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Previous studies have reported a higher risk of falls among tricyclic antidepressant (TCA) users compared to selective serotonin reuptake inhibitor (SSRI) users, yet SSRIs are known as a safer antidepressant class for use in older adults. This study examined the effects of antidepressant use on the risk of fall-related injuries after classifying antidepressant drugs, polypharmacy, and central nervous system (CNS) drugs by therapeutic classes and identifying factors influencing risk of fall-related injuries. A retrospective matched cohort study based on propensity scores was conducted among older adults, aged 70-89 years, who initiated antidepressant use between 1 January 2012 and 31 December 2014 using the national health insurance system senior cohort in Korea. The proportional hazard Cox regression model was used to examine the association between fall-related injuries and antidepressants. The subgroup analyses were performed to assess the risk of fall-related injuries by the number of concurrently administered medications, therapeutic classes of antidepressants, and CNS class medications. This study found that duloxetine, escitalopram, paroxetine, amitriptyline, imipramine, and trazodone significantly increased the risk of fall-related injuries in older adults. When antidepressants were prescribed to older adults, prescribers carefully considered factors including the dose, number of concurrently administered medications, and therapeutic classes of CNS.

Rationale: Monosialotetrahexosylganglioside (GM1) gangliosidosis is a rare lysosomal storage disorder caused by the deficiency of ß-galactosidase. Because clinical symptoms of GM1 gangliosidosis overlap with other neurodevelopmental disorders, the diagnosis of this disease is not easy, specifically in late infantile GM1 gangliosidosis. This report described a case of late-infantile GM1 gangliosidosis mistaken for juvenile idiopathic arthritis., Patient Concerns: A 16-year-old girl was referred to our hospital due to persistent multiple joint deformities and mental retardation, which could not be explained by juvenile idiopathic arthritis., Diagnosis: We made a diagnosis of late infantile GM1 gangliosidosis through enzyme assays and genetic testing after a skeletal survey., Interventions: The patient underwent cervical domeplasty and laminectomy for cord compression and received rehabilitation treatment., Outcomes: The patient is receiving multidisciplinary care at a tertiary center for variable skeletal disease and conditions associated with GM1 gangliosidosis., Lessons: Late infantile GM1 gangliosidosis should be considered in the differential diagnosis of progressive neurologic decline and skeletal dysostosis., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

To assess the utility of machine learning (ML) algorithms in predicting clinically relevant atrial high-rate episodes (AHREs), which can be recorded by a pacemaker. We aimed to develop ML-based models to predict clinically relevant AHREs based on the clinical parameters of patients with implanted pacemakers in comparison to logistic regression (LR). We included 721 patients without known atrial fibrillation or atrial flutter from a prospective multicenter (11 tertiary hospitals) registry comprising all geographical regions of Korea from September 2017 to July 2020. Predictive models of clinically relevant AHREs were developed using the random forest (RF) algorithm, support vector machine (SVM) algorithm, and extreme gradient boosting (XGB) algorithm. Model prediction training was conducted by seven hospitals, and model performance was evaluated using data from four hospitals. During a median follow-up of 18 months, clinically relevant AHREs were noted in 104 patients (14.4%). The three ML-based models improved the discrimination of the AHREs (area under the receiver operating characteristic curve: RF: 0.742, SVM: 0.675, and XGB: 0.745 vs. LR: 0.669). The XGB model had a greater resolution in the Brier score (RF: 0.008, SVM: 0.008, and XGB: 0.021 vs. LR: 0.013) than the other models. The use of the ML-based models in patient classification was associated with improved prediction of clinically relevant AHREs after pacemaker implantation., (© 2022. The Author(s).)

Anaerobic digestion (AD) is a technique that can be used to treat high concentrations of various organic wastes using a consortium of functionally diverse microorganisms under anaerobic conditions. Methane gas, a beneficial by-product of the AD process, is a renewable energy source that can replace fossil fuels following purification. However, detailed functional roles and metabolic interactions between microbial populations involved in organic waste removal and methanogenesis are yet to be known. Recent metagenomic approaches based on advanced high-throughput sequencing techniques have enabled the exploration of holistic microbial taxonomy and functionality of complex microbial populations involved in the AD process. Gene-centric and genome-centric analyses based on metagenome-assembled genomes are a platform that can be used to study the composition of microbial communities and their roles during AD. This review looks at how these up-to-date metagenomic analyses can be applied to promote our understanding and improved the development of the AD process., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Outbreaks of 2-methylisoborneol (2-MIB) contamination in drinking water sources cause inconvenient odor issues in the water distribution system. In this study, microscopy-based isolation with physiological and molecular phylogenetic characterization were performed to investigate and characterize the 2-MIB odor producers that caused an odor problem in the freshwater system of the North Han River in the autumn of 2018. A benthic cyanobacterium was isolated from 2-MIB odor-issue freshwater samples and was found to be phylogenetically affiliated with Pseudanabaena yagii (99.66% sequence similarity), which was recorded in South Korea for the first time. The 2-MIB synthesis gene sequences from the odor-issue freshwater samples showed 100% similarity with those in the P. yagii strains. Protein sequences of 2-MIB synthase observed in the genome of the isolated strain showed structural and functional characteristics similar to those observed in other Pseudanabaena species. The 2-MIB production rate increased slowly during mat formation on the vessel wall; however, it rapidly increased after the temperature dropped. The 2-MIB gene was continuously expressed regardless of the temperature changes. These results suggest that the 2-MIB odor issue in the North Han River might be caused by the release of 2-MIB from the mat-forming P. yagii species in a low-temperature freshwater environment.

Background: Combined methylmalonic acidemia and homocystinuria is a rare inherited disorder of intracellular cobalamin metabolism caused by biallelic variants in one of the following genes: MMACHC (cblC), MMADHC (cblD), LMBRD1 (cblF), ABCD4 (cblJ), THAP11 (cblX-like), and ZNF143 (cblX-like), or a hemizygous variant in HCFC1 (cblX). Prenatal diagnosis of combined methylmalonic acidemia with homocystinuria is crucial for high-risk couples since the disorder can be life-threatening for offspring. We would like to describe two infant deaths both of which are likely attributable to cblC despite not having a genetic confirmation, and subsequent pregnancy and prenatal genetic testing., Methods: Parental clinical exome sequencing and targeted Sanger sequencing of MMACHC gene in amniotic fluid was performed to check the carrier status of the fetus., Results: Parental clinical exome sequencing revealed a heterozygous pathogenic variant [NM_015506.2:c.217C>T (p.Arg73*)] in the MMACHC gene of the mother and [NM_015506.2:c.609G>A (p.Trp203*)] in the MMACHC gene of the father. Targeted Sanger sequencing of MMACHC gene in amniotic fluid revealed that the fetus carried only one nonsense variant [NM_015506.2:c.609G>A (p.Trp203*)], which was inherited from the father. The mother delivered a healthy baby and the neonate did not show any symptoms or signs of combined methylmalonic acidemia and homocystinuria after birth., Conclusion: We present a case of prenatal diagnosis with parental exome sequencing, which successfully diagnosed the carrier status of the fetus and parents in a combined methylmalonic acidemia and homocystinuria family., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Procalcitonin (PCT) is a clinically useful biomarker for early diagnosis and subsequent management of sepsis. We evaluated the analytical performance of a new automated chemiluminescent immunoanalyzer-based procalcitonin assay, AdvanSure i3 PCT assay (LG Life Sciences, Korea) on an AdvanSure i3 (LG Life Sciences) and compared it to the Elecsys BRAHMS PCT assay (Roche, Switzerland) on a Cobas e801 (Roche). Analytical performance was performed for the precision, linearity, and method comparison with the Elecsys BRAHMS PCT assay by Clinical and Laboratory Standards Institute guidelines. Clinical evaluations were conducted using 87 residual samples from admitted patients with suspected infection. The patients were classified based on Sepsis-3 classification. The AdvanSure i3 PCT assay exhibited a CV <5.5% for between-run precision and <6.5% for within-laboratory precision. The assay was linear up to 80.32 µg/L ( r  = 0.990). Statistical analysis showed that the two assays yielded a good correlation ( r  = 0.996), with a weighted kappa value of 0.94. Median plasma PCT level was significantly different between the non-sepsis and sepsis groups ( p  < .001) and the non-sepsis and septic shock groups ( p  < .0018). The AdvanSure i3 PCT assay showed good analytical performance and correlation with the Elecsys BRAHMS PCT assay for the sepsis patients. This new assay can be used as a diagnostic early marker of sepsis in clinical laboratories.

