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Colorants, especially synthetic colorants, play a crucial role in enhancing the aesthetic qualities of food owing to their cost-effectiveness and stability against environmental factors. Ensuring the safe and regulated use of colorants is essential for maintaining consumer trust in food safety. Various preparation and analytical technologies, which are continuously undergoing improvement, are currently used to quantify of synthetic colorants in food products. This paper reviews recent developments in analytical techniques for synthetic food colorants, detection and compares the operational principles, advantages, and disadvantages of each technology. Additionally, it also explores advancements in these technologies, discussing several invaluable tools of analysis, such as high-performance liquid chromatography, liquid chromatography–tandem mass spectrometry, electrochemical sensors, digital image analysis, near-infrared spectroscopy, and surface-enhanced Raman spectroscopy. This comprehensive overview aims to provide valuable insights into current progress and research in the field of food colorant analysis. [Display omitted] • Eco-friendly methods for extracting synthetic food colorants are gaining attention. • As analytics advance, smartphone-based image analysis is another focus area. • Electrochemical sensors analyze fewer colorants but are simple and easy to use. • Portable analytical devices are suitable for on-site monitoring. • HPLC and LC–MS/MS remain popular for simultaneous colorant analysis. [ABSTRACT FROM AUTHOR]

Ultraperformance liquid chromatography with photodiode array detection was used to simultaneously quantify 34 permitted and prohibited synthetic colorants in beverages and candies. Solvent extraction was employed to extract colorants from food samples, proving to be simpler, more rapid and cost-effective, and less labor-intensive than other pretreatment techniques. Additionally, a single-laboratory study was conducted to validate the above method. The results of this validation, which was performed using blank beverage and candy samples, demonstrated satisfactory linearity and detection/quantitation limits. According to the FDA guidelines for the validation of chemical methods, the method exhibited a recovery of 85.4–108 % and repeatability of 0.427–6.73 % for intra- and interday tests. The established method enabled the simultaneous analysis of 34 permitted and prohibited colorants within a short timeframe of 13 min, and its applicability was confirmed by analyzing 93 types of beverages and 32 types of candies available on the market to ensure that the colorant content in all products was within permissible limits. Thus, the developed method was concluded to be particularly suitable for the rapid, accurate, and convenient monitoring of colorant content in commercial products. [Display omitted] • The developed method can analyze 34 synthetic colorants within 13 min. • It is efficient owing to its simple sample preparation and rapid analysis. • Validation was conducted following FDA guidelines. • A total of 125 commercially available food products were analyzed. [ABSTRACT FROM AUTHOR]

Background: To reduce out‐of‐pocket costs, the Korean government expanded health insurance reimbursement in anti‐cancer drugs for cancer patients in 2013. Our objective was to examine the impact of the benefit coverage expansion policy on healthcare utilization and overall survival (OS) among patients with six types of solid cancer after the policy of expanding health insurance coverage. Methods: This study analyzed a before‐and‐after retrospective cohort of patients newly diagnosed with six types of solid cancer (stomach cancer, colorectal cancer, lung cancer, liver cancer, breast cancer, and prostate cancer) from January 1, 2009 to December 31, 2015 in Korea. The intervention was the expansion of reimbursement in 2013. Multivariate Cox proportional hazards regression was used to estimate the policy effect. Results: In total, 142,579 before and 147,760 patients after the benefit expansion, and after matched by age, gender, and stage, 132,440 before and 132,440 patients after policy were included in the analysis. Almost total medical expenditure increased for five types of cancer increased. The expansion of health insurance reimbursement was associated with significantly lower overall mortality compared with pre‐policy mortality for all six cancer sites. Conclusion: The policy of expanding health insurance reimbursement might have been associated with a significant increase in survival among cancer patients by ensuring access to health care and medicine. Although the reimbursement expansion timing differs for each cancer, it is believed that eliminating delayed treatment might rather lead to reduce medical expenses and improve health outcomes. [ABSTRACT FROM AUTHOR]

Androgen-receptor splice variant 7 (AR-V7) is associated with castration-resistant prostate cancer (CRPC) and resistance to anti-androgen therapy. Despite its clinical importance, the lack of efficient methods for AR-V7 analysis remains a challenge for broader use of this biomarker in routine clinical practice. Herein, we suggest a practical and non-invasive liquid biopsy method for analysis of AR-V7 in the RNA of urine-derived extracellular vesicles (EVs) without the need for blood withdrawal. Urine-derived EVs were isolated by a lab-on-a-disc integrated with six independent nanofiltration units (Exo-Hexa) allowing simultaneous processing of six individual samples. Rapid enrichment of EVs (＜30 min) from each 4 mL urine sample was followed by mRNA extraction, and AR-V7 and androgen receptor full-length (AR-FL) mRNA levels in the urinary EVs were quantified by droplet digital polymerase chain reaction (ddPCR) as absolute concentrations (copies per mL). Higher AR-V7 and lower AR-FL expressions were detected in urine-derived EVs from 14 patients with CRPC than in those from 22 patients with hormone-sensitive prostate cancer. Additionally, we found that AR-V7 transcript levels and the AR-V7/AR-FL ratio in urinary EVs were higher in patients with advanced prostate cancer. This study is the first to report that RNA of urine-derived EVs is a reliable source for AR-V7 expression analysis. The proposed method for quantifying AR-V7 in urinary EVs prepared by a lab-on-a-disc is therefore a simple and promising approach to liquid biopsy with great potential for therapeutic impact on prostate cancer. [ABSTRACT FROM AUTHOR]

The current challenge in using extracellular vesicles (EVs) as drug delivery vehicles is to precisely control their membrane permeability, specifically in the ability to switch between permeable and impermeable states without compromising their integrity and functionality. Here, we introduce a rapid, efficient, and gentle loading method for EVs based on tonicity control (TC) using a lab-on-a-disc platform. In this technique, a hypotonic solution was used for temporarily permeabilizing a membrane ("on" state), allowing the influx of molecules into EVs. The subsequent isotonic washing led to an impermeable membrane ("off" state). This loading cycle enables the loading of different cargos into EVs, such as doxorubicin hydrochloride (Dox), ssDNA, and miRNA. The TC approach was shown to be more effective than traditional methods such as sonication or extrusion, with loading yields that were 4.3-fold and 7.2-fold greater, respectively. Finally, the intracellular assessments of miRNA-497-loaded EVs and doxorubicin-loaded EVs confirmed the superior performance of TC-prepared formulations and demonstrated the impact of encapsulation heterogeneity on the therapeutic outcome, signifying potential opportunities for developing novel exosome-based therapeutic systems for clinical applications. [ABSTRACT FROM AUTHOR]

