Development of an Interoperable and Easily Transferable Clinical Decision Support System Deployment Platform: System Design and Development Study.

BACKGROUND: A 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. OBJECTIVE: In this paper, we introduce the common data model-based intelligent algorithm network environment (CANE) platform that supports the implementation and deployment of a CDSS. METHODS: CDSS 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. RESULTS: We 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. CONCLUSIONS: We 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.

Neutralization of Zika virus by E protein domain III-Specific human monoclonal antibody.

Zika virus (ZIKV) infection in both infants and adults is associated with neurological complications including, but not limited to, microcephaly and Guillain-Barre syndrome. Antibody therapy can be effective against virus infection. We isolated ZIKV envelope domain III-specific neutralizing antibodies (nAbs) from two convalescent patients with ZIKV infection. One antibody, 2F-8, exhibited potent in vitro neutralizing activity against Asian and American strains of ZIKV. To prevent FcγR-mediated antibody-dependent enhancement, we prepared IgG1 with LALA variation. A single dose of 2F-8 in the context of IgG1 or IgG1-LALA prior to or post lethal ZIKV challenge conferred complete protection in mice.

An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus.

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.

The effect of oxygen concentration on atelectasis formation during induction of general anesthesia in children: A prospective randomized controlled trial.

BACKGROUND: In adults, the use of lower oxygen concentration during induction is associated with less atelectasis formation without an increase in incidence of hypoxia. However, it is unknown whether this remains true in the pediatric patients. METHODS: Fifty-four pediatric patients who were scheduled to undergo elective lower abdominal surgery were randomized to one of three oxygenation groups: 100%, 80%, or 60% oxygen (in air). During anesthesia induction, patients were ventilated with sevoflurane in 100%, 80%, or 60% oxygen. Endotracheal intubation and mechanical ventilation were performed. Atelectasis was diagnosed using LUS, which was performed after anesthetic induction and at the end of surgery. RESULTS: We assessed atelectasis after anesthetic induction and at the end of surgery. After anesthetic induction, the number of atelectatic lung regions was significantly different among the three groups (median [IQR], 2.0 [1.0-2.5], 2.0 [1.0-2.8], and 3.0 [2.0-3.0] in the 60%, 80%, and 100% oxygen groups, p = .033) and between the 60% and 100% groups (p = .015), but not between 80% and 100% groups (p = .074). However, no differences in the number of atelectatic lung regions were found among the three groups at the end of surgery (2.0 [1.3-3.8], 3.0 [1.8-3.0], and 4.0 [2.0-4.0] in the 60%, 80%, and 100% oxygen groups; p = .169). CONCLUSION: Lower oxygen concentration during anesthetic induction is associated with less atelectasis formation immediately after anesthetic induction in children. In addition, applying 80% oxygen instead of 100% oxygen is not enough to prevent atelectasis formation, and 60% oxygen should be applied to prevent atelectasis. However, this effect does not last until the end of surgery.

Development and Validation of Unplanned Extubation Prediction Models Using Intensive Care Unit Data: Retrospective, Comparative, Machine Learning Study.

BACKGROUND: Patient 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. OBJECTIVE: This study aimed to develop and validate prediction models for UE in ICU patients using machine learning. METHODS: This 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. RESULTS: Among 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. CONCLUSIONS: We 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.

Electromyogram-Based Classification of Hand and Finger Gestures Using Artificial Neural Networks.

Electromyogram (EMG) signals have been increasingly used for hand and finger gesture recognition. However, most studies have focused on the wrist and whole-hand gestures and not on individual finger (IF) gestures, which are considered more challenging. In this study, we develop EMG-based hand/finger gesture classifiers based on fixed electrode placement using machine learning methods. Ten healthy subjects performed ten hand/finger gestures, including seven IF gestures. EMG signals were measured from three channels, and six time-domain (TD) features were extracted from each channel. A total of 18 features was used to build personalized classifiers for ten gestures with an artificial neural network (ANN), a support vector machine (SVM), a random forest (RF), and a logistic regression (LR). The ANN, SVM, RF, and LR achieved mean accuracies of 0.940, 0.876, 0.831, and 0.539, respectively. One-way analyses of variance and F-tests showed that the ANN achieved the highest mean accuracy and the lowest inter-subject variance in the accuracy, respectively, suggesting that it was the least affected by individual variability in EMG signals. Using only TD features, we achieved a higher ratio of gestures to channels than other similar studies, suggesting that the proposed method can improve the system usability and reduce the computational burden.

