Design, synthesis, and anti-melanogenic efficacy of 2-mercaptobenzoxazoles with nanomolar tyrosinase activity inhibition.

Tyrosinase is a metalloenzyme that contains copper(II) ions. We designed and synthesized eight known low-molecular-weight 2-mercaptobenzoxazole (2-MBO) analogs as tyrosinase inhibitors. Our focus was on the mercapto functional group, which interacts with copper ions. Analogs 1-3 exhibited mushroom tyrosinase inhibitory activity at the nanomolar level and demonstrated strong potency with extremely low half-maximal inhibitory concentration (IC50) values of 80-90 nM for l-dopa and 100-240 nM for l-tyrosine. Analogs 2, 4, and 5 showed the most potent anti-melanogenic effects in B16F10 cells, and their mode of action was demonstrated by kinetic analysis. Their anti-melanogenic effects were similar to the tyrosinase inhibition results, suggesting that their anti-melanogenic effects could be attributed to their tyrosinase inhibitory ability. Experiments using copper-chelating activity assays and changes in tyrosinase inhibitory activity with and without CuSO4 demonstrated that 2-MBO analogs inhibit tyrosinase activity by chelating the copper ions of tyrosinase. In conclusion, the 2-MBO analogs show potential as anti-melanogenic agents with potent tyrosinase inhibitory activity.

PPAR Pan Agonist MHY2013 Alleviates Renal Fibrosis in a Mouse Model by Reducing Fibroblast Activation and Epithelial Inflammation.

The peroxisome proliferator-activated receptor (PPAR) nuclear receptor has been an interesting target for the treatment of chronic diseases. Although the efficacy of PPAR pan agonists in several metabolic diseases has been well studied, the effect of PPAR pan agonists on kidney fibrosis development has not been demonstrated. To evaluate the effect of the PPAR pan agonist MHY2013, a folic acid (FA)-induced in vivo kidney fibrosis model was used. MHY2013 treatment significantly controlled decline in kidney function, tubule dilation, and FA-induced kidney damage. The extent of fibrosis determined using biochemical and histological methods showed that MHY2013 effectively blocked the development of fibrosis. Pro-inflammatory responses, including cytokine and chemokine expression, inflammatory cell infiltration, and NF-κB activation, were all reduced with MHY2013 treatment. To demonstrate the anti-fibrotic and anti-inflammatory mechanisms of MHY2013, in vitro studies were conducted using NRK49F kidney fibroblasts and NRK52E kidney epithelial cells. In the NRK49F kidney fibroblasts, MHY2013 treatment significantly reduced TGF-ß-induced fibroblast activation. The gene and protein expressions of collagen I and α-smooth muscle actin were significantly reduced with MHY2013 treatment. Using PPAR transfection, we found that PPARγ played a major role in blocking fibroblast activation. In addition, MHY2013 significantly reduced LPS-induced NF-κB activation and chemokine expression mainly through PPARß activation. Taken together, our results suggest that administration of the PPAR pan agonist effectively prevented renal fibrosis in both in vitro and in vivo models of kidney fibrosis, implicating the therapeutic potential of PPAR agonists against chronic kidney diseases.

One-Pot Synthesis of 1,3,4-Oxadiazines from Acylhydrazides and Allenoates.

The framework of 1,3,4-oxadiazine is crucial for numerous bioactive molecules, but only a limited number of synthetic methods have been reported for its production. In 2015, Wang's group developed a 4-(dimethylamino)pyridine (DMAP)-catalyzed [2 + 4] cycloaddition of allenoates with N-acyldiazenes, which provided an atom-efficient route for 1,3,4-oxadiazines. However, the practicality of this method was limited by the instability of N-acyldiazenes as starting materials. Building upon our ongoing research about the aerobic oxidation of hydrazides and their synthetic applications, we hypothesized that aerobic oxidative cycloadditions using acylhydrazides instead of N-acyldiazenes may provide a more practical synthetic route for 1,3,4-oxadiazines. In this manuscript, we describe a one-pot synthetic protocol for 1,3,4-oxadiazines from acylhydrazides and allenoates. The developed one-pot protocol consists of aerobic oxidations of acylhydrazides into N-acyldiazenes using NaNO2 and HNO3, followed by the DMAP-catalyzed cycloaddition of allenoate with the generated N-acyldiazenes. A variety of 1,3,4-oxadiazines were produced in good to high yields. In addition, the practicality of the developed method was demonstrated by a gram-scale synthesis of 1,3,4-oxadiazine.

Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects.

In this study, (Z)-2-(benzylamino)-5-benzylidenethiazol-4(5H)-one (BABT) derivatives were designed as tyrosinase inhibitors based on the structure of MHY2081, using a simplified approach. Of the 14 BABT derivatives synthesized, two derivatives ((Z)-2-(benzylamino)-5-(3-hydroxy-4-methoxybenzylidene)thiazol-4(5H)-one [7] and (Z)-2-(benzylamino)-5-(2,4-dihydroxybenzylidene)thiazol-4(5H)-one [8]) showed more potent mushroom tyrosinase inhibitory activities than kojic acid, regardless of the substrate used; in particular, compound 8 was 106-fold more potent than kojic acid when l-tyrosine was used as the substrate. Analysis of Lineweaver-Burk plots for 7 and 8 indicated that they were competitive inhibitors, which was confirmed via in silico docking. In experiments using B16F10 cells, 8 exerted a greater ability to inhibit melanin production than kojic acid, and it inhibited cellular tyrosinase activity in a concentration-dependent manner, indicating that the anti-melanogenic effect of 8 is attributable to its ability to inhibit tyrosinase. In addition, 8 exhibited strong antioxidant activity to scavenge 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and peroxynitrite and inhibited the expression of melanogenesis-associated proteins (tyrosinase and microphthalmia-associated transcription factor). These results suggest that BABT derivative 8 is a promising candidate for the treatment of hyperpigmentation-related diseases, owing to its inhibition of melanogenesis-associated protein expression, direct tyrosinase inhibition, and antioxidant activity.

Percutaneous Bone-Anchored Hearing Implant: Is It Clinically Useful in Korean?

BACKGROUND: The aim of this study is to investigate the clinical effectiveness of Ponto in Korea, a recently released percutaneous bone-anchored hearing implant. METHODS: 16 patients with single-sided deafness (SSD) and mixed or conductive hearing loss who underwent Ponto implantation from December 2018 to September 2020 were enrolled in the study. Puretone audiometry, the Korean version of the Hearing in Noise Test (K-HINT), sound localization test (SLT), and Pupillometry were performed pre- and three months post-operation. Standardized questionnaires, the Hearing Handicap Inventory for the Elderly (HHIE) and Speech, Spatial and Qualities of Hearing Scale (SSQ), were administered. RESULTS: The mean age of subjects was 55.5 (range, 48-67) years. Four males and 12 females participated in the study. The mean puretone average was 73.17 dB hearing level (HL) before surgery and significantly improved to 36.72 dB HL three months after surgery. The mean word recognition score improved from 26.0% to 90.75% after implantation. In the case of K-HINT, there was a significant difference in summation (Z = -2.250, P = 0.024) and head shadow effects (Z = -3.103, P = 0.002). There was no significant difference in root mean square error degree (RMSE) and hemifield identification scores for SLT testing. Pupillometry was performed to measure listening effort and the results revealed that the degree of pupillary dilatation decreased under the condition of quiet, 0 dB signal to noise ratio (SNR) and 3 dB SNR. The total score for HHIE decreased significantly (Z = -3.130, P = 0.002) while the SSQ score increased significantly (Z = -2.216, P = 0.027). CONCLUSIONS: The Ponto bone-anchored hearing system showed significant clinical benefit in Korean patients with conductive and mixed hearing loss and SSD.

