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The objective of the present study was to investigate the physicochemical characteristics and storage stability of water-in-oil-in-water (W/O/W) emulsions and spray-dried red ginseng extract capsules (RGEC) prepared using different secondary coating materials such as maltodextrin (MD), whey protein concentrate (WPC), or arabic gum (AG). The particle sizes of W/O/W emulsions and spray-dried RGEC coated with MD were considerably lower than those of W/O/W emulsions and spray-dried RGEC coated with WPC or AG. The zeta-potential value (−36 mV) of spray-dried RGEC coated with MD was significantly higher than that of spray-dried RGEC coated with WPC or AG (p

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.

Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.

This study was carried out to investigate physicochemical properties of different concentrations (0.1%, 0.3%, and 0.5%) of red ginseng hydrolyzates (RGH)- or red ginseng extract (RGE)-added Asiago cheeses (AC) during ripening at 14°C for 4 months. The moisture content significantly increased with increasing concentrations of both RGH- and RGE- added AC (p

Background: The primary aim of this proof-of-concept study was to investigate whether the Cardiac Power Index (CPI) could be a novel alternative method to assess fluid responsiveness in the prone position. Methods: Patients undergoing scheduled elective lumbar spine surgery in the prone position under general anesthesia were enrolled in the criteria of patients aged 19–75 years with American Society of Anesthesiologists (ASA) physical status I–II. The hemodynamic variables were evaluated before and after changes in posture after administering a colloid bolus (5 mL.kg−1) in the prone position. Fluid responsiveness was defined as an increase in the Stroke Volume Index (SVI) ≥ 10%. Results: A total of 28 patients were enrolled. In responders, the CPI (median [1/4Q–3/4Q]) decreased to 0.34 [0.28–0.39] W.m−2 (p = 0.035) after the prone position. After following fluid loading, CPI increased to 0.48 [0.37–0.52] W.m−2 (p < 0.008), and decreased SVI (median [1/4Q–3/4Q]) after prone increased from 26.0 [24.5–28.0] mL.m−2 to 33.0 [31.0–37.5] mL.m−2 (p = 0.014). Among non-responders, CPI decreased to 0.43 [0.28–0.53] W.m−2 (p = 0.011), and SVI decreased to 29.0 [23.5–34.8] mL.m−2 (p < 0.009). CPI exhibited predictive capabilities for fluid responsiveness as a receiver operating characteristic curve of 0.78 [95% Confidence Interval, 0.60–0.95; p = 0.025]. Conclusion: This study suggests the potential of CPI as an alternative method to existing preload indices in assessing fluid responsiveness in clinical scenarios, offering potential benefits for responders and non-responders.

Accumulating evidence supports the idea that necrotrophic plant pathogens interact with their hosts by controlling cell death. Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with a broad host range (>400 species). Previously, we established that oxalic acid (OA) is an important pathogenicity determinant of this fungus. In this report, we describe a mechanism by which oxalate contributes to the pathogenic success of this fungus; namely, that OA induces a programmed cell death (PCD) response in plant tissue that is required for disease development. This response exhibits features associated with mammalian apoptosis, including DNA laddering and TUNEL reactive cells. Fungal mutants deficient in OA production are nonpathogenic, and apoptotic-like characteristics are not observed following plant inoculation. The induction of PCD by OA is independent of the pH-reducing abilities of this organic acid, which is required for sclerotial development. Moreover, oxalate also induces increased reactive oxygen species (ROS) levels in the plant, which correlate to PCD. When ROS induction is inhibited, apoptotic-like cell death induced by OA does not occur. Taken together, we show that Sclerotinia spp.-secreted OA is an elicitor of PCD in plants and is responsible for induction of apoptotic-like features in the plant during disease development. This PCD is essential for fungal pathogenicity and involves ROS. Thus, OA appears to function by triggering in the plant pathways responsible for PCD. Further, OA secretion by Sclerotinia spp. is not directly toxic but, more subtly, may function as a signaling molecule.

To date, four main mechanisms mediating inhibition of influenza infection by anti-hemagglutinin antibodies have been reported. Anti-globular-head-domain antibodies block either influenza virus receptor binding to the host cell or progeny virion release from the host cell. Anti-stem region antibodies hinder the membrane fusion process or induce antibody-dependent cytotoxicity to infected cells. In this study we identified a human monoclonal IgG1 antibody (CT302), which does not inhibit both the receptor binding and the membrane fusion process but efficiently reduced the nucleus entry of viral nucleoprotein suggesting a novel inhibition mechanism of viral infection by antibody. This antibody binds to the subtype-H3 hemagglutinin globular head domain of group-2 influenza viruses circulating throughout the population between 1997 and 2007.

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here, we describe how IAV infection triggers cellular apoptosis and how this process can be exploited towards the development of new therapeutics, which might be more effective than the currently available anti-influenza drugs.