The potential utility of circulating tumour DNA (ctDNA) in patient blood for cancer diagnostics and real-time monitoring of disease progression is highly recognized. However, the lack of automated and efficient methods for cell-free DNA (cfDNA) isolation from peripheral blood has remained a challenge for broader acceptance of liquid biopsy in general clinical settings. Here, we demonstrate a lab-on-a-disc system equipped with newly developed, electromagnetically actuated, and reversible diaphragm valves that allows fully automated and rapid (＜30 min) isolation of cfDNA from whole blood (＞3 ml) to achieve high detection sensitivity by minimizing the degradation of fragile ctDNA as well as contamination of wild-type DNA from abundant blood cells. As a proof of concept study, we used the lab-on-a-disc to isolate cfDNA from patients with non-small cell lung cancer and successfully detected epidermal growth factor receptor gene mutations (L858R, T790M) during targeted drug therapy. The proposed lab-on-a-disc enables a fully automated, rapid, and point-of-care cfDNA enrichment starting from whole blood to facilitate the wide use of liquid biopsy in routine clinical practice. [ABSTRACT FROM AUTHOR]

The Fusarium fungi produce toxic substances called mycotoxins, which can cause disease and harmful effects in grains, livestock, and humans. Deoxynivalenol (DON), also known as vomitoxin, is one of the Fusarium mycotoxins that is known to cause vomiting in livestock. This study shows the occurrence of deoxynivalenol in feedstuffs (compound feed and feed ingredients) between 2009 and 2016 in South Korea. A total of 653 domestic samples were collected at five time points, including 494 compound feed samples and 159 feed ingredient samples. DON contamination levels were analyzed using high-performance liquid chromatography (HPLC) with pretreatment using an immunoaffinity column (IAC). The limit of detection (LOD) and the limit of quantification (LOQ) were estimated at 1-10 µg/kg and 3-35 µg/kg, respectively. Two compound feeds (two gestating sow feed samples) out of 160 pig feed samples exceeded the European Commission (EC) guidance value, while no feed ingredient samples exceeded the EC or South Korean guidance values. There were statistically significant differences in the mean contamination levels of compound feed and feed ingredients that indicated a decreasing trend over time. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between potentially inappropriate medicine (PIM) use, defined using the American Geriatric Society (AGS) 2012 Beers criteria, and the risk of hospitalization or emergency department (ED) visits in elderly patients, and to examine the most frequently used PIMs among patients with adverse outcomes.Design/setting: This was a retrospective study using National Health Insurance claims data from 2010 to 2012.Intervention(s): Elderly patients who took PIMs are compared to those who were not taking PIMs.Study Participants: Elderly patients (n = 79 552) who visited medical institutions in Jeju Island during 2011.Main Outcome Measure: Hospitalization and ED visits were evaluated according to whether the patients took PIMs during the study period. The most frequent medications used by the PIM group were also investigated.Results: The likelihood of hospitalization was higher in older patients who took at least one PIM than in those who were not taking PIMs during the study period (odds ratio 2.25, 95% confidence interval 2.09-2.44). Patients taking PIMs were more likely to visit EDs (odds ratio 1.59, 95% confidence interval 1.50-1.67). Among patients who were hospitalized or visited EDs, 45.5% had taken at least one PIM on that day. The most commonly used PIMs included chlorpheniramine maleate, diazepam, metoclopramide HCl and diclofenac sodium.Conclusion: Our findings indicate that PIM use can lead to negative health consequences, providing further evidence of the inappropriateness of these medications. Thus, pharmaceutical policies regarding PIM use may need to be implemented for elderly adults in Korea. [ABSTRACT FROM AUTHOR]

Ensuring consumer safety in the food industry requires rapid and reliable analytical techniques. This study presents a liquid chromatography with an ultraviolet detection method for the simultaneous determination of 20 preservatives in jerky samples, with a total analysis time of 24 min. Various sorbents and their combinations were evaluated for their matrix removal capabilities. The combination of C 18 endcapped SPE, Z-Sep+, and Envi-Carb demonstrated effective removal of proteins and fatty acids. Validation experiments confirmed satisfactory correlation coefficients (> 0.9970), low limit of quantification (0.24–4.85 mg/kg), and low relative standard deviation (2.2%). The average spiked recoveries were 70.4%–112.3% at concentrations above 20 mg/kg. Among the detected preservatives in jerky samples, including sorbic acid, ethyl p -hydroxybenzoate, methyl p -hydroxybenzoate, butylated hydroxyanisole, and p -cresol none exceed the legal limits. This method offers a rapid, straightforward approach for preservatives detection in jerky and has the potential for application in monitoring various dried meat products. [Display omitted] • Ultraviolet-based strategy was used for determining preservatives in jerky samples. • Food preservatives are used to prevent rancidity during storage and processing. • QuEChERS extraction with cold acetonitrile and a weak acid removed the jerky matrix. [ABSTRACT FROM AUTHOR]

Background: Inappropriate antibiotic use significantly contributes to antibiotic-resistance, resulting in reduced antibiotic efficacy and increasing physical burden and cost of disease. The goal of this study was to explore antibiotic usage patterns in South Korea using 2007–2014 health insurance claims data. Methods: We used the Health Insurance Review & Assessment Service data, which represents nearly the entire population of South Korea, to discern patterns in antibiotic prescribing practices. The daily dose, as defined by the World Health Organization ([defined daily doses]/1000 inhabitants/day, [DID]), was used as a measure of antibiotic use. Subgroup analyses were performed on the basis of patient characteristics (sex, age, and disease) and provider characteristics (type of medical institution). Results: Antibiotic use in DID increased from 23.5 in 2007 to 27.7 in 2014. The ≤ 6 years old age group showed the highest level of usage at 59.21 DID in 2014, and showed an increasing trend each year. DIDs of beta-lactam antibacterials, penicillins (J01C), other beta-lactam antibacterials (J01D), lincosamides and streptogramins (J01F), quinolone antibacterials (J01M), and other antibacterials (J01X) increased over time. Conclusion: This study provides valuable statistics regarding antibiotic usage in South Korea; this is important for guiding health policy with regard to antibiotic usage. There is a need for further study exploring antibiotics use and resistance. [ABSTRACT FROM AUTHOR]

