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Abstract Metallocenes are highly versatile organometallic compounds. The versatility of the metallocenes stems from their ability to stabilize a wide range of formal electron counts. To date, d-block metallocenes with an electron count of up to 20 have been synthesized and utilized in catalysis, sensing, and other fields. However, d-block metallocenes with more than formal 20-electron counts have remained elusive. The synthesis and isolation of such complexes are challenging because the metal–carbon bonds in d-block metallocenes become weaker with increasing deviation from the stable 18-electron configuration. Here, we report the synthesis, isolation, and characterization of a 21-electron cobaltocene derivative. This discovery is based on the ligand design that allows the coordination of an electron pair donor to a 19-electron cobaltocene derivative while maintaining the cobalt–carbon bonds, a previously unexplored synthetic approach. Furthermore, we elucidate the origin of the stability, redox chemistry, and spin state of the 21-electron complex. This study reveals a synthetic method, structure, chemical bonding, and properties of the 21-electron metallocene derivative that expands our conceptual understanding of d-block metallocene chemistry. We expect that this report will open up previously unexplored synthetic possibilities in d-block transition metal chemistry, including the fields of catalysis and materials chemistry.

ObjectivesObstructive sleep apnea (OSA) is a common sleep-related breathing disorder, yet many cases remain undiagnosed. The STOP-Bang questionnaire was developed to identify individuals at high risk of OSA. We aimed to investigate the prevalence of individuals with suspected OSA using the STOP-Bang risk stratification in the general population of South Korea. Additionally, we determined if the STOP-Bang risk stratification independently predicts cardiovascular morbidity.MethodsData from the eighth Korea National Health and Nutrition Examination Survey (2019–2020) were used. Participants aged ≥40 with complete data for STOP-Bang questionnaire were included. A STOP-Bang score of ≥5 classified individuals as high-risk whereas scores of 3–4 and less than 3 classified them as intermediate- and low-risk, respectively. The association between the high-risk group and cardiovascular morbidity was analyzed using complex sample logistic regression.ResultsAmong the 6,630 participants included, approximately 6.7% were classified as high-risk based on the STOP-Bang questionnaire. The prevalence of diagnosed OSA in the high-risk group was 4.0%. The high-risk group showed a significantly higher prevalence of cardiovascular morbidity (11.9%) compared to those in the low- and intermediate-risk groups (3.0 and 8.1%, respectively). After adjusting for variables associated with cardiovascular risk, the high-risk group remained an independent predictor of increased likelihood of cardiovascular morbidity compared to the low-risk group (odds ratio, 2.05; p = 0.002). When stratified by sex, STOP-Bang high-risk was significantly associated with cardiovascular morbidity in men; however, the same trend was not observed in women.ConclusionWe found a significant proportion of individuals at high risk of OSA is likely to remain undiagnosed in the general population of South Korea. The high-risk group demonstrated a higher burden of cardiovascular morbidity, and the STOP-Bang high-risk group was an independent predictor of cardiovascular morbidity.

Mycobacterium avium complex (MAC) infection is a growing public health concern worldwide, particularly affecting the elderly and immunocompromised population. The treatment of MAC lung disease relies on a combination of antibiotics in a three-drug regimen that includes macrolides, rifamycins, and ethambutol. Therefore, the investigation of antimicrobial susceptibility is crucial for successful treatment. This study aimed to assess the antibiotic susceptibility of the most prevalent MAC species causing MAC lung disease, Mycobacterium intracellulare, in the Southwestern Gyeongsang province of South Korea using a resazurin-based microtiter assay. A total of 97 strains of M. intracellulare were isolated and tested for antimicrobial susceptibility. The results demonstrated high susceptibility rates for two aminoglycosides (amikacin and streptomycin, 94.9% and 99%), rifampicin (90.9%), clarithromycin (98%), linezolid (100%), and moxifloxacin (94.9%) against M. intracellulare. However, notably high resistance rates were observed for ethambutol (97%) and clofazimine (98%) against M. intracellulare. In conclusion, our findings indicate relatively high susceptibility rates for these six antibiotics and significantly elevated resistance rates for clofazimine and ethambutol compared to other regions in South Korea and foreign countries. The investigated MIC data can offer valuable insights for developing an effective treatment regimen for MAC lung infection in this area.

Fully vaccinated people remain at risk of Coronavirus Disease 2019 (COVID-19). We examined association between prior vaccination and clinical outcomes in patients with COVID-19. Overall, 387 patients with mild-to-severe COVID-19 were enrolled. Patients were considered fully vaccinated at least 14, 7, and 14 days after receiving the second dose of ChAdOx1 nCoV-19 or mRNA-1273, second dose of BNT162b2, or single dose of Ad26.COV2.S, respectively. The primary outcomes (risk of pneumonia, requirement of supplemental oxygen, and progression to respiratory failure) were compared between vaccinated and unvaccinated patients. Logistic regression analysis was performed to identify factors associated with the outcomes. There were 204 and 183 patients in the vaccinated and unvaccinated groups, respectively. The vaccinated group was significantly older and had more comorbidities than the unvaccinated group. Patients in the unvaccinated group were significantly more likely to develop pneumonia (65.6% vs. 36.8%) or require supplemental oxygen (29.0 vs. 15.7%) than the vaccinated group. The vaccinated group had a significantly shorter time from symptom onset to hospital discharge than the unvaccinated group (10 vs. 11 days; p