Abstract Background Atelectasis can occur in many clinical practices. One way to prevent this complication is through the alveolar recruitment maneuver (ARM). However, hemodynamic compromise can accompany ARM. This study aims to predict ARM-induced hypotension using a non-invasive method. Methods 94 American Society of Anesthesiologists physical status I–II patients aged 19 to 75 with scheduled spinal surgery were enrolled. After anesthesia, we performed a stepwise ARM. Data on perfusion index, mean arterial pressure, heart rate, pleth variability index, cardiac index, and stroke volume variation was collected before induction of anesthesia (T0), just before ARM (T1), at the start of ARM (T2), 0.5 min (T3), 1 min (T4), 1.5 min (T5, end of ARM), and 2 min after the beginning of ARM (T6). Hypotension was defined as when the mean arterial pressure at T5 decreased by 20% or more compared to the baseline. The primary endpoint is that the perfusion index measuring before induction of anesthesia, which reflects the patients’ own vascular tone, was correlated with hypotension during ARM. Results Seventy-five patients (79.8%) patients developed hypotension during ARM. The pre-induction persufion index (Pi) (95% confidence interval) was 1.7(1.4–3.1) in the non-hypotension group and 3.4(2.4–3.9) in the hypotension group. (p

In this work, by controlling the oxygen flow rate (OFR) (from 0% to 30%), we suggest using a p-type copper aluminum oxide (p-CuAlO2) interlayer to enhance the high breakdown and low leakage current for β-Ga2O3-based power device applications. Results of AFM measurements on p-CuAlO2 films performed using various OFRs demonstrate that greater OFRs result in an increase in film roughness payable to the unavoidable leading of defects/oxygen vacancy (VO). We used XPS and TEM analysis to validate the surface elemental compositions, chemical states, band offsets and microstructural properties of p-CuAlO2/β-Ga2O3 heterojunction (HJ) with different OFRs. With increasing OFR from 0% to 17.6%, the VBO and CBO values of HJ were decreased from 1.73 eV to 1.23 eV and from 0.53 eV to 0.38 eV respectively. Then, with increasing OFR from 17.6% to 30%, VBO was decreased from 1.23 eV to 1.13 eV while CBO increased from 0.38 eV to 0.58 eV. The staggered-gap (type-II) across the p-CuAlO2/β-Ga2O3 HJ is identified the entire OFRs. The rising tendency of optical bandgap (Eg) of p-CuAlO2 with range of OFRs, a maximum Eg of 4.35 eV was obtained with OFR of 30%. Furthermore, the electrical and carrier transport properties of p-CuAlO2/β-Ga2O3 HJ were studied using I–V and C–V techniques. The reverse breakdown voltage (Vbr) of HJ is strongly dependent on OFRs. With increasing OFRs, Vbr was decreased from 937 V to 924 V, and then to 1000 V with increasing OFR from 0% to 17.6% and then to 30%. In addition, a decrease in the interface state density (NSS) with increasing OFRs was observed which indicates that oxygen may be an effective surface passivation. Analysis confirmed that Poole-Frenkel emission dominates the reverse leakage current of all the HJ samples. The type-II p-CuAlO2/β-Ga2O3 HJ may facilitate the design and manufacture of high-performance β-Ga2O3-based heterojunctions and advance optoelectronic devices.

Purpose: Early intervention after trauma is needed for reduction in clinical distress and prevention of chronic posttraumatic stress disorder (PTSD). This study describes findings from an open pilot trial of a brief stabilization psychotherapy based on imagery techniques for adults with acute PTSD (i.e., within 3 months of onset). Materials and Methods: Four sessions of 60-minute individual psychotherapy were conducted on 18 participants with PTSD within 3 months alter accidents, 15 of whom completed the treatment. The clinician-administered PTSD scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the Hamilton Depression and Anxiety Rating Scales, and self-questionnaires were administered at pre-treatment, post-treatment, and 6-month follow-up. Results: Eight (53.3%) of the 15 patients at post-treatment and 8 of the 9 patients at 6-month follow-up did not meet the DSM-5 criteria for PTSD. Reliable change of PTSD symptoms after treatment was observed in 6 of 15 (45.0%) patients at post-treatment and in 4 of 9 (45.0%) patients after 6 months. There was a significant decrease in PTSD, depression, anxiety, and impaired quality of life scores after treatment, and these gains were maintained after 6 months. No cases of exacerbated PTSD symptoms were observed among completers and non-completers. Conclusion: Our findings suggest that brief stabilization sessions are safe treatment options for acute PTSD (KCT0001918). [ABSTRACT FROM AUTHOR]

