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Over recent decades, the use of home mechanical ventilation (HMV) has steadily increased worldwide, with varying prevalence in different countries. The key indication for HMV is chronic respiratory failure with alveolar hypoventilation (e.g., neuromuscular and chest wall disease, obstructive airway diseases, and obesity-related respiratory failure). Most modern home ventilators are pressure-targeted and have sophisticated modes, alarms, and graphics, thereby facilitating optimization of the ventilator settings. However, different ventilators have different algorithms for tidal volume estimation and leak compensation, and there are also several different circuit configurations. Hence, a basic understanding of the fundamentals of HMV is of paramount importance to healthcare workers taking care of patients with HMV. When choosing a home ventilator, they should take into account many factors, including the current condition and prognosis of the primary disease, the patient's daily performance status, time (hr/day) needed for ventilator support, family support, and financial costs. In this review, to help readers understand the basic concepts of HMV use, we describe the indications for HMV and the factors that influence successful delivery, including interface, circuits, ventilator accessories, and the ventilator itself. [ABSTRACT FROM AUTHOR]

Objective: To assess the feasibility and accuracy of synthetic MRI compared to conventional T1 weighted and multi-echo spin-echo (MESE) sequences for obtaining T2 values in the knee joint at 3 Tesla. Methods: This retrospective study included 19 patients with normal findings in the knee joint who underwent both synthetic MRI and MESE pulse sequences for T2 quantification. T2 values of the two sequences at the articular cartilage, bone marrow and muscle were measured. Relative signal intensity (SI) of each structure and relative contrast among structures of the knee were measured quantitatively by T1 weighted sequences. Results:The mean T2 values for cartilage and muscle were not significantly different between MESE pulse sequences and synthetic MRI. For the bone marrow, the mean T2 value obtained by MESE sequences (124.3 ± 3.6 ms) was significantly higher than that obtained by synthetic acquisition (73.1 ± 5.3 ms). There were no significant differences in the relative SI of each structure between the methods. The relative contrast of bone marrow to muscle was significantly higher with conventional T1 weighted images, while that for bone marrow to cartilage was similar for both sequences. Conclusion: Synthetic MRI is able to simultaneously acquire conventional images and quantitative maps, and has the potential to reduce the overall examination time. It provides comparable image quality to conventional MRI for the knee joint, with the exception of the bone marrow. With further optimization, it will be possible to take advantage of the image quality of musculoskeletal tissue with synthetic imaging. Advances in knowledge: Synthetic MRI produces images of good contrast and is also a time-saving technique. Thus, it may be useful for assessing osteoarthritis in the knee joint in the early stages. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is frequently associated with bleeding and coagulopathy complications, which may lead to the need for transfusion of multiple blood products. However, blood transfusions are known to increase morbidity and mortality, as well as hospital cost, in critically ill patients. In current practice, patients on ECMO receive a transfusion, on average, of 1-5 packed red blood cells (RBCs)/day, with platelet transfusion accounting for the largest portion of transfusion volume. Generally, adult patients require more transfusions than neonates or children, and patients receiving venovenous ECMO for respiratory failure tend to need smaller transfusion volumes compared to those receiving venoarterial ECMO for cardiac failure. Observation studies have reported that a higher transfusion volume was associated with increased mortality. To date, the evidence for transfusion in patients undergoing ECMO is limited; most knowledge on transfusion strategies was extrapolated from studies in critically ill patients. However, current data support a restrictive blood transfusion strategy for ECMO patients, and a low transfusion trigger seems to be safe and reasonable. [ABSTRACT FROM AUTHOR]

This study examined the sensing properties of Bi2O3 nanorods decorated with Pd nanoparticles. Pd-decorated ß-Bi2O3 nanorods were prepared by immersing the Bi2O3 nanorods in ethanol/(50 mM)PdCl2 solution followed by UV irradiation and annealing. The Bi2O3 nanorods decorated with Pd nanoparticles showed faster and stronger response to acetone gas than the pristine Bi2O3 nanorods. Interestingly, the difference in response time between the Pd-decorated Bi2O3 nanorod sensor and pristine Bi2O3 nanorod sensor increased with increasing the acetone gas concentration. In contrast, the difference in recovery time between the two nanorod sensors decreased with increasing the acetone gas concentration. This difference can be explained using the chemical mechanism. The underlying mechanism for the enhanced response of the Bi2O3 nanorods decorated with Pd nanoparticles to acetone gas is also discussed. [ABSTRACT FROM AUTHOR]

Over the past decade, functionalization with bimetallic catalysts have been studied owing to their excellent catalytic activities for various reactions, whereas few studies have been performed on cofunctionalization with two different types of metal catalysts despite its simplicity. This study examined the sensing performances of Nb2O5 nanorods cofunctionalized with Pd and Au nanoparticles. Pd, Au-cofunctionalized Nb2O5 nanorods were prepared by a hydrothermal technique. The Nb2O5 nanorods cofunctionalized with Pd and Au nanoparticles showed far stronger response to ethanol gas than the Pd or Au-functionalized counterpart. The origin for the enhanced response of the Pd, Au-cofunctionalized Nb2O5 nanorods is discussed. [ABSTRACT FROM AUTHOR]