Abstract The production of pharmacological vaccines in plants has been an important goal in the field of plant biotechnology. GA733-2, the protein that is also known as colorectal carcinoma (CRC)-associated antigen, is a strong candidate to produce a colorectal cancer vaccine. Tomato is the one of the major targets for production of an edible vaccine, as tomato is a fruit consumed in fresh form. It also contains high content of vitamins that aid activation of immune response. In order to develop an edible colorectal cancer vaccine, the transgene rGA733-Fc that encodes a fusion protein of GA733-2, the fragment crystallizable (Fc) domain, and the ER retention motif (rGA733-Fc) was introduced into tomato plants (Solanum lycopersicum cv. Micro-Tom). The transgenic plants producing rGA733-Fc (rGA733-Fc OX ) protein were screened based on stable integration of transgene expression cassette and expression level of rGA733-Fc protein. Further glycosylation pattern analysis revealed that plant derived rGA733-Fc protein contains an oligomannose glycan structure, which is a typical glycosylation pattern found on ER-processing proteins. The red fruits of rGA733-Fc OX transgenic tomato plants containing approximately 270 ng/g FW of rGA733-Fc protein were orally administered to C57BL/6 mice. Oral administration of tomato fruits of the rGA733-Fc expressing transgenic plants delayed colorectal cancer growth and stimulated immune responses compared to oral administration of tomato fruits of the h-Fc expressing transgenic plants in the C57BL/6J mice. This is the first study showing the possibility of producing an edible colorectal cancer vaccine using tomato plants. This research would be helpful for development of plant-derived cancer edible vaccines.

Background/Aims There are few studies describing contemporary status of mechanical ventilation in Korea. We investigated changes in management and outcome of mechanical ventilation in Korea. Methods International, prospective observational cohort studies have been conducted every 6 years since 1998. Korean intensive care units (ICUs) participated in 2010 and 2016 cohorts. We compared 2016 and 2010 Korean data. Results Two hundred and twenty-six patients from 18 ICUs and 275 patients from 12 ICUs enrolled in 2016 and 2010, respectively. In 2016 compared to 2010, use of non-invasive ventilation outside ICU increased (10.2% vs. 2.5%, p = 0.001). Pressure-control ventilation was the most common mode in both groups. Initial tidal volume (7.1 mL/kg vs. 7.4 mL/kg, p = 0.372) and positive end-expiratory pressure (6 cmH2O vs. 6 cmH2O, p = 0.141) were similar, but peak pressure (22 cmH2O vs. 24 cmH2O, p = 0.011) was lower in 2016. More patients received sedatives (70.7% vs. 57.0%, p = 0.002) and analgesics (86.5% vs. 51.1%, p < 0.001) in 2016. The awakening (48.4% vs. 31.0%, p = 0.002) was more frequently attempted in 2016. The accidental extubation rate decreased to one tenth of what it was in 2010 (1.1% vs. 10.2%, p < 0.001). The ICU mortality did not change (31.4% vs. 35.6%, p = 0.343) but ICU length of stay showed a decreasing trend (9 days vs. 10 days, p = 0.054) in 2016. Conclusions There were temporal changes in care of patients on mechanical ventilation including better control of pain and agitation, and active attempt of awakening.

Background The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients. Methods Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015. Results A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-age-physiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality. Conclusion In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.

Objectives: This study was performed to evaluate the skin irritation toxicity of processed sulfur. Methods: All experiments were conducted at Medvill (Korea), an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP) regulations. In order to investigate skin irritation toxicity of processed sulfur, we divided the back of six rabbits into two control sites and two test sites. One of each of the two control and test sites was then designated abraded sites and intact sites. In test sites, 0.5 g of processed sulfur was applied to the back of the rabbit for 24 hours, and in control sites, 0.5 g of sterile distilled water was applied in the same way. We observed and evaluated mortality, weight, general symptoms, and skin irritation toxicity. This study was conducted with the approval of the Animal Ethics Committee (Approval number: IAC2020-1549). Results: In all experiments, no dead animals were observed. In all cases, skin coloration was observed at 24 hours after processed sulfur administration. This coloration lasted up to 48 hours and is believed to be the effect of the administration of test substances. Weight measurement indicated that weight was lost 72 hours after administration in three cases, but this is considered an accidental weight change. Normal weight gain was observed in the remaining subjects. In all animals, no skin irritation toxicity was observed, and the primary irritation index (P.I.I) was calculated as 0.0 according to Draize's evaluation method. Conclusion: The above findings suggest that it is relatively safe to apply a processed sulfur to the skin. Further research on this topic is needed to provide more specific evidence.

We performed a hydrogen combustion analysis in the Advanced Power Reactor 1400 MWe (APR1400) containment during a severe accident initiated by a small break loss of coolant accident (SBLOCA) which occurred at a lower part of the cold leg using a multi-dimensional hydrogen analysis system (MHAS) to confirm the integrity of the APR1400 containment. The MHAS was developed by combining MAAP, GASFLOW, and COM3D to simulate hydrogen release, distribution and combustion in the containment of a nuclear power plant during the severe accidents in the containment of a nuclear power reactor. The calculated peak pressure due to the flame acceleration by the COM3D, using the GASFLOW results as an initial condition of the hydrogen distribution, was approximately 555 kPa, which is lower than the fracture pressure 1223 kPa of the APR1400 containment. To induce a higher peak pressure resulted from a strong flame acceleration in the containment, we intentionally assumed several things in developing an accident scenario of the SBLOCA. Therefore, we may judge that the integrity of the APR1400 containment can be maintained even though the hydrogen combustion occurs during the severe accident initiated by the SBLOCA.