Pseudomonas aeruginosa is a ubiquitous human pathogen that causes severe infections. Although antibiotics, such as tobramycin, are currently used for infection therapy, their antibacterial activity has resulted in the emergence of multiple antibiotic-resistant bacteria. The 6-gingerol analog, a structural derivative of the main component of ginger, is a quorum sensing (QS) inhibitor. However, it has a lower biofilm inhibitory activity than antibiotics and the possibility to cause toxicity in humans. Therefore, novel and more effective approaches for decreasing dosing concentration and increasing biofilm inhibitory activity are required to alleviate P. aeruginosa infections. In this study, a 6-gingerol analog was combined with tobramycin to treat P. aeruginosa infections. The combined treatment of 6-gingerol analog and tobramycin showed strong inhibitory activities on biofilm formation and the production of QS-related virulence factors of P. aeruginosa compared to single treatments. Furthermore, the combined treatment alleviated the infectivity of P. aeruginosa in an insect model using Tenebrio molitor larvae without inducing any cytotoxic effects in human lung epithelial cells. The 6-gingerol analog showed these inhibitory activities at much lower concentrations when used in combination with tobramycin. Adjuvant effects were observed through increased QS-disrupting processes rather than through antibacterial action. In particular, improved RhlR inactivation by this combination is a possible target for therapeutic development in LasR-independent chronic infections. Therefore, the combined treatment of 6-gingerol analog and tobramycin may be considered an effective method for treating P. aeruginosa infections. IMPORTANCE Pseudomonas aeruginosa is a pathogen that causes various infectious diseases through quorum-sensing regulation. Although antibiotics are mainly used to treat P. aeruginosa infections, they cause the emergence of resistant bacteria in humans. To compensate for the disadvantages of antibiotics and increase their effectiveness, natural products were used in combination with antibiotics in this study. We discovered that combined treatment with 6-gingerol analog from naturally-derived ginger substances and tobramycin resulted in more effective reductions of biofilm formation and virulence factor production in P. aeruginosa than single treatments. Our findings support the notion that when 6-gingerol analog is combined with tobramycin, the effects of the analog can be exerted at much lower concentrations. Furthermore, its improved LasR-independent RhlR inactivation may serve as a key target for therapeutic development in chronic infections. Therefore, the combined treatment of 6-gingerol analog and tobramycin is suggested as a novel alternative for treating P. aeruginosa infections.

Background: The efficacy of implantable cardioverter defibrillators (ICDs) for primary prevention is controversial in patients with nonischemic heart failure (HF). We evaluated the mortality and predictors of mortality in patients with prophylactic ICD implantation for ischemic and nonischemic HF., Methods: From 2008 to 2017, 1097 patients (667, nonischemic HF and 430, ischemic HF) who underwent prophylactic ICD implantation, were identified from the Korean National Health Insurance Service database. We used propensity score overlap weighting to correct the differences between two groups., Results: Those with ischemic HF were older (67.0 ± 10.1 vs 61.8 ± 14.2 years), more often male (71.4% vs 63.7%), and had more comorbidities than patients with nonischemic HF. During a median follow-up of 37.3 months (interquartile range [IQR], 14.2-53.8 months), all-cause mortality was higher in unweighted patients with ischemic HF than in those with nonischemic HF (10.9 vs 6.4 per 100 person-years; hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.38-2.20; P  < .001). However, after weighting, the annual all-cause mortality rate was similar in both groups (9.5 vs 8.8 per 100 person-years), with no significant difference in the risk of all-cause mortality (HR, 1.08; 95% CI, 0.68-1.71; P  = .755). Older age and chronic kidney disease were independent predictors of all-cause mortality in both groups. There was no significant difference in cardiac and noncardiac mortality between the weighted nonischemic and ischemic HF groups., Conclusions: The all-cause, cardiac, and noncardiac mortality rates were similar between patients with nonischemic and ischemic HF who underwent prophylactic ICD implantation., Competing Interests: Dr Boyoung Joung has served as a speaker for Bayer, BMS/Pfizer, Medtronic, and Daiichi‐Sankyo and received research funds from Medtronic and Abbott. No fees were directly or personally received. Younghyun Kang and Hyung‐Deuk Park are employees of Medtronic Korea. The other authors have nothing to declare., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Acute kidney injury (AKI) is a major contributor to in-hospital morbidity and mortality. Vancomycin, one of the most commonly used antibiotics in a clinical setting, is associated with AKI, with its incidence ranging up to 43%. Despite the high demand, few studies have investigated serum biomarkers to detect vancomycin-induced kidney injury (VIKI). Here, we evaluated the diagnostic value of nine candidate serum biomarkers for VIKI. A total of 23,182 cases referred for vancomycin concentration measurement from January 2018 to December 2019 were screened and 28 subjects with confirmed VIKI were enrolled (VIKI group). Age- and sex- matched control group consisted of 21 subjects who underwent vancomycin therapy without developing VIKI (non-VIKI group), and 23 healthy controls (HC group). The serum concentrations of clusterin, retinol binding protein 4 (RBP4), interleukin-18 (IL-18), tumor necrosis factor receptor 1 (TNF-R1), C-X-C motif chemokine ligand 10 (CXCL10), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, trefoil factor-3 (TFF3), and cystatin C were compared among the three groups, and their correlations with estimated glomerular filtration rate (eGFR) and diagnostic values for VIKI were assessed. All of the biomarkers except clusterin and RBP4 exhibited significant elevation in the VIKI group. Serum TFF3, cystatin C, TNF-R1, and osteopontin demonstrated an excellent diagnostic value for VIKI (TFF3, area under the curve (AUC) 0.932; cystatin C, AUC 0.917; TNF-R1, AUC 0.866; osteopontin, AUC 0.787); and except osteopontin, a strong negative correlation with eGFR (TFF3, r = -0.71; cystatin C, r = -0.70; TNF-R1, r = -0.60). IL-18, CXCL10, and NGAL showed weak correlation with eGFR and moderate diagnostic value for VIKI. This study tested multiple serum biomarkers for VIKI and showed that serum TFF3, cystatin C, TNF-R1, and osteopontin could efficiently discriminate VIKI patients. Further studies are warranted to clarify the diagnostic value of these biomarkers in VIKI.