BackgroundA clinical decision support system (CDSS) is recognized as a technology that enhances clinical efficacy and safety. However, its full potential has not been realized, mainly due to clinical data standards and noninteroperable platforms. ObjectiveIn this paper, we introduce the common data model–based intelligent algorithm network environment (CANE) platform that supports the implementation and deployment of a CDSS. MethodsCDSS reasoning engines, usually represented as R or Python objects, are deployed into the CANE platform and converted into C# objects. When a clinician requests CANE-based decision support in the electronic health record (EHR) system, patients’ information is transformed into Health Level 7 Fast Healthcare Interoperability Resources (FHIR) format and transmitted to the CANE server inside the hospital firewall. Upon receiving the necessary data, the CANE system’s modules perform the following tasks: (1) the preprocessing module converts the FHIRs into the input data required by the specific reasoning engine, (2) the reasoning engine module operates the target algorithms, (3) the integration module communicates with the other institutions’ CANE systems to request and transmit a summary report to aid in decision support, and (4) creates a user interface by integrating the summary report and the results calculated by the reasoning engine. ResultsWe developed a CANE system such that any algorithm implemented in the system can be directly called through the RESTful application programming interface when it is integrated with an EHR system. Eight algorithms were developed and deployed in the CANE system. Using a knowledge-based algorithm, physicians can screen patients who are prone to sepsis and obtain treatment guides for patients with sepsis with the CANE system. Further, using a nonknowledge-based algorithm, the CANE system supports emergency physicians’ clinical decisions about optimum resource allocation by predicting a patient’s acuity and prognosis during triage. ConclusionsWe successfully developed a common data model–based platform that adheres to medical informatics standards and could aid artificial intelligence model deployment using R or Python.

BackgroundPatient safety in the intensive care unit (ICU) is one of the most critical issues, and unplanned extubation (UE) is considered the most adverse event for patient safety. Prevention and early detection of such an event is an essential but difficult component of quality care. ObjectiveThis study aimed to develop and validate prediction models for UE in ICU patients using machine learning. MethodsThis study was conducted in an academic tertiary hospital in Seoul, Republic of Korea. The hospital had approximately 2000 inpatient beds and 120 ICU beds. As of January 2019, the hospital had approximately 9000 outpatients on a daily basis. The number of annual ICU admissions was approximately 10,000. We conducted a retrospective study between January 1, 2010, and December 31, 2018. A total of 6914 extubation cases were included. We developed a UE prediction model using machine learning algorithms, which included random forest (RF), logistic regression (LR), artificial neural network (ANN), and support vector machine (SVM). For evaluating the model’s performance, we used the area under the receiver operating characteristic curve (AUROC). The sensitivity, specificity, positive predictive value, negative predictive value, and F1 score were also determined for each model. For performance evaluation, we also used a calibration curve, the Brier score, and the integrated calibration index (ICI) to compare different models. The potential clinical usefulness of the best model at the best threshold was assessed through a net benefit approach using a decision curve. ResultsAmong the 6914 extubation cases, 248 underwent UE. In the UE group, there were more males than females, higher use of physical restraints, and fewer surgeries. The incidence of UE was higher during the night shift as compared to the planned extubation group. The rate of reintubation within 24 hours and hospital mortality were higher in the UE group. The UE prediction algorithm was developed, and the AUROC for RF was 0.787, for LR was 0.762, for ANN was 0.763, and for SVM was 0.740. ConclusionsWe successfully developed and validated machine learning–based prediction models to predict UE in ICU patients using electronic health record data. The best AUROC was 0.787 and the sensitivity was 0.949, which was obtained using the RF algorithm. The RF model was well-calibrated, and the Brier score and ICI were 0.129 and 0.048, respectively. The proposed prediction model uses widely available variables to limit the additional workload on the clinician. Further, this evaluation suggests that the model holds potential for clinical usefulness.

Objective Children are sedated before undergoing diagnostic imaging tests in emergency medicine or pediatric sedation anesthesia units. The aim of this study was to identify variables potentially affecting the dose of ketamine required for induction of sedation in pediatric patients undergoing diagnostic imaging. Methods This retrospective study included children aged 0 to 18 years who underwent sedation with ketamine for computed tomography or magnetic resonance imaging in the pediatric sedation anesthesia unit of a tertiary medical center between January 2011 and August 2016. The children’s hemodynamic status and depth of sedation were monitored during the examination. We recorded data on demographics, categories of imaging tests, ketamine doses administered, adverse events, respiratory interventions, and duration of sedation. Data for patients who experienced adverse events were excluded. Results Sixty-six patients were included in the final analysis. Univariate linear regression analysis revealed that patient age, height, and body surface area (BSA) affected the sedative dose of ketamine administered. These three variables showed multicollinearity in multivariate linear regression analysis and were analyzed in three separate models. The model with the highest adjusted R-squared value suggested the following equation for determination of the dose of ketamine required to induce sedation: ketamine dose (mg)=-1.62+0.7×age (months)+36.36×BSA (m2). Conclusion Variables such as age and BSA should be considered when estimating the dose of ketamine required for induction of sedation in pediatric patients.