Background: Mild cognitive impairment (MCI), the early stage of dementia, requires effective intervention for symptom management and improving patients’ quality of life (QoL). Jujadokseo-hwan (JDH) is a Korean herbal medicine prescription used to improve MCI symptoms, such as memory deficit. This study evaluates the improvement in QoL through JDH. Alongside a clinical trial, it estimates the cost-effectiveness of JDH, compared to placebo, for MCI over 24 weeks. Methods: Changes in QoL were measured using the EuroQol-5 Dimensions (EQ-5D) and Korean version QoL-Alzheimer's Disease (KQOL-AD). Direct medical and non-medical costs were surveyed and incremental cost-effectiveness ratios (ICER) per QALY for JDH were produced. Results: In total, 64 patients were included in the economic evaluation (n = 35 in JDH, n = 29 in placebo). In the JDH group, EQ-5D and KQOL-AD improved by 0.020 (p = .318) and 3.40 (p = .011) over 24 weeks, respectively. In the placebo group, they increased by 0.001 (p=.920) and 1.07 (p=.130), respectively. The ICER was KRW 76,400,000 per QALY and KRW 108,000 per KQOL-AD for JDH, compared to the placebo group. Conclusion: JDH is not considered a cost-effective treatment option compared with placebo; however, it positively affects QoL improvement in patients with MCI.

Background Evidence for using high-flow nasal cannula (HFNC) in hypercapnia is still limited. Most of the clinical studies had been conducted retrospectively, and there had been conflicting reports for the effects of HFNC on hypercapnia correction in prospective studies. Therefore, more evidence is needed to understand the effect of the HFNC in hypercapnia. Methods We conducted a multicenter prospective observational study after applying HFNC to 45 hospitalized subjects who had moderate hypercapnia (arterial partial pressure of carbon dioxide [PaCO2], 43–70 mm Hg) without severe respiratory acidosis (pH

Abstract Background Triggering receptor expressed on myeloid cells 2 (TREM2) signaling is considered to regulate anti-inflammatory responses in macrophages, dendritic cell maturation, osteoclast development, induction of obesity, and Alzheimer’s disease pathogenesis. However, little is known regarding the effect of TREM2 on natural killer (NK) cells. Results Here, we demonstrated for the first time that CD3−CD122+NK1.1+ precursor NK (pNK) cells expressed TREM2 and their population increased in TREM2-overexpressing transgenic (TREM2-TG) mice compared with that in female C57BL/6 J wild type (WT) mice. Both NK cell-activating receptors and NK cell-associated genes were expressed at higher levels in various tissues of TREM2-TG mice than in WT mice. In addition, bone marrow-derived hematopoietic stem cells (HSCs) of TREM2-TG mice (TG-HSCs) successfully differentiated into NK cells in vitro, with a higher yield from TG-HSCs than from WT-HSCs. In contrast, TREM2 signaling inhibition by TREM2-Ig or a phosphatidylinositol 3-kinase (PI3K) inhibitor affected the expression of the NK cell receptor repertoire and decreased the expression levels of NK cell-associated genes, resulting in significant impairment of NK cell differentiation. Moreover, in melanoma-bearing WT mice, injection of bone marrow cells from TREM2-TG mice exerted greater antitumor effects than that with cells from WT control mice. Conclusions Collectively, our data clearly showed that TREM2 promoted NK cell development and tumor regression, suggesting TREM2 as a new candidate for cancer immunotherapy.

Background: The purpose of this article was to present a valid and reliable theoretical framework and method for the development of an integrated medical service model for the four major diseases. Methods: Methodologies for each process were presented based on three theoretical frameworks. The three theories were the double diamond process model, the Donabedian model, and the International Classification of Functioning, Disability, and Health model. Based on this, in the process of problem finding, a literature review, service user questionnaire, and interview methods were applied. For problem definition and solution, expert focus group interview and expert Delphi methods were applied. The subjects of the study were mainly selected from experts for each disease and users of medical services. For literature review, systematic literature review and subject range literature review were conducted, and for analysis, a meta-analysis was carried out. In the case of focus group interview and Delphi, the validity and reliability of domain derivation and sub-items were analyzed by applying the qualitative analysis method. Results: To develop an integrative medical service model, a theoretical framework and a systematic methodology were needed, and case studies were performed to prove its validity and reliability. This showed that the development of a medical service model needs to follow a scientific procedure. Conclusions: By introducing methodological approaches and procedures for the development of an integrated medical service model for the four major diseases, the researchers provided basic information on model development.

