The Association of Chronic Periodontitis as a Potential Risk Factor with Rheumatoid Arthritis: A Nested Case-Control Study Using a Korean National Health Screening Cohort.

Growing research has proposed that rheumatoid arthritis (RA) and chronic periodontitis (CP) share similar pathophysiological mechanisms involving inflammation and tissue destruction. However, the potential correlation of CP as a contributing factor for the occurrence of RA warrants validation in the Korean population, where both diseases are prevalent, especially considering the increasingly aging demographic in Korea. This study examined 5139 RA cases and 509,727 matched controls from a Korean national cohort dataset (2002-2019) by carefully employing propensity score matching to ensure comparability between groups. Baseline characteristics were compared using standardized differences, and logistic regression was employed to estimate the impact of CP history on RA likelihood while controlling for covariates. We fully examined medical records documenting CP occurrences within the two-year period leading up to the index date, conducting comprehensive subgroup analyses. While a 1-year history of CP did not show a significant association with likelihood of RA, a 2-year history of CP increased RA likelihood by 12%, particularly among older adults, females, rural residents, and those with certain comorbidities such as hypercholesterolemia. Interestingly, this association persisted even among individuals with non-smoking habits, normal weight, and infrequent alcohol consumption. These findings suggest that chronic CP exposure for at least 2 years may independently elevate RA risk in Korean adults. The association in certain subgroups appears to suggest a predisposition toward genetic susceptibilities over lifestyle and environmental factors. Predicting RA in CP patients may be challenging, emphasizing the importance of regular RA screening, especially in high-risk subgroups.

Associations between Chronic Kidney Disease and Migraine Incidence: Findings from a Korean Longitudinal Big Data Study.

While headaches frequently occur in individuals with chronic kidney disease (CKD), there are few statistical evaluations of their connection to migraines in population-based studies. In this nationwide longitudinal follow-up study of Korean health examination data (2002-2019), a total of 15,443 participants with CKD and 61,772 matched controls were enrolled. We applied overlap-weighted Cox proportional hazard regression models to assess hazard ratios, examining the correlation between CKD and the development of migraines. After accounting for various factors, we observed a modest reduction of approximately 11% in the likelihood of migraine occurrence among CKD patients (95% confidence intervals = 0.81-0.97) during the 16-year monitoring period. Subgroup analysis revealed a significant association among specific demographic and health conditions, including individuals aged 70 or older, females, overweight individuals, nonsmokers, and those without hypertension or diabetes. Our research may indicate a potential relationship between CKD and the onset of migraines in Korean adults, suggesting a slight reduction in the probability of the occurrence of migraines among those with CKD. These findings emphasize the need for attentive follow-up and preventive management in individuals without the identified protective factors, particularly in male CKD patients under the age of 70 with hypertension.

Investigating the Connection between Chronic Periodontitis and Parkinson's Disease: Findings from a Korean National Cohort Study.

Recent research suggests a potential relevance between chronic periodontitis (CP) and Parkinson's disease (PD), raising concerns about comorbid PD among elderly CP patients. However, the epidemiologic basis for this association remains unclear. Employing a nested case-control design, this study explored the association between CP and subsequent PD occurrences in Korean adults, leveraging a validated national population-based dataset covering the period from 2002 to 2019. It included 8794 PD patients and 35,176 matched control individuals, established through propensity score matching for age, sex, residential area, and income. Baseline characteristics were compared using standardized differences, and logistic regression was employed to assess the impact of CP histories on PD likelihood while controlling for covariates. We performed a thorough examination of CP events within both 1-year and 2-year intervals preceding the index date, incorporating subgroup analyses. Our analysis revealed no statistically significant association between CP history and PD development overall. However, subgroup analysis revealed a slightly increased likelihood of PD development among CP individuals with a high disease burden (Charlson Comorbidity Index score ≥ 2). In conclusion, although our study did not find a significant overall association between CP history and PD development, the elevated likelihood of PD in subgroups with high disease burden may suggest that comorbidities influence PD probability among certain CP patients. Considering comorbid conditions in PD screening for some individuals with CP may be also important.