Predictive Impact of Modified-Prognostic Nutritional Index for Acute Kidney Injury within 1-week after Living Donor Liver Transplantation.

Background. Acute kidney injury (AKI) is one of the common complications after living donor liver transplantation (LDLT) and is associated with increased mortality and morbidity. The prognostic nutritional index (PNI) has been used as a predictive model for postoperative complications. Here, we create a new predictive model based on the PNI and compared its predictive accuracy to other models in patients who underwent LDLT. Material and Methods: The data from 423 patients were collected retrospectively. The patients were dichotomized into the non-AKI and the AKI groups. Multivariate adjustment for significant postoperative variables based on univariate analysis was performed. A new predictive model was created using the results from logistic regression analysis, dubbed the modified-PNI model (mPNI). The area under the receiver operating characteristic curve (AUC) was generated to determine the diagnostic accuracy and cutoff value of individual models. The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated to investigate diagnostic improvement by the mPNI. Results: Fifty-four patients (12.7 %) were diagnosed with AKI within 1-week after LDLT. The mPNI had the highest predictive accuracy (AUC = 0.823). The model of end-stage liver disease (MELD) scores and PNI were 0.793 and 0.749, respectively, and the INR and serum bilirubin were 0.705 and 0.637, respectively. The differences in the AUCs were statistically significant among the mPNI, PNI, INR, and serum bilirubin. The cutoff value for mPNI was 8.7. The NRI was 10.4% and the IDI was 3.3%. Conclusions: The mPNI predicted AKI within 1-week better than other scoring systems in patients who underwent LDLT. The recommended cutoff value of mPNI is 8.7.

Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody.

Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.

Double Plant Homeodomain Fingers 2 (DPF2) Promotes the Immune Escape of Influenza Virus by Suppressing Beta Interferon Production.

The high mutation rates of the influenza virus genome facilitate the generation of viral escape mutants, rendering vaccines and drugs against influenza virus-encoded targets potentially ineffective. Therefore, we identified host cell determinants dispensable for the host but crucial for virus replication, with the goal of preventing viral escape and finding effective antivirals. To identify these host factors, we screened 2,732 human genes using RNA interference and focused on one of the identified host factors, the double plant homeodomain fingers 2 (DPF2/REQ) gene, for this study. We found that knockdown of DPF2 in cells infected with influenza virus resulted in decreased expression of viral proteins and RNA. Furthermore, production of progeny virus was reduced by two logs in the multiple-cycle growth kinetics assay. We also found that DPF2 was involved in the replication of seasonal influenza A and B viruses. Because DPF2 plays a crucial role in the noncanonical NF-κB pathway, which negatively regulates type I interferon (IFN) induction, we examined the relationship between DPF2 and IFN responses during viral infection. The results showed that knockdown of DPF2 resulted in increased expression of IFN-ß and induced phosphorylation of STAT1 in infected cells. In addition, high levels of several cytokines/chemokines (interleukin-8 [IL-8], IP-10, and IL-6) and antiviral proteins (MxA and ISG56) were produced by DPF2 knockdown cells. In conclusion, we identified a novel host factor, DPF2, that is required for influenza virus to evade the host immune response and that may serve as a potential antiviral target.IMPORTANCE Influenza virus is responsible for seasonal epidemics and occasional pandemics and is an ongoing threat to public health worldwide. Influenza virus relies heavily on cellular factors to complete its life cycle. Here we identified a novel host factor, DPF2, which is involved in influenza virus infection. Our results showed that DPF2 plays a crucial role in the replication and propagation of influenza virus. DPF2 functions in the noncanonical NF-κB pathway, which negatively regulates type I IFN induction. Thus, we investigated the relationship between the IFN response and DPF2 in influenza virus infection. Upon influenza virus infection, DPF2 dysregulated IFN-ß induction and expression of cytokines/chemokines and antiviral proteins. This study provides evidence that influenza virus utilizes DPF2 to escape host innate immunity.

A naturally truncated NS1 protein of influenza A virus impairs its interferon-antagonizing activity and thereby confers attenuation in vitro.