Nb2O5 nanosensors with good sensing properties toward hydrogen and oxygen gases at high temperatures have been reported, but sensing performances of Nb2O5-based gas sensors are still unsatisfactory. This study examined the sensing properties of Nb2O5-core/ZnO-shell nanorod sensors toward H2 gas. The responses of pristine Nb2O5 and Nb2O5-core/ZnO-shell nanorods to 10,000 ppm H2 at 300 °C were ~250% and ~586%, respectively. The response and recovery times of Nb2O5-core/ZnO-shell nanorods at 10,000 ppm H2 at 300 °C were 17 and 23 s, respectively, whereas those of pristine Nb2O5 nanorods were 23 and 32 s. The response of the core-shell nanowire sensor to H2 gas showed strong dependence on the shell layer thickness. The strongest response was obtained with a ZnO shell layer thickness of 46 nm, which is equal to the maximum depletion layer width in the shell. The origin of the enhanced sensing properties of Nb2O5-core/ZnO-shell nanorods toward H2 is also discussed. [ABSTRACT FROM AUTHOR]

This study compared the responses of Pd-functionalized and pristine titanate (TiO2) nanotube arrays to ethanol with those to acetone to determine the effects of functionalization of TiO2 nanotubes with Pd nanoparticles on the sensitivity and selectivity. The responses of pristine and Pd-functionalized TiO2 nanotube arrays to ethanol gas at 200 °C were ~2877% and ~21,253%, respectively. On the other hand, the responses of pristine and Pd-functionalized TiO2 nanotube arrays to acetone gas at 250 °C were ~1636% and 8746% respectively. In the case of ethanol sensing, the response and recovery times of Pd-functionalized TiO2 nanotubes (10.2 and 7.1 s) were obviously shorter than those of pristine TiO2 nanotubes (14.3 and 8.8 s), respectively. In contrast, in the case of acetone sensing the response and recovery times of Pd-functionalized TiO2 nanotubes (42.5 and 19.7 s) were almost the same as those of pristine TiO2 nanotubes (47.2 and 17.9 s). TiO2 nanotube arrays showed the strongest response to ethanol and Pd functionalization was the most effective in improving the response of TiO2 nanotubes to ethanol among six different types of gases: ethanol, acetone, CO, H2, NH3 and NO2. The origin of the superior sensing properties of Pd-functionalized TiO2 nanotubes toward ethanol to acetone is also discussed. [ABSTRACT FROM AUTHOR]

Background This study aimed to investigate the population pharmacokinetics (PK) profile and determine the optimal dosage regimen of cefepime in critically ill adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). Materials and Methods Population-PK models for cefepime were developed using a nonlinear mixed-effect modeling approach. The percentage of time within 24 h in which the free concentration exceeded the minimum inhibitory concentration (MIC) at a steady state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function was explored using Monte Carlo simulation. Results Twenty-one patients were prospectively enrolled in this study. Cefepime PK was best described using a two-compartment model in which creatinine clearance (CLCR) through Cockcroft-Gault (CG) was a significant covariate for the total clearance of cefepime. The simulation results to determine the optimal cefepime dosing regimen for 50%fT>MIC as treatment target with Cmin <20 mg/L as safety target showed that a dosage regimen of 2 g through intravenous (IV) infusion every 12 h administered over 4 h was optimal at an MIC of 4 mg/L, rather than the currently recommended dosage regimen of 2 g administered through IV infusion every 8 h, in patients with normal renal function (CLCR = 90 - 130 mL/min). For a treatment target of 100%fT>MIC with Cmin <35 mg/L as a safety target, a dosage regimen of 0.75 g administered through continuous infusion over 24 h would be sufficient at an MIC equal to or less than 8 mg/L in patients with renal dysfunction (CLCR = 10 - 30 mL/min). Conclusion Our results suggest that clinicians should consider renal function and potential neurotoxicity when deciding the dosing regimen of cefepime in critically ill patients with HAP or VAP. Therapeutic drug monitoring (TDM) to adjust cefepime trough levels may be useful to improve clinical outcomes and reduce cefepime neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Data on pulmonary hemodynamic parameters in patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) are scarce. Methods: The associations between pulmonary artery catheter parameters for the first 7 days of ECMO, fluid balance, and hospital mortality were investigated in adult patients (aged ≥19 years) who received venovenous ECMO for refractory ARDS between 2015 and 2017. Results: Twenty patients were finally included in the analysis (median age, 56.0 years; interquartile range, 45.5–68.0 years; female, n=10). A total of 140 values were collected for each parameter (i.e., 7 days×20 patients). Net fluid balance was weakly but significantly correlated with systolic and diastolic pulmonary arterial pressures (PAPs; r=0.233 and P=0.011; r=0.376 and P<0.001, respectively). Among the mechanical ventilation parameters, above positive end-expiratory pressure was correlated with systolic PAP (r=0.191 and P=0.025), and static compliance was negatively correlated with diastolic PAP (r=−0.169 and P=0.048). Non-survivors had significantly higher systolic PAPs than in survivors. However, in multivariate analysis, there was no significant association between mean systolic PAP and hospital mortality (odds ratio, 1.500; 95% confidence interval, 0.937–2.404; P=0.091). Conclusions: Systolic PAP was weakly but significantly correlated with net fluid balance during the early ECMO period in patients with refractory ARDS receiving ECM. [ABSTRACT FROM AUTHOR]