Enhancing Loop-Mediated Isothermal Amplification through Nonpowered Nanoelectric Preconcentration.

The global threat posed by the COVID-19 pandemic has catalyzed the development of point-of-care (POC) molecular diagnostics. While loop-mediated isothermal amplification (LAMP) stands out as a promising technique among FDA-approved methods, it is occasionally susceptible to a high risk of false positives due to nonspecific amplification of a primer dimer. In this work, we report an enhancing LAMP technique in terms of assay sensitivity and reliability through streamlined integration with a nonpowered nanoelectric preconcentration (NPP). The NPP, serving as a sample preparation tool, enriched the virus concentration in samples prior to the subsequent LAMP assay. This enrichment enabled not only to achieve more sensitive assay but also to shorten the assay time for all tested clinical samples by ∼10 min compared to the conventional LAMP. The shortened assay time suppresses the occurrence of nonspecific amplification by not providing the necessary incubation time, effectively suppressing misidentification by false positives. Utilizing this technique, we also developed a prototype of the POC NPP-LAMP kit. This kit offers a streamlined diagnostic process for nontrained individuals, from the sample enrichment, transfer of the enriched sample to LAMP assays, which facilitates on-site/on-demand diagnosis of SARS-CoV-2. This development holds the potential to contribute toward preventing not only the current outbreak but also future occurrences of pandemic viruses.

An elevated likelihood of stroke, ischemic heart disease, or heart failure in individuals with gout: a longitudinal follow-up study utilizing the National Health Information database in Korea.

Objective: Accumulating evidence from other countries indicates potential associations between gout and cardiovascular diseases; however, the associations of gout with cardiovascular diseases, particularly stroke, ischemic heart disease, and heart failure, remain ambiguous in the Korean population. We hypothesized that individuals with gout are at a higher likelihood of stroke, ischemic heart disease, or heart failure. This study expands upon previous research by ensuring a comparable baseline between patient and control groups and analyzing 16 years of data derived from an extensive healthcare database. Methods: We selected 22,480 patients with gout and 22,480 control individuals from the Korean National Health Insurance Service-Health Screening Cohort database (2002-2019), and matched them at a 1:1 ratio according to sex, age, income, and residence. A Cox proportional hazard model with weighted overlap was employed to examine the relationship between gout and the risk of stroke, ischemic heart disease, or heart failure after adjustment for several covariates. Results: The incidences of stroke, ischemic heart disease, or heart failure in participants with gout were slightly higher than those in controls (stroke: 9.84 vs. 8.41 per 1000 person-years; ischemic heart disease: 9.77 vs. 7.15 per 1000 person-years; heart failure: 2.47 vs. 1.46 per 1000 person-years). After adjustment, the gout group had an 11% (95% confidence interval [CI] = 1.04-1.19), 28% (95% CI = 1.19-1.37), or 64% (95% CI = 1.41-1.91) higher likelihood of experiencing stroke, ischemic heart disease, or heart failure, respectively, than the control group. Conclusion: The present findings suggest that individuals with gout in the Korean population, particularly those aged ≥ 60 years, were more likely to have stroke, ischemic heart disease, or heart failure.

Intracellular Adhesion Molecule-1 Improves Responsiveness to Immune Checkpoint Inhibitor by Activating CD8+ T Cells.