Hearing and Speech Perception for People With Hearing Loss Using Personal Sound Amplification Products.

BACKGROUND: Hearing loss (HL) is the most common chronic disease and has been linked to negative health outcomes. Hearing aids (HAs) are regarded as the gold standard for HL management, however, the adoption rate of HAs is relatively low for various reasons. With this background, hearing devices, such as personal sound amplification products (PSAPs) received significant attention as an alternative to conventional HAs. This study aimed to evaluate the clinical efficacy of PSAPs in patients with mild to moderately severe HL. METHODS: Nineteen patients with mild hearing loss (MHL), 23 with moderate hearing loss (MDHL), and 15 with moderately severe hearing loss (MSHL) participated in the study. Electroacoustic analysis, simulated real-ear measurements (REMs), and three clinical evaluations were implemented. RESULTS: All devices satisfied the electroacoustic tolerances. All devices provided sufficient gain for MHL and MDHL audiograms. However, in MSHL audiogram, the gains of PSAPs were insufficient, especially for high frequencies. In terms of clinical evaluations, sound-field audiometry showed significant improvements between aided and unaided thresholds in all groups for all devices (P < 0.001). Significant improvements of word recognition scores were only shown for HAs between aided and unaided conditions. The Korean version of the Hearing In Noise Test did not show any consistent findings for all devices and groups. CONCLUSION: Certain PSAPs are beneficial for improving hearing and speech perception in patients with HL. Well-chosen PSAPs could be an alternative hearing rehabilitation option for these patients.

Factors Influencing Hearing Aid Adoption in Patients With Hearing Loss in Korea.

BACKGROUND: The purpose of this study was two-fold: 1) to identify differences in the characteristics of adopters and non-adopters of hearing aids (HAs); and 2) to investigate factors influencing the purchase of HA. METHODS: This study was conducted among 1,464 subjects (818 male and 646 female) with hearing loss. A national face-to-face survey was performed from August 2019 to October 2020 by otologists or HA experts. The questionnaire consisted of three domains: demographic, audiological, and HA-related domains. Multivariate logistic regression analysis was performed after adjusting for degree of hearing loss. RESULTS: The mean age of the participants was 70.4 ± 12.2 years. Of the 1,464 respondents, 1,190 (81.3%) had already purchased HA. We identified educational level, household income, hearing loss period, place of HA purchase, and government HA assistance program status as factors influencing HA adoption. Among these factors, third party reimbursement was the most important factor affecting HA purchase intent. The main reasons for not adopting HA were feeling that their hearing was adequate, inability to afford HA, and perceptions that HA are uncomfortable. CONCLUSION: Various factors are involved in the purchase of HA, but disabled registration status and third party reimbursement were identified as the most critical factors. In the future, the government should take a more active role in increasing the distribution of HA to patients with hearing loss.

Evaluation of deep learning for COVID-19 diagnosis: Impact of image dataset organization.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has spread all over the world showing high transmissibility. Many studies have proposed diverse diagnostic methods based on deep learning using chest X-ray images focusing on performance improvement. In reviewing them, this study noticed that evaluation results might be influenced by dataset organization. Therefore, this study identified whether the high-performance values can prove the clinical application potential. METHODS: This study selected chest X-ray image databases which have been widely applied in previous studies. One database includes images for COVID-19, while the others consist of normal and pneumonia images. Then, the COVID-19 classification model was designed and trained on diverse database compositions and evaluated using confusion matrix-based metrics. Also, each database was analyzed by graphical representation methods. RESULTS: The performance was significantly different according to dataset composition. Overall, higher performance was identified on the dataset organized with different databases for each class, compared with the dataset from same database. Also, there were significant differences in the image characteristics between different databases. CONCLUSIONS: The experimental results indicate that model may be trained based on differences of the image characteristics between databases and not on lesion features. This shows that evaluation metrics can be influenced by dataset organization, and high metric values would not directly mean the potential for clinical application. These emphasize the importance of suitable dataset organization for applying COVID-19 diagnosis methods to real clinical sites. Radiologists should sufficiently understand about this issue as actual user of these methods.

