Optimized combination of Cervus nippon (Sika deer), Angelica (Dangui), and Rehmannia (Suk-jihwang) mitigates LPS-induced inflammation: exploring signaling pathways through plasma metabolomics.

This study aimed to determine the optimal combination of three anti-inflammatory materials [i.e., Cervus nippon Temminck (CT), Angelica gigas Nakai (AN), and Rehmannia glutinosa (RG)] for the strongest anti-inflammatory potential. Eighteen combinations of the three materials were tested in LPS-stimulated RAW264.7 cells via assessing nitric oxide (NO). The best combination from in vitro studies was administered to LPS-treated C57BL/6J mice for five days. Subsequently, plasma metabolites were profiled by bioinformatics analyses and validations. As results, 2, 20, and 50 µg/mL of CT, AN, and RG (TM) were the most effective combination suppressing inflammation. In mice, TM mitigated hepatic inflammatory markers. Similarly, the metabolomics indicated that TM may suppress NF-κB signaling pathway, thereby alleviating hepatic inflammation. TM also decreased systemic and hepatic pro-inflammatory cytokines. Collectively, we found the optimal combination of TM for mitigating inflammation; thus further studies on safety, mechanisms, and clinical models are warranted for human applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01476-x.

Lower-Body Fractures and the Risk of Dementia: A Nationwide Population-Based Study.

BACKGROUND AND PURPOSE: The association between physical activity and dementia has been shown in various observational studies. We aimed to determine the risk of dementia in the elderly with lower-body fractures. METHODS: We reconstructed a population-based matched cohort from the National Health Insurance Service-Senior Cohort data set that covers 511,953 recipients of medical insurance in South Korea. RESULTS: Overall 53,776 subjects with lower-body fractures were identified during 2006-2012, and triplicate control groups were matched randomly by sex, age, and years from the index date for each subject with a fracture. There were 3,573 subjects (6.6%) with and 7,987 subjects (4.9%) without lower-body fractures who developed dementia from 2008 up to 2015. Lower-body fractures were independently associated with a subsequent dementia diagnosis with a higher adjusted hazard ratio (aHR) (1.55, 95% confidence interval [CI]=1.49-1.62) compared with upper-body fractures (aHR=1.19, 95% CI=1.14-1.23). CONCLUSIONS: These results support the protective role of physical activity against dementia and highlight the importance of promoting fracture prevention in the elderly.

Machine learning application for classification of Alzheimer's disease stages using 18F-flortaucipir positron emission tomography.

BACKGROUND: The progression of Alzheimer's dementia (AD) can be classified into three stages: cognitive unimpairment (CU), mild cognitive impairment (MCI), and AD. The purpose of this study was to implement a machine learning (ML) framework for AD stage classification using the standard uptake value ratio (SUVR) extracted from 18F-flortaucipir positron emission tomography (PET) images. We demonstrate the utility of tau SUVR for AD stage classification. We used clinical variables (age, sex, education, mini-mental state examination scores) and SUVR extracted from PET images scanned at baseline. Four types of ML frameworks, such as logistic regression, support vector machine (SVM), extreme gradient boosting, and multilayer perceptron (MLP), were used and explained by Shapley Additive Explanations (SHAP) to classify the AD stage. RESULTS: Of a total of 199 participants, 74, 69, and 56 patients were in the CU, MCI, and AD groups, respectively; their mean age was 71.5 years, and 106 (53.3%) were men. In the classification between CU and AD, the effect of clinical and tau SUVR was high in all classification tasks and all models had a mean area under the receiver operating characteristic curve (AUC) > 0.96. In the classification between MCI and AD, the independent effect of tau SUVR in SVM had an AUC of 0.88 (p < 0.05), which was the highest compared to other models. In the classification between MCI and CU, the AUC of each classification model was higher with tau SUVR variables than with clinical variables independently, which yielded an AUC of 0.75(p < 0.05) in MLP, which was the highest. As an explanation by SHAP for the classification between MCI and CU, and AD and CU, the amygdala and entorhinal cortex greatly affected the classification results. In the classification between MCI and AD, the para-hippocampal and temporal cortex affected model performance. Especially entorhinal cortex and amygdala showed a higher effect on model performance than all clinical variables in the classification between MCI and CU. CONCLUSIONS: The independent effect of tau deposition indicates that it is an effective biomarker in classifying CU and MCI into clinical stages using MLP. It is also very effective in classifying AD stages using SVM with clinical information that can be easily obtained at clinical screening.