배경 The aim of this study was to investigate the population pharmacokinetic (PK) profile and determine an optimal dosage regimen of cefepime in adult critically ill patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). 방법 Population PK models for cefepime were developed using a nonlinear mixed effect modelling approach. The percentage of time within 24 hours in which the free concentration exceeds the minimum in- hibitory concentration (MIC) at a steady-state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function were explored using Monte-Carlo simulation. 결과 Twenty-one patients were prospectively enrolled in the study. The cefepime PK was best described by two-compartment models, in which creatinine clearance (CLCR) by Cockcroft-Gault (CG) was a sig- nificant covariate on total clearance for cefepime. The simulation results showed that the current cefe- pime dosing regimen would be sufficient for the attainment of 50%fT>MIC for Pseudomonas aeruginosa at MIC equal to or less than 8 mg/L in patients with normal renal function (CLCR = 60-130 mL/min). The continuous infusion of 6 g/day over 24 h can achieve the attainment of 100%fT>MIC at MIC equal to or less than 16 mg/L despite the presence of augmented renal clearance (CLCR = 130-170 mL/min). However, when to limit cefepime trough level below 20 mg/L to prevent potential neurotoxicity in patients with renal dysfunction, 1 g of cefepime (CLCR = 30-60 mL/min) and 0.5 g of cefepime (CLCR = 10-30 mL/min) every 12 h with a 4-h prolonged infusion would be sufficient for the attainment of 50%fT>MIC at MIC equal to or less than 8 mg/L. 배경 The aim of this study was to investigate the population pharmacokinetic (PK) profile and determine an optimal dosage regimen of cefepime in adult critically ill patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). 방법 Population PK models for cefepime were developed using a nonlinear mixed effect modelling approach. The percentage of time within 24 hours in which the free concentration exceeds the minimum in- hibitory concentration (MIC) at a steady-state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function were explored using Monte-Carlo simulation. 결과 Twenty-one patients were prospectively enrolled in the study. The cefepime PK was best described by two-compartment models, in which creatinine clearance (CLCR) by Cockcroft-Gault (CG) was a sig- nificant covariate on total clearance for cefepime. The simulation results showed that the current cefe- pime dosing regimen would be sufficient for the attainment of 50%fT>MIC for Pseudomonas aeruginosa at MIC equal to or less than 8 mg/L in patients with normal renal function (CLCR = 60-130 mL/min). The continuous infusion of 6 g/day over 24 h can achieve the attainment of 100%fT>MIC at MIC equal to or less than 16 mg/L despite the presence of augmented renal clearance (CLCR = 130-170 mL/min). However, when to limit cefepime trough level below 20 mg/L to prevent potential neurotoxicity in patients with renal dysfunction, 1 g of cefepime (CLCR = 30-60 mL/min) and 0.5 g of cefepime (CLCR = 10-30 mL/min) every 12 h with a 4-h prolonged infusion would be sufficient for the attainment of 50%fT>MIC at MIC equal to or less than 8 mg/L. [ABSTRACT FROM AUTHOR]

Background: Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. Methods: We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 · respiratory rate · tidal volume · (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed Results: A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P<0.001). In logistic regression analysis, only MPPCV was significantly associated with ICU mortality (odds ratio, 1.090; 95% confidence interval, 1.029-1.155; P=0.003). There was no significant effect of the interaction between MPPCV and use of NMBA on ICU mortality (P=0.579). Conclusions: MPPCV is associated with ICU mortality in patients mechanically ventilated with PCV mode, regardless of NMBA use. [ABSTRACT FROM AUTHOR]

Background: Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. Methods: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. Results: Recommendations for nine PICO (population, intervention, comparator, and outcome) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. Conclusions: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation. [ABSTRACT FROM AUTHOR]

