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Cold atmospheric microwave plasma (CAMP) is a promising therapeutic option for treating skin infections and wounds. Changes in biophysical skin parameters and the tolerability in dogs after applying CAMP is unknown.This study aimed to evaluate the in vivo effects of CAMP on skin biophysical parameters [hydration, transepidermal water loss (TEWL) and surface temperature] and tolerability in dogs.Twenty client-owned dogs with normal skin.Cold atmospheric microwave plasma treatment was performed for 30 s and 1, 2 and 4 min, respectively, at different sites of normal canine skin in the inguinal area. Hydration, TEWL and surface temperature were measured five, three and three times, respectively, before and after CAMP application. After treatment, pain and adverse effects were evaluated using a modified Melbourne Pain Scale and the modified short form Glasgow Composite Measure Pain Scale (modified CMPS-SF).Transepidermal water loss values significantly decreased with 4 min of treatment, and hydration decreased significantly with 2 min of treatment. Temperature increased significantly with increasing treatment time. For other parameters, no significant changes were observed. No significant pain response or adverse effects were observed in most dogs, aside from mild erythema in the treatment area after 4 min.Cold atmospheric microwave plasma treatment was well-tolerated and did not significantly change canine skin biophysical parameters. CAMP achieves basic recommendations for safe use and is a potential therapeutic option for various skin diseases in dogs.Contexte - Le CAMP (Cold Atmospheric Microwave Plasma) est une option thérapeutique prometteuse pour le traitement des infections cutanées et des plaies. Les modifications des paramètres biophysiques de la peau et la tolérance chez les chiens après l'application de CAMP sont inconnues. Objectif - Cette étude visait à évaluer les effets in vivo du CAMP sur les paramètres biophysiques de la peau [hydratation, perte d'eau transépidermique (TEWL) et température de surface] et la tolérance chez le chien. Animaux - Vingt chiens de propriétaires à peau normale. Matériels et méthodes - Le traitement CAMP a été effectué pendant 30 s et 1, 2 et 4 min, respectivement, sur différents sites de peau canine normale dans la région inguinale. L'hydratation, la TEWL et la température de surface ont été mesurées cinq, trois et trois fois, respectivement, avant et après l'application de CAMP. Après le traitement, la douleur et les effets indésirables ont été évalués à l'aide d'une échelle de douleur de Melbourne modifiée et de la forme courte modifiée de l'échelle de mesure de la douleur composite de Glasgow (CMPS-SF modifiée). Résultats - Les valeurs de TEWL ont diminué de manière significative après 4 minutes de traitement et l'hydratation a diminué de manière significative après 2 minutes de traitement. La température a augmenté de manière significative avec l'augmentation du temps de traitement. Pour les autres paramètres, aucun changement significatif n'a été observé. Aucune réponse significative à la douleur ni aucun effet indésirable n'ont été observés chez la plupart des chiens, à l'exception d'un léger érythème dans la zone de traitement après 4 minutes. Conclusion et signification clinique - Le traitement CAMP a été bien toléré et n'a pas modifié de manière significative les paramètres biophysiques de la peau canine. CAMP répond aux recommandations de base pour une utilisation sûre et constitue une option thérapeutique potentielle pour diverses maladies de la peau chez les chiens.Introducción- el plasma de microondas atmosférico frío (CAMP) es una opción terapéutica prometedora para el tratamiento de infecciones y heridas de la piel. Se desconocen los cambios en los parámetros biofísicos de la piel y la tolerabilidad en perros después de aplicar CAMP. Objetivo- este estudio tuvo como objetivo evaluar los efectos in vivo de CAMP en los parámetros biofísicos de la piel [hidratación, pérdida de agua transepidérmica (TEWL) y temperatura superficial] y la tolerabilidad en perros. Animales - Veinte perros de propietarios particulares con piel normal. Materiales y métodos - El tratamiento CAMP se realizó durante 30 s y 1, 2 y 4 min, respectivamente, en diferentes sitios de piel canina normal en el área inguinal. La hidratación, el TEWL y la temperatura superficial se midieron cinco, tres y tres veces, respectivamente, antes y después de la aplicación de CAMP. Después del tratamiento, el dolor y los efectos adversos se evaluaron mediante una escala de dolor de Melbourne modificada y la escala de dolor de medida compuesta de Glasgow de forma abreviada modificada (CMPS-SF modificada). Resultados- los valores de TEWL disminuyeron significativamente con 4 min de tratamiento y la hidratación disminuyó significativamente con 2 min de tratamiento. La temperatura aumentó significativamente con el aumento del tiempo de tratamiento. Para otros parámetros no se observaron cambios significativos. En la mayoría de los perros no se observaron reacciones