The non-structural protein of influenza A virus (NS1A protein) is a multifunctional protein that antagonizes host antiviral responses and contributes to efficient viral replication during infection. However, most of its functions have been elucidated by generating recombinant viruses expressing mutated NS1 proteins that do not exist in nature. Recently, the novel H3N8 A/Equine/Kyonggi/SA1/2011 (KG11) influenza virus was isolated in Korea from horses showing respiratory disease symptoms. KG11 virus contains a naturally truncated NS gene segment with the truncation in the NS1A coding region, resulting in truncation of the effector domain of the NS1A protein. Using this KG11 virus, we investigated the role of truncated NS1A protein in the virus life cycle and its effect on host immune responses were compared to the A/Equine/Miami/1/1963 H3N8 (MA63) virus, which encodes a full-length NS1A protein. The replication of KG11 virus was attenuated by 2 logs in multiple-cycle growth, and its plaque size was significantly smaller than that of the MA63 virus. To understand the attenuation of KG11 virus, we evaluated the level of activation in Akt and interferon regulatory factor 3 (IRF-3) pathways and measured the induction of downstream genes. Our results showed that the activation of Akt was reduced, whereas phosphorylation of IRF-3 was increased in cells infected with KG11 virus when compared to MA63-virus-infected cells. We also determined that the expression of antiviral and pro-inflammatory genes was significantly increased. Taken together, these results revealed that the KG11 virus expressing the naturally truncated NS1A protein impairs the inhibition of host antiviral responses, thereby resulting in the attenuation of viral replication.

Determination of the appropriate oropharyngeal airway size in adults: Assessment using ventilation and an endoscopic view.

INTRODUCTION: Size 9 and 8 airways for men and women, respectively, have been proposed as most appropriate based on endoscopy. However, a limitation of this guideline is that ventilation was not assessed. METHODS: In this retrospective review of prospectively collected data, 149 patients requiring tracheal intubation for general anesthesia were included. The adequacy for manual and pressure-controlled mechanical ventilation and views at the distal end of each airway was assessed using a fiber-optic bronchoscope with various airway sizes (7, 8, 9, 10, and 11). RESULTS: For men, size 9, 10, and 11 airways permitted clear manual and adequate mechanical ventilation; size 7 and 8 airways caused partially obstructed manual and inadequate mechanical ventilation. On endoscopy, size 7 and 8 airways caused complete obstruction by the tongue; size 10 and 11 airways either touched or passed beyond the tip of the epiglottis. For women, the size 7 airway caused partially obstructed manual and inadequate mechanical ventilation; size 9 and 10 airways provided clear manual and adequate mechanical ventilation. The size 8 airway permitted clear manual ventilation, though mechanical ventilation was inadequate in one patient. On endoscopy, the size 7 airway caused complete obstruction in >50% of women; size 9, 10, and 11 airways either touched or passed beyond the tip of the epiglottis. CONCLUSIONS: With respect to adequate ventilation in conjunction with an acceptable endoscopic view, size 9 and size 8 oropharyngeal airways appear to be the most appropriate sizes for clinical use in men and women, respectively.

Measuring the depth of the caudal epidural space to prevent dural sac puncture during caudal block in children.

BACKGROUND: Caudal blocks are performed through the sacral hiatus in order to provide pain control in children undergoing lower abdominal surgery. During the block, it is important to avoid advancing the needle beyond the sacrococcygeal ligament too much to prevent unintended dural puncture. This study used demographic data to establish simple guidelines for predicting a safe needle depth in the caudal epidural space in children. METHODS: A total of 141 children under 12 years old who had undergone lumbar-sacral magnetic resonance imaging were included. The T2 sagittal image that provided the best view of the sacrococcygeal membrane and the dural sac was chosen. We used Picture Achieving and Communication System (Centricity® PACS, GE Healthcare Co.) to measure the distance between the sacrococcygeal ligament and the dural sac, the length of the sacrococcygeal ligament, and the maximum depth of the caudal space. RESULTS: There were strong correlations between age, weight, height, and BSA, and the distance between the sacrococcygeal ligament and dural sac, as well as the length of the sacrococcygeal ligament. Based on these findings, a simple formula to calculate the distance between the sacrococcygeal ligament and dural sac was developed: 25 × BSA (mm). CONCLUSION: This simple formula can accurately calculate the safe depth of the caudal epidural space to prevent unintended dural puncture during caudal block in children. However, further clinical studies based on this formula are needed to substantiate its utility.