BackgroundChest computed tomography (CT) scans play an important role in the diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to describe the quantitative CT parameters in COVID-19 patients according to disease severity and build decision trees for predicting respiratory outcomes using the quantitative CT parameters.MethodsPatients hospitalized for COVID-19 were classified based on the level of disease severity: (1) no pneumonia or hypoxia, (2) pneumonia without hypoxia, (3) hypoxia without respiratory failure, and (4) respiratory failure. High attenuation area (HAA) was defined as the quantified percentage of imaged lung volume with attenuation values between −600 and −250 Hounsfield units (HU). Decision tree models were built with clinical variables and initial laboratory values (model 1) and including quantitative CT parameters in addition to them (model 2).ResultsA total of 387 patients were analyzed. The mean age was 57.8 years, and 50.3% were women. HAA increased as the severity of respiratory outcome increased. HAA showed a moderate correlation with lactate dehydrogenases (LDH) and C-reactive protein (CRP). In the decision tree of model 1, the CRP, fibrinogen, LDH, and gene Ct value were chosen as classifiers whereas LDH, HAA, fibrinogen, vaccination status, and neutrophil (%) were chosen in model 2. For predicting respiratory failure, the decision tree built with quantitative CT parameters showed a greater accuracy than the model without CT parameters.ConclusionsThe decision tree could provide higher accuracy for predicting respiratory failure when quantitative CT parameters were considered in addition to clinical characteristics, PCR Ct value, and blood biomarkers.

Background The use of sedative drugs may be an important therapeutic intervention during noninvasive ventilation (NIV) in intensive care units (ICUs). The purpose of this study was to assess the current application of analgosedation in NIV and its impact on clinical outcomes in Korean ICUs. Methods Twenty Korean ICUs participated in the study, and data was collected on NIV use during the period between June 2017 and February 2018. Demographic data from all adult patients, NIV clinical parameters, and hospital mortality were included. Results A total of 155 patients treated with NIV in the ICUs were included, of whom 26 received pain and sedation therapy (sedation group) and 129 did not (control group). The primary cause of ICU admission was due to acute exacerbation of obstructed lung disease (45.7%) in the control group and pneumonia treatment (53.8%) in the sedation group. In addition, causes of NIV application included acute hypercapnic respiratory failure in the control group (62.8%) and post-extubation respiratory failure in the sedation group (57.7%). Arterial partial pressure of carbon dioxide (PaCO2) levels before and after 2 hours of NIV treatment were significantly decreased in both groups: from 61.9±23.8 mm Hg to 54.9±17.6 mm Hg in the control group (P

Background The aim of this pilot study was to assess the safety and dosing of scolopendrid pharmacopuncture (SPP). Methods A total of 40 healthy Sprague-Dawley rats (males and 20 females 20) were selected following a 7-day inspection and acclimation period. SPP was administered via intramuscular injection, over a 2-week period using 3 doses including a high-dose [0.84 mg of scolopendrid per kg of body weight (BW)], a med-dose (0.42 mg/kg BW), and a low-dose (0.21 mg/kg BW). The control group was injected with sterile water into the muscles. Unusual changes caused by administration of the test substance were observed. Weight, feed intake, organ weight, and hematological examinations were compared among the groups. Using the SPSS statistical program, Levene’s test was performed to evaluate the homogeneity of variances, and a one-way ANOVA test was subsequently performed to assess the significance between each test group. Results During the experiment no animals died. Weight change, food consumption, organ weight, hematological test, and blood biochemical tests showed no significant differences in the treatment groups compared to controls. Conclusion No toxicological changes related to the administration of test substances were observed. Therefore, the LD50 (lethal-dose that kills 50%) of scolopendrid pharmacoupuncture in rats was greater than 0.84 mg/kg.

Background Use of appropriate antibiotics for the treatment of pneumonia is integral in patients admitted to intensive care units (ICUs). Although it is recommended that empirical treatment regimens should be based on the local distribution of pathogens in patients with suspected hospital-acquired pneumonia, few studies observe patients admitted to ICUs with nursing home–acquired pneumonia (NHAP). We found factors associated with the use of inappropriate antibiotics in patients with pneumonia admitted to the ICU via the emergency room (ER). Methods We performed a retrospective cohort study of 83 pneumonia patients with confirmed causative bacteria admitted to ICUs via ER March 2015–May 2017. We compared clinical parameters, between patients who received appropriate or inappropriate antibiotics using the Mann-Whitney U, Pearson's chi-square, and Fisher's exact tests. We investigated independent factors associated with inappropriate antibiotic use in patients using multivariate logistic regression. Results Among 83 patients, 30 patients (36.1%) received inappropriate antibiotics. NHAP patients were more frequently treated with inappropriate antibiotics than with appropriate antibiotics (47.2% vs. 96.7%, p

Safety issues arising from a hydrogen explosion accident in Korea are discussed herein. In order to increase the safety of hydrogen refueling stations (HRSs), the Korea Gas Safety Corporation (KGS) decided to install a damage-mitigation wall, also referred to as a barrier, around the storage tanks at the HRSs after evaluating the consequences of hypothetical hydrogen explosion accidents based on the characteristics of each HRS. To propose a new regulation related to the barrier installation at the HRSs, which can ensure a proper separation distance between the HRS and its surrounding protected facilities in a complex city, KGS planned to test various barrier models under hypothetical hydrogen explosion accidents to develop a standard model of the barrier. A numerical simulation to investigate the effect of the recommended barrier during hypothetical hydrogen explosion accidents in the HRS will be performed before installing the barrier at the HRSs. A computational fluid dynamic (CFD) code based on the open-source software OpenFOAM will be developed for the numerical simulation of various accident scenarios. As the first step in the development of the CFD code, we conducted a hydrogen vapor cloud explosion test with a barrier in an open space, which was conducted by the Stanford Research Institute (SRI), using the modified XiFoam solver in OpenFOAM-v1912. A vapor cloud explosion (VCE) accident may occur due to the leakage of gaseous hydrogen or liquefied hydrogen owing to a failure of piping connected to the storage tank in an HRS. The analysis results using the modified XiFoam predicted the peak overpressure variation from the near field to the far field of the explosion site through the barrier with an error range of approximately ±30% if a proper analysis methodology including the proper mesh distribution in the grid model is chosen. In addition, we applied the proposed analysis methodology using the modified XiFoam to barrier shapes that varied from that used in the test to investigate its applicability to predict peak overpressure variations with various barrier shapes. Through the application analysis, we concluded that the proposed analysis methodology is sufficient for evaluating the safety effect of the barrier, which will be recommended through experimental research, during VCE accidents at the HRSs.