Background: Biologically, hydrogen (H2) can be produced through dark fermentation and photofermentation. Dark fermentation is fast in rate and simple in reactor design, but H2 production yield is unsatisfactorily low as <4 mol H2/mol glucose. To address this challenge, simultaneous production of H2 and ethanol has been suggested. Co-production of ethanol and H2 requires enhanced formation of NAD(P)H during catabolism of glucose, which can be accomplished by diversion of glycolytic flux from the Embden-Meyerhof-Parnas (EMP) pathway to the pentose-phosphate (PP) pathway in Escherichia coli. However, the disruption of pgi (phosphoglucose isomerase) for complete diversion of carbon flux to the PP pathway made E. coli unable to grow on glucose under anaerobic condition. Results: Here, we demonstrate that, when glucose-6-phosphate dehydrogenase (Zwf) and 6-phosphogluconate dehydrogenase (Gnd), two major enzymes of the PP pathway, are homologously overexpressed, E. coli Δpgi can recover its anaerobic growth capability on glucose. Further, with additional deletions of ΔhycA, ΔhyaAB, ΔhybBC, ΔldhA, and ΔfrdAB, the recombinant Δpgi mutant could produce 1.69 mol H2 and 1.50 mol ethanol from 1 mol glucose. However, acetate was produced at 0.18 mol mol-1 glucose, indicating that some carbon is metabolized through the Entner-Doudoroff (ED) pathway. To further improve the flux via the PP pathway, heterologous zwf and gnd from Leuconostoc mesenteroides and Gluconobacter oxydans, respectively, which are less inhibited by NADPH, were overexpressed. The new recombinant produced more ethanol at 1.62 mol mol-1 glucose along with 1.74 mol H2 mol-1 glucose, which are close to the theoretically maximal yields, 1.67 mol mol-1 each for ethanol and H2. However, the attempt to delete the ED pathway in the Δpgi mutant to operate the PP pathway as the sole glycolytic route, was unsuccessful. Conclusions: By deletion of pgi and overexpression of heterologous zwf and gnd in E. coli ΔhycA ΔhyaAB ΔhybBC ΔldhA ΔfrdAB, two important biofuels, ethanol and H2, could be successfully co-produced at high yields close to their theoretical maximums. The strains developed in this study should be applicable for the production of other biofuels and biochemicals, which requires supply of excessive reducing power under anaerobic conditions. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the superficial hyperechoic band (SHEB) in articular cartilage by using ultrasonography (US) and to assess its correlation with histological images. Methods: In total, 47 regions of interest (ROIs) were analyzed from six tibial osteochondral specimens (OCSs) that were obtained after total knee arthroplasty. Ultrasonograms were obtained for each OCS. Then, matching histological sections from all specimens were obtained for comparison with the ultrasonograms. Two types of histological staining were used: Safranin-0 stain (SO) to identify glycosaminoglycans (GAG) and Masson's trichrome stain (MT) to identify collagen. In step 1, two observers evaluated whether there was an SHEB in each ROI. In step 2, the two observers evaluated which histological staining method correlated better with the SHEB by using the ImageJ software. Results: In step 1 of the analysis, 20 out of 47 ROIs showed an SHEB (42.6%, kappa=0.579). Step 2 showed that the SHEB correlated significantly better with the topographical variation in stainability in SO staining, indicating the GAG distribution, than with MT staining, indicating the collagen distribution (P<0.05, kappa=0.722). Conckjsion:The SHEB that is frequently seen in human artkular cartilage on high-resolution US correlated better with variations in SO staining than with variations in MT staining. Thus, we suggest that a SHEB is predominantly related to changes in GAG. Identifying an SHEB by US is a promising method for assessing the thickness of articular cartilage or for monitoring early osteoarthritis. [ABSTRACT FROM AUTHOR]

MgO nanorods were grown by the thermal evaporation of MgN powders on the Si (100) substrate coated with a gold thin film. The MgO nanorods grown on the Si (100) substrate were a few tens of nanometers in diameter and up to a few hundreds of micrometers in length. MgO/SiO core-shell nanorods were also fabricated by the sputter-deposition of SiOonto the MgO nanorods. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis results indicated that the cores and shells of the annealed core-shell nanorods were a face-centered cubic-type single crystal MgO and amorphous SiO, respectively. The photoluminescence (PL) spectroscopy analysis results showed that SiO coating slightly decreased the PL emission intensity of the MgO nanorods. The PL emission of the MgO/SiO core-shell nanorods was, however, found to be considerably enhanced by thermal annealing and strongly depends on the annealing atmosphere. The PL emission of the MgO/SiO core-shell nanorods was substantially enhanced in intensity by annealing in a reducing atmosphere, whereas it was slightly enhanced by annealing in an oxidative atmosphere. The origin of the PL enhancement by annealing in a reducing atmosphere is discussed with the aid of energy-dispersive X-ray spectroscopy analyses. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Branching enzymes (BEs) are essential in the biosynthesis of starch and glycogen and play critical roles in determining the fine structure of these polymers. The substrates of these BEs are long carbohydrate chains that interact with these enzymes via multiple binding sites on the enzyme's surface. By controlling the branched-chain length distribution, BEs can mediate the physiological properties of starch and glycogen moieties; however, the mechanism and structural determinants of this specificity remain mysterious. In this study, we identify a large dodecaose binding surface on rice BE I (BEI) that reaches from the outside of the active site to the active site of the enzyme. Mutagenesis activity assays confirm the importance of this binding site in enzyme catalysis, from which we conclude that it is likely the acceptor chain binding site. Comparison of the structures of BE from Cyanothece and BE1 from rice allowed us to model the location of the donor-binding site. We also identified two loops that likely interact with the donor chain and whose sequences diverge between plant BE1, which tends to transfer longer chains, and BEIIb, which transfers exclusively much shorter chains. When the sequences of these loops were swapped with the BEIIb sequence, rice BE1 also became a short-chain transferring enzyme, demonstrating the key role these loops play in specificity. Taken together, these results provide a more complete picture of the structure, selectivity, and activity of BEs. [ABSTRACT FROM AUTHOR]

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<0.001) and from 54.9±15.1 mm Hg to 51.1±15.1 mm Hg in the sedation group (P=0.048). No significant differences were observed in the success rate of NIV weaning, complications, length of ICU stay, ICU survival rate, or hospital survival rate between the groups. Conclusions: In NIV patients, analgosedation therapy may have no harmful effects on complications, NIV weaning success, and mortality compared to the control group. Therefore, sedation during NIV may not be unsafe and can be used in patients for pain control when indicated. [ABSTRACT FROM AUTHOR]

