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Natural hydroxyapatite (HA), derived from waste bones of several animal species, has received much attention as a material for bone grafts and fillers and has a role as a coating for metal implants because of its biocompatibility and non-toxicity. To investigate the applicability of HA derived from waste bones of novel animal sources, the biocompatibility and toxicity of a poly-L-lactic acid (PLA)-based composite containing HA derived from the backbone of the dolphin Neophocaena asiaeorientalis (HANA) were examined in Sprague-Dawley (SD) rats. HANA powder showed X-ray diffraction peak patterns that corresponded to those of standard HA. Among five composites prepared from different combinations of PLA and HANA (7:3, 6:4, 5:5, 4:6, and 3:7), a PLA/HANA composite manufactured with a 6:4 PLA:HANA ratio had high surface roughness (453 nm), 10.3 N of maximum load, and 451.9 MPa of module elasticity. After implantation in the subcutaneous region of SD rats for 8 weeks, the amount of confluent, aggregated structures of multilayered cells on the PLA/HANA implant surface was greater than that on the PLA surface, although both implants were completely covered with adhesive cells. During the implant period, the initial intact form of the PLA/HANA composite broke into small fragments with few inflammatory cells in the contact region and no indication of significant toxicity. Taken together, the results suggest that HANA may have good biocompatibility and be non-toxic as it did not induce an immune response in SD rats. [ABSTRACT FROM AUTHOR]

• 3D textile was applied to sensor to amplify the piezoresistive for the first time. • A 3D textile with monofilament acted as the transmitter to amplify the sensitivity. • The sensitivity can be adjusted by the length and density of the monofilament. • The wearable sensor can be attached the body to detect both bio-signals and motions. • Not only could simple pressing action be detected, but so could movement in four directions. Environmental issues have led to increasing interest in the use of biomass materials to make wearable sensors; cellulose is an environmentally-friendly material that has attracted particularly substantial attention. This study is the first to achieve amplified piezoresistive properties by applying a 3D textile structure to a sensor made of carbonized cellulose fabric (CCF). By using the pre-strained monofilament of 3D textile as a pressure transmitter, the local strain in the CCF can be increased to enlarge the contact area between the CCF fibers, which in turn improves the sensitivity by 9.6 times (32.13 kPa−1) at the same pressure (3.35 kPa−1). The results showed that large joint motions (finger and knee joint motion, gait) and bio-signals (wrist pulse, speaking, breathing, etc.) could be monitored in real time with excellent sensitivity. Further, different neck movements occurring in four directions could be detected through a 4-way sensor that utilizes compression behavior, which varies based on the difference in monofilament length and density of the four different 3D textiles. All collected information can be transmitted to the user's smartphone through the Bluetooth module, which indicates that the sensor is suitable for implementations in healthcare monitoring. The proposed sensor can both enable novel applications of 3D textiles as well as provide a convenient and cost-effective approach. [ABSTRACT FROM AUTHOR]

Composite-based piezoelectric devices have been widely investigated to realize a semi-permanent power supplier or self-powered sensors with high flexibility; however, their working temperatures are mostly restricted below 200 °C. Herein, we report high-temperature and flexible composite-based piezoelectric energy harvesters (f-PEHs) comprising lead-free (K,Na)NbO 3 (KNN)-based ceramic dispersants and polyimide matrix. The KNN-based ceramics with different BiScO 3 (BS) compositions of 0.0025 and 0.01 were synthesized via a solid-state reaction and characterized under high-temperature conditions. Thereafter, the output voltage, current signals, and effective power of f-PEHs with 0.0025BS- and 0.01BS-doped KNN-based particles were measured at the temperature range from room temperature (RT) to 300 °C. The 0.0025BS KNN-adopted f-PEH not only generated 130% higher output voltage (∼4 V) and 137% higher current (∼0.24 μA) than the device with 0.01BS-doped KNN at RT, but also has superior electrical outputs compared to those harvested from the 0.01BS KNN-adopted f-PEH over all temperature ranges. These measurement results corresponded well with the trend of change in piezoelectric voltage constants and piezoelectric figure of merit characterized from ceramic discs, respectively. Moreover, theoretical and quantitative analyses using finite element method simulations proved that 0.0025BS is more suitable for the fabrication of high-temperature f-PEH compared to 0.01BS. This work can serve as a guide for developing a fully flexible and high-temperature workable f-PEH to realize self-powered sensor systems in high-temperature environments. [Display omitted] • High-temperature workable flexible piezoelectric energy harvesters (f-PEHs) were fabricated using piezo-ceramic and polyimide. • Temperature-dependent piezoelectric properties of (K,Na)NbO 3 -based ceramics were characterized under high-temperature. • A fabricated energy harvester generated an output voltage of ∼4 V and a current of ∼0.24 μA under repeated bendings. • A fabricated energy harvester exhibits exceptional high-temperature stability over the temperature range from 30 to 300 °C. [ABSTRACT FROM AUTHOR]

Abstract: Titanium carbide (TiC) particles have been coated with nickel (Ni) particles to increase compatibility between the TiC particles and the metal matrix based on Ni, leading to the improvement in the dispersion of TiC particles into a molten matrix, as functions of the potential hydrogen (pH) of TiC suspension, and the heat-treatment condition. The TiC particles were dispersed into the aqueous solution with various pH values, and then nickel nitrate (Ni(NO3)2) as a Ni precursor was added at the TiC suspension. As the pH is increased the content of Ni phase on the surface of TiC particle is increased, due to the increment of attractive force between the TiC particle and the Ni ion by the augmentation of negative value on the surface of TiC particle. The Ni-coated TiC particles heat treated at 500°C under H2 atmosphere indicate the TiC and Ni phases only, whereas those heat treated at 1000°C under Ar atmosphere show a titanium oxide (TiO2) with the TiC and Ni phases, which is resulted from the oxidation of TiC particle by oxygen contained in Ar gas. The dispersibility of TiC particles into a molten metal would be improved through the coating of Ni particles (or phase), inducing the improvement and reliability of mechanical properties. [Copyright &y& Elsevier]

[Display omitted] • Cu 1- x Ni x @C NPs were synthesized by electric explosion of wire in CH 4 gas. • Carbon thickness and crystallinity could be tuned using Cu and Ni composition. • Thermal oxidation of Cu 1- x Ni x @C NPs was related to burn-off of carbon shells. • Electrical resistivity of the conductive film was mapped according to Ni content. • High temperature oxidation stability increased with increasing Ni content. In this paper, an efficient fabrication route is presented for carbon-coated Cu-Ni alloy nanoparticles (Cu 1- x Ni x @C NPs; x = 0–1.0) by means of electrical wire explosion under methane gas. The Cu-Ni binary system, which is considered to be an ideal isomorphous system, has carbon growth controllable by tuning the atomic fraction of Cu and Ni with largely different carbon solubility. As the Ni content increases, the average particle size and carbon layer thickness increase. It is notable that the carbon layer is very thin, <2 nm, regardless of the core size for pure Cu@C NPs. On the other hand, as the Ni content increases, the particle size dependence of the carbon-layer thickness becomes significant and the carbon layer is obviously tunable from amorphous to crystalline form. The high-temperature oxidation stability of Cu 1- x Ni x @C NPs is enhanced with increasing Ni content due to the higher thermal stability of carbon layers with greater thickness and high crystallinity. The conductive films were prepared using screen-printing of paste containing Cu 1- x Ni x @C NPs and the electrical resistivity was mapped according to the Ni content. The temperature stability of the sheet resistance and activation energy of oxidation for the conductive films increase with increasing Ni content. [ABSTRACT FROM AUTHOR]

Dermal absorption of chemicals is a key factor in risk assessment. This study investigated the effects of different amounts of application on dermal absorption and suggested an appropriate application dose for proper dermal absorption. Caffeine and testosterone were chosen as test compounds. An in vitro dermal absorption test was performed using a Franz diffusion cell. Different amounts (5, 10, 25, and 50 mg (or µL)/cm2) of semisolid (cream) and liquid (solution) formulations containing 1% caffeine and 0.1% testosterone were applied to rat and minipig (Micropig®) skins. After 24 h, the concentrations of both compounds remaining on the skin surface and in the stratum corneum, dermis and epidermis, and receptor fluid were determined using LC-MS / MS or HPLC. Dermal absorption of both compounds decreased with increasing amounts of application in both skin types (rat and minipig) and formulations (cream and solution). Especially, dermal absorptions (%) of both compounds at 50 mg (or µL)/cm2 was significantly lower compared to 5 or 10 mg (or µL)/cm2 in both rat and minipig skins. Therefore, a low dose (5 or 10 mg (or µL)/cm2) of the formulation should be applied to obtain conservative dermal absorption. [ABSTRACT FROM AUTHOR]