Objectives: KCHO-1(Mecasin), also called Gamijakyakgamchobuja-tang originally, is a combination of some traditional herbal medicines in East Asia. This medicine has been used mainly for alleviating neuropathic pains for centuries in Korean traditional medicine. KCHO-1 was developed to treat pain, joint contracture and muscular weakness in patients with amyotrophic lateral sclerosis. This study was carried out to investigate the chronic toxicity of KCHO-1 oral administration in rats for 26 weeks. Methods: Sprague-Dawely rats were divided into four groups and 10 rats were placed in the control group and the high-dose group, respectively. Group 1 was the control group and the remaining groups were the experimental groups. In the oral toxicity study, 500 mg/ kg, 1,000 mg/kg, and 2,000 mg/kg of KCHO-1 were administered to the experimental group, and 10 ml/kg of sterile distilled water was administered to the control group. Survival rate, body weight, feed intake, clinical signs, and visual findings were examined. Urinalysis, ophthalmologic examination, necropsy, organ weight, hematologic examination, blood chemical examination and histopathologic examination were performed. Results: Mortality and toxicological lesions associated with the administration of test substance were not observed in all groups. Conclusion: NOAEL(No observed adverse effect level) of KCHO-1 is higher than 2000 mg/kg/day. And, the above findings suggest that treatment with KCHO-1 is relatively safe.

Background Data on noninvasive ventilation (NIV) use in intensive care units (ICUs) are very limited in South Korea. Methods A prospective observational study was performed in 20 ICUs of university-affiliated hospitals from June 2017 to February 2018. Adult patients (age>18 years) who were admitted to the ICU and received NIV treatment for acute respiratory failure were included. Results A total of 156 patients treated with NIV were enrolled (mean age, 71.9±11.6 years). The most common indications for NIV were acute hypercapnic respiratory failure (AHRF, n=89) and post-extubation respiratory failure (n=44). The main device for NIV was an invasive mechanical ventilator with an NIV module (61.5%), and the majority of patients (87.2%) used an oronasal mask. After the exclusion of 32 do-not-resuscitate patients, NIV success rate was 68.5% (85/124); ICU and hospital mortality rates were 8.9% and 15.3%, respectively. However, the success rate was lower in patients with de novo respiratory failure (27.3%) compared to that of patients with AHRF (72.8%) or post-extubation respiratory failure (75.0%). In multivariate analysis, immunocompromised state, de novo respiratory failure, post-NIV (2 hours) respiratory rate, NIV mode (i.e., non-pressure support ventilation mode), and the change of NIV device were significantly associated with a lower success rate of NIV. Conclusion AHRF and post-extubation respiratory failure were the most common indications for NIV in Korean ICUs. Overall NIV success was achieved in 68.5% of patients, with the lowest rate in patients with de novo respiratory failure.

Objectives Pneumonia is one of the leading causes of death in the intensive care unit (ICU). Many biomarkers for predicted prognosis have been suggested; among these, procalcitonin (PCT) is known to increase in cases of bacterial infection. However, there have been many debates regarding whether PCT is an appropriate prognostic marker for pneumonia. Therefore, we investigated whether PCT can serve as a biomarker for pneumonia, and compared it with CURB-65, which is a known tool for predicting the prognosis of pneumonia. Methods Levels of PCT and CURB-65 scores were compared between 30-day non-survival (n = 30) and survival (n = 101) patients. Relationships between PCT and CURB-65 were determined by using linear regression analysis, as well as by using receiver operating characteristic (ROC) curve analysis and calculation of the area under the curve (AUC). High and low PCT groups were compared. Results High PCT and high CURB-65 score were positively associated with 30-day mortality. For the prediction of 30-day mortality, initial PCT and CURB-65 exhibited AUCs of 0.63 and 0.66; these were not significantly different (P = 0.132). We found that the high PCT group had a higher rate of initial treatment failure (91%, P = 0.004). Conclusions Initial PCT can be a prognostic biomarker for mortality in severe pneumonia, similar to the CURB-65 score. Initial high PCT was positively associated with initial treatment failure.