Forward osmosis (FO) hybrid systems have the potential to simultaneously recover nutrients and water from wastewater. However, the lack of membranes with high permeability and selectivity has limited the development and scale-up of these hybrid systems. In this study, we fabricated a novel thin-film nanocomposite membrane featuring an interlayer of Ti 3 C 2 T x MXene intercalated with carbon nanotubes (M/C-TFNi). Owing to the enhanced confinement effect on interfacial degassing and increased amine monomer sorption by the interlayer, the resulting M/C-TFNi FO membrane has a greater degree of cross-linking and roughness. In comparison with the thin-film composite (TFC) membrane without an interlayered structure, the M/C-TFNi membrane attained a water flux that was four times higher and a lower specific salt flux. Notably, the M/C-TFNi membrane exhibited excellent concentration efficiency for real municipal wastewater and enhanced rejection of ammonia nitrogen, which breaks the permeability-selectivity upper bound. This study provides a new avenue for the rational design and development of high-performance FO membranes for environmental applications.

Membrane fouling occurs when the operating flux exceeds a certain point (i.e., critical flux). Critical flux has therefore been widely adopted to determine the initial operating flux in membrane bioreactor (MBR) processes. The flux steeping method currently used to measure the critical flux is time-consuming and uneconomical. This study was conducted to develop a novel approach for the evaluation of critical flux. Given that particle fouling is dominant during the initial fouling stage, we hypothesized that particle properties may be closely related to critical flux. A critical flux prediction model with an R 2 of 0.9 was therefore derived, which indicates that particle properties regulate critical flux. The results imply that most of the fouling potential during the early stages of operation is caused by SS, and that the formation of cakes that comprise large particles is the dominant fouling mechanism. The new method proposed in this study reduced the measurement cost and time to evaluate critical flux by 3.5-and 8 times, respectively, compared to the flux-stepping method. In terms of practical application, the applicability of the model equation was identified by system reliability analysis, which indicates that the system failure increases significantly as the standard deviation of the variables increases. This study demonstrated that the prediction of critical flux and system reliability can be achieved through particle characteristic measurement. A similar approach is expected to be employed in real MBR plants as an economical and convenient fouling control strategy to solve problems involving resource shortages., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

As the most widely used anionic surfactant, linear alkylbenzene sulfonate (LAS) requires biological alkane degradation when it is treated using an activated sludge (AS) process in a wastewater treatment plant because of its structural carboxylic unavailability. As consumption of LAS is gradually increasing, LAS loading into the WWTP is accordingly increasing. However, fewer studies have examined the involvement of the AS microbial community in the LAS degradation. In this study, metagenomic approaches were used to define microbiomes involved in LAS degradation in AS, with a particular focus on ω-hydroxylation. The abundance and diversity of alkane-degrading genes were investigated, and these genes were integrated with reconstructed metagenome-assembled genomes (MAGs). Additionally, the association of functional genes and MAGs with respect to LAS degradation was investigated. The results showed that alkB and cytochrome P450 genes were only shared within specific MAGs. Unique sets of genes with diverse abundances were detected in each sample. The MAGs with the alkB and cytochrome P450 genes were strongly associated with the other MAGs and involved in positive commensal interactions. The findings provided significant insights into how the AS microbiomes, which have continuously treated anionic surfactants for decades, potentially metabolize LAS and interact with commensal bacteria., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The prognostic implication of cardiac troponin I (cTnI) values for the determination of the magnitude or duration of cause-specific death risk is limited. We included consecutive patients with maximal cTnI values within 24 h of their emergency department visits. Multivariate analyses using variables selected by the Bayesian information criterion were performed to investigate the impact of cTnI on the event rate, time-dependent risk, and dose-dependent risk of cardiovascular or non-cardiovascular death within 360 days. There were 5472 (14.9%) all-cause deaths including 881 (2.4%) cardiovascular deaths and 4591 (12.5%) non-cardiovascular deaths. In patients with positive cTnI, defined as the ≥ 99th percentile of the upper normal limit, the cumulative risk of cardiac and non-cardiac death was 4.4- and 1.4-fold higher, respectively, than that of negative cTnI, respectively. In the competing risk analysis, positive cTnI was linked to 2.4- and 1.2-fold higher risks of cardiovascular and non-cardiovascular death, respectively. The cTnI value showed a positive relationship with the risk of both cardiovascular and non-cardiovascular deaths. In the time-dependent risk analysis, the excess risk of cardiovascular death was mostly evident in the first few weeks. Higher cTnI value was associated with an increased risk of both cardiovascular and non-cardiovascular death, especially which was in the early period., (© 2021. The Author(s).)

Presepsin has been proposed as an early indicator for diagnosis and prognosis in sepsis. We aimed to evaluate the prognostic accuracy of presepsin levels and additional value for identifying high-risk patients when taken together with the current sepsis criteria. This was a single-center, prospective, observational study of patients with suspected sepsis. The primary outcome was 28-day mortality. The prognostic performance of presepsin was evaluated by the area under the receiver operating characteristic curve (AUC), according to the sepsis definition using the Sequential Organ Failure Assessment (SOFA) score change (delta SOFA ≥ 2) and lactate level ≥ 2 mmol/L. A total of 755 patients were included. The AUC of presepsin for predicting 28-day mortality was 0.747. Presepsin showed adequate prognostic accuracy regardless of the delta SOFA score or lactate level. High presepsin levels (>755 pg/mL) showed an independent association with 28-day mortality (adjusted odds ratio: 5.17), and significant differences in mortality were observed, even in patients with non-sepsis low lactate level. Compared with a single criterion of the delta SOFA score or lactate, the addition of the high presepsin criterion significantly increased discrimination. Presepsin showed fair prognostic performance regardless of the clinical sepsis criteria. Complementary use of presepsin with the Sepsis-3 criteria may identify more high-risk septic patients and provide useful prognostic information.

Background: Total cholesterol concentration measurement is important in the diagnosis of dyslipidemia and evaluation of cardiovascular disease risk factors. Measurement reliability for obtaining an accurate total cholesterol concentration requires procedure standardization. We evaluated the standardization status for total cholesterol concentration measurement through Korean external quality assessment (EQA) data analysis., Methods: This study involved 1,670 laboratories that participated in the EQA of total cholesterol concentration measurements in 2019 for 32 products from different manufacturers. The target concentrations of three quality control (QC) materials (samples A, B, and C) were measured using the reference method and compared with EQA data. The performance criteria for total cholesterol concentration measurement were based on the National Cholesterol Education Program guidelines, with ±3% inaccuracy., Results: The target values and inaccuracies of the QC material based on the reference method measurements were 254.65±7.64, 108.30±3.25, and 256.29±7.69 mg/dL (6.59±0.20, 2.80±0.08, and 6.63±0.20 mmol/L) for samples A, B, and C, respectively. The performance criteria were not met in 42.7% laboratories for sample A, 68.4% of laboratories for sample B, and 38.0% laboratories for sample C., Conclusions: Despite significant efforts to accurately measure total cholesterol concentrations, further actions are needed for measurement standardization. Manufacturers reporting values that differ from target values should check calibrator traceability; additional efforts to accurately measure total cholesterol concentrations are required for laboratories that use products from these manufacturers.