A fluorescence switch that consists of DNA-templated silver nanoclusters (DNA-AgNCs) triggered by silver ion (Ag + ) is developed to detect Ag + . The mechanism of the fluorescence switching of DNA-AgNCs is investigated by fluorescence spectroscopy, circular dichroism spectroscopy, DNA hybridization assay and mass spectrometry. Ag + induces a dimeric structure of Cyt 12 -AgNCs by forming a bridge between two Cyt 12 -AgNCs, where Cyt 12 is cytosine 12-mer; this dimer formation causes the fluorescence change of Cyt 12 -AgNCs from red to green. Using this Ag + -triggered fluorescence switch, we successfully detected Ag + at concentrations as low as 10 nM. Furthermore, we quantitatively detected the Ag + in the Silmazin ® , which is dermatological burn ointment having silver sulfadiazine. Ag + detection using this fluorescence switch has high selectivity and sensitivity, and short response time, and can be used successfully even in the presence of other metal ions. [ABSTRACT FROM AUTHOR]

Abstract: The work employs carbon dot (CD) which has been emerging as a fluorescent nanomaterial with excellent biocompatibility and perceived as a promising alternative to quantum dot (QD), to monitor the association/dissociation of polymeric carrier/plasmid DNA (pDNA) complex during transfection. To shed light on the underlying post-endosomal events and provide the insight to design rational and efficient gene delivery vector, the adopted strategy exploited the quenching of the fluorescence of CD by Au nanoparticles. The surface of CD and Au was modified with highly cationic polymer, polyethylenimine (PEI) and subsequent treatment with non-labeled pDNA gave rise to quenched delivery complex. High salt concentration triggered the dissociation of the complex with accompanied fluorescence recovery arising due to the increase in distance between CD and Au. The studies revealed the potential of the developed CD-PEI/Au-PEI/pDNA ternary nano-assembly as a highly efficient hybrid transfecting agent with high cell viability under the optimum condition. The changes occurred at the intracellular level during transfection especially post-endosomal step were monitored by fluorescence measurement using fluorescence microscope. This nano-assembly system was found to be very effective at monitoring the carrier/pDNA dissociation in a non-labeled manner, thus provides efficient strategy to study the mechanistic aspect of polymer-mediated pDNA delivery. [Copyright &y& Elsevier]

Abstract: A rapid, homogeneous, and in-situ labelable format designed to detect single nucleotide polymorphism (SNP) is presented. Fluorescent silver nanoclusters produced following hydride-mediated reduction of Ag+ bound to a partial double-stranded oligodeoxynucleotide were employed as probes for SNPs. The sensing mechanism is based on the fluorescence enhancement of silver nanoclusters through an irreversible cluster transfer upon hybridization. The key element of our design is modulating the “turn on” mechanism by introducing a competitor that can be displaced in response to a target DNA. In a controlled model system, the fluorescence intensity of silver nanoclusters is approximately 3-fold enhanced upon hybridization with a perfectly matched target DNA, and single-base mismatch detection is achieved within 5min, regardless of the position of mismatches. Human aldehyde dehydrogenase 2 (ALDH2), which is responsible for the oxidation of aldehydes to carboxylic acids, is then utilized as a target for SNP. Upon addition of a perfectly matched sequence, dramatically enhanced fluorescence intensity is observed (ca. 48-fold), and prompt SNP genotyping is accomplished. [Copyright &y& Elsevier]

Gene therapy aims to treat human disorders by introducing genetic materials into specific target cells or tissues. Despite the curability for the origIn of diseases by restoring missing functionalities, no technical feasibility of gene therapy has been established due to the lack of safe and efficient gene delivery systems. The emergence of nanotechnology has provided an opportunity to create nanomaterials that are suitable for the biomedical applications. Nanomaterials integrated with cationic polymers offer novel platforms that allow not only easy incorporation of genetic materials through electrostatic interactions but also further modifications to be upgraded to theranostics. In this article, current status of gene delivery utilizing hybrid nanomaterials that are composed of novel nanoplatforms and cationic polymers are highlighted. In particular, different strategies employed for the construction of nanomaterial-polymer hybrids are described. [ABSTRACT FROM AUTHOR]

Background/purpose: Infrared thermal images in patients suffering from herpes zoster (HZ) may exhibit thermal asymmetry due to the unilateral distribution of HZ lesions. This study examined the usefulness of infrared thermography in acute HZ as a predictor for the development of postherpetic neuralgia (PHN). Methods: The authors collected demographic and clinical data including age, sex, onset of skin lesion, pain intensity by a visual analogue scale (VAS) and the development of PHN from a total of 55 patients diagnosed with HZ. We evaluated the body surface thermographic parameters between the lesion and contralateral normal skin: maximal difference in the temperature (Δ T) and the size of the body surface area (BSA) showing thermal asymmetry. Results: Temperatures of the lesions were found to be warmer than the control side in most patients with acute HZ. We compared the patient group who developed PHN with those who did not. In univariate analysis, patients with PHN were older ( P=0.004), had a higher VAS score for pain ( P<0.001), higher Δ T ( P<0.001) and larger BSA ( P=0.001). In logistic regression analysis to identify independent risk factors of PHN, older age (>60 years old) and Δ T more than 0.5 °C were found to be statistically significant. [ABSTRACT FROM AUTHOR]

Abstract: TC1 (C8orf4) is associated with aggressive behavior and poor survival in cancer. We have recently reported that it is a target gene of NF-κB and regulates the Wnt/β-catenin pathway. Here, we show that TC1 is upregulated by various cellular stresses and mediates heat shock response. Heat shock and other cellular stresses including H2O2, 12-O-tetradecanoylphorbol 13-acetate (TPA), lipopolysaccharide (LPS), and UV enhance TC1 transcription in HeLa, KATO-III, HEK293T, and HK cells. TC1 protein then moves into the nuclei independently of NF-κB activation. TC1 upregulates heat shock proteins, and TC1-knockdown inhibits stress-induced downstream regulation significantly. Heat shock factor 1(HSF1) and TC1 upregulate each other, suggesting a potential positive feedback in the heat shock response regulation. Our data suggest that TC1 is a novel heat shock response regulator. [Copyright &y& Elsevier]

Presents information on a study which examined the effect of multiple roles of married women professors in South Korea. Discussion on the role changes and factors influencing potential role gratification and strain; Review of related literature: Methodology of the study; Results and discussion.