Development of Titanium Dioxide (TiO2)-Embedded Buoyant Photocatalyst Balls Using Expanded Polystyrene.

A new immobilization technique of nanoscale TiO2 powders to expanded polystryrene (EPS) balls with temperature-controlled melting method was developed for mass production, and the characterization of TiO2 powder-embedded EPS (TiEPS) balls was evaluated. Based on the scanning electron microscope (SEM) images and associated energy-dispersive X-ray spectroscopy (EDX) analysis, the components of intact EPS balls are carbon and oxygen whereas those of TiEPS balls are carbon, oxygen, and titanium, indicating that TiO2 powders were embedded on the surface of EPS balls. As also evident by the X-ray diffraction (XRD) and FTIR analyses, no significant changes in crystalline structure of TiO2 powders embedded on the EPS balls were found during the preparation and application processes of TiEPS balls. These characterization results indicated that the patches of TiO2 powders were soundly impregnated over the surface of EPS balls without the significant changes in crystalline structure of TiO2 powders and both structural changes and deformation of EPS polymer.

Application of Titanium Dioxide (TiO2)-Embedded Buoyant Photocatalyst Balls Using Expanded Polystyrene.

A new immobilization technique of nanoscale TiO2 powders to expanded polystryrene (EPS) balls with temperature-controlled melting method was validated for mass production, and the photocatalytic activity of TiO2 powder-embedded EPS (TiEPS) balls using methylene blue (MB) solution with different concentrations under ultraviolet irradiation and under the natural solar light irradiation. Whereas MB molecules were weakly adsorbed onto the surface of both TiO2 powders and supporting polymers without any specific interactions, the photocatalytic efficiency of TiEPS balls with UV (Kapp =0.016~0.043 min-1) was greater through coupled reaction processes (adsorption, photolysis, and photocatalysis). After 5-min sonication, more TiO2 powders on the TiEPS balls can be involved into the both adsorption and photocatalytic reactions of MB, and can increase the MB removal efficiencies. TiEPS balls can be reused for several consecutive runs without any significant decrease in photocatalytic activity until the recalcitrant contaminants were completely coated on the surface of TiEPS balls and loss of TiO2 powders embedded on the surface of TiEPS balls was significant. Based on the aforementioned results, self-floating TiEPS balls manufactured from this simple and cost-effective melting method can be used to remove the organic contaminants and to inhibit the excessive growth of harmful algae in the stagnant water body.

Automated classification of dense calcium tissues in gray-scale intravascular ultrasound images using a deep belief network.

BACKGROUND: IVUS is widely used to quantitatively assess coronary artery disease. The purpose of this study was to automatically characterize dense calcium (DC) tissue in the gray scale intravascular ultrasound (IVUS) images using the image textural features. METHODS: A total of 316 Gy-scale IVUS and corresponding virtual histology images from 26 patients with acute coronary syndrome who underwent IVUS along with X-ray angiography between October 2009 to September 2014 were retrospectively acquired and analyzed. One expert performed all procedures and assessed their IVUS scans. After image acquisition, the DC candidate and corresponding acoustic shadow regions were automatically determined. Then, nine image-base feature groups were extracted from the DC candidates. In order to reduce the dimensionalities, principal component analysis (PCA) was performed, and selected feature sets were utilized as an input for a deep belief network. Classification results were validated using 10-fold cross validation. RESULTS: The dimensionality of the feature map was efficiently reduced by 50% (from 66 to 33) without any performance decrease using PCA method. Sensitivity, specificity, and accuracy of the proposed method were 92.8 ± 0.1%, 85.1 ± 0.1%, and 88.4 ± 0.1%, respectively (p < 0.05). We found that the window size could largely influence the characterization results, and selected the 5 × 5 size as the best condition. We also validated the performance superiority of the proposed method with traditional classification methods. CONCLUSIONS: These experimental results suggest that the proposed method has significant clinical applicability for IVUS-based cardiovascular diagnosis.