Self-powered motion sensors have drawn many attentions for the last decade because it can be usefully applied to not only smart clothing and biomedical applications but also future remote controlling robotics systems. In this study, we develop a ceramic–polymer hybrid lead-free piezoelectric composite-based device to fabricate excellent flexible energy harvesters and kinetic motion sensing gloves. With the use of a composite composed of (K,Na)NbO 3 (KNN) piezoelectric particles and poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] matrix, the fabricated flexible energy harvester generates an open-circuit voltage of ~5 V and short-circuit current of ~1 μA under mechanical bending deformations. Moreover, the advantages of the P(VDF-TrFE) matrix for piezoelectric composite-based devices are validated by the results of the finite element method (FEM) simulation. Based on the hybrid piezoelectric composite, stable and reliable self-powered kinetic motion sensors are fabricated to monitor tiny biomechanical motions, i.e., the angles of finger hinges and various hand gestures. Our development successfully indicates that the hybrid lead-free piezoelectric composite can be applied to the active component of self-powered kinetic sensors for future low-power electronic motion detector. [Display omitted] ● Hybrid piezoelectric composite was fabricated by (K 0.5 Na 0.5)NbO 3 particles and P(VDF-TrFE). ● The flexible composite energy harvester generated ~5 V and ~1 μA under bending deformations. ● Monitoring human gesture was demonstrated by composite-based sensor onto a human finger. ● Self-powered kinetic motion sensor was used for detecting tiny biomechanical movements. [ABSTRACT FROM AUTHOR]

• Aligned BaTiO 3 nanotube arrays is vertically grown by electrochemical anodization. • High-performance piezoelectric property of a single BaTiO 3 nanotube is evaluated. • BaTiO 3 nanotube arrays-based flexible energy harvester is fabricated and analyzed. • Finite element analysis verifies the piezoelectricity of BaTiO 3 nanotube arrays. Synthesis approaches for diverse morphologies of 1D piezoelectric ceramic nanomaterials are still challenging to investigate nanoscale properties and applications. In this work, we demonstrated a vertically grown barium titanate (BaTiO 3 ; BT) nanotube (BT NT) arrays fabricated using optimized electrochemical anodization and hydrothermal reaction. The centimeter-scale synthesized BT NT arrays with a high aspect ratio of up to 300 showed the complete perovskite crystal structure and the notable piezoelectric coefficient of ~180 pm·V−1. A single BT NT-based piezoelectric device was fabricated on a flexible plastic substrate using a highly controlled focused ion beam-assisted method. The single BT NT device produced a piezoelectric voltage of ~150 mV and a current of ~3 nA when the NT was mechanically stimulated by bending and releasing, which are higher than previously reported values for 1D piezoelectric nanoscale materials. Finally, a flexible piezoelectric energy harvester (f-PEH) was achieved using vertically grown BT NT arrays with an elastomer as a vertically aligned nanocomposite; its generated maximum open-circuit voltage and short-circuit current were ~1.0 V and ~20 nA, respectively. The approach in this study can propose the vision for more advanced 1D piezoceramic nanomaterials and future piezoelectric nanodevices. [ABSTRACT FROM AUTHOR]

Objectives: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic., Methods: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities., Results: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1% vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities., Conclusion: Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.

Multipotent mesenchymal stromal/stem cell (MSC) spheroids generated in three-dimensional culture are of considerable interest as a novel therapeutic tool for regenerative medicine. However, the lack of reliable methods for storing MSC spheroids represents a significant roadblock to their successful use in the clinic. An ideal storage medium for MSC spheroids should function as both a vehicle for delivery and a cryoprotectant during storage of spheroids for use at a later time. In this study, we compared the outcomes after subjecting MSC spheroids to a freeze/thaw cycle in three Good Manufacturing Practices-grade cryopreservation media, CryoStor10 (CS10), Stem-Cellbanker (SCB), and Recovery Cell Culture Freezing Media (RFM) or conventional freezing medium (CM) (CM, Dulbecco's modified Eagle's medium containing 20% fetal bovine serum and 10% dimethyl sulfoxide) as a control for 2 months. The endpoints tested were viability, morphology, and expression of stem cell markers and other relevant genes. The results of LIVE/DEAD™ assays and annexin V/propidium iodide staining suggested that viability was relatively higher after one freeze/thaw cycle in CS10 or SCB than after freeze/thaw in CM or RFM. Furthermore, the relative "stemness" and expression of MSC markers were similar with or without freeze/thaw in CS10. Scanning electron microscopy also indicated that the surface morphology of MSC spheroids was well preserved after cryopreservation in CS10. Thus, even though it was tested for a short-term period, we suggest that CS10, which has been approved for clinical use by the U.S. Food and Drug Association, is a promising cryopreservation medium that would facilitate the development of MSC spheroids for future clinical use.

Background: Because patients infected with respiratory syncytial virus (RSV) have been reported to be older than patients infected with influenza virus, the more frequent incidence of complications in RSV-infected patients may be age-related. This study compared clinical characteristics and outcomes in hospitalized adults infected with RSV with findings in age- and sex-matched adults infected with influenza virus., Methods: The medical records of hospitalized adult patients infected with RSV or influenza virus at two university hospitals from 2013 to 2022 were retrospectively analyzed. Virus infection was confirmed by real-time polymerase chain reaction. Each RSV-infected patient was matched by age and sex with two influenza virus-infected patients, and their clinical symptoms, laboratory parameters and hospital courses were compared., Results: The study cohort consisted of 552 patients, 184 infected with RSV and 368 infected with influenza virus. Fever (71.2% vs. 79.9%, p  = .022) and cough (70.1% vs. 80.4%, p  = .007) were significantly less frequent in the RSV than in the influenza group, whereas white blood cell counts (9132/mm 3 vs. 7616/mm 3 , p  < .001) and C-reactive protein concentrations (10.25 vs. 8.88 mg/dL, p  = .029) were significantly higher in the RSV group. The frequency of oxygen therapy was higher (60.3% vs. 48.6%, p  = .010) and hospital stay was longer (8 vs. 6 days, p  = .003) in RSV than in influenza virus-infected patients., Conclusions: Clinical symptoms were less frequent, but disease was more severe, in hospitalized adult patients infected with RSV than in age- and sex-matched patients infected with influenza. Greater attention should be paid to diagnosing and preventing RSV infection in adults.