Immune checkpoint inhibitor (ICI) clinically benefits cancer treatment. However, the ICI responses are only achieved in a subset of patients, and the underlying mechanisms of the limited response remain unclear. 160 patients with non-small cell lung cancer treated with anti-programmed cell death protein-1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) are analyzed to understand the early determinants of response to ICI. It is observed that high levels of intracellular adhesion molecule-1 (ICAM-1) in tumors and plasma of patients are associated with prolonged survival. Further reverse translational studies using murine syngeneic tumor models reveal that soluble ICAM-1 (sICAM-1) is a key molecule that increases the efficacy of anti-PD-1 via activation of cytotoxic T cells. Moreover, chemokine (CXC motif) ligand 13 (CXCL13) in tumors and plasma is correlated with the level of ICAM-1 and ICI efficacy, suggesting that CXCL13 might be involved in the ICAM-1-mediated anti-tumor pathway. Using sICAM-1 alone and in combination with anti-PD-1 enhances anti-tumor efficacy in anti-PD-1-responsive tumors in murine models. Notably, combinatorial therapy with sICAM-1 and anti-PD-1 converts anti-PD-1-resistant tumors to responsive ones in a preclinical study. These findings provide a new immunotherapeutic strategy for treating cancers using ICAM-1.

PCR-like performance of rapid test with permselective tunable nanotrap.

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.

Tin Oxide/Vertically Aligned Graphene Hybrid Electrodes Prepared by Sonication-Assisted Sequential Chemical Bath Deposition for High-Performance Supercapacitors.

Hybrid electrodes comprising metal oxides and vertically aligned graphene (VAG) are promising for high-performance supercapacitor applications because they enhance the synergistic effect owing to the large contact area between the two constituent materials. However, it is difficult to form metal oxides (MOs) up to the inner surface of a VAG electrode with a narrow inlet using conventional synthesis methods. Herein, we report a facile approach to fabricate SnO2 nanoparticle-decorated VAG electrodes (SnO2@VAG) with excellent areal capacitance and cyclic stability using sonication-assisted sequential chemical bath deposition (S-SCBD). The sonication treatment during the MO decoration process induced a cavitation effect at the narrow inlet of the VAG electrode, allowing the precursor solution to reach the inside of the VAG surface. Furthermore, the sonication treatment promoted MO nucleation on the entire VAG surface. Thus, the SnO2 nanoparticles uniformly covered the entire electrode surface after the S-SCBD process. SnO2@VAG exhibited an outstanding areal capacitance (4.40 F cm-2) up to 58% higher than that of VAG electrodes. The symmetric supercapacitor with SnO2@VAG electrodes showed an excellent areal capacitance (2.13 F cm-2) and a cyclic stability of 90% after 2000 cycles. These results suggest a new avenue for sonication-assisted fabrication of hybrid electrodes in the field of energy storage.

Affordable on-site COVID-19 test using non-powered preconcentrator.

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.

Anodic SnO2 Nanoporous Structure Decorated with Cu2O Nanoparticles for Sensitive Detection of Creatinine: Experimental and DFT Study.

Advanced anodic SnO2 nanoporous structures decorated with Cu2O nanoparticles (NPs) were employed for creatinine detection. Anodization of electropolished Sn sheets in 0.3 M aqueous oxalic acid electrolyte under continuous stirring produced complete open top, crack-free, and smooth SnO2 nanoporous structures. Structural analyses confirm the high purity of rutile SnO2 with successful functionalization of Cu2O NPs. Morphological studies revealed the formation of self-organized and highly-ordered SnO2 nanopores, homogeneously decorated with Cu2O NPs. The average diameter of nanopores is ∼35 nm, while the average Cu2O particle size is ∼23 nm. Density functional theory results showed that SnO2@Cu2O hybrid nanostructures are energetically favorable for creatinine detection. The hybrid nanostructure electrode exhibited an ultra-high sensitivity of around 24343 µA mM-1 cm-2 with an extremely lower detection limit of ∼0.0023 µM, a fast response time (less than 2 s), and wide linear detection ranges of 2.5-45 µM and 100 µM to 15 mM toward creatinine. This is ascribed to the creation of highly active surface sites as a result of Cu2O NP functionalization, SnO2 band gap diminution, and the formation of heterojunction and Cu(1)/Cu(ll)-creatinine complexes through secondary amines which occur in the creatinine structure. The real-time analysis of creatinine in blood serum by the fabricated electrode evinces the practicability and accuracy of the biosensor with reference to the commercially existing creatinine sensor. The proposed biosensor demonstrated excellent stability, reproducibility, and selectivity, which reflects that the SnO2@Cu2O nanostructure is a promising candidate for the non-enzymatic detection of creatinine.