Curcumin Ameliorates Particulate Matter-Induced Pulmonary Injury through Bimodal Regulation of Macrophage Inflammation via NF-κB and Nrf2.

The direct effects of particulate matter (PM) on lung injury and its specific molecular mechanisms are unclear. However, experimental evidence has shown that oxidative stress-mediated inflammation in macrophages is the main pathological outcome of PM exposure. Curcumin has been reported to protect organs against the disturbance of homeostasis caused by various toxic agents through anti-inflammatory and antioxidative effects. However, the protective action of curcumin against PM-induced pulmonary inflammation and the underlying mechanism have not been thoroughly investigated. In this study, we established a PM-induced pulmonary inflammation mouse model using the intratracheal instillation method to investigate the protective ability of curcumin against PM-induced pulmonary inflammation. Compared to the mice treated with PM only, the curcumin-treated mice showed alleviated alveolar damage, decreased immune cell infiltration, and reduced proinflammatory cytokine production in both lung tissue and BALF. To evaluate the underlying mechanism, the mouse macrophage cell line RAW264.7 was used. Pretreatment with curcumin prevented the production of PM-induced proinflammatory cytokines by deactivating NF-κB through the suppression of MAPK signaling pathways. Furthermore, curcumin appears to attenuate PM-induced oxidative stress through the activation of Nrf2 and downstream antioxidant signaling. Our findings demonstrate that curcumin protects against PM-induced lung injury by suppressing oxidative stress and inflammatory activation in macrophages.

Influence of meteorological factors on development of spontaneous pneumothorax.

This study investigated the correlation between spontaneous pneumothorax (SP) and meteorological factors during different seasons. Patients who visited emergency rooms (ERs) in large cities in Korea and were discharged with SP from 2014 to 2016 were included in this study. Data on temperature, air pressure, and wind speed for each region were collected to obtain each factor's daily maximum, minimum, average, and changes. Days with more than 1 case of SP per million were referred to as pneumothorax days (PD) and those with less than 1 case of SP per million were referred to as non-pneumothorax days (NPD). The environmental factors were assessed on the same day (Day 0), 1 day prior (Day-1), and 2 days prior (Day-2) to PD and NPD per season. A total of 17,846 patients were included in this study. During winter, 4080 patients with SP visited the ERs of large cities with low population densities. The maximum temperature (0.16°C vs 0.76°C, 0.04°C vs 0.87°C, and 0.09°C vs 0.91°C), change in temperature (0.24°C vs 0.90°C, 0.38°C vs 0.81°C, and 0.41°C vs 0.83°C), average atmospheric pressure (0.16 vs 0.52 hPa, 0.25 vs 0.42 hPa, 0.34 vs 0.40 hPa), and maximum atmospheric pressure (0.15 vs 0.53 hPa, 0.28 vs 0.49 hPa, 0.33 vs 0.71 hPa) were greater for Day 0, Day-1, and Day-2, respectively, in PD than in NPD. Meanwhile, the average (0.31 vs 0.48 m/s, 0.28 vs 0.46 m/s, 0.20 vs 0.40 m/s), minimum (0.20 vs 0.31 m/s, 0.18 vs 0.25 m/s, 0.16 vs 0.25 m/s), and maximum (0.44 vs 0.67 m/s, 0.36 vs 0.71 m/s, 0.26 vs 0.58 m/s) wind speeds were slower, and the changes in wind speed (0.44 vs 0.67 m/s, 0.36 vs 0.71 m/s, 0.16 vs 0.25 m/s) were lower for all 3 days in PD than in NPD. High average and change in temperature, slow and unchanging wind speed, and high average and maximum atmospheric pressure were associated with SP. Since many findings of this study were contradictory to previous studies, it is assumed that the interaction of various factors affects SP.

Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy.

Cells respond to DNA damage by activating signaling and DNA repair systems, described as the DNA damage response (DDR). Clarifying DDR pathways and their dysregulation in cancer are important for understanding cancer etiology, how cancer cells exploit the DDR to survive endogenous and treatment-related stress, and to identify DDR targets as therapeutic targets. Cancer is often treated with genotoxic chemicals and/or ionizing radiation. These agents are cytotoxic because they induce DNA double-strand breaks (DSBs) directly, or indirectly by inducing replication stress which causes replication fork collapse to DSBs. EEPD1 and Metnase are structure-specific nucleases, and Metnase is also a protein methyl transferase that methylates histone H3 and itself. EEPD1 and Metnase promote repair of frank, two-ended DSBs, and both promote the timely and accurate restart of replication forks that have collapsed to single-ended DSBs. In addition to its roles in HR, Metnase also promotes DSB repair by classical non-homologous recombination, and chromosome decatenation mediated by TopoIIα. Although mutations in Metnase and EEPD1 are not common in cancer, both proteins are frequently overexpressed, which may help tumor cells manage oncogenic stress or confer resistance to therapeutics. Here we focus on Metnase and EEPD1 DNA repair pathways, and discuss opportunities for targeting these pathways to enhance cancer therapy.

Impact of the COVID-19 Pandemic on Emergency Department Workload and Emergency Care Workers' Psychosocial Stress in the Outbreak Area.

Background and Objectives: Due to the unexpected spread of coronavirus disease 2019 (COVID-19), there was a serious crisis of emergency medical system collapse. Healthcare workers working in the emergency department were faced with psychosocial stress and workload changes. Materials and Methods: This was a cross-sectional survey of healthcare workers in the emergency department in Daegu and Gyeongbuk, Korea, from November 16 to 25, 2020. In the survey, we assessed the general characteristics of the respondents; changes in the working conditions before and after the COVID-19 pandemic; and resulting post-traumatic stress disorder, depression and anxiety statuses using 49 questions. Results: A total of 529 responses were collected, and 520 responses were included for the final analyses. Changes in working conditions and other factors due to COVID-19 varied by emergency department level, region and disease group. Working hours, intensity, role changes, depression and anxiety scores were higher in the higher level emergency department. Isolation ward insufficiency and the risk of infection felt by healthcare workers tended to increase in the lower level emergency department. Treatment and transfer delay were higher in the fever and respiratory disease groups (M = 3.58, SD = 1.18; M = 4.08, SD = 0.95), respectively. In all the disease groups, both treatment and transfer were delayed more in Gyeongbuk than in Daegu. Conclusions: Different goals should be pursued by the levels and region of the emergency department to overcome the effects of the COVID-19 pandemic and promote optimal care.

Effects of dynamic response to coronavirus disease outbreak in a regional emergency medical center: A retrospective study.

ABSTRACT: Emergency departments (EDs) are on the frontline of the coronavirus disease (COVID-19) outbreak. To resolve the abrupt overloading of COVID-19-suspected patients in a community, each ED needs to respond in various ways. In our hospital, we increased the isolation beds through temporary remodeling and by performing in-hospital COVID-19 polymerase chain reaction testing rather than outsourcing them. The aim of this study was to verify the effects of our response to the newly developed viral outbreak.The medical records of patients who presented to an ED were analyzed retrospectively. We divided the study period into 3: pre-COVID-19, transition period of response (the period before fully implementing the response measures), and post-response (the period after complete response). We compared the parameters of the National Emergency Department Information System and information about isolation and COVID-19.The number of daily ED patients was 86.8 ±â€Š15.4 in the pre-COVID-19, 36.3 ±â€Š13.6 in the transition period, and 67.2 ±â€Š10.0 in the post-response period (P < .001). The lengths of stay in the ED were significantly higher in transition period than in the other periods [pre-COVID-19 period, 219.0 (121.0-378.0) min; transition period, 301 (150.0-766.5) min; post-response period, 281.0 (114.0-575.0) min; P < .001]. The ratios of use of an isolation room and fever (≥37.5°C) were highest in the post-response period [use of isolation room: pre-COVID-19 period, 0.6 (0.7%); transition period, 1.2 (3.3%); post-response period, 16.1 (24.0%); P < .001; fever: pre-COVID-19 period, 14.8(17.3%); transition period, 6.8 (19.1%); post-response period, 14.5 (21.9%), P < .001].During an outbreak of a novel infectious disease, increasing the number of isolation rooms in the ED and applying a rapid confirmation test would enable the accommodation of more suspected patients, which could help reduce the risk posed to the community and thus prevent strain on the local emergency medical system.