Background: Mortality rates associated with sepsis have increased progressively in Korea, but domestic epidemiologic data remain limited. The objective of this study was to investigate the characteristics, management and clinical outcomes of sepsis patients in Korea. Methods: This study is a multicenter retrospective cohort study. A total of 64,021 adult patients who visited an emergency department (ED) within one of the 19 participating hospitals during a 1-month period were screened for eligibility. Among these, patients diagnosed with sepsis based on the third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) were included in the study. Results: Using the Sepsis-3 criteria, 977 sepsis patients were identified, among which 36.5% presented with septic shock. The respiratory system (61.8%) was the most common site of infection. The pathogen involved was identified in 444 patients (45.5%) and multi-drug resistance (MDR) pathogens were isolated in 171 patients. Empiric antibiotic therapy was appropriate in 68.6% of patients, but the appropriateness was significantly reduced in infections associated with MDR pathogens as compared with non-MDR pathogens (58.8% vs. 76.0%, P<0.001). Hospital mortality was 43.2% and 18.5% in sepsis patients with and without shock, respectively. Of the 703 patients who survived to discharge, 61.5% were discharged to home and 38.6% were transferred to other hospitals or facilities. Conclusions: This study found the prevalence of sepsis in adult patients visiting an ED in Korea was 1.5% (15.2/1,000 patients). Patients with sepsis, especially septic shock, had a high mortality and were often referred to step-down centers after acute and critical care. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the characteristics and clinical outcomes of critically ill cancer patients admitted to intensive care units (ICUs) in Korea. Methods: This was a retrospective cohort study that analyzed prospective collected data from the Validation of Simplified Acute Physiology Score 3 (SAPS3) in Korean ICU (VSKI) study, which is a nationwide, multicenter, and prospective study that considered 5,063 patients from 22 ICUs in Korea over a period of 7 months. Among them, patients older than 18 years of age who were diagnosed with solid or hematologic malignancies prior to admission to the ICU were included in the present study. Results: During the study period, a total of 1,762 cancer patients were admitted to the ICUs and 833 of them were deemed eligible for analysis. Six hundred fifty-eight (79%) had solid tumors and 175 (21%) had hematologic malignancies, respectively. Respiratory problems (30.1%) was the most common reason leading to ICU admission. Patients with hematologic malignancies had higher Sequential Organ Failure Assessment (12 vs. 8, P<0.001) and SAPS3 (71 vs. 69, P<0.001) values and were more likely to be associated with chemotherapy, steroid therapy, and immunocompromised status versus patients with solid tumors. The use of inotropes/vasopressors, mechanical ventilation, and/or continuous renal replacement therapy was more frequently required in hematologic malignancy patients. Mortality rates in the ICU (41.7% vs. 24.6%, P<0.001) and hospital (53.1% vs. 38.6%, P=0.002) were higher in hematologic malignancy patients than in solid tumor patients. Conclusions: Cancer patients accounted for one-third of all patients admitted to the studied ICUs in Korea. Clinical characteristics were different according to the type of malignancy. Patients with hematologic malignancies had a worse prognosis than did patients with solid tumor. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia is common and important infectious disease in adults. This work represents an update to 2009 treatment guideline for community-acquired pneumonia in Korea. The present clinical practice guideline provides revised recommendations on the appropriate diagnosis, treatment, and prevention of community-acquired pneumonia in adults aged 19 years or older, taking into account the current situation regarding community-acquired pneumonia in Korea. This guideline may help reduce the difference in the level of treatment between medical institutions and medical staff, and enable efficient treatment. It may also reduce antibiotic resistance by preventing antibiotic misuse against acute lower respiratory tract infection in Korea. [ABSTRACT FROM AUTHOR]

Background: 3-Hydroxypropionic acid (3-HP) is an important platform chemical which can be produced biologically from glycerol. Klebsiella pneumoniae is an ideal biocatalyst for 3-HP because it can grow well on glycerol and naturally synthesize the essential coenzyme B12. On the other hand, if higher yields and titers of 3-HP are to be achieved, the sustained regeneration of NAD+ under anaerobic conditions, where coenzyme B12 is synthesized sustainably, is required. Results: In this study, recombinant K. pneumoniae L17 overexpressing aldehyde dehydrogenase (AldH) was developed and cultured in a bioelectrochemical system (BES) with the application of an electrical potential to the anode using a chronoamperometric method (+0.5 V vs. Ag/AgCl). The BES operation resulted in 1.7-fold enhancement of 3-HP production compared to the control without the applied potential. The intracellular NADH/NAD+ ratio was significantly lower when the L17 cells were grown under an electric potential. The interaction between the electrode and overexpressed AldH was enhanced by electron shuttling mediated by HNQ (2-hydroxy-1,4-naphthoquinone). Conclusions: Enhanced 3-HP production by the BES was achieved using recombinant K. pneumoniae L17. The quinone-based electron transference between the electrode and L17 was investigated by respiratory uncoupler experiments. This study provides a novel strategy to control the intracellular redox states to enhance the yield and titer of 3-HP production as well as other bioconversion processes. [ABSTRACT FROM AUTHOR]