Extensive Viable Middle East Respiratory Syndrome (MERS) Coronavirus Contamination in Air and Surrounding Environment in MERS Isolation Wards.

BACKGROUND: The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) outside the Middle East occurred in South Korea in 2015 and resulted in 186 laboratory-confirmed infections, including 36 (19%) deaths. Some hospitals were considered epicenters of infection and voluntarily shut down most of their operations after nearly half of all transmissions occurred in hospital settings. However, the ways that MERS-CoV is transmitted in healthcare settings are not well defined. METHODS: We explored the possible contribution of contaminated hospital air and surfaces to MERS transmission by collecting air and swabbing environmental surfaces in 2 hospitals treating MERS-CoV patients. The samples were tested by viral culture with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA) using MERS-CoV Spike antibody, and electron microscopy (EM). RESULTS: The presence of MERS-CoV was confirmed by RT-PCR of viral cultures of 4 of 7 air samples from 2 patients' rooms, 1 patient's restroom, and 1 common corridor. In addition, MERS-CoV was detected in 15 of 68 surface swabs by viral cultures. IFA on the cultures of the air and swab samples revealed the presence of MERS-CoV. EM images also revealed intact particles of MERS-CoV in viral cultures of the air and swab samples. CONCLUSIONS: These data provide experimental evidence for extensive viable MERS-CoV contamination of the air and surrounding materials in MERS outbreak units. Thus, our findings call for epidemiologic investigation of the possible scenarios for contact and airborne transmission, and raise concern regarding the adequacy of current infection control procedures.

Identification of novel membrane-associated prostaglandin E synthase-1 (mPGES-1) inhibitors with anti-influenza activities in vitro.

Influenza A virus (IAV) is a major public health concern that leads to high morbidity and mortality worldwide. Despite various vaccination programs and development of drugs targeting essential viral proteins, the emergence of drug-resistant variants has been frequently reported and the therapeutic options are limited. Because exaggerated inflammation is considered as an important factor in disease pathogenesis, immunomodulatory agents that effectively suppress cytokine responses are needed for the treatment of IAV infection. Membrane-associated prostaglandin E synthase-1 (mPGES-1) is an enzyme responsible for the production of prostaglandin E2 (PGE2) that is the best-characterized immune modulatory lipid in vitro and in vivo models of inflammation. In the present study, we tested the anti-influenza activities of mPGES-1 inhibitors, using a phenotype-based assay involving image analyses. Seven primary hits among 49 compounds targeting mPGES-1 exhibited anti-influenza activities against A/Puerto Rico/8/1934 (H1N1) in a dose-dependent manner. The most effective hit, MPO-0047, suppressed influenza-induced p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) activation. We also showed that mRNA levels of TNF-α, IL-8, CCL5/RANTES, and CXCL10/IP-10 were significantly reduced by the treatment of influenza-infected cells with MPO-0047. Exogenous PGE2 reversed the inhibitory effects of MPO-0047. Our results showed that this selective mPGES-1 inhibitor has anti-influenza effects by inhibiting PGE2 production, which suppresses the induction of pro-inflammatory genes. Taken together our data revealed that mPGES-1 inhibitor has the potential for further development as an influenza therapeutic agent.

Identification of pyrrolo[3,2-c]pyridin-4-amine compounds as a new class of entry inhibitors against influenza viruses in vitro.

Various influenza virus entry inhibitors are being developed as therapeutic antiviral agents in ongoing preparation for emerging influenza viruses, particularly those that may possess drug resistance to the current FDA-approved neuraminidase inhibitors. In this study, small molecules having the pyrrolopyridinamine (PPA), aminothiadiazole (ATD), dihydrofuropyridine carboxamide (HPC), or imidazopyridinamine (IPA) moiety were selected from a target-focused chemical library for their inhibitory activity against influenza A virus by high-throughput screening using the PR8GFP assay. Activity was evaluated by measuring changes the proportion of GFP-expressing cells as a reflection of influenza virus infection. Among them, PPA showed broad-spectrum activity against multiple influenza A viruses and influenza B virus. PPA was found to block the early stages of influenza virus infection using a time-of-addition assay. Using additional phenotypic assays that dissect the virus entry process, it appears that the antiviral activity of PPA against influenza virus can be attributed to interference of the post-fusion process: namely, virus uncoating and nuclear import of viral nucleoprotein complexes. Based on these results, PPA is an attractive chemical moiety that can be used to develop new antiviral drug candidates against influenza viruses.