Background: Fresh ginseng is typically accompanied by soil after harvest, leading to contamination with harmful fungi during storage and distribution. In this study, we investigated the incidence of fungal contamination in fresh ginseng (5-6 years old) purchased from 22 different stores in Geumsan, Korea., Results: The incidence of fungal contamination in the samples was 67.4-111.5%. Fusarium solani was the most abundant species in the head (38.5%) and fine root (19.3%) parts of the ginseng samples, whereas F. oxysporum was the most abundant in the main root (22.0%) part. We isolated Aspergillus, Fusarium and Penicillium spp. (total number of isolates: 395) from the ginseng samples, and 138 isolates were identified using phylogenetic analysis. Polymerase chain reaction-based screening of 65 mycotoxin-producing species revealed that two P. expansum isolates were positive for citrinin and/or patulin, and five F. oxysporum isolates were positive for fumonisin biosynthesis gene. One P. expansum isolate produced 738.0 mg kg -1 patulin, and the other produced 10.4 mg kg -1 citrinin and 12.0 mg kg -1 patulin on potato dextrose agar (PDA) medium. Among the 47 representative F. oxysporum isolates, 43 (91.5%) produced beauvericin (0.1-15.4 mg kg -1 ) and four of them (8.5%) produced enniatin B and enniatin B 1 (0.1-1.8 mg kg -1 ) as well. However, none of these toxins was detected in fresh ginseng samples., Conclusion: Fusarium solani and F. oxysporum were the most abundant species in fresh ginseng samples. Most F. oxysporum (43) and P. expansum (2) strains isolated from fresh ginseng produced beauvericin and enniatins (B and B 1 ), and patulin or citrinin, respectively, on PDA medium. This is the first report of the mycotoxigenic potential of P. expansum and F. oxysporum strains isolated from fresh ginseng. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Dry eye disease (DED) is an ophthalmic disease associated with poor quality and quantity of tears, and the number of patients is steadily increasing. The aim of this study was to determine plasma and urine metabolites obtained from DED scopolamine animal model where dry eye conditions (DRY) are induced. It was also of interest to examine whether DED (scopolamine) rat model was exacerbated by treatment with benzalkonium chloride (BAC). Subsequently, plasma and urine metabolites were analyzed using liquid chromatography (LC) and gas chromatography (GC)-mass spectrometry (MS), respectively. Data demonstrated that DED indicators such as tear volume, tear breakup time (TBUT), and corneal damage in the DED groups (DRY and BAC group) differed from those of control (CON). Similar results were noted in inflammatory factors such as interleukin (IL-1β), IL-6, and tumor necrosis factor (TNF)-α. In the partial least squares-discriminant analysis (PLS-DA) score plots, the three groups were distinctly separated from each other. In addition, the related metabolites were also associated with these distinct separations as evidenced by 9 and 14 in plasma and urine, respectively. Almost all of the selected metabolites were decreased in the DRY group compared to CON, and the BAC group was lower than the DRY. In plasma and urine, lysophosphatidylcholine/lysophosphatidylethanolamine, organic acids, amino acids, and sugars varied between three groups, and these metabolites were related to inflammation and oxidative stress. Data suggest that treatment with scopolamine with/without BAC-induced DED and affected the level of systemic metabolites involved in inflammation and oxidative stress.

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary and require safety evaluations, including antibiotic resistance, before use as a starter. In this research, we investigated the antibiotic resistance profiles of 26 AAB strains, including various species of Komagataeibacter and Acetobacter , against 10 different antibiotics using the E-test method. All strains exhibited resistance to aztreonam and clindamycin. Komagataeibacter species demonstrated a 50% resistance rate to ciprofloxacin, analogous to Acetobacter species, but showed twice the resistance rates to chloramphenicol and erythromycin. Genomic analysis of K. saccharivorans CV1 identified intrinsic resistance mechanisms, such as multidrug efflux pumps, thereby enhancing our understanding of antibiotic resistance in acetic acid-producing bacteria. These findings enhance understanding of antibiotic resistance in AAB for food safety and new antimicrobial strategies, suggesting the need for standardized testing methods and molecular genetic study.

Background: With the global increase in the older population, the proportion of those receiving care in long-term care facilities (LTCFs) has also been increasing. We assessed the epidemiology, antibiotic susceptibility, and colonization status of drug-resistant organisms in patients transferred from LTCFs., Methods: We retrospectively reviewed the medical records of patients transferred from LTCFs between 2017 and 2022. The reasons for admission, antimicrobial susceptibility, and colonization rates of carbapenem-resistant Enterobacterales (CRE), methicillin-resistant Staphylococcus aureus (MRSA), and carbapenem-resistant Acinetobacter baumannii (CRAB) were recorded. We analyzed the susceptibility and colonization rates by year to identify trends., Results: Of the 936 patients transferred from LTCFs, 54.3% were admitted to the intensive care unit and 12.5% died. The most common reason for admission was infection (n = 573, 61.2%), followed by gastrointestinal bleeding (n = 67, 7.2%) and cerebrovascular disorder (n = 65, 6.9%). A total of 452 Enterobacterales strains were isolated, and their susceptibility rates to ciprofloxacin and cefotaxime were 33.3% and 35.6%, respectively. A total of 54.9% were extended-spectrum beta-lactamase-producing strains, and 4.9% of them were carbapenem-resistant, both of which showed an increasing trend (P = 0.024 and P < 0.001, respectively). The prevalence rates of CRE, CRAB, and MRSA colonization were 9.2%, 7.1%, and 23.1%, respectively. CRE colonization showed a significant increase (P < 0.001), with carbapenemase-producing Enterobacterales accounting for 75.9% of cases., Conclusions: Patients transferred from LTCFs are primarily affected by infections and exhibit high resistance rates. The increasing trend in CRE colonization rates each year highlights the need for the implementation of rigorous infection control measures for effective management., (© 2024. The Author(s).)

Si has the highest theoretical capacity (4200 mA h g -1 ) among conventional anode materials, such as graphite (372 mA h g -1 ), but its large volume expansion leads to deterioration of the battery performance. To overcome this problem (issue), we investigated the use of polysaccharide-based 3D cross-linked network binders for Si anodes, in which the polysaccharide formed an effective 3D cross-linked network around Si particles via cross-linking of polysaccharide with citric acid (CA). Sodium alginate (SA), a natural polysaccharide extracted from brown algae, is a suitable binder material for Si anodes because its abundant hydroxyl (-OH) and carboxyl (-COOH) groups form hydrogen and covalent bonds with the -OH groups present on the Si surface. We found that CA-cross-linked (CA-SA) could effectively prevent the volume expansion of Si anodes through the formation of 3D cross-linked network structures. In addition, the CA-SA binders provide enhanced adhesion strength, enabling the fabrication of more robust electrodes than those prepared using binders with linear structures ("linear binders"). In particular, the fabricated Si-based electrode (high mass loading of 1.5 mg cm -2 ) with CA-SA binder exhibited outstanding areal capacity (∼2.7 mA h cm -2 ) and excellent cycle retention (∼100% after 100 cycles).

Background: In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19)., Methods: This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from August 2, 2022 to March 31, 2023., Results: Patients receiving molnupiravir had a higher prevalence of comorbidities (85.8% vs. 70.4%; P < 0.001) and a higher Charlson comorbidity index (2.8 ± 1.4 vs. 2.5 ± 1.5; P = 0.009) than those receiving nirmatrelvir/ritonavir. Three patients required hospitalization (nirmatrelvir/ritonavir group, n = 1 [0.4%]; molnupiravir group, n = 2 [0.8%]; P = 1.000). Nirmatrelvir/ritonavir was associated with a higher risk of adverse events than molnupiravir (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.27-3.03), especially for patients aged 65 years and older (OR, 3.04; 95% CI, 1.71-5.39). The severity of adverse events in both groups was mild to moderate and improved after discontinuation of medication. In the molnupiravir group, age ≥ 65 years (OR, 0.43 95% CI, 0.22-0.86) and appropriate vaccination (OR, 0.37; 95% CI, 0.15-0.91) reduced the occurrence of adverse events., Conclusion: The rates of hospitalization and death were low and not significantly different between high-risk patients who received either nirmatrelvir/ritonavir or molnupiravir. Although adverse events were more frequent with nirmatrelvir/ritonavir than with molnupiravir, none were severe. Nirmatrelvir/ritonavir can be safely used to treat COVID-19, while molnupiravir could be considered as an alternative treatment option for high-risk groups., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

The clinical application of mesenchymal stem cells (MSCs) is attracting attention due to their excellent safety, convenient acquisition, multipotency, and trophic activity. The clinical effectiveness of transplanted MSCs is well-known in regenerative and immunomodulatory medicine, but there is a demand for their improved viability and regenerative function after transplantation. In this study, we isolated MSCs from adipose tissue from three human donors and generated uniformly sized MSC spheroids (∼100 µm in diameter) called microblocks (MiBs) for dermal reconstitution. The viability and MSC marker expression of MSCs in MiBs were similar to those of monolayer MSCs. Compared with monolayer MSCs, MiBs produced more extracellular matrix (ECM) components, including type I collagen, fibronectin, and hyaluronic acid, and growth factors such as vascular endothelial growth factor and hepatocyte growth factor. Subcutaneously injected MiBs showed skin volume retaining capacity in mice. These results indicate that MiBs could be applied as regenerative medicine for skin conditions such as atrophic scar by having high ECM and bioactive factor expression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Park, Lee, Park, Yoo, Kwon, Park, Kang, Lee and Cho.)