significativas de dolor ni efectos adversos, aparte de un leve eritema en el área de tratamiento después de 4 min. Conclusión y significado clínico- el tratamiento con CAMP fue bien tolerado y no cambió significativamente los parámetros biofísicos de la piel canina. CAMP obtuvo recomendaciones básicas para un uso seguro y es una opción terapéutica potencial para diversas enfermedades de la piel en perros.Hintergrund - Kaltes atmosphärisches Mikrowellen Plasma (CAMP) ist eine vielversprechende therapeutische Option zur Behandlung von Hautinfektionen und Wunden. Veränderungen der biophysischen Hautparameter und der Toleranz bei Hunden nach Anwendung von CAMP ist bisher nicht bekannt. Ziel - Diese Studie zielte darauf ab, die in vivo Wirksamkeit von CAMP auf biophysische Parameter der Haut [Hydration, Transepidermaler Wasserverlust (TEWL) und die Oberflächentemperatur] und die Verträglichkeit bei Hunden zu evaluieren. Tiere - Es wurden zwanzig Hunde in Privatbesitz, alle mit normaler Haut, inkludiert. Materialien und Methoden - Eine CAMP Behandlung wurde für 30 s und 1, 2 bzw 4 Minuten an verschiedenen Stellen normaler Hundehaut in der Inguinalgegend durchgeführt. Hydration, TEWL und die Oberflächentemperatur wurde fünf, drei bzw dreimal vor und nach der CAMP Anwendung gemessen. Nach der Behandlung wurden Schmerz und Nebenwirkungen mittels modifizierter Melbourne Pain Scale sowie der modifizierten Kurzform der Glasgow Measure Pain Scale (modifizierte CMPS-SF) evaluiert. Ergebnisse - Die TEWL Werte nahmen nach 4 Minuten der Behandlung, die Hydration nach 2 Behandlungsminuten signifikant ab. Die Temperatur nahm mit zunehmender Behandlungsdauer signifikant zu. Für die anderen Parameter konnten keine signifikanten Veränderungen beobachtet werden. Es wurden bei den meisten Hunden keine signifikanten Schmerzreaktionen oder Nebenwirkungen beobachtet, außer einem geringen Erythem nach 4 Minuten in der behandelten Körperregion. Schlussfolgerungen und klinische Bedeutung - Die Behandlung mit CAMP wurde gut toleriert und veränderte die biophysischen Parameter der Hundehaut nicht signifikant. Daher kann die CAMP grundsätzlich zur sicheren Anwendung bei Hunden empfohlen werden und stellt eine potenzielle Therapieoption für verschiedene Hauterkrankungen bei Hunden dar.背景 - 低音大気圧マイクロ波プラズマ (CAMP) は、皮膚の感染症や創傷の治療法として有望である。イヌにCAMPを適用した場合の皮膚の生物物理学的パラメータの変化と忍容性は不明である。 目的 -本研究は、犬の皮膚の生物物理学的パラメータ (水和性、経皮水分蒸散量(TEWL) 、表面温度) および忍容性に及ぼすCAMPのin vivo効果を評価することを目的とした。 供試動物 - 正常な皮膚を持つオーナー所有犬20頭。 材料と方法 -正常なイヌの鼠径部皮膚の異なる部位に、CAMP処理を30秒、1分、2分、4分それぞれ実施した。水和性、TEWL、表面温度はCAMP塗布の前後にそれぞれ5回、3回、3回測定した。治療後、修正メルボルン疼痛尺度及び修正短形式グラスゴー複合測定疼痛尺度 (修正CMPS-SF) を用いて、疼痛および副作用を評価した。 結果 - TEWL値は4分間の治療で有意に減少し、水和性は2分間の治療で有意に減少した。表面温度は治療時間が長くなるにつれて有意に上昇した。その他のパラメータについては、有意な変化は認められなかった。4分後の治療部位の軽度の紅斑を除けば、ほとんどの犬で有意な疼痛反応や副作用は観察されなかった。 結論と臨床的意義 - CAMP治療は忍容性が高く、犬の皮膚の生物物理学的パラメータに有意な変化を与えなかった。CAMPは安全使用のための基本的な推奨事項を満たしており、犬の様々な皮膚疾患に対する潜在的な治療オプションであると考えられる。.背景-冷大气微波等离子体(CAMP)是治疗皮肤感染和伤口的一种有前景的治疗选择。尚不清楚应用CAMP后犬的生物物理皮肤参数变化和耐受性。 目的-本研究旨在评价CAMP对犬皮肤生物物理参数[水合作用、经表皮水分流失(TEWL)和表面温度]和耐受性的体内影响。 动物-20只皮肤正常的私家犬。 材料与方法-在腹股沟区正常犬皮肤不同部位分别进行CAMP治疗30s和1、2和4 min。应用CAMP前后分别测量5次、3次和3次水化、TEWL和表面温度。治疗后采用改良墨尔本疼痛量表和改良简明格拉斯哥综合测量疼痛量表(改良CMPS-SF)评价疼痛和不良反应。 结果-治疗4 min后,TEW L值显著下降,治疗2 min后, 水合作用显著下降。随着治疗时间的增加,温度显著增加。对于其他参数,未观察到显著变化。除4 min后治疗区域出现轻度红斑外,在大多数犬中未观察到显著的疼痛反应或不良反应。 结论和临床意义-CAMP治疗耐受性良好,未显著改变犬皮肤生物物理参数。CAMP实现了安全使用的基本建议,是犬各种皮肤病的潜在治疗选择.Contexto - O plasma frio atmosférico de micro-ondas (CAMP) é uma opção terapêutica promissora para o tratamento de infecções cutâneas e feridas. Não se sabe a respeito das alterações nos parâmetros biofísicos da pele e a tolerabilidade de cães após a aplicação de CAMP. Objetivo - Este estudo tem como objetivo avaliar os efeitos in vivo de CAMP nos parâmetros biofísicos da pele [hidratação, perda de água transepidérmica (TEWL) e temperatura da superfície] e a tolerabilidade em cães. Materiais e métodos - O tratamento com CAMP foi realizado por 30s e 1, 2 e 4 min, respectivamente, em diferentes locais da pele canina normal na região inguinal. Hidratação, TEWL e temperatura da superfície foram medidas cinco, três e três vezes, respectivamente, antes e após a aplicação do CAMP. Após o tratamento, a dor e os efeitos adversos foram avaliados usando uma escala de dor de Melbourne modificada e a escala de medida composta de dor de Glasgow modificada (CMPS-SF modificada). Resultados - Os valores de TEWL reduziram significativamente com o tratamento de 4 min, e a hidratação reduziu significativamente com dois minutos de tratamento. A temperatura aumentou significativamente com o aumento do tempo de tratamento. Não foram observadas alterações significativas para outros parâmetros. Não se observou uma resposta de dor significativa ou efeitos adversos na maioria dos cães, além de eritema leve na área tratada após 4 min. Conclusão e significância clínica - O tratamento com CAMP foi bem tolerado e não alterou significativamente os parâmetros biofísicos da pele canina. CAMP requer recomendações básicas de segurança na sua utilização e é uma opção terapêutica potencial para várias dermatopatias em cães.