Prevalence and Incidence of Dementia in South Korea: A Nationwide Analysis of the National Health Insurance Service Senior Cohort.

BACKGROUND AND PURPOSE: Dementia is rapidly becoming more common in the elderly population of South Korea, and there are regional difference in its demographics. This study investigated the trajectories in the prevalence and incidence of dementia based on the Seoul metropolitan area and other areas in South Korea using big data from the National Health Insurance Service (NHIS). METHODS: We examined a population-based elderly cohort obtained from the NHIS Senior Cohort (NHIS-SC) data set that comprises approximately half a million recipients of medical insurance in South Korea during 2003-2015. The age-standardized prevalence and incidence of dementia as well as their trajectories from 2003 were estimated. Regional differences in these rates between Seoul metropolitan area and other areas were also analyzed. RESULTS: The standardized prevalence of dementia per 100,000 increased significantly from 178.11 in 2003 to 5,319.01 in 2015 (p<0.001). The standardized prevalence of dementia was higher in other areas than in Seoul metropolitan area. The standardized incidence of dementia per 100,000 person-years also increased significantly, from 126.41 in 2003 to 2,218.25 in 2015 (p<0.001). The standardized incidence of dementia was similarly higher in other areas than in Seoul metropolitan area (p<0.001). CONCLUSIONS: This study has shown that the standardized prevalence and incidence of dementia increased steadily from 2003 to 2015 in South Korea based on the NHIS-SC data set, and differed between Seoul metropolitan area and other areas.

Clinical usefulness of deep learning-based automated segmentation in intracranial hemorrhage.

BACKGROUND: Doctors with various specializations and experience order brain computed tomography (CT) to rule out intracranial hemorrhage (ICH). Advanced artificial intelligence (AI) can discriminate subtypes of ICH with high accuracy. OBJECTIVE: The purpose of this study was to investigate the clinical usefulness of AI in ICH detection for doctors across a variety of specialties and backgrounds. METHODS: A total of 5702 patients' brain CTs were used to develop a cascaded deep-learning-based automated segmentation algorithm (CDLA). A total of 38 doctors were recruited for testing and categorized into nine groups. Diagnostic time and accuracy were evaluated for doctors with and without assistance from the CDLA. RESULTS: The CDLA in the validation set for differential diagnoses among a negative finding and five subtypes of ICH revealed an AUC of 0.966 (95% CI, 0.955-0.977). Specific doctor groups, such as interns, internal medicine, pediatrics, and emergency junior residents, showed significant improvement with assistance from the CDLA (p= 0.029). However, the CDLA did not show a reduction in the mean diagnostic time. CONCLUSIONS: Even though the CDLA may not reduce diagnostic time for ICH detection, unlike our expectation, it can play a role in improving diagnostic accuracy in specific doctor groups.

Comparison of the effects of shortening rest intervals on the quality of cardiopulmonary resuscitation, physiological parameters, and hemodynamic parameters in well-trained rescuers: Randomized simulation study.