Nanoelectrokinetic-assisted lateral flow assay for COVID-19 antibody test.

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.

Evaluation of cold atmospheric microwave plasma on skin physiological parameters and tolerability in dogs.

BACKGROUND: 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. OBJECTIVE: 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. ANIMALS: Twenty client-owned dogs with normal skin. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION AND CLINICAL SIGNIFICANCE: 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.

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.

Changes in the Mean of Medical Visits Due to Psychiatric Disease in Korean Children and Adolescents before and during the COVID-19 Pandemic.

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.

Prevalence of focal lamina cribrosa defects in eyes with pachychoroid disease spectrum.

AIM: To determine the prevalence of focal lamina cribrosa (LC) defect among patients with pachychoroid disease spectrum (PDS) in the absence of peripapillary retinoschisis. METHODS: This retrospective, cross-sectional study comprised of 180 patients with PDS, including polypoidal choroidal vasculopathy (PCV), central serous chorioretinopathy, and pachychoroidal neovasculopathy. Medical records and optic nerve head evaluations conducted using spectral-domain optical coherence tomography with enhanced depth imaging were reviewed. As a control group, 236 patients who underwent ophthalmologic evaluation for vitreous floaters, without obvious ocular disease, were also included. RESULTS: The mean age of the PDS group, which included 118 male patients (65.6%), was 57.4±11.1y. There was no significant difference between the two groups in age (P=0.710) or sex (P=0.248). Six patients (3.3%) in the PDS group and none in the control group showed focal LC defect (P=0.318). Among the six patients with focal LC defect in the PDS group, four eyes had PCV, one eye was the fellow eye of a PCV eye, and one eye had pachychoroidal neovasculopathy. CONCLUSION: Focal LC defect can be defected in patients with PDS in the absence of peripapillary retinoschisis. However, the prevalence of focal LC defect was not different significantly between PDS patients and those who did not have PDS.

Comparative genomic analysis of plasmids encoding metallo-ß-lactamase NDM-5 in Enterobacterales Korean isolates from companion dogs.

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-ß-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.

Gintonin facilitates brain delivery of donepezil, a therapeutic drug for Alzheimer disease, through lysophosphatidic acid 1/3 and vascular endothelial growth factor receptors.

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.

Ginseng gintonin attenuates the disruptions of brain microvascular permeability and microvascular endothelium junctional proteins in an APPswe/PSEN-1 double-transgenic mouse model of Αlzheimer's disease.

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 ß-amyloid plaque deposition, recovering cholinergic dysfunctions and upregulating hippocampal neurogenesis in the cortex and hippocampus. Although ß-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 ß-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 ß-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 ß-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 ß-amyloid plaque depositions and protection against brain microvascular damage in an AD animal model.

Effects of gintonin-enriched fraction on hippocampal gene expressions.

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, ß3-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.

Correction to: Gap between patient expectation and perception during pharmacist-patient communication at community pharmacy.

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.

Gap between patient expectation and perception during pharmacist-patient communication at community pharmacy.

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 < 0.01). Gap scores were highest for adverse drug reaction, drug-drug interaction, and past drug allergies (all, median 2). Gap scores were negatively associated with age 50-59 years, ≥ 60 years, and presence of ≥ 1 chronic illness. Patient perception of communication skills, especially regarding private space, were poor. Conclusions The information shared with pharmacists was significantly less than that expected by participants, and most pharmacist communication skills were evaluated as poor. Understanding the expectation of each patient and communicating accordingly with appropriate communication skills are necessary to improve patient-centered communication in community pharmacies.