Carbapenems are broad-spectrum antibiotics widely used for the treatment of human infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, emerging carbapenemase-producing Enterobacterales (CPE) are rising as a public threat to human and animal health. We screened clinical bacterial isolates from 241 dogs and 18 cats hospitalized at Veterinary Medical Teaching Hospital, Seoul National University, from 2018 to 2020 for carbapenemase production. In our study, 5 strains of metallo-β-lactamase NDM-5-producing Escherichia coli and Klebsiella pneumoniae were isolated from 4 different dogs. Multilocus sequence typing (MLST) results showed that all E. coli strains were ST410 and all K. pneumoniae strains were ST378. Whole genome analysis of the plasmid showed that blaNDM-5 is carried on a IncX3 plasmid, showing a high concordance rate with plasmids detected worldwide in human and animal isolates. The blaNDM gene was associated with the bleMBL gene and the ISAba125 element, truncated with the IS5 element. The results of this study show that CPE has already become as a threat to both animals and humans in our society, posing the necessity to solve it in terms of "One Health". Therefore, preventive strategies should be developed to prevent the spread of CPE in animal and human societies.

A synthesis and patterning process of luminescent graphene quantum dots (GQDs) is highly desirable in applications to industrial- and bio-fields. In this paper, a novel strategy to obtain GQDs is proposed and demonstrated by an ion-beam assisted chemical vapor deposition (CVD). Ion-beam irradiation provides catalyst sources for the GQD creation. The luminescent GQDs are generated using a Fe-implanted Si wafer by a two-step annealing process: i) A formation step of nano-sized Fe catalyst particles and ii) a synthesis step of GQDs by a CVD method. Under the 1st annealing step of the Fe-implanted Si wafer, Fe nanoparticles (FeNPs) are created by the diffusion and aggregation of Fe atoms. Due to the high temperature atmosphere in the 2nd annealing step, FeNPs are then completely removed, and thus only high-purity and -quality GQDs are finally produced. In our work, patterned GQDs were fabricated by using a metallic mask during the ion-beam irradiation. Furthermore, various GQD patterns were also demonstrated by combining the conventional semiconductor manufacturing process and our ion-beam assisted CVD technique.

Highly sensitive rapid testing for COVID-19 is essential for minimizing virus transmission, especially before the onset of symptoms and in asymptomatic cases. Here, we report bioengineered enrichment tools for lateral flow assays (LFAs) with enhanced sensitivity and specificity (BEETLES2), achieving enrichment of SARS-CoV-2 viruses, nucleocapsid (N) proteins and immunoglobulin G (IgG) with 3-minute operation. The limit of detection is improved up to 20-fold. We apply this method to clinical samples, including 83% with either intermediate (35%) or low viral loads (48%), collected from 62 individuals (n = 42 for positive and n = 20 for healthy controls). We observe diagnostic sensitivity, specificity, and accuracy of 88.1%, 100%, and 91.9%, respectively, compared with commercial LFAs alone achieving 14.29%, 100%, and 41.94%, respectively. BEETLES2, with permselectivity and tunability, can enrich the SARS-CoV-2 virus, N proteins, and IgG in the nasopharyngeal/oropharyngeal swab, saliva, and blood serum, enabling reliable and sensitive point-of-care testing, facilitating fast early diagnosis.

A simple, affordable point of care test (POCT) is necessary for on-site detection of coronavirus disease 2019 (COVID-19). The lateral flow assay (LFA) has great potential for use in POCT mainly because of factors such as low time consumption, low cost, and ease of use. However, it lacks sensitivity and limits of detection (LOD), which are essential for early diagnostics. In this study, we proposed a non-powered preconcentrator (NPP) based on nanoelectrokinetics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Antigen (Ag) lateral flow assay. The non-powered preconcentrator is composed of glass fiber-based composite paper and ion permselective material, and it can be simply operated by force balancing gravitational, capillary, and depletion-induced forces. The proposed approach helps enrich the SARS-CoV-2 viral nucleocapsid (N) proteins based on a 10-min operation, and it improved the LOD by up to 10-fold. The corresponding virus enrichment, which was evaluated using the reverse-transcriptase polymerase chain reaction (RT-PCR), revealed an improvement in ΔCt values 3. We successfully demonstrated the enhancement of the NPP-assisted LFA, we extended to applying it to clinical samples. Further, we demonstrated an affordable, easy-to-implement form of LFA by simply designing NPP directly on the LFA buffer tube.

Advanced anodic SnO

The COVID-19 pandemic has been suggested to have adverse impacts on psychiatric disorders. This study aimed to investigate the changes in medical visits due to a wide range of psychiatric disorders in children during the COVID-19 pandemic. The medical visits of all Korean children and adolescents (0–19 years old) due to the 12 following psychiatric disorders were investigated: autism; attention-deficit/hyperactivity disorder (ADHD); depressive disorder; bipolar disorder; primary insomnia; schizophrenia; panic disorder; hypochondriasis; posttraumatic stress disorder (PTSD); anxiety disorder; anorexia nervosa; and adephagia. The mean medical visits before and during the COVID-19 pandemic were compared. The mean number of clinical visits due to autism, ADHD, depressive disorder, bipolar disorder, panic disorder, hypochondriasis, PTSD, anxiety disorder, and anorexia nervosa was higher during the COVID-19 pandemic than before the COVID-19 pandemic (all p < 0.05). The higher mean number of medical visits due to psychiatric disorders was maintained in age and sex subgroups. The female and adolescent groups demonstrated a higher mean number of medical visits due to psychiatric disorders during the COVID-19 pandemic. The medical visits due to many psychiatric disorders were higher during the COVID-19 pandemic than before COVID-19 in children and adolescents in Korea. Women and adolescents were more susceptible to psychiatric disorders during the COVID-19 pandemic.