A novel intensity-based multi-level classification approach for coronary plaque characterization in intravascular ultrasound images.

BACKGROUND: Intravascular ultrasound (IVUS) is a commonly used diagnostic imaging method for coronary artery disease. Virtual histology (VH) characterizes the plaque components into fibrous tissue (FT), fibro-fatty tissue (FFT), necrotic core (NC), or dense calcium (DC). However, VH can obtain only a single-frame image in one cardiac cycle, and specific software is needed to obtain the radio frequency data. This study proposed a novel intensity-based multi-level classification model for plaque characterization. METHODS: The plaque-containing regions between the intima and the media-adventitia were segmented manually for all IVUS frames. A total of 54 features including first order statistics, grey level co-occurrence matrix, Law's energy measures, extended grey level run length matrix, intensity, and local binary pattern were estimated from the plaque-containing regions. After feature extraction, optimal features were selected using principle component analysis (PCA), and these were utilized as the input for the classification models. Plaque components were classified into FT, FFT, NC, or DC using an intensity-based multi-level classification model consisting of three different nets. Net 1 differentiated low-intensity components into FT/FFT and NC/DC groups. Then, net 2 subsequently divided FT/FFT into FT or FFT, whereas the remainder and high-intensity components were classified into NC or DC via net 3. To improve classification accuracy, each net utilized three different input features obtained by PCA. Classification performance was evaluated in terms of sensitivity, specificity, accuracy, and receiver operating characteristic curve. RESULTS: Quantitative results indicated that the proposed method showed significantly high classification accuracy for all tissue types. The classifiers had classification accuracies of 85.1%, 71.9%, and 77.2%, respectively, and the areas under the curve were 0.845, 0.704, and 0.783. In particular, the proposed method achieved relatively high sensitivity (82.0%) and specificity (87.1%) for differentiating between the FT/FFT and NC/DC groups. CONCLUSIONS: These results confirmed the clinical applicability of the proposed approach for IVUS-based tissue characterization.

The effect of resistant starch (RS) on the bovine rumen microflora and isolation of RS-degrading bacteria.

Resistant starch (RS) in the diet reaches the large intestine without degradation, where it is decomposed by the commensal microbiota. The fermentation of RS produces secondary metabolites including short-chain fatty acids (SCFAs), which have been linked to a variety of physiological and health effects. Therefore, the availability of RS as a prebiotic is a current issue. The objectives of this study were (1) to use metagenomics to observe microbial flora changes in Bos taurus coreanae rumen fluid in the presence of RS and (2) to isolate RS-degrading microorganisms. The major microbial genus in a general rumen fluid was Succiniclasticum sp., whereas Streptococcus sp. immediately predominated after the addition of RS into the culture medium and was then drastically replaced by Lactobacillus sp. The presence of Bifidobacterium sp. was also observed continuously. Several microorganisms with high RS granule-degrading activity were identified and isolated, including B. choerinum FMB-1 and B. pseudolongum FMB-2. B. choerinum FMB-1 showed the highest RS-hydrolyzing activity and degraded almost 60% of all substrates tested. Coculture experiments demonstrated that Lactobacillus brevis ATCC 14869, which was isolated from human feces, could grow using reducing sugars generated from RS by B. choerinum FMB-1. These results suggest that Bifidobacterium spp., especially B. choerinum FMB-1, are the putative primary degrader of RS in rumen microbial flora and could be further studied as probiotic candidates.

Limited evidence of fungicide-driven triazole-resistant Aspergillus fumigatus in Hamilton, Canada.

Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen that can cause aspergillosis in humans. Over the last decade there have been increasing global reports of treatment failure due to triazole resistance. An emerging hypothesis states that agricultural triazole fungicide use causes clinical triazole resistance. Here we test this hypothesis in Hamilton, Ontario, Canada, by examining a total of 195 agricultural, urban, and clinical isolates using 9 highly polymorphic microsatellite markers. For each isolate, the in vitro susceptibilities to itraconazole and voriconazole, 2 triazole drugs commonly used in the management of patients, were also determined. Our analyses suggested frequent gene flow among the agricultural, urban environmental, and clinical populations of A. fumigatus and found evidence for widespread sexual recombination within and among the different populations. Interestingly, all 195 isolates analyzed in this study were susceptible to both triazoles tested. However, compared with the urban population, agricultural and clinical populations showed significantly reduced susceptibility to itraconazole and voriconazole, consistent with ecological niche-specific selective pressures on A. fumigatus populations in Hamilton. Frequent gene flow and genetic recombination among these populations suggest greater attention should be paid to monitor A. fumigatus populations in Hamilton and other similar jurisdictions.

Increased frequency of IL-6-producing non-classical monocytes in neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system that preferentially affects the optic nerves, spinal cord, and area postrema. A series of evidence suggested that B cells play a fundamental role in the pathogenesis of NMOSD. However, there are still gaps left to be answered in NMOSD pathogenesis suggesting the roles of other immune cells. This study aimed to investigate the monocyte inflammatory characteristics, monocyte subset frequency and cytokine production, and cell-surface molecule expression in NMOSD, multiple sclerosis (MS), and healthy controls (HC). METHODS: Peripheral blood mononuclear cells of 20 aquaporin 4IgG-positive NMOSD patients, 20 MS patients, and 20 healthy controls were collected to analyze the monocyte subsets and to purify monocytes. To mimic the adaptive immunity, we have activated the monocytes using CD40L and IFN-γ to observe the production of cytokines and expression of cell-surface molecules. RESULTS: NMOSD monocytes showed a remarkable increase in the production of pro-inflammatory cytokines (IL-6, IL-1ß) and increased expression of cell-surface molecules (CD80, HLA, ICAM-1, CD16), as well as a decrease in the levels of anti-inflammatory cytokine IL-10, compared to healthy control (HC) monocytes. As expected, MS monocytes also exhibit increased inflammatory cytokine production and increased cell-surface molecule expression compared to HC monocytes. Further analysis of monocyte subsets revealed that NMOSD monocytes have an increased frequency of the non-classical monocyte subset (CD14+CD16++) and a decreased frequency of the classical monocyte subset (CD14++CD16+) compared to HC monocytes. This finding was distinctly different from that of MS monocytes, which had an increased intermediate monocyte (CD14+CD16+) subset. In addition, these NMOSD non-classical monocyte subsets were highly dedicated, IL-6-producing monocytes. CONCLUSIONS: Increased expression of cell-surface molecules and a reciprocal dysregulation of inflammatory and anti-inflammatory cytokines in NMOSD monocytes suggest an altered monocyte inflammatory response. CD14+CD16++ non-classical monocyte subset was more abundant in NMOSD monocytes than in HC or MS monocytes, and NMOSD non-classical monocyte subset had dysregulated IL-6 production, a phenotype which has been reported to be highly associated with NMOSD pathogenesis.

The effect of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of cilostazol and its active metabolites in healthy Korean subjects.