Simple Summary: We found a novel cyclic pentadepsipeptide, N-methylsansalvamide (MSSV), and evaluated its anti-tumor action against bladder cancer using in vitro and in vivo model systems. Additionally, we report its anti-angiogenic responses both in vitro and in vivo. Moreover, acute toxicity test and tissue staining for liver function revealed that orally administered MSSV (2000 mg/kg for 14 days) exerted no harmful effects as it did not cause animal death, undesirable weigh alteration, adverse clinical symptoms, and abnormal biochemical marker levels (AST, ALT). Here, we explored the anti-tumor efficacy of a cyclic pentadepsipeptide, N-methylsansalvamide (MSSV), in bladder cancer. MSSV inhibited the proliferation of both bladder cancer 5637 and T24 cells, which was attributed to the G1-phase cell cycle arrest, apoptosis induction, and alteration of mitogen-activated protein kinases (MAPKs) and protein kinase b (AKT) signaling pathways. Additionally, the treatment of bladder cancer cells with MSSV suppressed migratory and invasive potential via the transcription factor-mediated expression of matrix metalloproteinase 9 (MMP-9). MSSV abrogated vascular endothelial growth factor (VEGF)-induced angiogenic responses in vitro and in vivo. Furthermore, our result showed the potent anti-tumor efficacy of MSSV in a xenograft mouse model implanted with bladder cancer 5637 cells. Finally, acute toxicity test data obtained from blood biochemical test and liver staining indicated that the oral administration of MSSV at 2000 mg/kg caused no adverse cytotoxic effects. Our preclinical data described the potent anti-angiogenic and anti-tumor efficacy of MSSV and showed no signs of acute toxicity, thereby suggesting the putative potential of oral MSSV as a novel anti-tumor agent in bladder cancer treatment. [ABSTRACT FROM AUTHOR]

MoS2 crystals grown by chemical vapor deposition are suited for realization of practical 2D semiconductor-based electronics. In order to construct complementary circuits with n-type MoS2, another p-type semiconductor, whose performance can be adjusted corresponding to that of MoS2 in the limited chip area, has to be sought. Herein, we present a method for tuning switching threshold voltages of complementary inverters simply via inkjet printing without changing their channel dimensions. Random networks of inkjet printed single-walled carbon nanotubes are formed as p-channels beside MoS2, and their density and thickness are controlled by varying the number of printed layers. As a result, p-type transistor characteristics as well as inverter characteristics are facilely tuned only by varying the number of printed layers. [ABSTRACT FROM AUTHOR]

A photoresponsive drug releasing system based on mesoporous silica nanoparticles (MSN) was developed. A model drug was decorated on the surfaces via singlet oxygen sensitive linkers and a singlet oxygen-generating photosensitizer was loaded in the mesopores of the MSN. An on-demand drug releasing system was successfully developed by irradiation with long-wavelength light. [ABSTRACT FROM AUTHOR]

Simple Summary: Considering the spatiotemporal heterogeneity, more frequent monitoring of the disease progress using less-invasive liquid biopsy technologies is highly desired. Here, we demonstrate that epidermal growth factor receptor (EGFR) mutations could be readily detected from minimally invasive bronchial washing (BW)-derived EVs with good accuracy. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than in plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. We demonstrate the clinical potential of BW-derived EVs as a liquid-biopsy sample for prognosis and precision medicine in patients with lung cancer. The detection of epidermal growth factor receptor (EGFR) mutation, based on tissue biopsy samples, provides a valuable guideline for the prognosis and precision medicine in patients with lung cancer. In this study, we aimed to examine minimally invasive bronchial washing (BW)-derived extracellular vesicles (EVs) for EGFR mutation analysis in patients with lung cancer. A lab-on-a-disc equipped with a filter with 20-nm pore diameter, Exo-Disc, was used to enrich EVs in BW samples. The overall detection sensitivity of EGFR mutations in 55 BW-derived samples was 89.7% and 31.0% for EV-derived DNA (EV-DNA) and EV-excluded cell free-DNA (EV-X-cfDNA), respectively, with 100% specificity. The detection rate of T790M in 13 matched samples was 61.5%, 10.0%, and 30.8% from BW-derived EV-DNA, plasma-derived cfDNA, and tissue samples, respectively. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. The EGFR mutations can be readily detected in BW-derived EVs, which demonstrates their clinical potential as a liquid-biopsy sample that may aid precise management, including assessment of the treatment response and drug resistance in patients with lung cancer. [ABSTRACT FROM AUTHOR]

• Polyethylene glycol with 100–10000 Da can be simultaneously analyzed. • These polymers can be quantitated using high-performance liquid chromatography. • These polymers can be identified in extracted ion chromatogram in mass analysis. • Polyethylene glycol in food supplement tablets can be extracted and easily analyzed. Polyethylene glycol (PEG) are widely applied in detergents, cosmetics, and food additives. A simultaneous analytical method was developed to detection the polyethylene glycol (100–10000 Da). High-performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) could analyze successively PEG products. The method was verified with liquid chromatography–electrospray ionization mass spectrometry (LC-ESI-MS/MS). The retention times of PEG 200–8000 ranged from 1.97 to 12.33 min. Method validation was performed to the International Conference on Harmonization (ICH) guidelines and the Korea Ministry of Food and Drug Safety (MFDS); linearity: R2 > 0.997, LOD: 7.47–16.24 µg/mL, LOQ: 22.40–75 µg/mL, repeatability (%RSD): 0.2–2.5, recovery (%): 90.4–104.9% for film-coated tablet, 80.1–95.9% for sugar-coated tablet. A total of 115 PEG could be identified by extracted ion chromatography in mass analysis, based on the charge state represented as [M+Na++H 3 O+ n-1. This method can be applied for successive identification of PEGs in PEG-containing products. [ABSTRACT FROM AUTHOR]