The constituents of meat and meat by-product are susceptible to degradation processes, especially, the control of oxidative processes is critical. The main factors that influence their lipid oxidation are fat content and fatty acid composition. The aim of this study was to validate AOAC method 996.06 for analysis of fatty acid in meat by-products and to provide their accurate, precise, and reliable information in the Korean Food Composition Database. A total of 19 fatty acids were identified. The head, small intestine, stomach, and heart of pigs and the feet of chickens contained higher contents of total fatty acids, whereas the blood of cow had the lowest content. In particular, meat by-products other than the liver, blood, and stomach of cows and the stomach and small intestine of pigs contained higher contents of unsaturated fatty acids. Their main fatty acids were oleic acid, palmitic acid, linoleic acid, and stearic acid., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01223-8., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Korean Society of Food Science and Technology 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This study investigated the effect of cooking method on the content and true retention of vitamin E and K in legumes and vegetables, which are commonly consumed in Korea. Among eight isomers of vitamin E, α- and γ-tocopherol were detected at 0.44-1.03 and 2.05-2.11 mg/100 g, respectively, in legumes including chick pea, kidney bean, lentil, pea, and sword bean and they were decreased after boiling. Phylloquinone (vitamin K 1 ) was present at a range of 31.33 to 91.34 μg/100 g in legumes and true retention was reduced after boiling. In 21 kinds of vegetables, α-tocopherol and phylloquinone were present at 0.14-1.85 mg/100 g and 34.55-510.83 μg/100 g, respectively. α-Tocopherol and phylloquinone increased in most vegetables after cooking via blanching, boiling, steaming, and grilling. This study revealed that cooking changed vitamin E and K contents of legumes and vegetables and the changes were dependent on the type of food and cooking method., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01206-9., Competing Interests: Conflict of interestThe 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., (© The Korean Society of Food Science and Technology 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Fusarium head blight (FHB) is one of the most serious diseases in barley and wheat, as it is usually accompanied by the production of harmful mycotoxins in the grains. To identify FHB-resistant breeding resources, we evaluated 60 elite germplasm accessions of barley (24) and wheat (36) for FHB and mycotoxin accumulation. Assessments were performed in a greenhouse and five heads per accession were inoculated with both Fusarium asiaticum (Fa73, nivalenol producer) and F. graminearum (Fg39, deoxynivalenol producer) strains. While the accessions varied in disease severity and mycotoxin production, four wheat and one barley showed <20% FHB severity repeatedly by both strains. Mycotoxin levels in these accessions ranged up to 3.9 mg/kg. FHB severity was generally higher in barley than in wheat, and Fa73 was more aggressive in both crops than Fg39. Fg39 itself, however, was more aggressive toward wheat and produced more mycotoxin in wheat than in barley. FHB severity by Fa73 and Fg39 were moderately correlated in both crops (r = 0.57/0.60 in barley and 0.42/0.58 in wheat). FHB severity and toxin production were also correlated in both crops, with a stronger correlation for Fa73 (r = 0.42/0.82 in barley, 0.70 in wheat) than for Fg39.

Background: Nirmatrelvir/ritonavir was Korea's first oral antiviral agent to treat coronavirus disease 2019 (COVID-19). We analyzed the nirmatrelvir/ritonavir prescription rate and treatment outcomes in treatment-eligible patients with COVID-19 receiving home-based care., Materials and Methods: We retrospectively collected data of patients with COVID-19-eligible for nirmatrelvir/ritonavir treatment from January 14, 2022, to February 15, 2022. We analyzed the prescription rate of nirmatrelvir/ritonavir, the reasons for non-prescription, and patient outcomes., Results: A total of 414 patients were included, of whom 44.2% were male, and the mean age was 64.6 (standard deviation [SD] = 8.5). Approximately 73.2% (n = 303) of patients were not prescribed nirmatrelvir/ritonavir. More than fourth-fifths of the patients refused nirmatrelvir/ritonavir treatment (n = 262, 86.5%). The mean symptom duration was significantly shorter in the prescription group (5.2 days [SD = 2.3] vs. 4.4 days [SD = 1.9], P = 0.001). A total of 6 (1.4%) patients were hospitalized, and none of the patients who received nirmatrelvir/ritonavir required admission. Among the patients prescribed nirmatrelvir/ritonavir (n = 111), 17 (15.3%) patients experienced side effects, and 5 (4.5%) patients discontinued nirmatrelvir/ritonavir due to side effects., Conclusion: The nirmatrelvir/ritonavir prescription rate was low, with more than fourth-fifths of non-prescriptions being due to patient refusal. Symptom resolution was faster, and no life-threatening side effects were reported. Accurate information about drug safety must be provided to patients to make informed decisions regarding nirmatrelvir/ritonavir treatment., Competing Interests: No conflict of interest., (Copyright © 2022 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Ertapenem is one of the carbapenems recommended for treating extended-spectrum β-lactamase (ESBL)-producing Enterobacterales . However, efficacy data are limited. We compared 30-day mortality rates for patients receiving ertapenem and other carbapenems for treatment of ESBL-producing Enterobacterales bacteremia. A multicenter, retrospective study was performed from January 2013 to December 2020 at three hospitals. Patients who received only members of one group of carbapenems (group 1 or group 2) throughout their treatment for ESBL-producing Escherichia coli or Klebsiella pneumoniae bacteremia were enrolled. To compare 30-day all-cause mortality rates in the two groups, propensity score matching was used to control for selection bias. Subgroup analyses were performed for several subgroups. Secondary outcomes included Clostridioides difficile infection (CDI) and the emergence of multidrug-resistant Gram-negative bacteria within 90 days after initiation of carbapenem treatment. One-to-one propensity score matching yielded 162 pairs of patients from the total of 603 patients included. There was no difference in 30-day mortality rates between ertapenem and the other carbapenems in adjusted analyses (hazard ratio, 0.60 [95% confidence interval [CI], 0.29 to 1.22]) of the propensity score-matched cohorts. A similar result was obtained in a subgroup analysis of patients who suffered severe sepsis or septic shock and those who did not ( P  = 0.54 for interaction). Emergence of CDI (odds ratio [OR], 0.99 [95% CI, 0.44 to 2.20]) and carbapenem-resistant Enterobacterales (OR, 1.31 [95% CI, 0.51 to 3.53]) did not differ between the two groups. Our study suggests that the efficacy of ertapenem may be comparable to that of the other carbapenems in treatment of ESBL-producing E. coli and K. pneumoniae bacteremia.

Objective: As the number of patients with COVID-19 increased, at-home care was introduced for the first time in South Korea. This study aimed to analyse the characteristics and outcomes of patients who were treated under at-home care., Design, Setting and Participants: This retrospective cohort study targeted patients under at-home care for COVID-19 in Yeongdeungpo-gu in Seoul, Korea, from 18 October 2021 to 12 December 2021. The public health centre selected eligible patients for at-home care and registered with our institution. Nurses monitored patients, and doctors decided to transfer healthcare facilities and release the quarantined patients according to their symptoms., Outcome Measures: Patient characteristics during the course of at-home care., Results: A total of 1422 patients were enrolled and 9574 patient-days were managed. Most patients were aged ≥60 years (22.7% (n=323)), and 82.8% did not have underlying conditions. The median length of care for patients was 8 days (IQR: 5-10 days). During the study period, 986 (69.3%) patients were released from quarantine, 82 (5.8%) patients were transferred to facilities and 354 (24.9%) patients were still under at-home care at the end of the study period. The most common cause of transfer was sustained fever (n=30; 36.6%), followed by dyspnoea and desaturation (n=17; 20.7%). Factors associated with transfer were diabetes (OR: 3.591, 95% CI 1.488 to 8.665, p=0.004), pregnancy (OR: 5.839, 95% CI 1.035 to 32.935, p=0.046) and being presymptomatic at diagnosis (OR: 4.015, 95% CI 1.559 to 10.337, p=0.004)., Conclusions: There were no specific problems related to patient safety when operating at-home care. Patients with risk factors, such as diabetes, were more likely to be transferred to healthcare facilities. For safe at-home care, it is necessary to prepare for an appropriate response to the emergency., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Silicon-based electrodes are widely recognized as promising anodes for high-energy-density lithium-ion batteries (LIBs). Silicon is a representative anode material for next-generation LIBs due to its advantages of being an abundant resource and having a high theoretical capacity and a low electrochemical reduction potential. However, its huge volume change during the charge-discharge process and low electrical conductivity can be critical problems in its utilization as a practical anode material. In this study, we solved the problem of the large volume expansion of silicon anodes by using the carbon coating method with a low-cost phenolic resin that can be used to obtain high-performance LIBs. The surrounding carbon layers on the silicon surface were well made from a phenolic resin via a solvent-assisted wet coating process followed by carbonization. Consequently, the electrochemical performance of the carbon-coated silicon anode achieved a high specific capacity (3092 mA h g -1 ) and excellent capacity retention (~100% capacity retention after 50 cycles and even 64% capacity retention after 100 cycles at 0.05 C). This work provides a simple but effective strategy for the improvement of silicon-based anodes for high-performance LIBs.