To investigate how the seed microbial community structure affects the improvement of methanogenesis efficiency through direct interspecies electron transfer (DIET), a biomethane potential (BMP) test was conducted using sludge collected from a total of six anaerobic digesters. DIET-stimulating microbial populations were investigated by 16S rRNA gene sequence analysis. Correlations between microbial community composition and methane production performance by DIET were analyzed. The methane production rate increased under all conditions when granular activated carbon (GAC) was injected regardless of the inoculum type. However, redundancy analysis indicated a significant correlation between the inoculum microbial community and lag time. In a network analysis, Methanolinea species distributed in the inocula formed a single modularity with lag time, suggesting that the methanogens in the inocula might reduce the lag time of methanogenesis through DIET. Overall, this study revealed that the inoculum microbial community composition is an important factor affecting methane production efficiency by DIET., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study investigated the effects of particle transfer to the covers of aerosol samplers during transportation of wood dust and welding fume samples. Wood dust samples were collected in a sanding chamber using four sampler types: closed-face cassettes (CFC), CFC with Accu-CAP inserts, disposable inhalable samplers (DIS), and Institute of Occupational Medicine (IOM). Welding fumes were collected in a walk-in chamber using the same samplers, with Solu-Sert replacing Accu-CAP. The samples were divided into two groups, with one group transported by air and the other by land. They were returned in the same manner and analyzed gravimetrically for wood dust and chemically for welding fumes. For wood dust, IOM showed a significantly higher percentage of particles transferred to the covers compared with the other samplers regardless of the transportation mode (p < 0.0001; 64% by air and 15% by land), while other samplers showed less than or close to 10% (3.5-12%). When the percentages of particle transfer to the covers were compared between the air and land transportation, both IOM and CFC samples showed differences between modes of transportation, while others did not. For welding fumes, most samples (61% of samples for copper [Cu] and 76% of samples for manganese [Mn]) showed nondetectable amounts of the analyte on the covers. For all samplers, the particle transfer to the covers for both transportation modes ranged from 0.2-33% for Cu and less than 4.5% for Mn. Overall, this study confirms that particle transfer to sampler covers during transport highly depends upon the transportation mode and sampler type for wood dust, whereas particle transfer seems minimal for welding fumes. The findings of this study are based on two materials and limited sample sizes. Further investigation considering different industry types and tasks, particle size ranges, and materials might be necessary. Nevertheless, occupational professionals should account for this transfer when handling and analyzing samples in practice.

The incidence of vancomycin-associated acute kidney injury (VAKI) varies from 5-43%, and early detection of VAKI is important in deciding whether to discontinue nephrotoxic agents. Oxidative stress is the main mechanism of VAKI, and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been examined with respect to their involvement in ischemia/reperfusion damage in experimental animal models. In the current study, we assessed 5-HT and 5-HIAA as novel biomarkers for detecting VAKI in patients who have infections or compromised renal function, using a mass spectrometry-based metabolomics approach. We conducted amino acid profiling analysis and measurements of 5-HT and 5-HIAA using serum from subjects with VAKI ( n = 28) and non-VAKI control subjects ( n = 69), consisting of the infection subgroup ( n = 23), CKD subgroup ( n = 23), and healthy controls (HCs, n = 23). 5-HT was significantly lower in the VAKI group than in the non-VAKI groups, and the concentration of 5-HIAA and the ratio of 5-HIAA to 5-HT (5-HIAA/5-HT) showed higher values in the VAKI group. The infection subgroup presented a significantly greater 5-HIAA/5-HT ratio compared with the HC subgroup. Our study revealed that increased 5-HIAA/5-HT ratio has the potential to act as a VAKI surrogate marker, reflecting acute oxidative stress and inflammation.

Betulinic acid (BA) is a major constituent of Zizyphus seeds that have been long used as therapeutic agents for sleep-related issues in Asia. BA is a pentacyclic triterpenoid. It also possesses various anti-cancer and anti-inflammatory effects. Current commercially available sleep aids typically use GABAergic regulation, for which many studies are being actively conducted. However, few studies have focused on acetylcholine receptors that regulate wakefulness. In this study, we utilized BA as an antagonist of α3β4 nicotinic acetylcholine receptors (α3β4 nAChRs) known to regulate rapid-eye-movement (REM) sleep and wakefulness. Effects of BA on α3β4 nAChRs were concentration-dependent, reversible, voltage-independent, and non-competitive. Site-directed mutagenesis and molecular-docking studies confirmed the binding of BA at the molecular level and showed that the α3 subunit L257 and the β4 subunit I263 residues affected BA binding. These data demonstrate that BA can bind to a binding site different from the site for the receptor's ligand, acetylcholine (ACh). This suggests that BA may be an effective antagonist that is unaffected by large amounts of ACh released during wakefulness and REM sleep. Based on the above experimental results, BA is likely to be a therapeutically useful sleep aid and sedative.

Membrane bioreactors (MBRs) are considered a promising tool for resource recovery in wastewater treatment. Nevertheless, membrane fouling is an inevitable phenomenon that deteriorates the MBR performance. Although many studies have attempted to elucidate the effect of sludge characteristics on MBR fouling, they posed certain limitations. Most of the previous studies focused on the initial sludge or employ the results of short-term batch tests without long-term transmembrane pressure (TMP) profiles in the interpretation of fouling behaviors. This study was conducted considering these limitations to determine the sludge characteristics most closely related to long-term TMP profiles and to identify their role in fouling behaviors. In long-term TMP profiles, critical time (t c ; time to TMP jump) and fouling rates (the increase in the TMP slope) were used as fouling indexes, which were used to correlate with average values of sludge characteristics before and after experiments. According to the results, the concentration of the total soluble microbial product (SMP) and extracted extracellular polymeric substance (eEPS) in sludge significantly increased by 1.9 times and up to 28 times after experiment. The increase in the SMP and eEPS caused early TMP jumps and resulted in low-fouling rates by increasing particle size. Owing to the increase in the SMP and eEPS concentration, the origin of fouling potential was shifted from suspended solids to colloids and soluble materials. Fouling resistance caused by soluble material increased by up to 11.38 times., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Surgical treatment of tumors, epileptic foci or of vascular origin, requires a detailed individual pre-surgical workup and intra-operative surveillance of brain functions to minimize the risk of post-surgical neurological deficits and decline of quality of life. Most attention is attributed to language, motor functions, and perception. However, higher cognitive functions such as social cognition, personality, and the sense of self may be affected by brain surgery. To date, the precise localization and the network patterns of brain regions involved in such functions are not yet fully understood, making the assessment of risks of related post-surgical deficits difficult. It is in the interest of neurosurgeons to understand with which neural systems related to selfhood and personality they are interfering during surgery. Recent neuroscience research using virtual reality and clinical observations suggest that the insular cortex, medial prefrontal cortex, and temporo-parietal junction are important components of a neural system dedicated to self-consciousness based on multisensory bodily processing, including exteroceptive and interoceptive cues (bodily self-consciousness (BSC)). Here, we argue that combined extra- and intra-operative approaches using targeted cognitive testing, functional imaging and EEG, virtual reality, combined with multisensory stimulations, may contribute to the assessment of the BSC and related cognitive aspects. Although the usefulness of particular biomarkers, such as cardiac and respiratory signals linked to virtual reality, and of heartbeat evoked potentials as a surrogate marker for intactness of multisensory integration for intra-operative monitoring has to be proved, systemic and automatized testing of BSC in neurosurgical patients will improve future surgical outcome.