Background: A computerized drug utilization review (DUR) program has provided physicians and pharmacists with alerts on drug-drug interactions (DDIs), drug-age precautions and therapeutic duplication in Korea since 2010.Objective: The purpose of this study was to evaluate the impact of the DUR program on health outcomes associated with DDIs.Methods: An uncontrolled before-after study was performed to investigate the impact of the nationwide DUR program on DDIs and related health outcomes. The study population consisted of people who used two types of DDI pairs before DUR implementation (from January 2009 to December 2010) and post-DUR implementation (from January 2012 to December 2013); (i) benzodiazepines with concurrent use of metabolic enzyme inhibitors and (ii) QTc (heart-rate corrected QT interval) prolongation agents. The main outcome measures were all-cause and cause-specific hospitalization admissions or emergency department (ED) visits.Results: This study included 107 874 people who used benzodiazepines with enzyme inhibitors and 8489 who received co-medication of QTc prolongation agents. For patients receiving a combination of benzodiazepines and enzyme inhibitors, both all-cause hospitalization and cause-specific hospitalization decreased after DUR implementation, from 43.2% to 41.7% and from 4.6% to 4.5% (adjusted odds ratio [OR] = 0.96; 95% confidence interval (CI), 0.93-0.98; OR = 0.89, 95% CI = 0.84-0.99, respectively). For patients receiving co-medication of QTc prolongation agents, all-cause hospitalization (54.2%) was lower than before (54.9%) (OR = 0.87, 95% CI = 0.79-0.96), but no significant change was found for cause-specific hospitalization and ED visits.Conclusion: Implementation of a DUR program may reduce the adverse health outcomes posed by DDIs in patients on combination of benzodiazepines and enzyme inhibitors potentially QTc-prolongation agents. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the pattern of changes in antibiotic prescription and antimicrobial resistance (AMR) in Escherichia coli in South Korea between 2007 and 2018. We collected data related to antibiotic prescription and AMR in E. coli from the national surveillance system. We used the Mann–Kendall test and Spearman's correlation to identify the trends of antibiotic prescription and AMR in E. coli and to examine the relationship between them, respectively. Although we noted a significant decreasing trend of ampicillin and gentamicin prescriptions in all medical institutions, we identified a higher level of AMR in long-term care facilities than in other medical institutions. We did not identify a significant positive correlation between ampicillin and gentamicin prescriptions and their resistance in E. coli. However, we found a significant positive correlation between cefotaxime prescription and its resistance in E. coli in hospitals, long-term care facilities, and clinics. Our results strongly suggest that long-term care facilities in South Korea have the potential to sustain AMR epidemics and that more efforts are needed to curb AMR in E. coli. Further epidemiological studies using enhanced AMR surveillance are warranted. [ABSTRACT FROM AUTHOR]

This study investigated the distribution of twelve mycotoxins (aflatoxins B1, B2, G1, and G2; ochratoxin A; fumonisins B1 and B2; deoxynivalenol; nivalenol; zearalenone; T-2 toxin; and HT-2 toxin) in corn and corn by-products (corn bran, cornstarch, corn gluten, corn gluten feed, corn germ, light steep water, and corn steep liquor) produced by wet-milling in Korea. Fifty-two samples were collected from three factories producing cornstarch and other corn by-products. The samples were pretreated on an immunoaffinity column (IAC), and then the levels of the 12 mycotoxins were analyzed simultaneously by liquid chromatography-coupled triple-quadrupole mass spectrometry (LC-MS/MS). Fusarium mycotoxins were mainly found in raw corn and corn gluten feed samples. Other mycotoxins—such as aflatoxins, ochratoxin A, and HT-2 toxin—were detected in tiny amounts below the limit of quantification (LOQ) in cornstarch, corn germ, and corn bran. Ochratoxin A and nivalenol were mainly carried over into cornstarch. Aflatoxin B1, deoxynivalenol, T-2 toxin, HT-2 toxin, and the fumonisins were concentrated in corn gluten feed. Zearalenone was evenly distributed in all corn by-products except cornstarch during the milling process. [ABSTRACT FROM AUTHOR]

Platelets play crucial roles in hemostasis and immunity. Over the last decades, clinical evidence has revealed the significance of platelets as complementary biomarkers for the detection and treatment of various diseases, including cancer. Due to a lack of well standardized convenient isolation methods for platelets, pre-analytical factors such as complex handling procedures negatively impact the quality of the platelet samples, including overactivation, low purity, and poor reproducibility. This may lead to biased interpretation of various downstream analyses, such as proteomic and genomic analyses. Herein, we describe a fully automated lab-on-a-disc-based method of platelet isolation from a small volume of blood (<1 mL). This method provides higher yields (>4 folds) and purity (>99%) and lower platelet activation than the conventional method. Moreover, it was also superior in the detection of platelet-related RNAs CD41, PF4, and P2Y12 due to lower contamination with white blood cells. [ABSTRACT FROM AUTHOR]

Despite three decades of use and related research efforts, how automotive HUD can be designed to best serve the driver is still an on-going research issue. For any human-machine system, studying the experiences of the existing users is an important first step towards design improvement and innovation. Nonetheless, surprisingly few studies have investigated the user experience of the existing commercial automotive HUD systems. In an effort to address the research gap, the current study conducted a user survey on the usage contexts and design improvement points of the existing automotive HUD systems focusing on eleven high-priority HUD information items selected among those displayed by the existing commercial HUD systems. A total of fifty-one drivers with significant prior HUD use experience participated. Design implications were derived from the survey responses. They may be useful for improving the existing automotive HUD systems in both the system functions and the interface/interaction design. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are potent antigen-presenting cells with high sentinel ability to scan their neighborhood and to initiate an adaptive immune response. Whereas chemotactic migration of mature DCs (mDCs) towards lymph nodes is relatively well documented, the migratory behavior of immature DCs (imDCs) in tumor microenvironments is still poorly understood. Here, microfluidic systems of various geometries, including mazes, are used to investigate how the physical and chemical microenvironment influences the migration pattern of imDCs. Under proper degree of confinement, the imDCs are preferentially recruited towards cancer vs. normal cells, accompanied by increased cell speed and persistence. Furthermore, a systematic screen of cytokines, reveals that Gas6 is a major chemokine responsible for the chemotactic preference. These results and the accompanying theoretical model suggest that imDC migration in complex tissue environments is tuned by a proper balance between the strength of the chemical gradients and the degree of spatial confinement. [ABSTRACT FROM AUTHOR]