Background: Noninvasive prenatal testing (NIPT) using massively parallel sequencing of cell-free DNA (cfDNA) is increasingly being used to predict fetal chromosomal abnormalities. However, concerns over erroneous predictions which occur while performing NIPT still exist in pregnant women at high risk for fetal aneuploidy. We performed the largest-scale clinical NIPT study in Korea to date to assess the risk of false negatives and false positives using next-generation sequencing. Methods: A total of 447 pregnant women at high risk for fetal aneuploidy were enrolled at 12 hospitals in Korea. They underwent definitive diagnoses by full karyotyping by blind analysis and received aneuploidy screening at 11-22 weeks of gestation. Three steps were employed for cfDNA analyses. First, cfDNA was sequenced. Second, the effect of GC bias was corrected using normalization of samples as well as LOESS and linear regressions. Finally, statistical analysis was performed after selecting a set of reference samples optimally adapted to a test sample from the whole reference samples. We evaluated our approach by performing cfDNA testing to assess the risk of trisomies 13, 18, and 21 using the sets of extracted reference samples. Results: The adaptive selection algorithm presented here was used to choose a more optimized reference sample, which was evaluated by the coefficient of variation (CV), demonstrated a lower CV and higher sensitivity than standard approaches. Our adaptive approach also showed that fetal aneuploidies could be detected correctly by clearly splitting the z scores obtained for positive and negative samples. Conclusions: We show that our adaptive reference selection algorithm for optimizing trisomy detection showed improved reliability and will further support practitioners in reducing both false negative and positive results. [ABSTRACT FROM AUTHOR]

Background: Noninvasive prenatal testing (NIPT) to detect fetal aneuploidy using next-generation sequencing on ion semiconductor platforms has become common. There are several sequencers that can generate sufficient DNA reads for NIPT. However, the approval criteria vary among platforms and countries. This can delay the introduction of such devices and systems to clinics. A comparison of the sensitivity and specificity of two different platforms using the same sequencing chemistry could be useful in NIPT for fetal chromosomal aneuploidies. This would improve healthcare authorities' confidence in decision-making on sequencing-based tests. Methods: One hundred and one pregnant women who were predicted at high risk of fetal defects using conventional prenatal screening tests, and who underwent definitive diagnosis by full karyotyping, were enrolled from three hospitals in Korea. Most of the pregnant women (69.79 %) received NIPT during weeks 11-13 of gestation and 30.21 % during weeks 14-18. We used Ion Torrent PGM and Proton semi-conductor-based sequencers with 0.3× sequencing coverage depth. The average total reads of 101 samples were approximately 4.5 and 7.6 M for PGM and Proton, respectively. A Burrows-Wheeler Aligner (BWA) algorithm was used for the alignment, and a z-score was used to decide fetal trisomy 21. Interactive dot diagrams from the sequencing data showed minimal z-score values of 2.07 and 2.10 to discriminate negative versus positive cases of fetal trisomy 21 for the two different sequencing systems. Results: Our z-score-based discrimination method resulted in 100 % positive and negative prediction values for both ion semiconductor PGM and Proton sequencers, regardless of their sequencing chip and chemistry differences. Both platforms performed well at an early stage (11-13 weeks of gestation) compared with previous studies. Conclusions: These results suggested that, using two different sequencers, NIPT to detect fetal trisomy 21 in early pregnancy is accurate and platform-independent. The data suggested that the amount of sequencing and the application of common, simple, and robust statistical analyses are more important than sequencing chemistry and platform types. This result has practical implications in countries where PGM is approved for NIPT but the Proton system is not. [ABSTRACT FROM AUTHOR]

Background: Fermentative hydrogen (H2) production suffers from low carbon-to-H2 yield, to which problem, coproduction of ethanol and H2 has been proposed as a solution. For improved co-production of H2 and ethanol, we developed Escherichia coli BW25113 ΔhycA ΔhyaAB ΔhybBC ΔldhA ΔfrdAB Δpta-ackA ΔpfkA (SH8*) and overexpressed Zwf and Gnd, the key enzymes in the pentose-phosphate (PP) pathway (SH8*_ZG). However, the amount of accumulated pyruvate, which was significant (typically 0.20 mol mol-1 glucose), reduced the co-production yield. Results: In this study, as a means of reducing pyruvate accumulation and improving co-production of H2 and ethanol, we developed and studied E. coli SH9*_ZG with functional acetate production pathway for conversion of acetyl-CoA to acetate (pta-ackA+). Our results indicated that the presence of the acetate pathway completely eliminated pyruvate accumulation and substantially improved the co-production of H2 and ethanol, enabling yields of 1.88 and 1.40 mol, respectively, from 1 mol glucose. These yields, significantly, are close to the theoretical maximums of 1.67 mol H2 and 1.67 mol ethanol. To better understand the glycolytic flux distribution, glycolytic flux prediction and RT-PCR analyses were performed. Conclusion: The presence of the acetate pathway along with activation of the PP pathway eliminated pyruvate accumulation, thereby significantly improving co-production of H2 and ethanol. Our strategy is applicable to anaerobic production of biofuels and biochemicals, both of which processes demand high NAD(P)H. [ABSTRACT FROM AUTHOR]