BACKGROUND: Cardiopulmonary resuscitation (CPR) performance depends on individual ability and training. Well-trained or professional rescuers can maintain high-quality CPR for longer than laypeople. This study aimed to examine the effects of reducing resting intervals on CPR performance, physiological parameters, and hemodynamic parameters during prolonged CPR in well-trained providers. METHODS: The study enrolled 90 volunteers from the paramedic students of our institution. They were randomly divided into 3 groups: 2 minutes, 1 minute 45 seconds, and 1 minute 30 seconds rest groups. Each participant performed 5 cycles of chest compression only CPR (2 min/cycle) with different resting intervals according to grouping. CPR quality, physiological variations, and hemodynamic variations were measured for each cycle and compared across the groups. RESULTS: Of the 90 volunteers, 79 well-trained providers were finally included. The variation of the average chest compression depth across the 5 cycles showed significant differences between the 3 groups: from cycle 1 to 2: 1.2 (3.1) mm, -0.8 (2.0) mm, and -2.0 (3.0) mm in the 2 minutes, 1 minute 45 seconds, and 1 minute 30 seconds groups, respectively (P < .001); from cycle 1 to 3: 0.0 (3.0) mm, -0.7 (3.2) mm, and -2.6 (3.9) mm, respectively (P = .030). However, all 3 groups maintained the recommended rate and chest compression depth for all 5 cycles. Physiological and hemodynamic parameters showed no significant differences between the groups. CONCLUSIONS: Well-trained providers were able to maintain high-quality CPR despite reducing rest intervals. Adjusting the rest interval may help maintain overall CPR quality in special situations or where layperson rescuers are involved.

External validation of multimodal termination of resuscitation rules for out-of-hospital cardiac arrest patients in the COVID-19 era.

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.

The role of microRNA-33 as a key regulator in hepatic lipogenesis signaling and a potential serological biomarker for NAFLD with excessive dietary fructose consumption in C57BL/6N mice.

Limited studies reported mechanisms by which microRNAs (miRNA) are interlinked in the etiology of fructose-induced non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the significance of miRNAs in fructose-induced NAFLD pathogenesis through unbiased approaches. In experiment I, C57BL/6N mice were fed either water or 34% fructose for six weeks ad libitum. In experiment II, time course effects of fructose intervention were monitored using the same conditions; mice were killed at the baseline, fourth, and sixth weeks. Bioinformatic analyses for hepatic proteomics revealed that SREBP1 is the most significant upstream regulator influenced by fructose; miR-33-5p (miR-33) was identified as the key miRNA responsible for SREBP1 regulation upon fructose intake, which was validated by in vitro transfection assay. In experiment II, we confirmed that the longer mice consumed fructose, the more severe liver injury markers (e.g., serum AST) appeared. Moreover, hepatic Srebp1 mRNA expression was increased depending upon the duration of fructose consumption. Hepatic miR-33 was time-dependently decreased by fructose while serum miR-33 expression was increased; these observations indicated that miR-33 from the liver might be released upon cell damage. Finally we observed that fructose-induced ferroptosis might be a cause of liver toxicity, resulting from oxidative damage. Collectively, our findings suggest that fructose-induced oxidative damage induces ferroptosis, and miR-33 could be used as a serological biomarker of fructose-induced NAFLD.

Impact of the coronavirus disease 2019 outbreak on the transportation of patients requiring emergency care.