We investigated the longevity rates of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after a complete ChAdOx1 nCoV-19 vaccination, which are rare and important to estimate their efficacy and establish a vaccination strategy. We assessed the positivity rates and changes of titers before (T0) and at one month (T1), four months (T2), and seven months (T3) after a ChAdOx1 nCoV-19 vaccination using five SARS-CoV-2 antibody assays. A total of 874 serum samples were obtained from 228 (T0 and T1), 218 (T2), and 200 (T3) healthcare workers. The positive rates for all five assays were 0.0-0.9% at T0, 66.2-92.5% at T1, 98.2-100.0% at T2, and 66.0-100.0% at T3. The positive rates at T3 were decreased compared to those at T2. The median antibody titers of all the assays at T3 were significantly decreased compared to those at T2 (860.5 to 232.0 U/mL for Roche total, 1041.5 to 325.5 AU/mL for Abbott IgG, 10.9 to 2.3 index for Siemens IgG, 99.5% to 94.7% for SD Biosensor V1, and 88.5% to 38.2% for GenScript). A third-dose scheme can be considered based on our data generated from five representative assays. Our findings contribute insights into SARS-CoV-2 antibody assays and appropriate vaccination strategies.

Background: This study was undertaken to compare the sensitivities of mice strains during tumor induction by transcription activator-like effector nucleases (TALEN)-mediated Trp53 mutant gene. Alterations of their tumorigenic phenotypes including survival rate, tumor formation and tumor spectrum, were assessed in FVB/N-Trp53 em2Hwl /Korl and C57BL/6-Trp53 em1Hwl /Korl knockout (KO) mice over 16 weeks., Results: Most of the physiological phenotypes factors were observed to be higher in FVB/N-Trp53 em2Hwl /Korl KO mice than C57BL/6-Trp53 em1Hwl /Korl KO mice, although there were significant differences in the body weight, immune organ weight, number of red blood cells, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), total bilirubin (Bil-T) and glucose (Glu) levels in the KO mice relative to the wild type (WT) mice. Furthermore, numerous solid tumors were also observed in various regions of the surface skin of FVB/N-Trp53 em2Hwl /Korl KO mice, but were not detected in C57BL/6-Trp53 em1Hwl /Korl KO mice. The most frequently observed tumor in both the Trp53 KO mice was malignant lymphoma, while soft tissue teratomas and hemangiosarcomas were only detected in the FVB/N-Trp53 em2Hwl /Korl KO mice., Conclusions: Our results indicate that the spectrum and incidence of tumors induced by the TALEN-mediated Trp53 mutant gene is greater in FVB/N-Trp53 em2Hwl /Korl KO mice than C57BL/6-Trp53 em1Hwl /Korl KO mice over 16 weeks., (© 2021. The Author(s).)

Reliable results for serological positivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody after the second dose of AstraZeneca (AZ) vaccination are important to estimate the real efficacy of vaccination. We evaluated positivity rates and changes in semiquantitative antibody titers before and after the first and second ChAdOx1 nCoV-19 vaccinations using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A total of 674 serum samples were obtained from 228 participants during three blood sampling periods. A questionnaire on symptoms, severity, and adverse reaction duration was completed by participants after the second vaccination. The overall positive rates for all assays were 0.0 to 0.9% before vaccination, 66.2 to 92.5% after the first vaccination, and 98.2 to 100.0% after the second vaccination. Median antibody titers in five assays after the second dose of vaccination were increased compared to those after the first dose (106.4-fold increase for Roche total antibody, 3.6-fold for Abbott IgG, 3.6-fold for Siemens, 1.2-fold for SD Biosensor V1 neutralizing antibody, and 2.2-fold for GenScript neutralizing antibody). Adverse reactions were reduced after the second dose in 89.9% of participants compared to after the first dose. Overall, the second vaccination led to almost 100% positivity rates based on these SARS-CoV-2 antibody assays. The results should be interpreted with caution, considering the characteristics of the applied assays. Our findings could inform decisions regarding vaccination and the use of immunoassays, thus contributing to SARS-CoV-2 pandemic control.

Reliable results regarding serologic positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody before and after AstraZeneca (AZ) vaccination are essential for estimating the efficacy of vaccination. We assessed positivity rates and associated factors using five SARS-CoV-2 antibody assays. A total of 228 paired serum samples (456 samples) were obtained from 228 participants. After baseline sampling, the second sampling was conducted between 11 and 28 days after the first dose of the AZ vaccine. Sera were tested using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A questionnaire on the symptoms, severity, and duration of adverse reactions was completed by all participants. The overall positivity rates for SARS-CoV-2 antibody were 84.6% for the Roche assay, 92.5% for the Abbott assay, 75.4% for the Siemens assay, 90.7% for the SD Biosensor assay, and 66.2% for the GenScript assay after the first dose of the AZ vaccine. The positivity rates and antibody titers of sera obtained between 21 and 28 days were significantly higher than those obtained between 11 and 20 days in all five assays. More-severe adverse reactions and longer durations of adverse reactions were related to higher SARS-CoV-2 antibody levels. The agreements and correlations among the assays applied were substantial (к, 0.73 to 0.95) and strong (ρ, 0.83 to 0.91). A single dose of the AZ vaccine led to high positivity rates based on the five assays. Days after vaccination and adverse reactions could help estimate serologic conversion rates. The results should be interpreted cautiously considering the assays and cutoffs applied. Our findings could inform decisions regarding vaccination and laboratory settings and could thus contribute to the control of the spread of SARS-CoV-2 infection.