Background Gintonin is a ginseng-derived exogenous G-protein–coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood–brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. Methods We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. Conclusions We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.

Fluorescent graphene quantum dots (GQDs) have a significant potential in the application to bio-fields. However, most of the GQDs synthesized by existing methods face limitations due to the harmful chemicals involved in their synthesis and the presence of various oxygen functional groups, both of which affect the biocompatibility of the GQDs. Here, we present a simple approach to fabricating fluorescent and biocompatible high-quality GQDs with low oxygen content without the involvement of harmful chemicals. High-quality GQDs are synthesized by hydrogen-assisted pyrolysis of silicon carbide and this dry synthesis process allows the GQDs to possess high crystallinity with no unwanted chemicals on the surface. Subsequently, the high-quality GQDs are slightly oxidized through sonication in ethanol, but the treated GQDs (t-GQDs) still retain their high crystallinity. The t-GQDs exhibit strong ultraviolet/blue light emission with a high yield of 30.9%, a phenomenon that can be attributed to intrinsic emission resulting from the low oxygen content of the t-GQDs. Furthermore, the t-GQDs show low cytotoxicity even at a high concentration of 200 μg/mL due to the absence of harmful chemicals during their synthesis and the low oxygen content of the t-GQDs. These results demonstrate the excellence of the t-GQDs and their applicability in bio-fields.

A lateral flow assay (LFA) platform is a powerful tool for point-of-care testing (POCT), especially for self-testing. Although the LFA platform provides a simple and disposable tool for Coronavirus disease of 2019 (COVID-19) antigen (Ag) and antibody (Ab) screening tests, the lower sensitivity for low virus titers has been a bottleneck for practical applications. Herein, we report the combination of a microfluidic paper-based nanoelectrokinetic (NEK) preconcentrator and an LFA platform for enhancing the sensitivity and limit of detection (LOD). Biomarkers were electrokinetically preconcentrated onto a specific layer using the NEK preconcentrator, which was then coupled with LFA diagnostic devices for enhanced performance. Using this nanoelectrokinetic-assisted LFA (NEK-LFA) platform for self-testing, the severe acute respiratory syndrome coronavirus 2 Immunoglobulin G (SARS-CoV-2 IgG) sample was preconcentrated from serum samples. After preconcentration, the LOD of the LFA was enhanced by 32-fold, with an increase in analytical sensitivity (16.4%), which may offer a new opportunity for POCT and self-testing, especially in the COVID-19 pandemic and endemic global context.

The concept of a Major/Minor system was applied to use urban flood prediction techniques, based on rainfall forecasts and real-time simulations, to reduce flood damage, by notifying a possible flood risk in advance. The SWMM one dimensional (1D)-two dimensional (2D) model has become the standard approach used in urban flood modeling, as it can realistically express the interaction between drainage networks and road surfaces. However, it is limited to the flood analysis of small areas due to its two-dimensional model characteristics, such as its long simulation time. Therefore, the SWMM 1D-1D model, which is fast enough to be applied to real-time simulations, is applied to real-time flood forecasting. To improve the accuracy of the model, SWMM 1D-1D model was calibrated using the SWMM 1D-2D model simulation results, and the SWMM 1D-1D model simulation results were extracted using the SWMM5 DLL and EXCEL VBA to analyze the flood situation. Finally, the applicability of the SWMM 1D-1D model was reviewed based on a rainfall event that occurred on 25 August 2014, assuming an hour of predicted rainfall.

Background Ginseng has been widely used as a health-promoting tonic. Gintonin present in ginseng acts as a lysophosphatidic acid (LPA) receptor ligand that activates six LPA receptor subtypes. The LPA6 subtype plays a key role in normal hair growth, and mutations in the LPA6 receptor impair normal human hair growth. Currently, human hair loss and alopecia are concerning issues that affect peoples' social and day-to-day lives. Objective We investigated the in vitro and in vivo effects of a gintonin-enriched fraction (GEF) on mouse hair growth. Methods Human hair follicle dermal papilla cells (HFDPCs) and six-week-old male C57BL/6 mice were used. The mice were divided into the four groups: control, 1% minoxidil, 0.75% GEF, and 1.5% GEF. The dorsal hair was removed to synchronize the telogen phase. Each group was treated topically, once a day, for 15 days. We analyzed hair growth activity and histological changes. Results GEF induced transient [Ca2+]i, which stimulated HFDPC proliferation and caused 5-bromo-2′-deoxyuridine (BrdU) incorporation in a concentration-dependent manner. GEF-mediated HFDPC proliferation was blocked by the LPA receptor antagonist and Ca2+ chelator. HFDPC treatment with GEF stimulated vascular endothelial growth factor release. Topical application of GEF and minoxidil promoted hair growth in a dose-dependent manner. Histological analysis showed that GEF and minoxidil increased the number of hair follicles and hair weight. Conclusion Topical application of GEF promotes mouse hair growth through HFDPC proliferation. GEF could be one of the main components of ginseng that promote hair growth and could be used to treat human alopecia., Highlights • Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. • LPA receptor is involved in human hair growth. • Gintonin-enriched fraction (GEF) stimulates proliferation of human hair follicle dermal papilla cells via the LPA receptor. • Topical application of GEF promotes mouse hair growth. • GEF can be applied for human alopecia.