The first confirmed community transmission of coronavirus disease 2019 in Daegu Metropolitan City, South Korea, occurred on February 18, 2020. In the following 70-day period, approximately 6000 new cases occurred, severely impacting the medical service system. This study investigated the crisis-impact on the local emergency transport system.Emergency medical service activity reports were retrospectively reviewed to determine patient demographics and initial vital signs. Delay in reaching the patient, transporting the patient to the hospital, and returning to the fire station were assessed and categorized based on patients' initial vital signs. The study period was divided into 4 groups (1/1-2/18, 2/19-3/3, 3/4-3/31, and 4/1-04/30) and intergroup differences were analyzed.When compared to Period 1, the time-difference between the request to attend a scene and arrival at the scene was delayed in Periods 2, 3, and 4 by 4 minute 58 s, 3  minute 24 seconds, and 2 minute 20 seconds, respectively; that between arriving at the scene and at the hospital was delayed by 7  minute 43 seconds, 6 minutes 59 seconds, and 4 minutes 30 seconds, respectively; and that between arriving at the hospital and returning to the fire station was delayed by 29  minute 3 second, 25  minute 55 second, and 18  minute 44 second, respectively. In Period 2, for patients with symptoms of severe illness when compared to patients lacking such symptoms, the time-difference between the request to attend the scene and arrival at a hospital and between arrival at the hospital and returning to the fire station were 6 to 23 minute and 12 to 48 minute longer, respectively. Most of the delays impacted patients with a fever. In terms of condition, the statistical effect size for delay in transport time was from large to small: fever, hypoxia, abnormal respiratory rate, respiratory symptom, and hypotension.Outbreaks of infectious disease cause a paradoxical state in emergency medical transport systems, inducing delays in the transport of severely ill patients. Therefore, maintenance and improvement of the medical service system for both patients with infectious disease and those with other severe illnesses is required.

Confirmation of COVID-19 in Out-of-Hospital Cardiac Arrest Patients and Postmortem Management in the Emergency Department during the COVID-19 Outbreak.

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.

Deep-learning algorithms for the interpretation of chest radiographs to aid in the triage of COVID-19 patients: A multicenter retrospective study.

The recent medical applications of deep-learning (DL) algorithms have demonstrated their clinical efficacy in improving speed and accuracy of image interpretation. If the DL algorithm achieves a performance equivalent to that achieved by physicians in chest radiography (CR) diagnoses with Coronavirus disease 2019 (COVID-19) pneumonia, the automatic interpretation of the CR with DL algorithms can significantly reduce the burden on clinicians and radiologists in sudden surges of suspected COVID-19 patients. The aim of this study was to evaluate the efficacy of the DL algorithm for detecting COVID-19 pneumonia on CR compared with formal radiology reports. This is a retrospective study of adult patients that were diagnosed as positive COVID-19 cases based on the reverse transcription polymerase chain reaction among all the patients who were admitted to five emergency departments and one community treatment center in Korea from February 18, 2020 to May 1, 2020. The CR images were evaluated with a publicly available DL algorithm. For reference, CR images without chest computed tomography (CT) scans classified as positive for COVID-19 pneumonia were used given that the radiologist identified ground-glass opacity, consolidation, or other infiltration in retrospectively reviewed CR images. Patients with evidence of pneumonia on chest CT scans were also classified as COVID-19 pneumonia positive outcomes. The overall sensitivity and specificity of the DL algorithm for detecting COVID-19 pneumonia on CR were 95.6%, and 88.7%, respectively. The area under the curve value of the DL algorithm for the detection of COVID-19 with pneumonia was 0.921. The DL algorithm demonstrated a satisfactory diagnostic performance comparable with that of formal radiology reports in the CR-based diagnosis of pneumonia in COVID-19 patients. The DL algorithm may offer fast and reliable examinations that can facilitate patient screening and isolation decisions, which can reduce the medical staff workload during COVID-19 pandemic situations.

Revised Triage and Surveillance Protocols for Temporary Emergency Department Closures in Tertiary Hospitals as a Response to COVID-19 Crisis in Daegu Metropolitan City.