Background: This study aimed to evaluate the reliability and validity of short form of the Core Seven Emotions Inventory (CSEI-s) scale. Methods: The participants were third-grade Korean Medicine University students As with the original CSEI, the scales in the short form (CSEI-s) were composed of seven factors and consisted of 28 items in total. The internal consistency coefficient was calculated, and a confirmatory factor analysis was conducted to verify the reliability of the short form scale. Finally, to verify the validity of the abbreviated scale, a correlation analysis with the abbreviated scale and the CSEI-s scale was conducted. Results: A 178 among 200 initial participants were included in the analysis (mean age: 24.5 years). The results of the exploratory factor analysis made from the 28 items of the seven factors of the CSEI-s showed that the factor loadings were as high as 0.64–0.89, excluding the tenth item of fear (0.52), and the model fit also had a good confirmatory factor with the analysis result. The results of the reliability verification showed that the Cronbach α values of all seven subscales of the short-form CSEI scale were 0.7 or higher, and the overall reliability was 0.83. A factor analysis revealed that the factor loadings were adequate, and their reliability and validity were confirmed for the CSEI-s scale, making it applicable to measuring the core seven emotions of patients in clinical practice. Conclusion: CSEI-s scale may apply to measure core emotions of the patient in a clinical setting. Keywords: Seven emotions, Psychological assessment, Short form, Validation, CSEI (Core Seven Emotions Inventory)

Johne's disease (JD) is a chronic granulomatous enteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), which induces persistent diarrhea and cachexia. JD causes huge economic losses to the dairy industry due to reduced milk production and premature culling. Infected animals excrete MAP via feces during the prolonged subclinical stage without exhibiting any clinical signs. Therefore, accurate detection of subclinical stage animals is crucial for successful eradication of JD in the herd. In the current study, we analyzed serum samples of MAP-infected and non-infected cattle to identify potential biomarker candidates. First, we identified 12 differentially expressed serum proteins in subclinical and clinical shedder groups compared to the healthy control group. Second, we conducted ELISA for three selected biomarkers (alpha-2-macroglobulin (A2M), alpha-1-beta glycoprotein, and transthyretin) and compared their diagnostic performance with that of two commercial ELISA diagnostic kits. Serum A2M levels were significantly higher in the MAP-exposed, subclinical shedder, subclinical non-shedder, and clinical shedder groups than in the healthy control group, suggesting its possible use as a diagnostic biomarker for MAP infection. Furthermore, A2M demonstrated a sensitivity of 90.4%, and a specificity of 100% while the two commercial ELISA kits demonstrated a sensitivity of 67.83 and 73.04% and a specificity of 100%, respectively. In conclusion, our results suggest that measuring A2M by ELISA can be used as a diagnostic tool to detect MAP infection, considerably improving the detection rate of subclinical shedders and MAP-exposed animals that are undetectable using current diagnostic tools.

ObjectivesNeuron-specific enolase (NSE) is frequently used to predict neurological outcomes in patients with hypoxic brain injury. Hanging can cause hypoxic brain damage, and survivors can suffer from neurological deficits that may impair daily activities. Here, we investigated the utility of the initial serum NSE level as a predictor of neurological outcomes in near-hanging patients with decreased consciousness.MethodsThis retrospective multicenter study was conducted in patients who visited the emergency department due to near-hanging injury from October 2013 to February 2019 at three university hospitals in Korea. They were divided into two groups according to the presence of out-of-hospital cardiac arrest. The neurological outcome was determined using the Cerebral Performance Category (CPC) measured at the time of discharge. Multivariate analysis was performed to determine whether initial serum NSE is an independent predictor of neurological outcome.ResultsOf the 70 patients included in the study, 44 showed a poor neurological outcome (CPC score = 3-5). Among the 52 patients with cardiac arrest, only 10 (19.2%) were discharged with good neurological outcome (CPC score = 1-2). In the whole cohort, a high serum NSE level was a significant predictor of poor neurological outcome (odds ratio [OR], 1.343; 95% confidence interval [CI], 1.003-1.800, p = 0.048). Among the patients with cardiac arrest, a high serum NSE level was a significant predictor of poor neurological outcome (OR, 1.138; 95% CI, 1.009-1.284, p = 0.036).ConclusionsIn near-hanging patients, a high initial serum NSE level is an independent predictor of poor neurological outcome.

Background. Nontuberculous mycobacteria (NTM) are widely present in environments, such as soil and water, and have recently been recognized as important pathogenic bacteria. The incidence of NTM-related infections is steadily increasing. As the diagnosis and treatment of NTM infection should be distinguished from tuberculosis, and the treatment should be specific to the species of NTM acquired, accurate species identification is required. Methods. In this study, two-step multiplex PCR (mPCR) and multigene sequence-based analysis were used to accurately identify NTM species in 320 clinical isolates from Gyeongsang National University Hospital (GNUH). In particular, major mycobacterial strains with a high isolation frequency as well as coinfections with multiple species were diagnosed through two-step mPCR. Multigene sequencing was performed to accurately identify other NTM species not detected by mPCR. Variable regions of the genes 16S rRNA, rpoB, hsp65, and 16S-23S rRNA internal transcribed spacer were included in the analysis. Results. Two-step mPCR identified 234 (73.1%) cases of M. intracellulare, 26 (8.1%) cases of M. avium subsp. avium, and 13 (4.1%) cases of M. avium subsp. hominissuis infection. Additionally, 9 (2.8%) M. fortuitum, 9 (2.8%) M. massiliense, 2 (0.6%) M. abscessus, and 4 (1.2%) M. kansasii isolates were identified. Coinfection was identified in 7 (2.2%) samples. The sixteen samples not classified by two-step mPCR included 6 (1.9%) cases of M. chimaera, 4 (1.3%) M. gordonae, 1 (0.3%) M. colombiense, 1 (0.3%) M. mageritense, and 1 (0.3%) M. persicum identified by sequence analysis. Conclusions. The results of this study suggest a strategy for rapid detection and accurate identification of species using two-step mPCR and multigene sequence-based analysis. To the best of our knowledge, this study is the first to report the identification of NTM species isolated from patients in Gyeongnam/Korea.