Bacillus cereus is a Gram-positive that is ubiquitous in foods and the wider environment. The B. cereus emetic toxin, cereulide, synthesized by nonribosomal peptide synthetase ( NRPS), can cause either gastrointestinal disorders and/or emetic form of food poisoning. In this study, 108 B. cereus isolates from foods were tested for a correlation between the presence of emetic toxin genes and cereulide production. Based on 16S rRNA sequence analysis, 107 isolates were identical to B. cereus spp. Further experiments showed that fourteen isolates exhibited 1,271, 2,200 and 188-bp bands, corresponding to amplification of the ces1, ces2 and NRPS gene, respectively. However, only 7 out of 13 strains possessing the NRPS, ces1, and ces2 genes produced cereulide in liquid culture. Strain number 93, isolated from fresh vegetables, produced the highest levels of cereulide (11.17 μg/mL); maximum cereulide levels were observed after 4 days of cultivation at 30C in LB broth. The amount of cereulide produced differed between each isolate. Practical Applications The incident of Bacillus cereus in food could cause food poisoning. The results of our study on the presence of B. cereus in spoiled foods demonstrated that not all the food poisoning B. cereus spp. have the ability to synthesize the emetic toxin, cereulide. Nonribosomal peptide synthetase and cereulide synthetase genes could be used as biological markers for differentiation of cereulide producing and nonproducing B. cereus. Estimation of cereulide level reveals that the amounts of cereulide produced by some strains were very high and could be a threat to human health if consumed in contaminated foods. This study presents proper methods to select cereulide producing food-poisoning B. cereus spp. and gives more information on the condition of cereulide production to prevent future cases of emetic food poisoning. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) have great potential to provide minimally invasive ways for the early detection of cancer metastasis and for the response monitoring of various cancer treatments. Despite the clinical importance and progress of CTC-based cancer diagnostics, most of the current methods of enriching CTCs are difficult to implement in general hospital settings due to complex and time-consuming protocols. Among existing technologies, size-based isolation methods provide antibody-independent, relatively simple, and high throughput protocols. However, the clogging issues and lower than desired recovery rates and purity are the key challenges. In this work, inspired by antifouling membranes with liquid-filled pores in nature, clog-free, highly sensitive (95.9 ± 3.1% recovery rate), selective (>2.5 log depletion of white blood cells), rapid (>3 mL/min), and label-free isolation of viable CTCs from whole blood without prior sample treatment is achieved using a stand-alone lab-on-a-disc system equipped with fluid-assisted separation technology (FAST). Numerical simulation and experiments show that this method provides uniform, clog-free, ultrafast cell enrichment with pressure drops much less than in conventional size-based filtration, at 1 kPa. We demonstrate the clinical utility of the point-of-care detection of CTCs with samples taken from 142 patients suffering from breast, stomach, or lung cancer. [ABSTRACT FROM AUTHOR]

The article reports on the a case of a 69-year-old man with gastric cancer who experienced changes to his fingernails following the initiation of chemotherapy.

A lab-on-a-disc is a unique microfluidic platform that utilizes centrifugal force to pump liquids. This offers many benefits for point-of-care devices because it eliminates the need for connections to multiple pumps and complex tubing connections. A wide range of applications including clinical chemistry, immunoassay, cell analysis, and nucleic acid tests could be demonstrated on a spinning disc. To enable the performance of assays in a fully integrated and automated manner, the robust actuation of integrated valves is a prerequisite. However, conventional passive-type valves incur a critical drawback in that their operation is dependent on the rotational frequency, which is easily influenced by the channel geometry and chemistry, in addition to the physical properties of the liquids to be transferred. Even though a few active-type valving techniques permit the individual actuation of valves, independent of the rotational frequency, complex procedures for the fabrication as well as actuation mechanisms have prevented their broader acceptance in general applications. Here, we report on a lab-on-a-disc incorporating individually addressable diaphragm valves (ID valves) that enable the reversible and thermally stable actuation of multiple valves with unprecedented ease and robustness. These ID valves are configured from an elastic epoxy diaphragm embedded on a 3D printed push-and-twist valve, which can be easily actuated by a simple automatic driver unit. As a proof of concept experiment, an enzyme-linked immunosorbent assay (ELISA) and a polymerase chain reaction (PCR) were performed on a disc in a fully automated manner to demonstrate the robust, reversible, leak-free, and thermally stable actuation of the valves. [ABSTRACT FROM AUTHOR]

Bovine intestinal alkaline phosphatase (biALP), a membrane-bound plasma metalloenzyme, maintains intestinal homeostasis, regulates duodenal surface pH, and protects against infections caused by pathogenic bacteria. The N -glycans of biALP regulate its enzymatic activity, protein folding, and thermostability, but their structures are not fully reported. In this study, the structures and quantities of the N -glycans of biALP were analyzed by liquid chromatography−electrospray ionization-high energy collision dissociation−tandem mass spectrometry. In total, 48 N -glycans were identified and quantified, comprising high-mannose [6 N -glycans, 33.1 % (sum of relative quantities of each N -glycan)], hybrid (6, 11.9 %), and complex (36, 55.0 %) structures [bi- (13, 26.1 %), tri- (16, 21.5 %), and tetra-antennary (7, 7.4 %)]. These included bisecting N -acetylglucosamine (33, 56.6 %), mono-to tri-fucosylation (32, 53.3 %), mono-to tri-α-galactosylation (16, 20.7 %), and mono-to tetra-β-galactosylation (36, 58.5 %). No sialylation was identified. N -glycans with non-bisecting GlcNAc (9, 10.3 %), non-fucosylation (10, 13.6 %), non-α-galactosylation (26, 46.2 %), and non-β-galactosylation (6, 8.4 %) were also identified. The activity (100 %) of biALP was reduced to 37.3 ± 0.2 % (by de-fucosylation), 32.7 ± 2.9 % (by de-α-galactosylation), and 0.2 ± 0.2 % (by de-β-galactosylation), comparable to inhibition by 10−4 to 101 mM EDTA, a biALP inhibitor. These results indicate that fucosylated and galactosylated N -glycans, especially β-galactosylation, affected the activity of biALP. This study is the first to identify 48 diverse N -glycan structures and quantities of bovine as well as human intestinal ALP and to demonstrate the importance of the role of fucosylation and galactosylation for maintaining the activity of biALP. [Display omitted] • N -glycans of biALP regulates its activity, but their structures have not been fully reported. • Forty-eight N -glycans were identified and quantified in biALP by LC-ESI-HCD-MS/MS. • De-fucosylation or de-galactosylation of N -glycans in biALP reduced enzymatic activity. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which addresses a population-based study on what the authors refer to as the factors that are associated with potentially inappropriate medication (PIM) use in elderly Koreans in an outpatient medical care setting, and it mentions drug prescription data.

