Conclusion: Among the previous nine BLS and ALS TOR rules, KoCARC TOR rule I was most suitable for predicting poor survival outcomes and showed improved diagnostic performance. Further research on variations in resources and treatment protocols among facilities, regions, and cultures will be useful in determining the feasibility of TOR rules for COVID-19 patients worldwide.

Background: Pulseless electrical activity (PEA) is increasingly observed in out-of-hospital cardiac arrest (OHCA), but outcomes are still poor. We aimed to assess the relationship between QRS characteristics and outcomes of patients with OHCA with initial PEA (OHCA-P)., Methods: This prospective observational study included patients aged at least 18 years who developed OHCA-P between 1 January 2016 and 31 December 2018, and were enrolled in the Daegu Emergency Medical Services registry, South Korea. We performed multivariable logistic regression analyses to identify the associations between QRS characteristics and OHCA-P outcomes, in which QRS complexes were considered separately (model 1) and simultaneously (model 2). The primary outcome was survival to hospital discharge and the secondary outcome was a favourable neurological outcome., Results: Of the 3659 patients with OHCA, 576 were enrolled (median age 73 years; 334 men). A higher QRS amplitude was associated with survival to hospital discharge and a favourable neurological outcome in model 1 (adjusted OR (aOR) 1.077 and 1.106, respectively; 95% CI 1.021 to 0.136 and 1.029 to 1.190, respectively) and model 2 (aOR 1.084 and 1.123, respectively; 95% CI 1.026 to 1.145 and 1.036 to 1.216, respectively). A QRS width of <120 ms was associated with survival to hospital discharge and a favourable neurological outcome in model 1 (aOR 3.371 and 4.634, respectively; 95% CI 1.633 to 6.960 and 1.562 to 13.144, respectively) and model 2 (aOR 3.213 and 5.103, respectively; 95% CI 1.568 to 6.584 and 1.682 to 15.482, respectively). Survival to hospital discharge and neurological outcome were not associated with QRS frequency., Conclusion: OHCA-P outcomes were better when the initial QRS complex showed a higher amplitude or narrower width., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak., Materials and Methods: We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA., Results: Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA ( P = 0.018). Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 - 100) and a specificity of 22.5% (95% CI: 13.5 - 34.0)., Conclusion: The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR., Competing Interests: No conflicts of interest., (Copyright © 2020 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: In February and March 2020, healthcare providers and citizens in Daegu, South Korea, experienced the onslaught of a large-scale community epidemic of COVID-19. This had a profound impact on patients who experienced out-of-hospital cardiac arrest (OHCA)., Methods: We conducted a retrospective observational study of 171 OHCA patients based on the multicenter WinCOVID registry. Demographic and clinical characteristics, overall survival, COVID-19 related data, as well as personal protective equipment (PPE) and resuscitation techniques used during the COVID-19 outbreak were evaluated and compared with outcomes from a 2018 historical cohort (n ​= ​158)., Results: Among the interventions, high-level PPE was introduced and standard cardiopulmonary resuscitation was changed to chest compressions using mechanical devices. All OHCA patients were treated as confirmed or suspicious for COVID-19 regardless of symptoms. Furthermore, complete or partial closures of emergency centers and the number of medical personnel requiring self-isolation decreased in response to the introduction of isolated resuscitation units. However, the adjusted odds ratio and 95% confidence intervals for survival discharge and favorable neurologic outcome were 0.51 (0.25-0.97) and 0.45 (0.21-1.07) compared with those in the 2018 historical cohort., Conclusions: Responses to the COVID-19 pandemic included changes to current PPE strategies and introduction of isolated resuscitation units; the latter intervention reduced the number of unexpected closures and quarantines of emergency resources early on during the COVID-19 outbreak. Given the possibility of future outbreaks, we need to have revised resuscitation strategies and the capacity to commandeer emergency resources for OHCA patients., (© 2020 The Author(s).)