Background and Objectives: Gastric cancer remains a major unmet clinical problem worldwide. Although conventional medical treatments are available, their curative effects are generally unsatisfactory. Consequently, it remains necessary to search natural products for potential alternatives in treating gastric cancer patients. Ocimum x africanum Lour. is a culinary herb that has been used in folk medicine for various diseases, but little is known regarding its anti-cancer activity against gastric cancer cells. In the current study, we focus on the anti-cancer mechanisms of O. x africanum essential oil (OAEO) in the AGS human gastric cancer cell line. Materials and Methods: After OAEO treatment, AGS cell viability was evaluated by MTT assay. Cell migration and apoptotic nuclear morphology were determined by wound-healing assay and DAPI staining, respectively. Gene expression levels of apoptosis-related genes were quantified by qRT–PCR. Differential protein expression was determined with an LC–MS/MS-based proteomics approach to identify the key proteins that may be important in the anti-cancer mechanisms of OAEO on AGS cells. The chemical constituents of OAEO were identified by GC–MS analysis. Results: We found OAEO to exhibit a potent growth-inhibiting effect on AGS cells, with an IC50 value of 42.73 µg/mL. After OAEO treatment for 24 h, AGS cell migration was significantly decreased relative to the untreated control. OAEO-treated AGS cells exhibited common features of apoptotic cell death, including cell shrinkage, membrane blebbing, chromatin condensation, and nuclear fragmentation. Apoptotic cell death was confirmed by qRT–PCR for apoptosis-related genes, revealing that OAEO decreased the expression of anti-apoptotic genes (BCL2 and BCL-xL) and activated pro-apoptotic genes and apoptotic caspase genes (TP53, BAX, CASP9, CASP12, and CASP3). Moreover, expression of CASP8 was not changed after treatment. Proteomic analysis revealed that OAEO may produce a signature effect on protein clusters relating to unfolded protein accumulation, thereby inducing severe ER stress and also impairing ribosome synthesis. STRING analysis revealed seven up-regulated and 11 down-regulated proteins, which were significantly associated with protein folding and ribosome biogenesis, respectively. Using GC–MS analysis, 6-methyl-5-hepten-2-one, citral, neral, and linalool were found to be the major chemical constituents in OAEO. Conclusions: Taken together, these results indicate that OAEO has a potential anti-proliferative effect on AGS cells. Our molecular findings show evidence supporting an important role of ER stress and ribosome biogenesis impairment in mediating the induction of cell death by OAEO through the mitochondrial-apoptotic pathway. This study, therefore, provides fundamental knowledge for future applications using OAEO as an alternative therapy in gastric cancer management.

Background: Post-traumatic stress disorder (PTSD) has become an important public health problem. However, the conventional therapeutic strategy, including pharmacotherapy and cognitive behavioral therapy, has limitations. Neurofeedback is a technique that utilizes electroencephalography (EEG) signaling to monitor human physiological functions and is widely used to treat patients with PTSD. The purpose of our study is to assess the efficacy and safety level of neurofeedback treatment in patients with PTSD using quantitative EEG. Methods: This is a randomized, waitlist-controlled, assessor-blinded, clinical trial. Forty-six patients with PTSD will be randomly assigned at a 1:1 ratio into two groups. The participants in the treatment group will receive neurofeedback treatment for 50 min, twice a week, for 8 weeks (16 sessions). Quantitative EEG will be utilized to monitor the physiological functions and brain waves of the participants. A four-week follow-up period is planned. The participants in the control group will wait for 12 weeks. The primary outcome is the Korean version of PTSD Checklist-5 (PCL-5-K) score. The PCL-5-K scores on week 8 will be compared between the two groups. Anxiety, depression, insomnia, emotions, EEG, quality-of-life, and safety level will be assessed as secondary outcomes. Discussion: This trial will describe a clinical research methodology for neurofeedback in patients with PTSD. The numerous subjective and objective secondary outcomes add to the value of this trial’s results. It will also suggest a therapeutic strategy for utilizing quantitative EEG in patients with PTSD. Our trial will provide basic evidence for the management of PTSD via an integrative treatment. Trial registration: Clinical Research Information Service (CRIS): KCT0003271.

Particulate matter (PM) exposure may cause adverse health effects such as respiratory disorders. We evaluated the protective effects of various Opuntia ficus-indica (OFI) extracts on airway inflammation associated with exposure to PM10D with an aerodynamic diameter +/CD4+, CD3+/CD8+, and Gr-1+/CD11b) in bronchoalveolar lavage fluid (BALF) and lungs. OFI extracts decreased the expression of cytokines and chemokines, including chemokine (C-X-C motif) ligand (CXCL)-1, interleukin (IL)-17, macrophage inflammatory protein-2, tumor necrosis factor (TNF)-α, cyclooxygenase-2, IL-1α, IL-1β, IL-5, IL-6, transient receptor potential cation channel subfamily V member 1, and mucin 5AC, and inhibited IRAK-1, TNF-α, and CXCL-1 localization in BALF and lungs of mice with PM10D-induced airway inflammation. Serum asymmetric and symmetric dimethyl arginine levels were also decreased by OFI extracts treatment. Moreover, all OFI extracts restored histopathological damage in the trachea and lungs of mice with PM10D-induced airway inflammation. These results indicate that OFI extracts may be used to prevent and treat airway inflammation and respiratory diseases.