Abstract: Tussilagone (TSL), isolated from the flower of buds of Tussilago farfara (Compositae), is a sesquiterpenoid that is known to exert a variety of pharmacological activities. In the present study, we demonstrated that TSL exerts anti-inflammatory activities in murine macrophages by inducing heme oxygenase-1 (HO-1) expression. Treatment of RAW264.7 cells with TSL-induced HO-1 protein expression in a dose- and time-dependent manner without the induction of HO-1 mRNA expression. TSL-mediated HO-1 protein induction was not inhibited by treatment with actinomycin D, a transcriptional inhibitor, but by cycloheximide, a translational inhibitor. Moreover, mitogen-activated protein kinases (MAPKs) inhibitors such as SB203580, SP600125, and U0126 did not block TSL-mediated HO-1 protein expression, suggesting that the TSL-mediated HO induction may be regulated at the translational level. Consistent with the notion that HO-1 has anti-inflammatory properties, TSL inhibited the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin E2 (PGE2) as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and murine peritoneal macrophages. Inhibition of HO-1 activity by treatment with zinc protoporphyrin IX (ZnPP), a specific HO-1 inhibitor, abrogated the inhibitory effects of TSL on the production of NO and PGE2 in LPS-stimulated RAW264.7 cells. Taken together, TSL may be an effective HO-1 inducer that has anti-inflammatory effects, and a valuable compound for modulating inflammatory conditions. [Copyright &y& Elsevier]

Abstract: Follicular dendritic cells (FDC) play crucial roles in immune regulation. TNF-α has been shown to be essential to the FDC network. However, the molecular regulation of FDC proliferation has not been characterized. Here, we show that TC1(C8orf4), a novel positive regulator of the Wnt/β-catenin pathway in vertebrates, is upregulated by IL-1β and TNF-α in the human FDC-like line HK. TC1 enhances HK cell proliferation, while TC1-knockdown inhibits the proliferation induced by IL-1β, suggesting a role of TC1 as a regulator of FDC proliferation. The regulation by pro-inflammatory cytokines suggests that TC1 might be implicated in linking local inflammation to immune response by stimulating FDC. [Copyright &y& Elsevier]

Correction for 'Immature dendritic cells navigate microscopic mazes to find tumor cells' by Eujin Um et al., Lab Chip, 2019, 19, 1665–1675. [ABSTRACT FROM AUTHOR]

Highlights • Simultaneous HPLC analysis of sodium iron/sodium copper chlorophyllins (SIC/SCC). • Inertsil ODS-2 column and methanol/water/acetic acid mobile phase used in HPLC. • Detection performed at wavelength of 395 nm. • Main components were Fe-isochlorine e4 (for SIC) and Cu-isochlorine e4 (for SCC). Abstract A simultaneous method for analyzing sodium iron chlorophyllin (SIC) and sodium copper chlorophyllin (SCC) using high-performance liquid chromatography was developed. This method employed an Inertsil ODS-2 column and diode array detection at 395 nm, using methanol–water (97:3 and 80:20, v/v) containing 1% acetic acid as the mobile phase. Liquid chromatography–tandem mass spectrometry was used to identify the main components of SIC and SCC as Fe-isochlorine e4 and Cu-isochlorine e4, respectively. The limits of detection and quantitation of SIC were 1.2 and 4.1 mg/kg, respectively, while those of SCC were 1.4 and 4.8 mg/kg, respectively. For intraday and interday tests, the SIC recoveries from candy ranged from 81% to 101%, while SCC recoveries ranged from 100% to 109%. The developed method can be applied to the rapid determination of SIC and SCC in candy. [ABSTRACT FROM AUTHOR]

Background: Adherence to inhaled medication regimens affects chronic obstructive pulmonary disease (COPD) prognosis and quality of life, and reduces the use of healthcare services, resulting in cost savings.Objectives: To examine the effects of adherence to inhaled medication regimens on healthcare utilization and costs in high-grade COPD patients.Methods: We performed an observational retrospective cohort study using a longitudinal data set from the Korean Health Insurance Review and Assessment Service (2008-2013) containing healthcare services’ information for 50 million beneficiaries. The study population was high-grade COPD patients. “Adherent” was defined as a patient attaining a medication possession ratio (MPR) ≥ 80%. We estimated the effects of adherence on the use of intensive care units (ICUs) and emergency rooms (ERs) using a multivariate logistic regression, and estimated the effects on costs (all-cause and COPD-related) using a generalized linear model, with adjustment for patient sociodemographic characteristics, health status, and comorbidities.Results: Of 9086 high-grade COPD patients, adherence declined from 34.7 to 22.3% over 4 years. Adherence was inversely associated with use of ICUs and costs, and this association got stronger as the adherence period lengthened. Over the 4-year period, the adherent group had a lower likelihood of using ICUs [odds ratio (OR) = 0.74, 95% confidence interval (CI) 0.60-0.91] than the non-adherent group. Similarly, the adherent group had a 10.4% lower all-cause cost (p < 0.001) and an 11.7% lower COPD-related cost (p < 0.0001) versus the non-adherent group.Conclusions: Adherence reduces healthcare utilization and costs, so adherence is not only clinically effective but also economically efficient. However, less than one-quarter of this population remained adherent over the 4-year period, suggesting that strategies are needed to improve adherence. [ABSTRACT FROM AUTHOR]