Background/Aims: To investigate the treatment efficacy and renal safety of long-term tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients with preserved renal function. Methods: The medical records of 919 CHB patients who were treated with TDF therapy were reviewed. All patients had preserved renal function with an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2. Results: A total of 426 patients (184 treatment-naive and 242 treatment-experienced) were included for analysis. A virologic response (VR) was defined as achieving an undetectable serum hepatitis B virus (HBV) DNA level, and the overall VR was 74.9%, 86.7%, and 89.4% at the 1, 2, and 3-year follow-ups, respectively. Achieving a VR was not influenced by previous treatment experience, TDF combination therapy, or antiviral resistance. In a multivariate analysis, being hepatitis B e antigen positive at baseline and having a serum HBV DNA level ≥2,000 IU/mL at 12 months were associated with lower VR rates during the long-term TDF therapy. The overall renal impairment was 2.9%, 1.8%, and 1.7% at the 1, 2, and 3-year follow-ups, respectively. With regard to renal safety, underlying diabetes mellitus (DM) and an initial eGFR of 60 to 89 mL/min/1.73 m2 were significant independent predictors of renal impairment. Conclusions: TDF therapy appears to be an effective treatment option for CHB patients with a preserved GFR. However, patients with underlying DM and initial mild renal dysfunction (eGFR, 60 to 89 mL/min/1.73 m2) have an increased risk of renal impairment. (Gut Liver 2019;13:93-103.)

Background Recently, gintonin and gintonin-enriched fraction (GEF) have been isolated from ginseng, a herbal medicine. Gintonin induces [Ca2+]i transition in cultured hippocampal neurons and stimulates acetylcholine release through LPA receptor activation. Oral administration of GEF is linked to hippocampus-dependent cognitive enhancement and other neuroprotective effects; however, effects of its long-term administration on hippocampal gene expression remains unknown. Here, we used next-generation sequence (NGS) analysis to examine changes in hippocampal gene expressions after long-term oral administration of GEF. Methods C57BL/6 mice were divided into three groups: control group, GEF50 (GEF 50 mg/kg, p.o.), and GEF100 (GEF 100 mg/kg, p.o.). After 22 days, total RNA was extracted from mouse hippocampal tissues. NGS was used for gene expression profiling; quantitative-real-time PCR and western blot were performed to quantify the changes in specific genes and to confirm the protein expression levels in treatment groups. Results NGS analysis screened a total of 23,282 genes, analyzing 11-related categories. We focused on the neurogenesis category, which includes four genes for candidate markers: choline acetyltransferase (ChAT) gene, β3-adrenergic receptor (Adrb3) gene, and corticotrophin-releasing hormone (Crh) gene, and tryptophan 2,3-dioxygenase (Tdo2) gene. Real-time PCR showed a marked overexpression of ChAT, Adrb3, and Crh genes, while reduced expression of Tdo2. Western blot analysis also confirmed increased ChAT and decreased Tdo2 protein levels. Conclusion We found that GEF affects mouse hippocampal gene expressions, associated with memory, cognitive, anti-stress and anti-anxiety functions, and neurodegeneration at differential degree, that might explain the genetic bases of GEF-mediated neuroprotective effects.

Graphene quantum dots (GQDs) can be highly beneficial in various fields due to their unique properties, such as having an effective charge transfer and quantum confinement. However, defects on GQDs hinder these properties, and only a few studies have reported fabricating high-quality GQDs with high crystallinity and few impurities. In this study, we present a novel yet simple approach to synthesizing high-quality GQDs that involves annealing silicon carbide (SiC) under low vacuum while introducing hydrogen (H) etching gas, no harmful chemicals are required in the process. The fabricated GQDs are composed of a few graphene layers and possess high crystallinity, few defects and high purity, while being free from oxygen functional groups. The edges of the GQDs are hydrogen-terminated. High-quality GQDs form on the etched SiC when the etching rates of Si and C atoms are monitored. The size of the fabricated GQDs and the surface morphology of SiC can be altered by changing the operating conditions. Collectively, a novel route to high-quality GQDs will be highly applicable in fields involving sensors and detectors.

This study concerns the accessibility of health information for people with disabilities. More specifically, by interviewing policy elites who have backgrounds in this area, we seek to obtain their opinions regarding the type of information people with disabilities require, and people with disabilities overall awareness of such information. Based on the information obtained, we also aim to identify methods of improving this accessibility. A focus group interview was conducted involving policy elites who had previously participated in decision-making processes for health policy. These elites were sourced from the fields of academia, medicine, and government. Content analysis was performed using NVivo 10, which is a computer-assisted/aided qualitative data-analysis software. The focus-group participants felt that relevant information for people with disabilities is provided in a fragmentary manner through several channels that have relatively low reliability, which creates difficulties for a significant portion of the target recipients. Discussions regarding the type of health information required by people with disabilities yielded the following topic clusters: information regarding health-care providers who specialize in specific disability types and regarding health behaviors for certain lifecycles, and information that helps people with disabilities return to society. Further, the focus group recommended 2 means of providing essential health information to PWDs in the future. As short-term strategies, the participants proposed simplifying the existing, fragmented information channels and the creation of a comprehensive web-based information portal with an associated call center. As a long-term strategy, they proposed the development of smart-device-based information services that are tailored to the needs of individuals. Efforts to reduce the disparities in health information for people with disabilities are essential for addressing the existing inequality regarding the availability of health information.