Background: 3-Hydroxypropionic acid (3-HP) is an important platform chemical that boasts a variety of industrial applications. Gene expression systems inducible by 3-HP, if available, are of great utility for optimization of the pathways of 3-HP production and excretion. Results: Here we report the presence of unique inducible gene expression systems in Pseudomonas denitrificans and other microorganisms. In P. denitrificans, transcription of three genes (hpdH, mmsA and hbdH-4) involved in 3-HP degradation was upregulated by 3-HP by the action of a transcriptional regulator protein, LysR, and a cis-acting regulatory site for LysR binding. Similar inducible systems having an LysR transcriptional regulator were identified in other microorganisms that also could degrade 3-HP. A docking study showed that the 3-HP binding pocket is located between the N-terminal helix-turn-helix motif and the C-terminal cofactor-binding domain. Conclusions: This LysR-regulated 3-HP-inducible system should prove useful for control of the level of gene expression in response to 3-HP. [ABSTRACT FROM AUTHOR]

Since the chemical/electrical stability and catalytic activity are essential conditions for catalyst counter electrodes (CCEs) in dye-sensitized solar cells (DSSCs), a simple dipping method is employed for evaluating the chemical stability of CCE candidates in an iodine-based liquid electrolyte (I-electrolyte). The chemical stabilities and transition mechanisms of the CCEs are successfully analyzed by studying the chemical transitions in X-ray photoelectron spectroscopy (XPS) core levels after dipping in the I-electrolyte. All films including the Pt film undergo degradation depending on the type of material. While dipping in the I-electrolyte, Cu and Au films scarcely dissolves as their respective metal sulfides, and the Al film gradually loss its metallic properties owing to Al2O3 growth. On the other hand, a previously unknown transition mechanism of organic conducting CCEs is determined based on the proposed method. Compared to the other metal films, the poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) and multi wall carbon nanotube (MWCNT)/PEDOT:PSS films undergo an entirely unique transition mechanism, which results from the chemical adsorption of organic molecules onto PEDOT:PSS molecules in the I-electrolyte. Consequently, these chemical structure transitions correspond well to the degrees of alternation in the electrical properties of DSSCs with all the investigated CCEs. [ABSTRACT FROM AUTHOR]

A novel nonheme chloroperoxidase (R/iEstl), with promiscuous esterase activity for enantioselective hydrolysis of ethyl (S)-2,2- dimethylcyclopropanecarboxylate, was identified from a shotgun library of Rhodococcus sp. strain ECU1013. RhEstl was overexpressed in Escherichia coli BL21(DE3), purified to homogeneity, and functionally characterized. Fingerprinting analysis revealed that RT/Est 1 prefers para-nitrophenyl (pNP) esters of short-chain acyl groups. pNP esters with a cyclic acyl moiety, especially that with a cyclobutanyl group, were also substrates for R/iEstl. The Km values for methyl 2,2-dimethylcyclopropanecarboxylate (DmCpCm) and ethyl 2,2-dimethylcyclopropane carboxylate (DmCpCe) were 0.25 and 0.43 mM, respectively. RhEst 1 could serve as an efficient hydrolase for the bioproduction of optically pure (S)-2,2-dimethyl cyclopropane carboxylic acid (DmCpCa), which is an important chiral building block for cilastatin. As much as 0.5 M DmCpCe was enantioselectively hydrolyzed into (S)-DmCpCa, with a molar yield of 47.8% and an enantiomeric excess (ee) of 97.5%, indicating an extremely high enantioselectivity (E = 240) of this novel and unique biocatalyst for green manufacturing of highly valuable chiral chemicals. [ABSTRACT FROM AUTHOR]

Background: The role of extended-spectrum β-lactamase (ESBL)-producing or multidrug-resistant (MDR) organisms in patients with sepsis secondary to urinary traction infection (UTI) has not been investigated extensively in the intensive care unit (ICU) setting. Methods: Patients with UTI sepsis admitted to the ICU were retrospectively enrolled in this study (January 2009-December 2012). We investigated the impact of ESBL-producing and ESBL-negative MDR organisms on hospital outcome. Results: In total, 94 patients were enrolled (median age, 73.0 years; female, 81.9%), and ESBL-producing and ESBL-negative MDR organisms accounted for 20.2% (n = 19) and 30.9% (n = 29), respectively. Both patients with ESBL-producing and ESBL-negative MDR organisms were more likely to experience a delay in adequate antibiotic therapy than those with non-ESBL/non-MDR organisms (p < 0.001 and p = 0.032, respectively). However, only patients with ESBL-producing organisms showed a higher mortality rate (ESBL vs. ESBL-negative MDR vs. non-ESBL/non-MDR, 31.6% vs. 10.3%.vs. 10.9%, respectively). In multivariate analyses, ESBL production was significantly associated with hospital mortality (odds ratio, 11.547; 95% confidence interval, 1.047-127.373), and prior admission was a significant predictor of ESBL production. Conclusions: Although both ESBL-producing and ESBL-negative MDR organisms are associated with delayed administration of appropriate antibiotics, only ESBL production is a significant predictor of hospital mortality among patients with UTI sepsis in the ICU setting. [ABSTRACT FROM AUTHOR]