Background: The use of circulating tumor cells (CTCs) as an early diagnostic biomarker and prognostic indicator after surgery or chemotherapy has been suggested for various cancers. This study aimed to evaluate CTCs in patients who underwent gastrectomy for gastric cancer and to explore their clinical usefulness in the early diagnosis of gastric cancer. Methods: A total of 116 patients with gastric cancer who underwent gastrectomy and 31 healthy volunteers were prospectively included between 2014 and 2015. Peripheral blood samples were collected before gastrectomy, and CTCs were examined using a centrifugal microfluidic system with a new fluid-assisted separation technique. Results: After creating a receiver operating characteristic curve to identify the discriminative CTC value needed differentiate patients with gastric cancer from healthy volunteers, sensitivity and specificity were nearly optimized at a CTC threshold of 2 per 7.5 mL of blood. Of the 102 persons with a CTC level ≥2 per 7.5 mL of blood, 99 (97.1%) had gastric cancer, and of the 45 persons with a CTC level <2 per 7.5 mL of blood, 28 (62.2%) were healthy controls. Accordingly, the sensitivity and specificity for the differentiation of patients with gastric cancer from healthy controls were 85.3% and 90.3%, respectively. However, the presence of CTCs was not associated with any clinicopathologic features such as staging, histologic type, or mucin phenotype. Conclusion: Although we could not prove the clinical feasibility of CTCs for gastric cancer staging, our results suggest a potential role of CTCs as an early diagnostic biomarker of gastric cancer. [ABSTRACT FROM AUTHOR]

To better understand the role of Opa in gonococcal infections, we created and characterized a derivative of MS11 (MS11Δopa) that had the coding sequence for all 11 Opa proteins deleted. The MS11Δopa bacterium lost the ability to bind to purified lipoo-ligosaccharide (LOS). While nonpiliated MS11Δopa and nonpiliated Opa-expressing MS11 cells grew at the same rate, nonpiliated MS11Δopa cells rarely formed clumps of more than four bacteria when grown in broth with vigorous shaking. Using flow cytometry analysis, we demonstrated that MS11Δopa produced a homogeneous population of bacteria that failed to bind monoclonal antibody (MAb) 4B 12, a MAb specific for Opa. Opa-expressing MS11 cells consisted of two predominant populations, where ~ 85% bound MAb 4B 12 to a significant level and the other population bound little if any MAb. Approximately 90% of bacteria isolated from a phenotypically Opa-negative colony (a colony that does not refract light) failed to bind MAb 4B12; the remaining 10% bound MAb to various degrees. Piliated MS11Δopa cells formed dispersed microcolonies on ME180 cells which were visually distinct from those of piliated Opa-expressing MS11 cells. When Opa expression was reintroduced into MS11Δopa, the adherence ability of the strain recovered to wild-type levels. These data indicate that Opa contributes to both bacterium-bacterium and bacterium-host cell interactions. [ABSTRACT FROM AUTHOR]

Highlights from the article: Nanobiointerfaces: Human Platelet Membrane Functionalized Microchips with Plasmonic Codes for Cancer Detection (Adv. Funct. In article number 1902669, Yoon-Kyoung Cho and co-workers describe a microfluidic chip equipped with a platelet membrane-cloaked surface, the "PLT-Chip", which takes advantage of the strong and specific interaction between platelets and cancer-derived extracellular vesicles. Cancer, extracellular vesicles, plasmonic coupling, platelets.

The possibility of functional roles played by platelets in close alliance with cancer cells has inspired the design of new biomimetic systems that exploit platelet–cancer cell interactions. Here, the role of platelets in cancer diagnostics is leveraged to design a microfluidic platform capable of detecting cancer‐derived extracellular vesicles (EVs) from ultrasmall volumes (1 µL) of human plasma samples. Further, the captured EVs are counted by direct optical coding of plasmonic nanoprobes modified with EV‐specific antibodies. Owing to the inherent properties of platelets for multifaceted interaction with cancer cells, the microfluidic chip equipped with a biologically interfaced platelet membrane‐cloaked surface (denoted "PLT‐Chip") can capture a significantly higher number of EVs from multiple types of cancer cell lines (prostate, lung, bladder, and breast) than the normal cell‐derived EVs. Furthermore, this chip allows the monitoring of the growth of tumor spheroids (100 µm–2.5 mm) and clearly distinguishes the plasma of cancer patients from that of normal healthy controls. This robust, multifaceted, and cancer‐specific binding affinity, coupled with excellent biocompatibility, is a unique feature of platelet membrane‐cloaked surfaces, which therefore represent promising alternatives to antibodies for application in EVs‐based cancer theranostics. [ABSTRACT FROM AUTHOR]

Ribosomal S6 kinase 2 (RSK2), regulated by Ras/Raf/MEKs/ERKs, transmits upstream activation signals to downstream substrates including kinases and transcription and epigenetic factors. We observed that ELK members, including ELK1, 3, and 4, highly interacted with RSK2. We further observed that the RSK2-ELK3 interaction was mediated by N-terminal kinase and linker domains of RSK2, and the D and C domains of ELK3, resulting in the phosphorylation of ELK3. Importantly, RSK2-mediated ELK3 enhanced c-fos promoter activity. Notably, chemical inhibition of RSK2 signaling using kaempferol (a RSK2 inhibitor) or U0126 (a selective MEK inhibitor) suppressed EGF-induced c-fos promoter activity. Moreover, functional deletion of RSK2 by knockdown or knockout showed that RSK2 deficiency suppressed EGF-induced c-fos promoter activity, resulting in inhibition of AP-1 transactivation activity and Ras-mediated foci formation in NIH3T3 cells. Immunocytofluorescence assay demonstrated that RSK2 deficiency reduced ELK3 localization in the nucleus. In MDA-MB-231 breast cancer cells, knockdown of RSK2 or ELK3 suppressed cell proliferation with accumulation at the G1 cell cycle phase, resulting in inhibition of foci formation and anchorage-independent cancer colony growth in soft agar. Taken together, these results indicate that a novel RSK2/ELK3 signaling axis, by enhancing c-Fos-mediated AP-1 transactivation activity, has an essential role in cancer cell proliferation and colony growth. [ABSTRACT FROM AUTHOR]