Background: There have been recent proposals to categorize healthcare-associated infections (HCAIs) separately from community-acquired infections (CAIs). The aim of this study was to compare the antibiotic resistance of pathogens causing CAIs, HCAIs, and hospital-acquired infections (HAIs) in Korea, and to investigate the need for different empirical antibiotics therapy for CAIs and HCAIs., Materials and Methods: This prospective study was conducted in a university hospital between March and December 2019. Inpatients who underwent a bacterial culture within 2 days of hospitalization, with a Enterobacteriaceae strain identified at the infection site and available antibiotic susceptibility results, were included in the analysis. Infections were classified as CAIs, HCAIs or HAIs, depending on the source., Results: Of the 146 patients included in the analysis, the prevalence of fluoroquinolone-resistant Enterobacteriaceae was 18.8%, 38.5%, and 55.0%; the prevalence of pathogens showing third-generation cephalosporins resistance was 8.3%, 50.0%, and 60.0%; and the prevalence of pathogens showing piperacillin-tazobactam resistance was 8.3%, 7.7%, 15.0% in the CAIs, HCAIs, and HAIs groups, respectively. The prevalence of extended-spectrum beta-lactamase-positive pathogens was 6.3%, 47.3%, and 55.0% in the CAIs, HCAIs, and HAIs group, respectively, with no significant difference between the HCAIs and HAIs groups. Resistance patterns of the HCAIs group more closely resembled those of the HAIs group than those of the CAIs group., Conclusion: The pathogens isolated from patients with HCAIs showed resistance patterns that were more similar to those of patients with HAIs than those with CAIs. Thus, CAIs and HCAIs should be distinguished from each other when selecting antibiotic agents., Competing Interests: No conflicts of interest., (Copyright © 2021 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: For protection against coronavirus disease 2019 (COVID-19), the Korean government recommended the KF94 mask or that a mask at the same level as the KF94 should be worn when contacting a patient with COVID-19. Furthermore, adequately fitted N95 respirators and KF94 masks are essential. We investigated the fit tests to determine whether healthcare workers had adequate protection with N95 respirators and KF94 masks., Methods: In this prospective single-center simulation study, five N95 respirators (two made in the USA by 3M and three made in Korea) and six KF94 masks, the Korean standard medical masks, were tested. The fit factor (FF) and leakage rate were evaluated using a two-fit test device. Adequate protection (defined as FF ≥ 100 or leakage rate ≤ 5) rates were compared between N95 respirators and KF94 masks, and between made in Korea and the 3M N95 respirators. For KF94 masks, adequate protection rates were compared before and after ear strap fixation., Results: Overall, 30 participants were enrolled, and 330 fit tests were performed for FF and leakage rate. Adequate protection rates of all tested N95 respirators and KF94 masks were 22.7% (n = 75) by FF and 20.6% (n = 68) by leakage rate. N95 respirators showed a significantly higher adequate protection rate than KF94 masks for FF (48.7% vs. 1.1%, P < 0.001) and leakage rate (42.0% vs. 2.8%, P < 0.001). Adequate protection rate of 3M-made N95 respirators was significantly higher than that of those made in Korea (83.3% vs. 25.6% in FF, P < 0.001; 73.3% vs. 21.1% in leakage rate, P < 0.001). In KF94 masks, after fixation of ear strap with a hook, adequate protection rate improved significantly (1.1% vs. 12.8% in FF, P < 0.001; 2.8% vs. 11.1%, P < 0.001)., Conclusion: Although adequate protection rate of N95 respirators was higher than that of KF94 masks, N95 respirator protection rate was not optimum. Thus, it is necessary to minimize exposure to risk by selecting an appropriate mask or respirator that adequately fits each person, and by wearing respirators or masks appropriately, before contacting the patients. With their superior protection rate, wearing N95 respirators is recommended instead of KF94 masks, especially when performing aerosol-generating procedures., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Dry eye disease (DED) is a chronic and progressive lesion on the ocular surface and induces symptoms, such as burning sensation, itchy eyes, heavy eyes, tired eyes, dry feeling, facial flushing, and blurred vision. The present study was performed to develop DED biomarkers using metabolomics in a rat model. DED was induced by injecting scopolamine and exposing rats to a dry condition. Scopolamine (12 mg/kg/day for 7 days) was subcutaneously injected to male Sprague-Dawley rats. The rats were placed in dry condition with air-flow and dehumidifier. Tear volume and tear breakup time (TBUT) were measured, and eyes were examined through fluorescein staining to assess DED. Mucosal damage and immune reactions were also determined. Plasma and urinary endogenous metabolites were determined using 1 H-NMR analysis. Compared with control tear and TBUT levels were significantly decreased in the DED group whereas corneal damage was significantly increased. The levels of interleukins (IL-6) and IL-1β significantly elevated in the cornea and lacrimal glands in the DED group. TNF-α was numerically increased but not significantly different between groups. Pattern recognition using principal component analysis (PCA) and orthogonal projections to latent structure-discriminant analysis (OPLS-DA) of the NMR spectra in global profiling revealed different clusters between DED and control groups. Target profiling demonstrated that PCA and OPLS-DA score plots were separated between DED and controls in plasma and urine. Subsequently, 9 plasma metabolites were selected to examine different clustering between groups, and 26 urinary metabolites were also selected. Plasma metabolites showed a non-significant rising tendency in the DED group. Urinary phenylalanine, phenylacetate, pantothenate, glycine, succinate, methanol, valine, propylene glycol, histidine, threonine, lactate, and acetate were significantly different between control and DED rats. These results may contribute to understanding the metabolic regulation that is involved in DED and might be useful for potential biomarkers related to DED in rats.

Carbapenem-resistant gram negative pathogen (CR-GNP) infection in burn patients is a growing concern since treatment options are limited and resistance to the main line of treatment, colistin, is increasing. The goal of this study was to compare treatment outcomes of colistin monotherapy versus colistin-based combination therapy for CR-GNP bacteremia in burn patients. A retrospective observational study was conducted between 2014 and 2017 in Hangang Sacred Heart Hospital located in Seoul, South Korea. Among the burn patients admitted to the burn intensive care unit with CR-GNP bacteremia due to wound infections, colistin monotherapy or colistin-based combination therapy were investigated. We determined both eradication rate within seven days as well as mortality rate within 30 days. A total of 84 burn patients with CR-GNP bacteremia were analyzed-32 were treated with colistin monotherapy and 52 with colistin-based combination therapy. We found that eradication rate within 7 days and 30-day mortality rate were not significantly different between the two groups (71.9% versus 75.0%, P = 0.752 and 31.2% versus 38.5%, P = 0.503). In the Cox regression analysis, Charlson's comorbidity index, renal replacement therapy before colistin use, and duration of antibiotics were associated with 30-day mortality (HR, 1.23; 95% CI, 1.02-1.49; P = 0.030, HR, 2.28; 95% CI, 1.05-4.94; P = 0.037 and HR, 0.94; 95% CI, 0.89-0.99, P = 0.042, respectively). Colistin-based combination therapy did not show significant differences with regard to microbiologic and clinical outcomes compared with colistin monotherapy., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Mulberry leaves have antioxidant activity and anti‑inflammatory effects in several types of cells. However, the efficacy of mulberry leaves fermented with Cordyceps militaris remains unknown. Therefore, the present study aimed to investigate whether the ethanol extracts of mulberry leaves fermented with C. militaris (EMfC) can prevent lipopolysaccharide (LPS)‑induced inflammation and autophagy in macrophages. To achieve this, RAW264.7 cells pretreated with three different dose of EMfCs were subsequently stimulated with LPS, and examined for alterations in the regulatory factors of inflammatory responses and key parameters of the autophagy signaling pathway. EMfC treatment inhibited the generation of reactive oxidative species; however, significant activity was observed for 2,2‑diphenyl‑1‑picrylhydrazyl (DPPH) radical scavenging (IC50=579.6703 mg/ml). Most regulatory factors in inflammatory responses were significantly inhibited following treatment with EMfC, without any significant cellular toxicity. EMfC‑treated groups exhibited marked suppression of nitrogen oxide (NO) levels, mRNA expression levels of iNOS/COX‑2, levels of all inflammatory cytokines (TNF‑α, IL‑1β and IL‑6) and phosphorylation of MAPK members, as well as recovery of cell cycle progression. Furthermore, similar effects were observed in the LPS‑induced autophagy signaling pathway of RAW264.7 cells. The expression levels of microtubule‑associated protein 1A/1B‑light chain 3 (LC3) and Beclin exhibited a dose‑dependent decrease in the EMfC+LPS‑treated groups compared with in the Vehicle+LPS‑treated group, whereas the phosphorylation of PI3K and mTOR were enhanced in a dose‑dependent manner in the same groups. Overall, the results of the present study provide evidence that exposure to EMfC protects against LPS‑induced inflammation and autophagy in RAW264.7 cells. These results indicated that EMfC is a potential candidate for treatment of inflammatory diseases.

Background: Carbapenemase-producing Enterobacteriaceae (CPE) are emerging as a worldwide threat. Long-term care facilities (LTCFs) are considered a reservoir for CPE and play a central role in transmission to acute care hospitals. We investigated the CPE positivity in patients exposed to CPE in LTCFs. Furthermore, we analyzed the CPE positivity rates in the environment exposed to CPE., Methods: We collected rectal swab specimens from patients residing in LTCFs who were exposed to CPE. Environmental sampling was performed by infection control practitioners from sites classified as patient private space, common space in the patient room, common space other than patient rooms, and nursing station. Each sample was cultured on a Chrom Klebsiella pneumoniae carbapenemase (KPC) agar for CPE screening. The positive isolates were subjected to a polymerase chain reaction to identify the presence of bla KPC , bla VIM , bla IMP , bla OXA-48 , and bla NDM and determine CPE genotype., Results: From 65 index cases, a total of 24 hospitals and 481 patients were enrolled; 414 patients who had resided in the same patient room as a patient with confirmed CPE and 67 patients who were newly admitted to that patient room. A total of 117 (24.3%) patients were positive for CPE among which 93 (22.5%, 93/414) were already admitted patients and 24 (35.8%, 24/67) were newly admitted patients. A total of 163 CPEs were detected and K. pneumoniae (n = 104, 63.8%) was the most common bacteria followed by Escherichia coli (n = 43, 26.4%) and Citrobacter koseri (n = 11, 6.7%). Environmental sampling was performed in 24 hospitals and 604 sites. A total of 12 sites (2.0%) were positive for CPE and sink in the nursing station (n = 6, 4.2%) was the most contaminated space., Conclusion: CPE colonization rates in patients exposed to CPE in LTCFs were higher than those found in acute care hospitals. Proper infection control measures for detecting and reducing CPE colonization in patients residing in LTCFs are required. Newly admitted patients could also be carriers; therefore, infection control for newly admitted patients also needs to be thorough., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