Gintonin is a newly discovered ingredient of ginseng and plays an exogenous ligand for G protein-coupled lysophosphatidic acid receptors. We previously showed that gintonin exhibits diverse effects from neurotransmitter release to improvement of Alzheimer&rsquo, s disease-related cognitive dysfunctions. However, previous studies did not show whether gintonin has protective effects against environmental heavy metal. We investigated the effects of gintonin-enriched fraction (GEF) on methylmercury (MeHg)-induced neurotoxicity and learning and memory dysfunction and on organ MeHg elimination. Using hippocampal neural progenitor cells (hNPCs) and mice we examined the effects of GEF on MeHg-induced hippocampal NPC neurotoxicity, on formation of reactive oxygen species (ROS), and on in vivo learning and memory functions after acute MeHg exposure. Treatment of GEF to hNPCs attenuated MeHg-induced neurotoxicity with concentration- and time-dependent manner. GEF treatment inhibited MeHg- and ROS inducer-induced ROS formations. Long-term treatment of GEF also improved MeHg-induced learning and memory dysfunctions. Oral administration of GEF decreased the concentrations of MeHg in blood, brain, liver, and kidney. This is the first report that GEF attenuated MeHg-induced in vitro and in vivo neurotoxicities through LPA (lysophosphatidic acids) receptor-independent manner and increased organ MeHg elimination. GEF-mediated neuroprotection might achieve via inhibition of ROS formation and facilitation of MeHg elimination from body.

Mesenchymal stromal cells (MSCs) isolated from numerous tissues including human fetal tissue are currently used in cell therapy and regenerative medicine. Among fetal tissues, the umbilical cord (UC) is one of the sources for both MSCs and endothelial cells (ECs). To establish ectopic vascularized bone tissue formation, UC-derived MSCs and ECs were isolated. UC-MSCs expressing human BMP-2 (hBMP-2-MSCs) were generated using an adenoviral system to promote bone formation. These cells were then transplanted with Matrigel into the subcutaneous tissue of an immune deficient NSG mouse, and bone tissue was analyzed after several weeks. The osteogenic differentiation ability of MSCs was elevated by transduction of the hBMP-2 expressing adenoviral system, and vascularization of bone tissue was enhanced by human umbilical vein endothelial cells (HUVEC). In this study, our results provide evidence that MSCs and HUVECs from human umbilical cord are suitable cells to investigate bone tissue engineering. The results also suggest that the co-transplantation of hBMP2-MSCs and HUVECs may be a simple and efficient strategy for improving tissue generation and angiogenesis in bone tissue engineering using stem cells.

It has been previously indicated that gintonin, which is a novel exogenous ginseng-derived lysophosphatidic acid (LPA) receptor ligand, restores memory dysfunctions in an APPswe/PSEN-1 double-transgenic mouse model of Alzheimer's disease (AD Tg mice) by attenuating β-amyloid plaque deposition, recovering cholinergic dysfunctions and upregulating hippocampal neurogenesis in the cortex and hippocampus. Although β-amyloid plaque depositions in AD is accompanied with disruptions of brain microvessels, including the brain-blood barrier (BBB), it is unknown whether gintonin exerts protective effects on brain microvascular dysfunctions in AD Tg mice. In the present study, the effects of gintonin-enriched fraction (GEF) on the changes in β-amyloid plaque depositions, brain permeability of Evans blue, and microvascular junctional proteins were investigated in AD Tg mice. Long-term oral administration of GEF reduced β-amyloid plaque depositions in the cortex and hippocampus of AD Tg mice. GEF treatment also reduced the permeability of Evans blue through BBB and decreased immunoreactivity of platelet endothelial cell adhesion molecule-1 (a marker of BBB disruption) in the cortex and hippocampus of AD Tg mice in a dose-dependent manner. However, GEF elevated the protein expression of occludin, claudin-5 and zonula occludens-1, which are tight-junction proteins. The present results demonstrated that long-term oral GEF treatment not only attenuates β-amyloid plaque depositions in the brain but also exhibits protective effects against microvascular disruptions in AD Tg mice. Finally, GEF exhibits anti-AD effects through attenuation of β-amyloid plaque depositions and protection against brain microvascular damage in an AD animal model.

Gintonin is a newly discovered component of ginseng and acts as a ligand for G protein-coupled lysophosphatidic acid (LPA) receptors. It is currently unclear whether gintonin has skin-related effects. Here, we examined the effects of a gintonin-enriched fraction (GEF) on [Ca2+]i transient induction in human dermal fibroblasts (HDFs). We found that GEF treatment transiently induced [Ca2+]i in a dose-dependent manner. GEF also increased cell viability and proliferation, which could be blocked by Ki16425, an LPA1/3 receptor antagonist, or 1,2-Bis(2-aminophenoxy)ethane-N,N,N&prime, N&prime, tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), a calcium chelator. We further found that GEF stimulated hyaluronic acid (HA) release from HDFs in a dose- and time-dependent manner, which could be attenuated by Ki16425, U73122, a phospholipase C inhibitor, 2-Aminoethoxydiphenyl borate (2-APB), an IP3 receptor antagonist, and BAPTA-AM. Moreover, we found that GEF increased HA synthase 1 (HAS1) expression in a time-dependent manner. We also found that GEF stimulates collagen release and the expression of collagen 1, 3, and 7 synthases in a time-dependent manner. GEF-mediated collagen synthesis could be blocked by Ki16425, U73122, 2-APB, and BAPTA-AM. GEF treatment also increased the mRNA levels of LPA1-6 receptor subtypes at 8 h and increased the protein levels of LPA1-6 receptor subtypes at 8 h. Overall, these results indicate that the GEF-mediated transient induction of [Ca2+]i is coupled to HA and collagen release from HDFs via LPA receptor regulations. We can, thus, conclude that GEF might exert a beneficial effect on human skin physiology via LPA receptors.