We recently reported 2,4,5-trimethylpyridin-3-ol with C(6)-azacyclonol, whose code name is BJ-1207, showing a promising anticancer activity by inhibiting NOX-derived ROS in A549 human lung cancer cells. The present study was focused on structural modification of the azacyclonol moiety of BJ-1207 to find a compound with better anticancer activity. Ten new compounds (3A-3J) were prepared and evaluated their inhibitory actions against proliferation of eighteen cancer cell lines as a primary screening. Among the ten derivatives of BJ-1207, the effects of compounds 3A and 3J on DU145 and PC-3, androgen-refractory cancer cell lines (ARPC), were greater than the parent compound, and compound 3A showed better activity than 3J. Antitumor activity of compound 3A was also observed in DU145-xenografted chorioallantoic membrane (CAM) tumor model. In addition, the ligand-based target prediction and molecular docking study using DeepZema® server showed compound 3A was a ligand to M3 muscarinic acetylcholine receptor (M3R) which is overexpressed in ARPC. Carbachol, a muscarinic receptor agonist, concentration dependently increased proliferation of DU145 in the absence of serum, and it also activated NADPH oxidase (NOX). The carbachol-induced proliferation and NOX activity was significantly blocked by compounds 3A in a concentration-dependent manner. This finding might become a new milestone in the development of pyridinol-based anti-cancer agents against ARPC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is increasingly used for immunosuppressive drug tests. However, most LC-MS/MS tests are laboratory-developed and their agreement is unknown in different Korean laboratories. This interlaboratory comparison study evaluated test reproducibility and identified potential error sources., Methods: Test samples containing three concentrations of tacrolimus, sirolimus, everolimus, cyclosporine, and mycophenolic acid were prepared by pooling surplus samples from patients undergoing routine therapeutic drug monitoring and tested in duplicate in the participating 10 clinical laboratories. Reconstitution and storage experiments were conducted for the commonly used commercial calibrator set. The robust estimators of reproducibility parameters were calculated. Spearman's rank correlation coefficient (rho, ρ) was used to evaluate the correlation between drugs. Multiple linear regression was used to determine whether the experimental conditions alter the calibration curves., Results: The reproducibility coefficient of variation exceeded 10% only for sirolimus concentrations 1 and 2 (10.8% and 12.5%, respectively) and everolimus concentrations 1 and 2 (12.3% and 11.4%, respectively). The percent difference values showed weak correlations between sirolimus and everolimus (ρ=0.334, P =0.175). The everolimus calibration curve slope was significantly altered after reconstitution following prolonged 5°C storage ( P =0.015 for 14 days; P =0.025 for 28 days); the expected differences at 6 ng/mL were 0.598% for 14 days and 0.384% for 28 days., Conclusions: LC-MS/MS test reproducibility for immunosuppressive drugs seems to be good in the Korean clinical laboratories. Continuous efforts are required to achieve test standardization and harmonization, especially for sirolimus and everolimus.

Nanofiltration (NF) with high water flux and precise separation performance with high Li + /Mg 2+ selectivity is ideal for lithium brine recovery. However, conventional polyamide-based commercial NF membranes are ineffective in lithium recovery processes due to their undesired Li + /Mg 2+ selectivity. In addition, they are constrained by the water permeance selectivity trade-off, which means that a highly permeable membrane often has lower selectivity. In this study, we developed a novel nonpolyamide NF membrane based on metal-coordinated structure, which exhibits simultaneously improved water permeance and Li + /Mg 2+ selectivity. Specifically, the optimized Cu- m -phenylenediamine (MPD) membrane demonstrated a high water permeance of 16.2 ± 2.7 LMH/bar and a high Li + /Mg 2+ selectivity of 8.0 ± 1.0, which surpassed the trade-off of permeance selectivity. Meanwhile, the existence of copper in the Cu-MPD membrane further enhanced anti-biofouling property and the metal-coordinated nanofiltration membrane possesses a pH-responsive property. Finally, a transport model based on the Nernst-Planck equations has been developed to fit the water flux and rejection of uncharged solutes to the experiments conducted. The model had a deviation below 2% for all experiments performed and suggested an average pore radius of 1.25 nm with a porosity of 21% for the Cu-MPD membrane. Overall, our study provides an exciting approach for fabricating a nonpolyamide high-performance nanofiltration membrane in the context of lithium recovery.

Biofouling is a major operational problem in the reverse osmosis (RO) process, affecting the membrane performance. Although sodium hypochlorite (NaOCl) is used to chemically clean the biofouled membranes, high concentrations of NaOCl cause morphological and chemical damage to the RO membrane. The objective of this study is to enhance chemical cleaning efficiency by combining with a dispersion agent (linoleic acid, LA) that does not harm the RO membrane, to overcome the disadvantages of NaOCl. Biofilm cells were initially dispersed with LA treatment and biofouled layers were subsequently cleaned using NaOCl at low concentration. The optimized combination resulted in 3.9-4.4 times higher flux recovery efficiency than that with individual treatments. Furthermore, the combination decreased the volume and thickness of the biofilm as well as the amount of extracellular polymeric substances. Taken together, the combined treatment of LA and NaOCl significantly improves RO biofouling control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

External quality assessment (EQA) is important for evaluating clinical laboratories and enhancing their testing quality. EQA schemes are variable; thus, it is crucial that the EQA organizers share their experiences to continuously improve the EQA scheme. The Korean Association of External Quality Assessment Service (KEQAS) has been the leading, authorized EQA institute for the standardization and quality management of laboratory testing in Korean medical institutions since 1976. The EQA scheme underwent a major change in 2016, and the number of EQA programs increased significantly since then. The key changes implemented in EQA scheme include a fully computerized assessment to accelerate feedback and unification of the testing and reporting methods. We provide an overview of the EQA schemes and performance evaluation criteria of the KEQAS and suggest directions for achieving the global harmonization of EQA.

Irritable bowel syndrome (IBS) is a chronic disease that causes abdominal pain and an imbalance of defecation patterns due to gastrointestinal dysfunction. The cause of IBS remains unclear, but intestinal-brain axis problems and neurotransmitters have been suggested as factors. In this study, chanoclavine, which has a ring structure similar to 5-hydroxytryptamine (5-HT), showed an interaction with the 5-HT 3A receptor to regulate IBS. Although its derivatives are known to be involved in neurotransmitter receptors, the molecular physiological mechanism of the interaction between chanoclavine and the 5-HT 3A receptor is unknown. Electrophysiological experiments were conducted using a two-electrode voltage-clamp analysis to observe the inhibitory effects of chanoclavine on Xenopus oocytes in which the h5-HT 3A receptor was expressed. The co-application of chanoclavine and 5-HT resulted in concentration-dependent, reversible, voltage-independent, and competitive inhibition. The 5-HT 3A response induced by 5-HT was blocked by chanoclavine with half-maximal inhibitory response concentration (IC 50 ) values of 107.2 µM. Docking studies suggested that chanoclavine was positioned close F130 and N138 in the 5-HT 3A receptor-binding site. The double mutation of F130A and N138A significantly attenuated the interaction of chanoclavine compared to a single mutation or the wild type. These data suggest that F130 and N138 are important sites for ligand binding and activity. Chanoclavine and ergonovine have different effects. Asparagine, the 130th amino acid sequence of the 5-HT 3A receptor, and phenylalanine, the 138th, are important in the role of binding chanoclavine, but ergonovine has no interaction with any amino acid sequence of the 5-HT 3A receptor. The results of the electrophysiological studies and of in silico simulation showed that chanoclavine has the potential to inhibit the hypergastric stimulation of the gut by inhibiting the stimulation of signal transduction through 5-HT 3A receptor stimulation. These findings suggest chanoclavine as a potential antiemetic agent for excessive gut stimulation and offer insight into the mechanisms of 5-HT 3A receptor inhibition.

Context.—: The clinical applications of point-of-care testing (POCT) are gradually increasing in many health care systems. Recently, POCT devices using molecular genetic method techniques have been developed. We need to examine clinical pathways to see where POCT can be applied to improve them., Objective.—: To introduce up-to-date POCT items and equipment and to provide the content that should be prepared for clinical application of POCT., Data Sources.—: Literature review based on PubMed searches containing the terms point-of-care testing, clinical chemistry, diagnostic hematology, and clinical microbiology., Conclusions.—: If medical resources are limited, POCT can help clinicians make quick medical decisions. As POCT technology improves and menus expand, areas where POCT can be applied will also increase. We need to understand the limitations of POCT so that it can be optimally used to improve patient management., Competing Interests: The author has no relevant financial interest in the products or companies described in this article.