A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein.

The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-ß-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action.

Physicochemical and Sensory Properties of Red Ginseng Extracts or Red Ginseng Hydrolyzates-added Asiago Cheese during Ripening.

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<0.05). While RGHAC and RGEAC were more yellow and darker with increasing concentrations than that of control (p<0.05), the color was not influenced from the hydrolysis. In texture analysis, hardness, cohesiveness, and chewiness of RGHAC and RGEAC significantly decreased compared to the control during the ripening (p<0.05). In sensory analysis, bitterness and ginseng flavor and taste scores increased significantly with increasing the concentrations of RGH and RGE during ripening (p<0.05). In conclusion, the addition of RGH and RGE into cheese slightly influenced the properties of Asiago cheese, and similarities were observed between RGHAC and RGEAC. Thus, the lower concentrations (0.1% to 0.3%) of RGH and RGE added to AC were preferred for color, texture, and sensory during the ripening, therefore, these cheeses would be worth developing commercially.

Mammalian adaptation in the PB2 gene of avian H5N1 influenza virus.

The substitution of glutamic acid (E) for lysine (K) at position 627 of the PB2 protein of avian H5N1 viruses has been identified as a virulence and host range determinant for infection of mammals. Here, we report that the E-to-K host-adaptive mutation in the PB2 gene appeared from day 4 and 5 along the respiratory tracts of mice and was complete by day 6 postinoculation. This mutation correlated with efficient replication of the virus in mice.

Conversion of oxazolidinediones to isoindoloisoquinolinones via intramolecular Friedel­Crafts reaction.

Treatment of oxazolidinediones with TiCl4 in CH2Cl2 resulted in conversion to isoindoloisoquinolinones via intramolecular Friedel­Crafts reaction with extrusion of CO2 in the transformation. The alkaloid nuevamine has been synthesized under these conditions in a regiospecific manner.

Assessing different brain oxygenation components in elderly patients under propofol or sevoflurane anesthesia: A randomized controlled study.

STUDY OBJECTIVE: Elderly patients undergoing pathophysiological changes necessitate clinical tools for cerebral monitoring. This prospective randomized controlled study aimed to explore how cerebral monitoring using Δo2Hbi, ΔHHbi, and ΔcHbi manifests in elderly patients under either propofol or sevoflurane anesthesia. DESIGN: Single-center, prospective, randomization. SETTING: A single tertiary hospital (Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea). PATIENTS: Enrolled 100 patients scheduled for urologic surgery under general anesthesia. Inclusion criteria were (a) age 70-80 years, (b) American Society of Anesthesiologists (ASA) physical status I-II. INTERVENTION: Patients were double-blind randomized to receive propofol-based or sevoflurane anesthesia. Cerebral oximetry-related parameters were measured at 5, 10, 15, 20, and 30 min in a setting devoid of surgery-related factors. MEASUREMENTS: The primary outcome focused on the Δo2Hbi pattern in the left and right sides within the propofol and sevoflurane groups. MAIN RESULTS: We analyzed 100 patients, 50 patients in each group. In the propofol group, the left Δo2Hbi decreased from 1.4 (3.7) at 5 min to -0.1 (1.8) at 30 min (P < 0.0001), and the right Δo2Hbi decreased from 2.9 (4.2) at 5 min to -0.06 (2.3) at 30 min (P < 0.0001). In the sevoflurane group, the left Δo2Hbi decreased from 1.1 (3.4) at 5 min to -1.4 (4.4) at 30 min (P < 0.0001), and the right Δo2Hbi decreased from 2.0 (3.2) at 5 min to -1.2 (3.9) at 30 min (P < 0.0001). There were no significant differences between the two groups. ΔHHbi did not exhibit significant changes after an initial decrease at 5 min and showed no significant differences between the two groups. CONCLUSIONS: In cerebral oximetry, Δo2Hbi and ΔHHbi could emerge as a valuable approach for discerning changes in the underlying baseline status of the brain in elderly patients during anesthesia.