Astrocytes are a unique brain cell-storing glycogen and express lysophosphatidic acid (LPA) receptors. Gintonin is a ginseng-derived exogenous G protein-coupled LPA receptor ligand. Accumulating evidence shows that astrocytes serve as an energy supplier to neurons through astrocytic glycogenolysis under physiological and pathophysiological conditions. However, little is known about the relationships between LPA receptors and astrocytic glycogenolysis or about the roles of LPA receptors in hypoxia and re-oxygenation stresses. In the present study, we examined the functions of gintonin-mediated astrocytic glycogenolysis in adenosine triphosphate (ATP) production, glutamate uptake, and cell viability under normoxic, hypoxic, and re-oxygenation conditions. The application of gintonin or LPA to astrocytes induced glycogenolysis in concentration- and time-dependent manners. The stimulation of gintonin-mediated astrocytic glycogenolysis was achieved through the LPA receptor-Gαq/11 protein-phospholipase C-inositol 1,4,5-trisphosphate receptor-intracellular calcium ([Ca2+]i) transient pathway. Gintonin treatment to astrocytes increased the phosphorylation of brain phosphorylase kinase, with sensitive manner to K252a, an inhibitor of phosphorylase kinase. Gintonin-mediated astrocytic glycogenolysis was blocked by isofagomine, a glycogen phosphorylase inhibitor. Gintonin additionally increased astrocytic glycogenolysis under hypoxic and re-oxygenation conditions. Moreover, gintonin increased ATP production, glutamate uptake, and cell viability under the hypoxic and re-oxygenation conditions. Collectively, we found that the gintonin-mediated [Ca2+]i transients regulated by LPA receptors were coupled to astrocytic glycogenolysis and that stimulation of gintonin-mediated astrocytic glycogenolysis was coupled to ATP production and glutamate uptake under hypoxic and re-oxygenation conditions, ultimately protecting astrocytes. Hence, the gintonin-mediated astrocytic energy that is modulated via LPA receptors helps to protect astrocytes under hypoxia and re-oxygenation stresses.

We present a novel approach to preparing non-toxic sunscreen active ingredients by electron irradiation of poly(methyl methacrylate) (PMMA) and polystyrene (PS) nanoparticles (NPs). Electron irradiation modifies the molecular structure of the polymers, generating conjugated aliphatic carbon–carbon double bonds in PMMA and conjugated aromatic rings in PS. The conjugation length increases as the electron fluence increases, leading to hyperchromic and bathochromic shifts in the UV-vis absorption spectra of the irradiated polymer NPs. Consequently, the irradiated polymer NPs become capable of UV absorption and the UV-absorbing properties are improved with increasing electron fluence. The UV-screening performance of the electron-irradiated polymer NPs are found to be superior to those of commercially available sunscreen ingredients. In addition, in vitro cytotoxicity and phototoxicity test results show that the irradiated polymer NPs exhibit excellent biocompatibility.

Background Assessing and satisfying patient expectation are essential in successful patient-centered communication. Recognizing the gap between patient expectation and perception during pharmacist–patient communication can help to identify communication problems and suggest ways to improve communication. Objective To evaluate the gap between patient expectation and perception of sharing information and communications skills during pharmacist–patient communication. Setting Community pharmacies in South Korea. Method A questionnaire was developed to collect expectation and perception of sharing information and communication skills. Items for sharing information included drug effect, dosage/route of administration, adverse drug reactions, storage, drug–drug interactions, drug–food interactions, managing a missed dose or overdose, co-medication, and past drug allergies. Communication skills included friendliness, expertise, easy language, emphasis on main content, confirmation of understanding, enough time, calm environment, and private space. A cross-sectional survey was conducted in 500 convenience sample using an online or written questionnaire in May 2018. Responses about patient expectation and perception were scored using 4-point Likert scales. Gap between patient expectation and perception was calculated as the differences among 4-point Likert scores. Factors associated with patient expectation and gap scores were evaluated using a multivariable regression method. Main outcome measure Patient expectation and perception of sharing information, as well as perception of communication skills during pharmacist–patient communication (questionnaire consisting 35 items). Results This study analyzed responses of 460 participants who answered all items on the questionnaire. Most respondents agreed or strongly agreed that they want to share information with pharmacists. All items had significant gap between patient expectation and perception (p

Background: Gintonin is a ginseng-derived exogenous ligand of the G protein-coupled lysophosphatidic acid (LPA) receptor. We previously reported that gintonin stimulates gliotransmitter release in primary cortical astrocytes. Astrocytes play key roles in the functions of neurovascular systems. Although vascular endothelial growth factor (VEGF) is known to influence the normal growth and maintenance of cranial blood vessels and the nervous system, there is little information about the effect of gintonin on VEGF regulation in primary astrocytes, under normal and hypoxic conditions. Methods: Using primary cortical astrocytes of mice, the effects of gintonin on the release, expression, and distribution of VEGF were examined. We further investigated whether the gintonin-mediated VEGF release protects astrocytes from hypoxia. Results: Gintonin administration stimulated the release and expression of VEGF from astrocytes in a concentration- and time-dependent manner. The gintonin-mediated increase in the release of VEGF was inhibited by the LPA1/3 receptor antagonist, Ki16425; phospholipase C inhibitor, U73122; inositol 1,4,5-triphosphate receptor antagonist, 2-APB; and intracellular Ca2+ chelator, BAPTA. Hypoxia further stimulated astrocytic VEGF release. Gintonin treatment stimulated additional VEGF release and restored cell viability that had decreased due to hypoxia, via the VEGF receptor pathway. Altogether, the regulation of VEGF release and expression and astrocytic protection mediated by gintonin under hypoxia are achieved via the LPA receptor–VEGF signaling pathways. Conclusion: The present study shows that the gintonin-mediated regulation of VEGF in cortical astrocytes might be neuroprotective against hypoxic insults and could explain the molecular basis of the beneficial effects of ginseng on the central nervous system. Keywords: Astrocytes, Gintonin, Hypoxia, Lysophosphatidic acid receptor, Vascular endothelial growth factor