Conductive materials can serve as biocatalysts during direct interspecies electron transfer for methanogenesis in anaerobic reactors. However, the mechanism promoting direct interspecies electron transfer in anaerobic reactors, particularly under environments in which diverse substrates and microorganisms coexist, remains to be elucidated from a scientific or an engineering point of view. Currently, many molecular microbiological approaches are employed to understand the fundamentals of this phenomenon. Here, the direct interspecies electron transfer mechanisms and relevant microorganisms identified to date using molecular microbiological methods were critically reviewed. Moreover, molecular microbiological methods for direct interspecies electron transfer used in previous studies and important findings thus revealed were analyzed. This review will help us better understand the phenomena of direct interspecies electron transfer using conductive materials and offer a framework for future molecular microbiological studies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Elevated cardiac troponin is not uncommon in patients visiting emergency department (ED) even without coronary artery disease, but its prognostic implication is not well understood in such patients., Methods: In this retrospective single-center registry, we investigated clinical outcome of patients visiting ED without documented coronary artery disease. Patients were categorized according to the maximal value of Siemens ADVIA Centaur TnI-Ultra assay (TnI) within 24 h after visit. Primary endpoint was 180-day all-cause death that included cardiac and non-cardiac death., Results: A total of 35,205 patients with median age 61 years and male gender 54.7% were included. Below the lowest level of detection (LOD) (≤0.006 ng/mL), between LOD and assay-specific <99th percentile (0.007-0.039 ng/mL), below median of ≥99th percentile (0.040-0.149 ng/mL), and above median of ≥99th percentile (≥0.150 ng/mL) TnI were found in 18,502 (52.6%), 11,338 (32.2%), 3,029 (8.6%), and 2,336 (6.6%) patients. In the 180-day follow-up period, 4,341 (12.3%) all-cause death including 694 (2.0%) cardiovascular death and 3,647 (10.4%) non-cardiovascular death developed. The risks of all-cause, cardiovascular, and non-cardiovascular death increased across higher TnI strata (hazard ratio [HR]=1.3 to 2.4; 2.0 to 9.3; 1.3 to 1.7; p<0.001, all). Analyses of multivariate models showed consistent results., Conclusions: In patients visiting ED, elevated TnI was associated with higher risk of 180-day cardiovascular and non-cardiovascular death. Patients with elevated TnI may need additional evaluation or careful follow-up even without primary diagnosis of coronary artery disease., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

A membrane bioreactor (MBR) integrates process such as membrane filtration and biological treatment of activated sludge. However, organic, inorganic and biological matters cause membrane fouling, which seriously affects membrane performance. The goal of this study was to evaluate the biofouling inhibition capacity of raffinose during the MBR process. The results showed that 0-1,000 μM raffinose significantly reduced the formation of the P. aeruginosa and S. aureus co-culture biofilm by about 25-52 % in a concentration-dependent manner. In addition, the effect of raffinose on the microfiltration membrane biofilm was tested in a flow reactor and lab-scale MBR unit. The results showed that the co-culture biofilm and transmembrane pressure were decreased by raffinose treatment compared to those by furanone C-30 treatment. These results clearly demonstrated that raffinose, broad-spectrum biofilm inhibitor, inhibits biofilm formation in mixed cultures and could be used to mitigate biofouling in MBR processes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bacterial biofilm formation causes serious problems in various fields of medical, clinical, and industrial settings. Antibiotics and biocide treatments are typical methods used to remove bacterial biofilms, but biofilms are difficult to remove effectively from surfaces due to their increased resistance. An alternative approach to treatment with antimicrobial agents is using biofilm inhibitors that regulate biofilm development without inhibiting bacterial growth. In the present study, we found that linoleic acid (LA), a plant unsaturated fatty acid, inhibits biofilm formation under static and continuous conditions without inhibiting the growth of Pseudomonas aeruginosa. LA also influenced the bacterial motility, extracellular polymeric substance production, and biofilm dispersion by decreasing the intracellular cyclic diguanylate concentration through increased phosphodiesterase activity. Furthermore, quantitative gene expression analysis demonstrated that LA induced the expression of genes associated with diffusible signaling factor-mediated quorum sensing that can inhibit or induce the dispersion of P. aeruginosa biofilms. These results suggest that LA is functionally and structurally similar to a P. aeruginosa diffusible signaling factor (cis-2-decenoic acid) and, in turn, act as an agonist molecule in biofilm dispersion., (© 2020 Wiley Periodicals LLC.)

Despite the importance of microbial communities in ecosystem functions, the mechanisms underlying the assembly of rare taxa over time are poorly understood. It remains largely unknown whether rare taxa exhibit similar assembly processes to common taxa in local communities. We herein retrieved the 16S rRNA sequences of bacteria collected bimonthly for 2 years from the Pohang wastewater treatment plant. The transient-rare taxa showed different abundance distributions from the common taxa. Transient-rare taxon assemblages also exhibited higher temporal variations than common taxon assemblages, suggesting the distinct ecological patterns of the two assemblages. A multivariate analysis revealed that environmental parameters accounted for 25.3 and 61.6% of temporal variations in the transient-rare and common taxon assemblages, respectively. The fitting of all observed taxa to a neutral community model revealed that 96.4% of the transient-rare taxa (relative abundance, 71.4%) and 73.3% of the common taxa (relative abundance, 45.6%) followed the model, suggesting that stochastic mechanisms were more important than deterministic ones in the assembly of the transient-rare taxa. Collectively, the present results indicate that the transient-rare bacterial taxa at the Pohang wastewater treatment plant differed from the common taxa in ecological patterns, suggesting that dispersal is a key process in their assembly.

The Barricor tube (Becton Dickinson [BD], Sunnyvale, CA, USA) was recently developed to mechanically separate plasma by increasing the centrifugation rate. We compared the Barricor tube with existing serum- and plasma-based tubes based on 35 biochemical analytes and preanalytical turnaround time (TAT). Blood samples were collected from 30 healthy volunteers in a Barricor tube, serum separating tube (SST, Vacutainer SST II Tube 8.5 mL, #368972; BD), or plasma separating tube (PST, Vacutainer PST Tube 8.0 mL, #367964; BD) in random order. Next, 27 chemistry analytes, six immunochemistry analytes, and two cardiac markers were compared using Passing-Bablok regression and the Bland-Altman method. Preanalytical TAT was measured for each tube. The Barricor tube exhibited bias exceeding the desirable limit for nine and four analytes compared with the SST and PST, respectively. The Barricor tube lactate dehydrogenase value showed a bias of -10.29% and -9.86% compared with that of the SST and PST, respectively. The preanalytical TAT of Barricor tube was 8.8 minutes, which was the shortest among the three tubes. The clinical performance of the Barricor tube was equivalent to that of the SST and PST for most analytes, with an apparent advantage in preanalytical TAT. When using the Barricor tube, the reference range needs to be changed for some analytes that exceed the desirable bias limit.