The disease burden of respiratory syncytial virus (RSV) infection in the adult population has not been well characterized compared to children. Investigation of the clinical characteristics and disease burden of adult RSV infection would help to establish public health policy and a future vaccine strategy. We retrospectively collected medical records of hospitalized adult patients who were diagnosed with RSV infection from January 2012 to December 2015 from three tertiary hospitals. Baseline characteristics, clinical outcomes and economic charge during hospitalization were compared by age groups (19-49 years, 50-64 years, and ≥ 65 years) using Chi-square test. The odds of risk factors of RSV pneumonia were calculated using binary logistic regression. A total of 204 patients from three hospitals were enrolled. Patients who older than 65 years were 132 (64.7%). 118 (57.8%) patients had clinically confirmed pneumonia and 22 (10.8%) died in a hospital. The median medical cost of RSV pneumonia was 2,855.26 USD (interquartile range, 1,561.85-5,379.55) per each admission. Solid cancer (adjusted OR, 3.85; 95% CI, 1.65-9.02, p = 0.002) and hematologic malignancy (all patients had pneumonia) were shown to be risk factors for RSV pneumonia. RSV infection in South Korea seemed to have a significant burden among adults as pneumonia, care in the intensive care unit and mortality. Nationwide awareness and further effort to recognize the current burden, prepare specific treatment, and prevent adult RSV infection would be necessary.

The aim of this study was to determine the effects of anti-wrinkle and skin-whitening of fermented black ginseng (FBG) in human subjects and to examine underlying biochemical mechanisms of action. A clinical study was performed to evaluate efficacy and safety using a 1% FBG cream formulation. Twenty-three subjects were recruited and instructed to apply control or FBG creams each on half of their face twice daily for 8 weeks. After 8 weeks, FBG cream significantly reduced the appearance of eye wrinkles compared to prior to exposure and control cream. Skin color was significantly brightened using FBG cream in comparison with a control cream. To determine the mechanism of actions involved in anti-wrinkle and skin-whitening effects various concentrations of FBG were applied to human fibroblast CCD-986sk and mouse melanoma B16F1 cells. Collagen synthesis in CCD-986sk cells was improved significantly at 1, 3, 10, or 30 µg/ml of FBG. At 30 µg/ml, FBG significantly inhibited (73%) collagenase, and matrix metalloproteinase-1 (MMP-1) compared to control. Tyrosinase activity and DOPA (3,4-dihydroxy-L-phenylalanine) oxidation were significantly decreased at all tested concentrations. Melanin production in B16F1 cells was concentration-dependently reduced from 15% to 60% by all concentrations of FBG. These results suggested that a 1% FBG cream exerted anti-wrinkle and skin-whitening effects.

Infection is the leading cause of mortality in severe burn patients, benefitting from periodic monitoring of changes in bacterial prevalence and antibiotic resistance trends. This single facility retrospective study evaluated blood culture results for patients hospitalized in the burn intensive care unit (BICU) from January 2012 to December 2017. A total of 969 samples from 420 patients were reviewed. Isolated pathogens were recorded by year and the number of days of hospitalization. Results showed that Acinetobacter baumanni was the most predominant isolated pathogen, followed closely by Pseudomonas aeruginosa, Klebsiella spp., and Enterococcus spp. Throughout this 6-year study, several significant trends were noted; Klebsiella species increased, while P. aeruginosa decreased. Staphylococcus aureus and Klebsiella species gradually increased, and P. aeruginosa doubled as the length of hospital stay increased to 22 days. Interestingly, as the length of the hospital stay increased, the proportion of Carbapenem-resistant Enterobacteriaceae (CRE) significantly increased up to 45.0% at 22 days (P=0.003). Conversely, the proportion of Acinetobacter baumannii gradually decreased as the days hospitalized increased. Overall, the rate of multidrug-resistant (MDR) bacteremia found in burn patients was substantially higher than that in other patients and appeared from the earliest phase of hospitalization. Therefore, early use of antibiotics targeting MDR Gram-negative bacteria in burn patients admitted to the BICU might be warranted. Further, since CRE infections increase in abundance over time, significant effort should be made to manage the initial CRE infections of burn patients before they can multiply into a life-threatening situation., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Several techniques have been employed for deletion of the NKX3.1 gene, resulting in developmental defects of the prostate, including alterations in ductal branching morphogenesis and prostatic secretions as well as epithelial hyperplasia and dysplasia. To investigate whether the CRISPR/Cas9-mediated technique can be applied to study prostate carcinogenesis through exon I deletion of NKX3.1 gene, alterations in the prostatic intraepithelial neoplasia (PIN) and their regulatory mechanism were observed in the prostate of NKX3.1 knockout (KO) mice produced by the CRISPR/Cas9-mediated NKX3.1 mutant gene, at the ages of 16 and 24 weeks. The weight of dorsal-lateral prostate (DLP) and anterior prostate (AP) were observed to be increased in only the 24 weeks KO mice, although morphogenesis was constant in all groups. Obvious PIN 1 and 2 lesions were frequently detected in prostate of the 24 weeks KO mice, as compared with the same age wild type (WT) mice. Ki67, a key indicator for PIN, was densely stained in the epithelium of prostate in the 24 weeks KO mice, while the expression of p53 protein was suppressed in the same group. Also, both the 16 and 24 weeks KO mice reveal inhibition of the PI3K/AKT/mTOR pathway in the prostate. However, prostate specific antigen (PSA) levels and Bax/Bcl-2 expressions were decreased in the prostate of 16 weeks KO mice, and were increased in only the 24 weeks KO mice. Taken together, the results of the present study provide additional evidence that CRISPR/Cas9-mediated exon 1 deletion of the NKX3.1 gene successfully induces PIN lesions, along with significant alterations of Ki67 expression, EGFR signaling pathway, and cancer-regulated proteins.

Arbutin, a natural polyphenol, possesses numerous biological activities including whitening, anti-oxidant, anti-cancer, anti-inflammatory activities, as well as strong reducing power, making it an ideal bioactive ingredient for preparing gold nanoparticles (GNPs). Previously, we developed a novel green, mild synthetic method for GNPs using glycosides such as arbutin as reducing agents and stabilizers. Herein, we optimized the synthetic method for glycoside-GNPs using arbutin, methyl β-D-glucoside, and phenyl β-D-glucoside and validated their whitening efficacy in vitro and in vivo. The resulting glycoside-GNPs were predominantly mono-dispersed and spherical (10.30-17.13 nm diameter). Compared with arbutin itself, arbutin-GNP complexes (GNP-A1 and GNP-P2) displayed enhanced whitening capabilities. Furthermore, GNP-P2 exhibited enhanced anti-inflammatory activity and lacked the toxicity associated with arbutin. Bioactive glycoside-GNP complexes may open new directions for cosmeceuticals, and GNP-P2 may serve as a useful whitening ingredient in future cosmeceutical applications.

Great progress in the field of piezoelectricity of (K,Na)NbO 3 (KNN) lead-free ceramics, driven by emerging rhombohedral-tetragonal (R-T) phase boundary, has instigated research activity regarding elaborate controls of the phase boundary structure. Through phase-microstructure-property mapping in KNN ceramics doped with Bi-containing perovskite oxides, in this study we for the first time report the existence of a certain R-T phase boundary state by which to create maximum piezoelectric response in KNN systems. This phase boundary condition is usually comprised of approximately 15% R phase and 85% T phase, regardless of the choice of dopant material. Any deviation from this phase composition, either by inclusion of orthorhombic (O) phase or by enrichment of R phase, has a negative effect on the value of d 33 . These findings can provide useful guidance for chemical doping control associated with the type of phase boundary and the phase composition for advanced KNN-based materials.