A novel yet simple approach to fabricate and pattern wrinkled surfaces on polymers is presented. Only by irradiating an electron beam onto a polymer, wrinkles are created on the polymer surface. Electron irradiation produces a bilayer polymeric structure comprising a degrading upper layer and a pristine bottom layer. Electron irradiation also increases the polymer surface temperature to a point much higher than the glass-transition temperature of the upper layer, leading to drastic thermal expansion of the upper layer. As a result, significant compressive force is applied to form surface wrinkles. The mechanism behind the wrinkle formation and the effects of electron irradiation parameters on the wrinkle characteristics are discussed. In addition, by this electron irradiation approach, a patterned wrinkle structure is uniquely prepared.

PURPOSE To evaluate clinical risk factors of disease progression after cataract surgery using phacoemulsification with posterior chamber intraocular lens implantation, in eyes with chronic angle-closure glaucoma (CACG) and coexisting cataract. DESIGN Retrospective study. METHODS The data of 56 eyes of 45 CACG patients who had undergone uncomplicated phacoemulsification with posterior chamber intraocular lens implantation were retrospectively analyzed. Disease progression was defined as glaucomatous optic nerve change or visual field (VF) deterioration according to the European Glaucoma Society guideline. Correlations between VF progression and various preoperative and postoperative factors were determined by χ and independent t tests. Linear regression analysis [(odds ratio (OR)] was used to determine predictive risk factors for disease progression using univariate and multivariate analyses. RESULTS The mean postoperative follow-up period was 45.13 ± 17.54 (24 to 84) months. Fourteen eyes (25%) with cataracts diagnosed with CACG progressed after phacoemulsification, but the remaining 42 eyes (75%) did not. According to univariate analysis, disease progression was significantly associated with older age, more number of preoperative/postoperative antiglaucoma drugs, higher scores of preoperative pattern standard deviation, and lower scores of preoperative and postoperative visual field index (VFI) (P

In the original publication of the article the order of authors has been interchanged and now the same has been provided correctly in this correction.

A simple approach to producing tunable lasing is explored. In this work, a basic planar lasing system with a layer of light emitting conjugated polymer, MEH-PPV, sandwiched between a distributed Bragg reflector (DBR) and silver is utilized. By irradiating MEH-PPV with electrons, the photoluminescence (PL) spectrum of MEH-PPV undergoes blueshift and peak broadening, which in turn alters the lasing wavelength. Furthermore, patterning the MEH-PPV layer by electron irradiation and employing filters allow lasing to be controlled to occur only at certain areas. Thus, our approach allows the fabricated system to possess significant tunability, a highly sought out trait in the field of lasing. The detailed methodology by which tunable lasing is achieved is discussed along with the mechanism behind the irradiation-induced blueshift of the PL spectrum.

To evaluate and compare the efficacy and safety of combined phacoemulsification and goniosynechialysis (PEGS) to phacoemulsification alone (PE) in patients with medically well-controlled chronic angle-closure glaucoma (CACG) with cataracts.Thirty eyes diagnosed with CACG and requiring cataract surgery from January 2008 to October 2010 were prospectively randomized, 15 each to PE and PEGS. Changes in peripheral anterior synechiae (PAS), intraocular pressure (IOP), anterior chamber depth, and number of antiglaucoma drugs from baseline to 2 months after the operation were analyzed, as were the type and number of complications.The PE group showed decreases in PAS (118.67±95.38 degrees) and IOP (2.33±2.38 mm Hg) and a significant reduction in the number of antiglaucoma drugs (0.53±0.83, P0.05) from before to 2 months after surgery. The PEGS group showed similar decreases in PAS (114.00±90.95 degrees), and IOP (4.53±4.16 mm Hg) and number of antiglaucoma drugs (1.20±1.32) (P0.05). However, the amount of decline in both the groups did not show any significantly difference in PAS, reduction of IOP, or number of antiglaucoma drugs (P0.05), The increase in anterior chamber depth from baseline to 2 months after surgery was significantly greater in the PEGS group (P=0.003).The IOP-lowering effects of PEGS do not differ significantly from those of PE in medically well-controlled CACG patients with cataract. These results suggest that additional goniosynechialysis during phacoemulsification is not necessary in such patients.

In this study, 61 local meteorological station data elements by weather disasters over the past 30-year period subject to rainfall, wind and snow, regional variations were analyzed using the normalization method. Also rainfall-Wind, snowfall-wind continued to analyze the complex nature of the maximum hourly and analyzed. The analysis results, In the case of regional characteristics Rainfall and snowfall has been increased in the West coast and the Honam region showed a tendency to increase the wind from the west coast and the island. Complex nature of the rainfall and wind was shown in Gangwon Province, on the south coast region typhoon moving path when the snow and wind do not have a clear characteristics were analyzed by non-wind side effect greater action to snow.

Objectives: The Korean government implemented a smoke-free regulation for pubs with a net indoor area of ≥100 m on January 1, 2014. The purpose of this study was to determine the indoor levels of concentrations of particulate matter smaller than 2.5 μm (PM2.5) in implemented and non-implemented pubs in Seoul and Changwon. Methods: PM2.5 concentrations in fifty-two 100-150 m 2 (implemented) and fifty-seven