The separation properties of polyamide reverse osmosis and nanofiltration membranes, widely applied for desalination and water reuse, are constrained by the permeability-selectivity upper bound. Although thin-film nanocomposite (TFN) membranes incorporating nanomaterials exhibit enhanced water permeance, their rejection is only moderately improved or even impaired due to agglomeration of nanomaterials and formation of defects. A novel type of TFN membranes featuring an interlayer of nanomaterials (TFNi) has emerged in recent years. These novel TFNi membranes show extraordinary improvement in water flux (e.g., up to an order of magnitude enhancement) along with better selectivity. Such enhancements can be achieved by a wide selection of nanomaterials, ranging from nanoparticles, one-/two-dimensional materials, to interfacial coatings. The use of nanostructured interlayers not only improves the formation of polyamide rejection layers but also provides an optimized water transport path, which enables TFNi membranes to potentially overcome the longstanding trade-off between membrane permeability and selectivity. Furthermore, TFNi membranes can potentially enhance the removal of heavy metals and micropollutants, which is critical for many environmental applications. This review critically examines the recent developments of TFNi membranes and discusses the underlying mechanisms and design criteria. Their potential environmental applications are also highlighted.

Background: The prognostic ability of cardiac troponin I (TnI) has been demonstrated in general populations and among cardiovascular disease patients, but it has not been evaluated in cancer patients., Hypothesis: This study assumes to have the prognostic ability of cardiac troponin in cancer patients visiting the emergency department., Methods: Cancer patients visiting the emergency department were enrolled in this retrospective cohort study. Patients with previously known coronary artery disease or clinically indicated coronary angiography were not included. The maximal value from Siemens ADVIA Centaur troponin I Ultra assay within 24 hours was assessed. The primary endpoint was 180-day all-cause death, including cardiovascular and noncardiovascular death., Results: A total of 9135 cancer patients (mean age: 63 years, male gender: 60%) were enrolled. Lowest (0.006 ng/mL), assay-specific <99th % (0.007-0.039 ng/mL), below median ≥ 99th % (0.040-0.129 ng/mL), and above median ≥ 99th % (≥0.130 ng/mL) TnI were found in 4487 (49.1%), 3158 (34.6%), 852 (9.3%), and 638 (7.0%) patients, respectively. There was 3192 (34.9%) all-cause deaths including 137 (1.5%) cardiovascular and 3047 (33.4%) noncardiovascular deaths in the 180-day follow-up period. The risks of all-cause, cardiovascular, and noncardiovascular death increased across higher TnI strata (hazard ratio [HR] = 1.3-2.9; 2.1-9.3; 1.3-1.8; P < .001, all). These findings were consistent within clinical subgroups including solid and hematologic cancers., Conclusions: Cancer patients visiting the emergency department with elevated troponin I were at increased risk of 180-day death. Cancer patients with elevated TnI may need additional evaluation or careful follow-up even without cardiovascular disease diagnosis., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Teicoplanin is used to treat serious gram-positive infections. Optimal teicoplanin trough levels are considered to be ≥ 10 μg/mL. Despite its wide use in various clinical settings, data on teicoplanin trough level in pediatric patients are limited. Therefore, the aim of this study was to investigate the therapeutic drug level monitoring of teicoplanin in Korean pediatric patients, including those with impaired renal function., Methods: A retrospective study was performed in pediatric patients (age ≤ 18 years old) who received teicoplanin from September 2014 to April 2018. The regimen included a loading dose of 10 mg/kg/dose at 12 hours' interval three times in a row, and a maintenance dose of 10 mg/kg/dose commenced at 24 hours of interval after the loading dose, with a maximum of 400 mg/dose, respectively. The first therapeutic drug levels were measured. Distribution and characteristics of trough levels in patients with decreased renal function and those with bacteremia were also assessed., Results: A total of 187 trough levels were collected from 143 patients. Hematologic and oncologic diseases were the most common underlying diseases (83.2%, n = 119). One hundred eighty trough levels were first measured, and their median value was 16.2 μg/mL (range, 2.3-100 μg/mL) and the median interval between initial teicoplanin injection and 1st trough level was 96.5 hours (range 47.6-179.3 hours). Lower steady-state levels were observed in younger age group (median, 13.5 vs. 18.0 μg/mL, P = 0.038). Median trough levels were higher in patients with decreased renal functions ( P < 0.001). In addition, among eight with gram-positive bacteremia, seven of them had a favorable outcome., Conclusion: This study provides additive information on trough level monitoring of teicoplanin in children with impaired renal function and treatment effect in patients with gram-positive bacteremia. Careful monitoring for steady state trough levels of teicoplanin is warranted., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

In this study, Cudrania tricuspidata (CT) containing abundant phytochemicals, such as xanthones and flavonoids, was evaluated as an additive to fortify the functionality and organoleptic quality of fermented milk. The physicochemical, functional, and sensory properties of fermented milk supplemented with different concentrations of CT powder were investigated. Increasing amounts of CT powder elevated the malic acid concentration, increasing the total acidity and decreasing the pH of fermented milk supplemented with CT powder. The viable cell count and free sugar contents of fermented milk indicated that supplementing with CT powder improved lactic acid fermentation slightly. The color of fermented milk supplemented with CT powder was darker, redder, yellower, and more pleasing than the control fermented milk. The total phenolic and flavonoid contents of fermented milk supplemented with CT powder rose as the concentration of supplemented CT powder increased, resulting in enhanced antioxidant and antimutagenic activities. The CT powder improved the functionality of the fermented milk; still, at 2% or more, it had some unfavorable sensory properties, such as sourness, taste, and texture, which reduced the overall consumer preference. Therefore, a CT powder concentration of 0.5% or 1% may be acceptable to consumers.

The Muscat Bailey A (MBA) grape, one of the most prominent grape cultivars in Korea, contains considerable amounts of monoterpene alcohols that have very low odor thresholds and significantly affect the perception of wine aroma. To develop a potential wine starter for Korean MBA wine, nine types of non- Saccharomyces yeasts were isolated from various Korean food materials, including nuruk , Sémillon grapes, persimmons, and Muscat Bailey A grapes, and their physiological, biochemical, and enzymatic properties were investigated and compared to the conventional wine fermentation strain, Saccharomyces cerevisiae W-3. Through API ZYM analysis, Wickerhamomyces anomalus JK04, Hanseniaspora vineae S7, Hanseniaspora uvarum S8, Candida railenensis S18, and Metschnikowia pulcherrima S36 were revealed to have β-glucosidase activity. Their activities were quantified by culturing in growth medium composed of different carbon sources: 2% glucose, 1% glucose + 1% cellobiose, and 2% cellobiose. W. anomalus JK04 and M. pulcherrima S36 showed the highest β-glucosidase activities in all growth media; thus, they were selected and utilized for MBA wine fermentation. MBA wines co-fermented with non- Saccharomyces yeasts ( W. anomalus JK04 or M. pulcherrima S36) and S. cerevisiae W-3 showed significantly increased levels of linalool, citronellol, and geraniol compared to MBA wine fermented with S. cerevisiae W-3 (control). In a sensory evaluation, the flavor, taste, and overall preference scores of the co-fermented wines were higher than those for the control wine, suggesting that W. anomalus JK04 and M. pulcherrima S36 are favorable wine starters for improving Korean MBA wine quality.

Vertically aligned carbon nanotube (VACNT) membranes have attracted significant attention for water purification owing to their ultra-high water permeability and antibacterial properties. In this paper, we critically review the recent progresses in the synthesis of VACNT arrays and fabrication of VACNT membrane methods, with particular emphasis on improving water permeability and anti-biofouling properties. Furthermore, potential applications of VACNT membranes other than water purification (e.g., conductive membranes, electrodes in proton exchange membrane fuel cells, and solar electricity-water generators) have been introduced. Finally, future outlooks are provided to overcome the limitations of commercialization and desalination currently faced by VACNT membranes. This review will be useful to researchers in the broader scientific community as it discusses current and new trends regarding the development of VACNT membranes as well as their potential applications.