A few clues about correlation between endoplasmic reticulum (ER) stress and mulberry ( Morus alba ) leaves were investigated in only the experimental autoimmune myocarditis and streptozotocin-induced diabetes. To investigate whether a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) could suppress ER in fatty liver, alterations in the key parameters for ER stress response were measured in high fat diet (HFD)-induced obese C57L/6 mice treated with EMfC for 12 weeks. The area of adipocytes in the liver section were significantly decreased in the HFD+EMfC treated group as compared to the HFD+Vehicle treated group, while their level was higher in HFD+Vehicle treated group than No treated group. The level of the eukaryotic initiation factor 2 alpha (eIF2α) and inositol-requiring enzyme 1 beta (IRE1α) phosphorylation and CCAAT-enhancer-binding protein homologous protein (CHOP) expression were remarkably enhanced in the HFD+Vehicle treated group. However, their levels were restored in the HFD+EMfC treated group, although some differences were detected in the decrease rate. Similar recovery was observed on the ER stress-induced apoptosis. The level of Caspase-3, Bcl-2 and Bax were decreased in the HFD+EMfC and HFD+orlistat (OT) treated group compared to the HFD+Vehicle treated group. The results of the present study therefore provide first evidence that EMfC with the anti-obesity effects can be suppressed ER stress and ER stress-induced apoptosis in the hepatic steatosis of HFD-induced obesity model., Competing Interests: Conflict of interests: The authors declare that there is no financial conflict of interests to publish these results.

Regulation of gastrointestinal hormones have been reported in animal models for constipation undergoing laxative therapy when administered herbal products. We undertook to investigate whether the laxative activity of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) affects the regulation of gastrointestinal hormones, by examining the concentration of four hormones and the activation of their receptors in the loperamide (Lop)-induced constipation model. Stool parameters, including number, weight and water content, were significantly recovered in the Lop+GEGR treated group, relative to the Lop+vehicle treated group; however, food intake and water consumption were maintained at a constant level. Also, a similar recovery was detected for thickness of mucosa, muscle and flat luminal surface in the Lop+GEGR treated group. Furthermore, concentration of the four gastrointestinal hormones evaluated, namely, cholecystokinin (CCK), gastrin (GAS), somatostatin (SS) and motilin (MTL), were lower in the Lop+vehicle treated group than the No treated group, but were remarkably enhanced in the Lop+GEGR treated group. Moreover, the downstream signaling pathway of MTL and SS receptors were recovered after GEGR administration. Results of the present study therefore indicate that the laxative effects of GEGR treatment may be tightly related with the regulation of gastrointestinal hormones in the Lop-induced constipation model., Competing Interests: Conflict of interests: The authors declare that there is no financial conflict of interests to publish these results.

Introduction: Roots of Asparagus cochinchinensis , which have pharmacologically active ingredients, have received great attention because they show good therapeutic effects for various inflammatory diseases without specific toxicity. This study investigated the anti-asthmatic effects of a butanol extract of Asparagus cochinchinensis roots that had been fermented with Weissella cibaria (BAW) and its possible underlying cholinergic regulation. Methods: Alterations of the anti-asthmatic markers and the molecular response factors were measured in an ovalbumin (OVA)-induced asthma model after treatment with BAW. Results: Treatment with BAW decreased the intracellular reactive oxygen species (ROS) production in lipopolysaccharides (LPS) activated RAW264.7 cells. The results of the animal experiments revealed lower infiltration of inflammatory cells and bronchial thickness, and a significant reduction in the number of macrophages and eosinophils, concentration of OVA-specific IgE, and expression of Th2 cytokines in the OVA + BAW treated group. In addition, a significant recovery of goblet cell hyperplasia, MMP-9 expression, and the VEGF signaling pathway was observed upon airway remodeling in the OVA + BAW treated group. Furthermore, these responses of BAW were linked to recovery of acetylcholine esterase (AChE) activity and muscarinic acetylcholine receptor (mAChR) M3 downstream signaling pathway in epithelial cells, smooth muscle cells, and afferent sensory nerves of OVA + BAW-treated mice. Conclusion: Overall, these findings are the first to provide evidence that the therapeutic effects of BAW can prevent airway inflammation and remodeling through the recovery of cholinergic regulation in structural cells and inflammatory cells of the chronic asthma model.

To evaluate the carcinogenicity of p27 knockout (KO) mice with RNA-guided endonuclease (RGENs)-mediated p27 mutant exon I gene (IΔ), alterations in the carcinogenic phenotypes including tumor spectrum, tumor suppressor proteins, apoptotic proteins and cell cycle regulators were observed in p27 (IΔ) KO mice after treatment with 7,12-Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)(DT) for 5 months. The target region (544~571 nt) in exon I of the p27 gene was successfully disrupted in p27 (IΔ) KO mice using the RGEN-induced non-homologous end joining (NHEJ) technique. After DT exposure for 5 months, a few solid tumors (identified as squamous cell carcinoma) developed on the surface of back skin of DT-treated p27 (IΔ) KO mice. Also, squamous cell hyperplasia with chronic inflammation was detected in the skin dermis of DT-treated p27 (IΔ) KO mice, while the Vehicle+p27 (IΔ) KO mice and WT mice maintained their normal histological skin structure. A significant increase was observed in the expression levels of tumor suppressor protein (p53), apoptotic proteins (Bax, Bcl-2 and Caspase-3) and cell-cycle regulator proteins (Cyclin D1, CDK2 and CDK4) in the skin of DT-treated p27 (IΔ) KO mice, although their enhancement ratio was varied. Taken together, the results of the present study suggest that squamous cell carcinoma and hyperplasia of skin tissue can be successfully developed in new p27 (IΔ) KO mice produced by RGEN-induced NHEJ technique following DT exposure for 5 months., Competing Interests: Conflict of interests: The authors declare that there is no financial conflict of interests to publish these results.

The butanol extract of Asparagus cochinchinensis roots fermented with Weissella cibaria (BAfW) significantly suppressed the inflammatory response induced by lipopolysaccharide (LPS) treatment in RAW264.7 cells. To investigate the dose dependence and durability of BAfW on the anti-asthma effects, alterations in key parameters were measured in ovalbumin (OVA)-challenged Balb/c mice treated with the different doses of BAfW at three different time points. The number of immune cells, OVA-specific IgE level, thickness of respiratory epithelium and mucus score decreased significantly in a dose-dependent manner in response to treatment with 125 to 500 mg/kg BAfW ( P <0.05), although the highest level was detected in the 500 mg/kg treated group. Moreover, the decrease in these parameters was maintained from 24 to 48 h in the 500 mg/kg of BAfW treated group. At 72 h, the effects of BAfW on the number of immune cells, OVA-specific IgE level and thickness of respiratory epithelium partially disappeared. Overall, this study provides the first evidence that the anti-asthma effect of BAfW may reach the maximum level in OVA-challenged Balb/c mice treated with 500 mg/kg and that these effects can last for 48 h., Competing Interests: Conflict of interests: The authors declare that there is no financial conflict of interests to publish these results.

A correlation between endoplasmic reticulum (ER) stress and laxative effects was first reported in a constipation model treated with an aqueous extract of Liriope platyphylla (AEtLP) roots. To investigate the correlation between the laxative effect of uridine (Urd) and ER stress response, alterations in the key parameters for ER stress were measured in loperamide (Lop) induced constipation Sprague Dawley (SD) rats treated with Urd. The efficacy of the laxative effect of Urd was notable on the symptoms of chronic constipation, including alteration of stool parameters and structure of the transverse colon, in Lop induced constipated SD rats. In the PERK/eIF2-ATF4 pathway of ER stress response, the levels of eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation and DNA damage-inducible protein (GADD34) transcripts were significantly enhanced in the Lop+Vehicle treated group. However, the levels were restored in the Lop+Urd treated group, although few differences were detected in the decrease rate. Similar changes were observed for levels of inositol-requiring enzyme 1 beta (IRE1β) phosphorylation and X-box binding protein 1 (XBP-1) transcript in the IRE1α/XBP pathway. Furthermore, the number of ER stress-induced apoptotic cells and Bax and Bcl-2 expression were recovered in the Lop+Urd treated group compared to the Lop+Vehicle treated group. The results of the present study therefore provide first evidence that the laxative effects of Urd may be tightly correlated with the recovery of ER stress response in constipation models., Competing Interests: Conflict of interests: The authors declare that there is no financial conflict of interests to publish these results.