PEGylated Eudragit L100 (ELP)-containing proliponiosomes (PLNs) were developed for improved oral delivery of celecoxib (CXB). The successful introduction of PEG 2000 or 5000 to Eudragit L100 (EL) was confirmed via proton nuclear magnetic resonance analysis of which calculated molar substitution ratio of PEG to EL was 36.0 or 36.7, respectively. CXB, ELP, phospholipid, and non-ionic surfactants were dissolved in dimethyl sulfoxide and lyophilized to produce CXB-loaded PLNs (CXB@PLNs). The physical state of CXB@PLNs was evaluated using differential scanning calorimetry and powder X-ray diffractometry, which revealed that crystalline CXB was transformed into amorphous form after the fabrication procedure. The reconstitution of CXB@PLNs in aqueous media generated CXB-loaded liponiosomes with nano-sized mean diameters and spherical morphology. CXB@PLNs displayed enhanced dissolution rate and permeability compared to CXB suspension. In vivo pharmacokinetic studies performed on rats demonstrated the improved oral bioavailability of CXB@PLNs compared to that of CXB suspension. No serious systemic toxicity was observed in the blood biochemistry tests performed on rats. These results suggest that the developed PLNs could be promising oral delivery systems for improving the bioavailability of poorly water-soluble drugs, such as CXB.

Background: Recovery after out-of-hospital cardiac arrest (OHCA) is difficult, and emergency medical services (EMS) systems apply various strategies to improve outcomes. Multi-dispatch is one means of providing high-quality cardiopulmonary resuscitation (CPR), but no definitive best-operation guidelines are available. We assessed the effects of a basic life support (BLS)-based dual-dispatch system for OHCA., Methods: This prospective observational study of 898 enrolled OHCA patients, conducted in Daegu, Korea from March 1, 2015 to June 30, 2016, involved patients > 18 years old with suspected cardiac etiology OHCA. In Daegu, EMS started a BLS-based dual-dispatch system in March 2015, for cases of cardiac arrest recognition by a dispatch center. We assessed the association between dual-dispatch and OHCA outcomes using multivariate logistic regressions. We also analyzed the effect of dual-dispatch according to the stratified on-scene time., Results: Of 898 OHCA patients (median, 69.0 years; 65.5% men), dual-dispatch was applied in 480 (53.5%) patients. There was no difference between the single-dispatch group (SDG) and the dual-dispatch group (DDG) in survival at discharge and neurological outcomes (survival discharge, P = 0.176; neurological outcomes, P = 0.345). In the case of less than 10 minutes of on-scene time, the adjusted odds ratio was 1.749 (95% confidence interval [CI], 0.490-6.246) for survival discharge and 6.058 (95% CI, 1.346-27.277) for favorable neurological outcomes in the DDG compared with the SDG., Conclusion: Dual-dispatch was not associated with better OHCA outcomes for the entire study population, but showed favorable neurological outcomes when the on-scene time was less than 10 minutes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

Background: Heatstroke is one of the most serious heat-related illnesses. However, establishing public policies to prevent heatstroke remains a challenge. This study aimed to investigate the most relevant climate elements and their warning criteria to prevent outdoor heatstroke (OHS)., Methods: We investigated heatstroke patients from five major hospitals in Daegu metropolitan city, Korea, from June 1 to August 31, 2011 to 2016. We also collected the corresponding regional climate data from Korea Meteorological Administration. We analyzed the relationship between the climate elements and OHS occurrence by logistic regression., Results: Of 70 patients who had heatstroke, 45 (64.3%) experienced it while outdoors. Considering all climate elements, only mean heat index (MHI) was related with OHS occurrence ( p =0.019). Therefore, the higher the MHI, the higher the risk for OHS (adjusted odds ratio, 1.824; 95% confidence interval, 1.102-3.017). The most suitable cutoff point for MHI by Youden's index was 30.0°C (sensitivity, 77.4%; specificity, 73.7%)., Conclusion: Among the climate elements, MHI was significantly associated with OHS occurrence. The optimal MHI cutoff point for OHS prevention was 30.0°C., Competing Interests: No potential conflicts of interest relevant to this article was reported., (Copyright © 2019 Yeungnam University College of Medicine.)