AIMS: The primary objective of this study was to evaluate the effects of Ginkgo biloba extracts (GBE) on the pharmacokinetics of cilostazol and its metabolites. The secondary objective was to assess the effect of GBE on the pharmacodynamics of cilostazol. METHODS: A randomized, double-blind, two-way crossover study was conducted with 34 healthy Korean subjects. All subjects were given an oral dose of cilostazol (100 mg) plus GBE (80 mg) or cilostazol (100 mg) plus placebo twice daily for 7 days. Plasma concentrations of cilostazol and its active metabolites (3,4-dehydrocilostazol and 4'-trans-hydroxycilostazol) were measured using liquid chromatography-tandem mass spectroscopy on day 7 for pharmacokinetic assessment. The adenosine diphosphate-induced platelet aggregation and bleeding time were measured at baseline and on day 7 for pharmacodynamic assessment. RESULTS: The geometric mean ratios of area under the concentration-time curve for dosing interval for cilostazol plus GBE vs. cilostazol plus placebo were 0.96 (90% confidence interval, 0.89-1.03; P = 0.20) for cilostazol, 0.96 (90% confidence interval, 0.90-1.02; P = 0.30) for 3,4-dehydrocilostazol and 0.98 (90% confidence interval, 0.93-1.03; P = 0.47) for 4'-trans-hydroxycilostazol. The change of aggregation after administration of cilostazol plus GBE seemed to be 1.31 times higher compared with cilostazol plus placebo, without statistical significance (P = 0.20). There were no significant changes in bleeding times and adverse drug reactions between the treatments. CONCLUSIONS: Co-administration of GBE showed no statistically significant effects on the pharmacokinetics of cilostazol in healthy subjects. A large cohort study with long-term follow-up may be needed to evaluate the possible pharmacodynamic interaction between cilostazol and GBE, given that there was a remarkable, but not statistically significant, increase in inhibition of platelet aggregation.

Prevalence of antimicrobial resistance in normal rectal flora of patients undergoing transrectal ultrasonography-guided prostate biopsy in Korea.

OBJECTIVES: To determine the prevalence of antimicrobial resistance in the normal rectal flora of patients undergoing transrectal ultrasonography-guided prostate biopsy in Korea. METHODS: Between May 2010 and October 2010, rectal swabs were cultured from patients before transrectal ultrasonography-guided prostate biopsy in three tertiary referral centers of Jeonbuk Province, Korea. Rectal swabs were collected using cotton-tipped culture swabs in a standard collection system immediately before prostate biopsy. The swabs were cultured on eosin methylene blue and McConkey agar at 37°C. Antimicrobial sensitivity tests were carried out according to National Committee for Clinical Laboratory Standards guidelines. RESULTS: Of the 160 patients who had a rectal swab taken before prostate biopsy, microorganisms were isolated in 125 patients. Escherichia coli was isolated from the rectal swabs of 95 patients. The mean age was 68.1 years, the median serum prostate specific antigen was 5.6 ng/mL and the mean prostate volume measured by transrectal ultrasonography was 43.8 mL. Of the E. coli, 33.7%, 29.1%, 26.7%, 23.3%, 12.8%, 9.3%, 5.8%, 1.2% and 0% were resistant to ampicillin, piperacillin, levofloxacin, trimethoprim sulfamethoxazole, gentamicin, cephalothin, cefotaxim, amikacin and meropenem, respectively. CONCLUSIONS: There is a high level of resistance to ciprofloxacin and ampicillin, and a very low level of resistance to amikacin in the E. coli in the bowel flora. The prevalence of resistance to ciprofloxacin in Korea is significantly higher than that reported in Western countries.

Carbon-nanotube-grafted glass-fiber-reinforced composites: Synthesis and mechanical properties.