Although the oestrogen level is thought to be involved in the occurrence of bronchiectasis, limited data are available on the relationship between female reproductive factors and the risk of bronchiectasis. We performed a population-based retrospective cohort study of 959,523 premenopausal women and 1,362,401 postmenopausal women without a previous history of bronchiectasis who participated in a health screening exam in 2009 in South Korea. In premenopausal women, compared with a later age at menarche (≥16 years), an earlier menarche (

Canavalia gladiata (C. gladiata) and Arctium lappa (A. lappa), used in traditional medicine and food. However, their preventive effects in dextran sulphate sodium (DSS)-induced inflammatory bowel disease (IBD) remain unclear. We found that the C. gladiata and A. lappa mixture suppressed inflammation in LPS-induced RAW 264.7 cells. The mixture increased the population and activation of immune cells, up-regulation of cell cycle, and induction of IgA and IgG production in wild-type mice. Furthermore, the extract mixture prevented clinical IBD symptoms and restored IgA production in IBD mice. Similarly, a mixture of the marker compounds, chicoric acid and lupeol, ameliorated IBD-associated clinical signs, improved the population and activation of immune cells and functional defects in natural killer (NK) cells and reduced production of IgA in these mice. In conclusion, the C. gladiata and A. lappa mixture ameliorated progression of DSS-induced IBD by enhancing immune responses and recovering functional immune cell defects.

A 21-year-old woman was admitted with a 1-day history of headache. Her neurological examination findings were normal. Computed tomography angiography revealed an oval, well-enhanced dilated vascular lesion in the anterior interhemispheric fissure with a developmental venous anomaly characterized by caput medusae centripetally in the right hemisphere. On the magnetic resonance image, an anterior persistent falcine sinus was connected with the middle portion of the superior sagittal sinus. Cerebral angiography revealed the persistent falcine sinus located in the anterior falx and the parenchymal developmental venous anomaly with caput medusae. In addition, the venous phase of cerebral angiography demonstrated the obstruction of both the inferior sagittal sinus and the bridging vein between the superior thalamostriate and the internal cerebral vein. To our knowledge, this is a very rare case of the combination of an anterior persistent falcine sinus and a developmental venous anomaly. Keywords: Persistent falcine sinus, Developmental venous anomaly

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes paralysis of limb, swallowing, and breathing muscles. Riluzole, the Food and Drug Administration-approved drug for ALS, provides minimal benefit, prolonging patient life by only 2–3 months. Previous studies have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with retrospective studies providing suggestive evidence for a beneficial effect of Mecasin. The aim of this study was to develop a protocol to determine the proper dosage of Mecasin. Methods This is a phase II-A, multi-center, randomized study with three arms. Thirty-six patients with ALS will be randomly assigned to one of three groups, each receiving the standard treatment with 100 mg of riluzole in addition to one of 1.6 g of Mecasin, 2.4 g of Mecasin, or a placebo. The Primary outcome is the Korean version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised result after 12 weeks of treatment. Secondary outcomes include results of the Short Form Health Survey-8, Medical Research Council Scale, Visual Analogue Scale for Pain, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Patient Global Impression of Change, pulmonary function test, forced expiratory volume in 1 s and its ratio to forced vital capacity, creatine kinase, and body weight. The frequencies of total adverse events and serious adverse events will be described and documented. The trial protocol has been approved by the Institutional Review Board of the Wonkwang University Gwangju and Sanbon Hospital (2016–5-4 and 2016–34-01, respectively). An Investigational New Drug status (30731) was granted by the Korea Food and Drug Administration. Discussion This trial will aim to identify the optimal dosage of Mecasin. Additionally, it will test the efficacy and safety of Mecasin in conjunction with standard treatment, riluzole, for alleviating the functional decline in patients with ALS. Trial registration Korean National Clinical Trial Registry CRIS; KCT0001984. Registered on 28 July 2016.

Abstract Background Hesperidin is a flavonoid with antioxidant, anti-inflammatory, and immune modulatory activities. Photoaging is a consequence of chronic exposure to the sun and ultraviolet (UV) radiation. This study was designed to evaluate the efficacy of hesperidin against photoaging of dorsal skin in hairless mice. Methods Hairless male mice (6-week-old) were divided into three groups (n = 7): control, UVB-treated vehicle, and UVB-treated hesperidin groups. UVB-irradiated mice from hesperidin group were orally administered 0.1 mL of water containing 100 mg/kg body weight per day hesperidin. Results The mean length and depth of wrinkles in the UVB-treated hesperidin group significantly improved after the oral administration of hesperidin, which significantly inhibited the increase in epidermal thickness and epidermal hypertrophy (P < 0.05). UVB irradiation of mice induced epidermal barrier dysfunction including an increase in the transepidermal water loss (TEWL); however, hesperidin decreased the TEWL. UVB irradiation increased the expression of MMP-9 and pro-inflammatory cytokines whereas UVB-treated hesperidin group showed reduced expression. These results indicate that hesperidin showed anti-photoaging activity in the UVB-irradiated hairless mice. In conclusion, hesperidin inhibited the UVB-induced increase in skin thickness, wrinkle formation, and collagen fiber loss in male hairless mice. Conclusions These results suggest that hesperidin shows potent anti-photoaging activity by regulating MMP-9 expression through the suppression of MAPK-dependent signaling pathways.