Background: The role of N-terminal pro-B-type natriuretic peptide (NT- pro-BNP) as a prognostic factor in patients admitted to the intensive care unit (ICU) is not yet fully established. We aimed to determine whether NT-pro-BNP is predictive of ICU mortality in a multicenter cohort of critically ill patients. Methods: A total of 1440 patients admitted to 22 ICUs (medical, 14; surgical, six; multidisciplinary, two) in 15 tertiary or university-affiliated hospitals between July 2010 and January 2011 were assessed. Patient data, including NT-pro-BNP levels and Simplified Acute Physiology Score (SAPS) 3 scores, were recorded prospectively in a web-based database. Results: The median age was 64 years (range, 53-73 years), and 906 (62.9%) patients were male. The median NT-pro-BNP level was 341 pg/mL (104-1,637 pg/mL), and the median SAPS 3 score was 57 (range, 47-69). The ICU mortality rate was 18.9%, and hospital mortality was 24.5%. Hospital survivors showed significantly lower NT-pro-BNP values than nonsurvivors (245 pg/mL [range, 82-1,053 pg/mL] vs. 875 pg/mL [241-5,000 pg/mL], respectively; p < 0.001). In prediction of hospital mortality, the area under the curve (AUC) for NT-pro-BNP was 0.67 (95% confidence interval [CI], 0.64-0.70) and SAPS 3 score was 0.83 (95% CI, 0.81-0.85). AUC increment by adding NT-pro-BNP is minimal and likely no different to SAPS 3 alone. Conclusions: The NT-pro-BNP level was more elevated in nonsurvivors in a multicenter cohort of critically ill patients. However, there was little additional prognostic power when adding NT- pro-BNP to SAPS 3 score. [ABSTRACT FROM AUTHOR]

Highlights: [•] Boundary of GDE N-domain was defined by protease digestion. [•] N-domain of GDE showed α-1,4-transferase activity. [•] N-domain of GDE showed α-1,6-glycosidase activity. [•] D535 and E564 in N-domain are essential for transferase but not for glucosidase activity. [ABSTRACT FROM AUTHOR]

The top-valued platform chemical, 3-hydroxypropionic acid (3-HP), has a wide range of industrial applications but its biological production is not well established. Previously, the production of 3-HP from glycerol was demonstrated using a recombinant Escherichia coli strain expressing glycerol dehydratase ( dhaB) and aldehyde dehydrogenase ( aldH). The present investigation focuses on the effect of the culture conditions on the production of 3-HP from glycerol. The physicochemical parameters, such as pH, IPTG concentration, liquid-to-flask volume ratio, and substrate concentration, were examined in flask-scale experiments and obtained the highest titer of 3-HP at 4.4 g l–1 in 48 h. When a fed-batch process was carried out in a bioreactor under pH-regulated conditions, the recombinant E. coli produced 3-HP at 31 g l–1 in 72 h with a yield of 0.35 mol mol–1 glycerol. The maximum specific rate of 3-HP production was estimated to be 3.41 mmol g–1 cdw h–1 between 12 and 24 h. Other than 3-HP, propionic acid (3.4 g l–1), 1,3-propanediol (2.4 g l–1), and lactic acid (1.6 g l–1) were produced as the major by-products. This paper reports for the first time a commercially meaningful high titer of 3-HP production. [ABSTRACT FROM AUTHOR]

Caseinomacropeptide is a polypeptide of 64 amino acid residues (106-169) derived from the C-terminal part of the mammalian milk k-casein. This macropeptide has various biological activities and is used as a functional food ingredient as well as a pharmaceutical compound. The gene encoding the human caseinomacropeptide (hCMP) was synthesized and expressed with an α-factor secretion signal in the two yeast strains, Saccharomyces cerevisiae and Pichia pastoris. The complete polypeptide of the recombinant hCMP was produced and secreted in a culture medium by both the strains, but the highest production was observed in S. cerevisiae with a galactose-inducible promoter. In a fed-batch bioreactor culture, 2.5 g/l of the recombinant hCMP was obtained from the S. cerevisiae at 97 h. [ABSTRACT FROM AUTHOR]

Poly(3, 4-ethylenedioxythiophene) (PEDOT) polymerized with poly(4-styrenesulfonate) (PSS) is one of the most widely used conducting organic electrodes owing to its outstanding optical/electrical properties and high work function. Because its work function depends significantly on the molecular arrangements between PEDOT and PSS molecules on the surface, the contact position of PEDOT:PSS films on organic semiconductors (OSCs) must also be an essential consideration. However, existing analysis methods based on in situ deposition/analysis are limited in their ability to accurately investigate the electronic structures of the buried interface regions under the solution-processed electrode or OSC layer in organic devices. Therefore, to overcome such limitations, we propose a top-down method based on photoemission spectroscopy analysis combined with Ar gas cluster ion beam (GCIB) sputtering. Through this method, both energy-level alignments and molecular distributions at various OSC/electrode interfaces can be successfully characterized without reference to any deposition process. [ABSTRACT FROM AUTHOR]