BACKGROUND: When an emergency-care patient is diagnosed with an emerging infectious disease, hospitals in Korea may temporarily close their emergency departments (EDs) to prevent nosocomial transmission. Since February 2020, multiple, consecutive ED closures have occurred due to the coronavirus disease 2019 (COVID-19) crisis in Daegu. However, sudden ED closures are in contravention of laws for the provision of emergency medical care that enable the public to avail prompt, appropriate, and 24-hour emergency medical care. Therefore, this study ascertained the vulnerability of the ED at tertiary hospitals in Daegu with regard to the current standards. A revised triage and surveillance protocol has been proposed to tackle the current crisis. METHODS: This study was retrospectively conducted at 6 level 1 or 2 EDs in a metropolitan city where ED closure due to COVID-19 occurred from February 18 to March 26, 2020. The present status of ED closure and patient characteristics and findings from chest radiography and laboratory investigations were assessed. Based on the experience from repeated ED closures and the modified systems that are currently used in EDs, revised triage and surveillance protocols have been developed and proposed. RESULTS: During the study period, 6 level 1 or 2 emergency rooms included in the study were shut down 27 times for 769 hours. Thirty-one confirmed COVID-19 cases, of whom 7 died, were associated with the incidence of ED closure. Typical patient presentation with respiratory symptoms of COVID-19 was seen in less than 50% of patients, whereas abnormal findings on chest imaging investigations were detected in 93.5% of the study population. The chest radiography facility, resuscitation rooms, and triage area were moved to locations outside the ED, and a new surveillance protocol was applied to determine the factors warranting quarantine, including symptoms, chest radiographic findings, and exposure to a source of infection. The incidence of ED closures decreased after the implementation of the revised triage and surveillance protocols. CONCLUSION: Triage screening by emergency physicians and surveillance protocols with an externally located chest imaging facility were effective in the early isolation of COVID-19 patients. In future outbreaks of emerging infectious diseases, efforts should be focused toward the provision of continued ED treatment with the implementation of revised triage and surveillance protocols.

Preparedness of personal protective equipment and implementation of new CPR strategies for patients with out-of-hospital cardiac arrest in the COVID-19 era.

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 â€‹= â€‹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.

Trehalose Protects the Probiotic Yeast Saccharomyces boulardii against Oxidative Stress-Induced Cell Death.

Saccharomyces boulardii is the only probiotic yeast with US Food and Drug Administration approval. It is routinely used to prevent or treat acute diarrhea and other gastrointestinal disorders, including the antibiotic-associated diarrhea caused by Clostridium difficile infections. The formation of reactive oxygen species (ROS), specifically H2O2 during normal aerobic metabolism, contributes to programmed cell death and represents a risk to the viability of the probiotic microbe. Moreover, a loss of viability reduces the efficacy of the probiotic treatment. Therefore, inhibiting the accumulation of ROS in the oxidant environment could improve the viability of the probiotic yeast and lead to more efficacious treatment. Here, we provide evidence that supplementation with a non-reducing disaccharide, namely trehalose, enhanced the viability of S. boulardii exposed to an oxidative environment by preventing metacaspase YCA1-mediated programmed cell death through inhibition of intracellular ROS production. Our results suggest that supplementation with S. boulardii together with trehalose could increase the viability of the organism, and thus improve its effectiveness as a probiotic and as a treatment for acute diarrhea and other gastrointestinal disorders.

IDH2 deficiency increases bone mass with reduced osteoclastogenesis by limiting RANKL expression in osteoblasts.

Mitochondria are not only responsible for cellular energy production but are also involved in signaling, cellular differentiation, cell death, and aging. Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the decarboxylation of isocitrate to α-ketoglutarate, accompanied by NADPH production. IDH2 plays a central role in mitochondrial function in multiple cell types and various organs, including the heart, kidneys, and brain. However, the function of IDH2 in bone tissue is yet to be elucidated. Here, we report that disruption of IDH2 in mice results in high bone mass due to decreased osteoclast number and resorption activity. Although IDH2 played no cell-intrinsic role in osteoclasts, IDH2-deficient animals showed decreased serum markers of osteoclast activity and bone resorption. Bone marrow stromal cells/osteoblasts from Idh2 knockout mice were defective in promoting osteoclastogenesis due to a reduced expression of a key osteoclastogenic factor, receptor activator of nuclear factor-κB ligand (RANKL), in osteoblasts in vivo and in vitro through the attenuation of ATF4-NFATc1 signaling. Our findings suggest that IDH2 is a novel regulator of osteoblast-to-osteoclast communication and bone metabolism, acting via the ATF4-NFATc1-RANKL signaling axis in osteoblasts, and they provide a rationale for further study of IDH2 as a potential therapeutic target for the prevention of bone loss.