Glass fibers (GFs) are commonly used as reinforcements for advanced polymer composites. To improve the interfacial shear properties and mechanical properties of GF-reinforced composites (GFRPs), carbon nanotubes (CNTs) are directly grafted onto GFs using chemical vapor deposition (CVD). However, this process requires high temperatures, which causes thermal degradation of GFs, deteriorating their mechanical properties. In this study, a low-temperature CNT-grafting process was investigated using a bimetallic catalyst introduced onto a GF fiber surface via precursor solutions. The mechanical properties of the CNT-grafted GFs fabricated at different CVD temperatures were evaluated; they consistently showed low tensile strengths at temperatures above 400 °C. Subsequently, various CNT-grafted GFRPs were manufactured, and their mechanical properties were characterized. Interestingly, the flexural strengths of the composites increased with maintained tensile strength, despite a deterioration of the CNT-grafted GF reinforcements due to the CVD process. This could be attributed to the improved interfacial shear strength (IFSS) of the CNT-grafted GFs at the fiber level, and the enhanced compressive strength and interlaminar shear strength (ILSS) of CNT-grafted GFRPs at the composite level. Considering the properties of GF through CVD processes, particularly in relation to temperature, and factors such as IFSS, ILSS, tensile, compressive and flexural properties of composite materials, grafting CNTs on GF via a CVD system demonstrated its highest optimality at 450 °C.

Apple AirPods Pro as a Hearing Assistive Device in Patients with Mild to Moderate Hearing Loss.

PURPOSE: This study aimed to assess the feasibility of the Apple AirPods Pro with the headphone accommodation feature as a hearing assistive device for patients with mild to moderate hearing loss (HL). MATERIALS AND METHODS: The study included a total of 35 participants with mild to moderate HL. To determine the degree of HL in the participants, a screening test using pure-tone audiometry was conducted prior to the main tests of functional gain, word recognition score (WRS), and sentence recognition in noisy environments. The study employed two hearing devices: the Bean (a personal sound amplification product, PSAP) and the AirPods Pro. RESULTS: Regarding functional gain, there were no significant differences between the Bean and the AirPods Pro at all frequencies, except 8 kHz. In terms of WRS, both the Bean and the AirPods Pro had higher scores than the unaided condition. In sentence recognition, both the Bean and the AirPods Pro had higher scores than the unaided condition. During real-ear measurement, the Bean demonstrated consistent frequency responses, while the AirPods had a deviation exceeding 10 dB SPL at 6 kHz in the left ear. This deviation was absent for all other frequencies. CONCLUSION: This study shows that the Apple AirPods Pro, with its headphone accommodation feature, performed similarly to a validated PSAP and improved hearing compared to unaided conditions.

In vitro and in vivo anti-pigmentation effects of 2-mercaptobenzimidazoles as nanomolar tyrosinase inhibitors on mammalian cells and zebrafish embryos: Preparation of pigment-free zebrafish embryos.

Recently, 10 2-mercaptobenzo[d]imidazole (2-MBI) compounds (1-10) were synthesized. Although all 2-MBI compounds are tyrosinase inhibitors that inhibit mushroom tyrosinase at extremely low concentrations (IC50 values: 20-740 nM) and effectively inhibit the browning of apples, to our knowledge, no studies have determined whether 2-MBI compounds inhibit mammalian tyrosinase. Mammalian tyrosinase is different from mushroom tyrosinase in its distribution within the cell and has structural characteristics that are different from mushroom tyrosinase in amino acid sequence and in the presence of a quaternary structure. Thus, the effect of the 10 2-MBI compounds on mammalian tyrosinase activity was investigated in B16F10 cells. Six compounds (1-6) exhibited stronger intracellular tyrosinase inhibition than that of kojic acid and phenylthiourea (PTU), which are known to be the most potent tyrosinase inhibitors; their strong tyrosinase inhibitory activity robustly inhibited intracellular melanin production in B16F10 cells. None of the tested 2-MBI compounds exhibited appreciable cytotoxicity in HaCaT and B16F10 cells. To confirm the anti-melanogenic efficacy of the 2-MBI compounds in vivo, a zebrafish embryo model was used. At concentrations 100 times lower than kojic acid, most 2-MBI compounds demonstrated much stronger depigmentation efficacy than that of kojic acid, and three 2-MBI compounds (2-4) showed depigmentation activity similar to or more potent than that of PTU, resulting in nearly pigment-free zebrafish embryos. These results suggest that 2-MBI compounds may be potential therapeutic agents for hyperpigmentation-related disorders.