Whereas impaired multisensory processing of bodily stimuli and distorted body representation are well-established in various chronic pain disorders, such research has focused on exteroceptive bodily cues and neglected bodily signals from the inside of the body (or interoceptive signals). Extending existing basic and clinical research, we investigated for the first time interoception and its neurophysiological correlates in patients with complex regional pain syndrome (CRPS). In three different experiments, including a total of 36 patients with CRPS and 42 aged-gender matched healthy controls, we measured interoceptive sensitivity (heart beat counting task, HBC) and neural responses to heartbeats (heartbeat evoked potentials, HEPs). As hypothesized, we observed reduced sensitivity in perceiving interoceptive bodily stimuli, i.e. their heartbeat, in two independent samples of CRPS patients (studies 1 and 2). Moreover, the cortical processing of their heartbeat, i.e. the HEP, was reduced compared to controls (study 3) and reduced interoceptive sensitivity and HEPs were related to CRPS patients' motor impairment and pain duration. By providing consistent evidence for impaired processing of interoceptive bodily cues in CRPS, this study shows that the perceptual changes occurring in chronic pain include signals originating from the visceral organs, suggesting changes in the neural body representation, that includes next to exteroceptive, also interoceptive bodily signals. By showing that impaired interoceptive processing is associated with clinical symptoms, our findings also encourage the use of interoceptive-related information in future rehabilitation for chronic pain., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Pseudomonas aeruginosa ( P. aeruginosa ) is an opportunistic human pathogen that forms biofilms and produces virulence factors via quorum sensing (QS). Blocking the QS system in P. aeruginosa is an excellent strategy to reduce biofilm formation and the production of virulence factors. RhlR plays an essential role in the QS system of P. aeruginosa . We synthesized 55 analogues based on the chemical structure of 4-gingerol and evaluated their RhlR inhibitory activities using the cell-based reporter strain assay. Comprehensive structure-activity relationship studies identified the alkynyl ketone 30 as the most potent RhlR antagonist. This compound displayed selective RhlR antagonism over LasR and PqsR, strong inhibition of biofilm formation, and reduced production of virulence factors in P. aeruginosa . Furthermore, the survival rate of Tenebrio molitor larvae treated with 30 in vivo greatly improved. Therefore, compound 30 , a pure RhlR antagonist, can be utilized for developing QS-modulating molecules in the control of P. aeruginosa infections.

The draft genome sequence of Pseudanabaena yagii GIHE-NHR1, a filamentous cyanobacterium, is reported here. Comparative genome analysis suggests that this strain can produce an odor-causing compound (2-methylisoborneol) in water. The genome information is expected to improve the understanding of the putative 2-methylisoborneol production by the bacterium., (Copyright © 2020 Jeong et al.)

In this study, a laboratory-scale acidogenic dynamic membrane bioreactor (DMBR) was operated with or without alginate immobilization under various hydraulic retention times. The interactions between biofilm formation, metabolic flux and predicted functional genes were investigated in the DMBR. Regardless of the alginate immobilization, hydrogen yield was increased after biofilm was formed on a supporting material. Metabolic flux shifts from homoacetogenic to hydrogenic pathways along with biofilm formation was confirmed by flux balance analysis for metabolites. KEGG ortholog count prediction of functional genes from microbial consortia using bioinformatics package (PICRUSt). Predicted enzymes showed similar levels of functional gene expression regardless of the immobilization status. PICRUSt result showed strong evidence of the functional relationship among hydrogen production, biofilm formation, and metabolic pathway. Taken together, this study provides to estimate characteristics of biofilm formation changes and to better understand the microbial metabolism of DMBR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Advanced oxidation processes have gained significant attention for treating tetracycline (TC) and oxytetracycline (OTC), however, their oxidation using the photo-Fenton process has not been sufficiently studied. Although degradations of TC and OTC were enhanced by increasing H 2 O 2 and Fe 2+ within the ranges investigated (H 2 O 2  = 20-50 mg/L and Fe = 1-10 mg/L) under UV irradiation, further experiments for the photo-Fenton process were conducted with 20 mg/L of H 2 O 2 and 5 mg/L of Fe 2+ to balance efficiency and cost. The photo-Fenton process (UV/H 2 O 2 /Fe 2+ ) was shown to be more effective to remove TC and OTC than H 2 O 2 , ultraviolet (UV), and UV/H 2 O 2 at the same doses of oxidants. Inorganic anions and cations were shown to inhibit the degradation of TC and OTC during the photo-Fenton process, in the following order: HPO 4 2-  > HCO 3 -  ≫ SO 4 2-  > Cl - and Cu 2+ ≫ Ca 2+  > Na + . The TC and OTC degradation are generally improved by increasing pH, which is opposite to the k pCBA,obs values, caused by increasing the deprotonation degree of TC and OTC. Four and nine transformation products of TC and OTC, respectively, were detected over the treatment period. Among the transformation products, m/z 443.14 (C 22 H 22 N 2 O 8 ) formed during TC degradation, and m/z 433.16 (C 20 H 20 N 2 O 9 ) and m/z 415.15 (C 20 H 18 N 2 O 8 ) formed during OTC degradation, were reported for the first time. Vibrio fischeri toxicity assessment indicated that the inhibition ratio was decreased with a decreasing TC concentration, while, OTC transformation lead to higher toxicity. The product (m/z 477.15b) was determined to be the compound causing toxicity during degradation of OTC by using the quantitative structure activity relationship (QSAR). This toxic transformation product caused higher inhibition ratios than its parental compound (OTC), but its further oxidization resulted in decreasing the inhibition ratios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The draft genome sequence of Raphidiopsis ( Cylindrospermopsis ) raciborskii strain GIHE 2018, a filamentous nitrogen-fixing and potentially harmful cyanobacterium, is reported here. This is the first strain isolated from a shallow freshwater pond in South Korea. This information is expected to improve our understanding of the phylogeography of this species., (Copyright © 2020 Jeong et al.)

Voluntary action is a fundamental element of self-consciousness. The readiness potential (RP), a slow drift of neural activity preceding self-initiated movement, has been suggested to reflect neural processes underlying the preparation of voluntary action; yet more than fifty years after its introduction, interpretation of the RP remains controversial. Based on previous research showing that internal bodily signals affect sensory processing and ongoing neural activity, we here investigated the potential role of interoceptive signals in voluntary action and the RP. We report that (1) participants initiate voluntary actions more frequently during expiration, (2) this respiration-action coupling is absent during externally triggered actions, and (3) the RP amplitude is modulated depending on the respiratory phase. Our findings demonstrate that voluntary action is coupled with the respiratory system and further suggest that the RP is associated with fluctuations of ongoing neural activity that are driven by the involuntary and cyclic motor act of breathing.

To understand the effect of inoculum concentration on direct interspecies electron transfer (DIET) for methanogenesis, batch-type anaerobic bioreactors with different inoculum concentrations were operated with and without supplemented granular activated carbon (GAC). With decrease in inoculum concentration, GAC-supplemented bioreactors showed faster methane production rates and reduced lag times. Geobacter species were specifically enriched on the GAC surfaces under lower inoculum concentration conditions. Together, the relative abundance of aceticlastic methanogens (competitors of Geobacter species for acetate) gradually decreased when the inoculum concentration increased. These results suggested that the specific enrichment of Geobacter species by outcompeting with aceticlastic methanogens through low inoculum concentrations on GAC surfaces accelerated methanogenesis by DIET via GAC in anaerobic bioreactors. Taken together, the results of this study suggested that inoculum concentration is an important factor in stimulating DIET for methane production., (Copyright © 2019 Elsevier Ltd. All rights reserved.)