This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Objective: The Scales for Outcomes in Parkinson’s Disease–Cognition (SCOPA-Cog) was developed to assess cognition in patients with Parkinson’s disease (PD). In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPACog (K-SCOPA-Cog). Methods: We enrolled 129 PD patients with movement disorders from 31 clinics in South Korea. The original version of the SCOPA-Cog was translated into Korean using the translation-retranslation method. The test–retest method with an intraclass correlation coefficient (ICC) and Cronbach’s alpha coefficient were used to assess reliability. Spearman’s rank correlation analysis with the Montreal Cognitive Assessment-Korean version (MOCA-K) and the Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity. Results: The Cronbach’s alpha coefficient was 0.797, and the ICC was 0.887. Spearman’s rank correlation analysis revealed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively). Conclusion Our results demonstrate that the K-SCOPA-Cog has good reliability and validity.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Purpose: To assess characteristics the application of mobile medication system and medication administration error (MAE) alerts in a general hospital. Methods: The subject hospital adopted a mobile medication system in 2016. All medication administrations in the general wards and ICUs were automatically recorded in real-time using identification barcodes, drug barcodes, and hand-held point-of-care devices. MAE alert logs were recorded from April 1st 2017 to March 31st 2018. For this study analysis was done using Pearson’s chi-squared test for potentially related factors of MAE alerts included administration time, order type, medication route, and length of nurse’s employment. Results: The total number of medications during the period of this study was 3,227,990. Among them, 2,698,317 medication doses were recorded, resulting in the system application rate of 83.6%. The system application rate was significantly correlated with all factors related to potential MAE alters. In this study 23,314 MAE alerts(0.9% of the total medication doses) were identified. The MAE alerts were related to new (OR=2.26, p<.001) and emergency (OR=2.25, p<.001) orders, and administration at a non-standard time (OR=2.032, p<.001). Medication route (p<.001), and nurse’s employment duration(p<.001) were also related. Conclusion A mobile medication system contributes to improving patient safety by preventing potential MAEs. The MAE alerts were related to administration time, order type, medication route, and duration of nurse’s employment. In order to prevent medication administration errors, it is necessary to standardize the process of medication and create an environment in which medication administration can be performed in a planned situation.

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis(Vc) is the first relay site for the orofacial nociceptive inputs via the thin myelinatedAδ and unmyelinated C primary afferent fibers. Borneol, one of the valuable timehonoredherbal ingredients in traditional Chinese medicine, is a popular treatmentfor anxiety, anesthesia, and antinociception. However, to date, little is known asto how borneol acts on the SG neurons of the Vc. To close this gap, the whole-cellpatch-clamp technique was applied to elucidate the antinociceptive mechanismresponding for the actions of borneol on the SG neurons of the Vc in mice. In thevoltage-clamp mode, holding at –60 mV, the borneol-induced non-desensitizinginward currents were not affected by tetrodotoxin, a voltage-gated Na+ channelblocker, 6-cyano-7-nitro-quinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA)glutamate receptor antagonist and DL-2-amino-5-phosphonopentanoic acid, anNMDA receptor antagonist. However, borneol-induced inward currents were partiallydecreased in the presence of picrotoxin, a -aminobutyric acid (GABA)A receptorantagonist, or strychnine, a glycine receptor antagonist, and was almost suppressedin the presence of picrotoxin and strychnine. Though borneol did not show any effecton the glycine-induced inward currents, borneol enhanced GABA-mediatedresponses. Beside, borneol enhanced the GABA-induced hyperpolarization under thecurrent-clamp mode. Altogether, we suggest that borneol contributes in part towardmediating the inhibitory GABA and glycine transmission on the SG neurons of the Vcand may serve as an herbal therapeutic for orofacial pain ailments.

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis(Vc) is the first relay site for the orofacial nociceptive inputs via the thin myelinatedAδ and unmyelinated C primary afferent fibers. Borneol, one of the valuable timehonoredherbal ingredients in traditional Chinese medicine, is a popular treatmentfor anxiety, anesthesia, and antinociception. However, to date, little is known asto how borneol acts on the SG neurons of the Vc. To close this gap, the whole-cellpatch-clamp technique was applied to elucidate the antinociceptive mechanismresponding for the actions of borneol on the SG neurons of the Vc in mice. In thevoltage-clamp mode, holding at –60 mV, the borneol-induced non-desensitizinginward currents were not affected by tetrodotoxin, a voltage-gated Na+ channelblocker, 6-cyano-7-nitro-quinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA)glutamate receptor antagonist and DL-2-amino-5-phosphonopentanoic acid, anNMDA receptor antagonist. However, borneol-induced inward currents were partiallydecreased in the presence of picrotoxin, a -aminobutyric acid (GABA)A receptorantagonist, or strychnine, a glycine receptor antagonist, and was almost suppressedin the presence of picrotoxin and strychnine. Though borneol did not show any effecton the glycine-induced inward currents, borneol enhanced GABA-mediatedresponses. Beside, borneol enhanced the GABA-induced hyperpolarization under thecurrent-clamp mode. Altogether, we suggest that borneol contributes in part towardmediating the inhibitory GABA and glycine transmission on the SG neurons of the Vcand may serve as an herbal therapeutic for orofacial pain ailments.

Background: and PurposeImpulse-control disorder is an important nonmotor symptom of Parkinson's disease (PD) that can lead to financial and social problems, and be related to a poor quality of life. A nationwide multicenter prospective study was performed with the aim of validating the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (K-QUIP-RS). Methods: The K-QUIP-RS was constructed using forward and backward translation, and pretesting of the prefinal version. PD patients on stable medical condition were recruited from 27 movement-disorder clinics. Participants were assessed using the K-QUIP-RS and evaluated for parkinsonian motor and nonmotor statuses and for PD-related quality of life using a predefined evaluation battery. The test–retest reliability of the K-QUIP-RS was assessed over an interval of 10–14 days, and correlations between the KQUIP-RS and other clinical scales were analyzed. Results: This study enrolled 136 patients. The internal consistency of the K-QUIP-RS was indicated by a Cronbach's α coefficient of 0.846, as was the test–retest reliability by a Guttman split-half coefficient of 0.808. The total K-QUIP-RS score was positively correlated with the scores for depression and motivation items on the Unified PD Rating Scale (UPDRS), Montgomery-Asberg Depression Scale, and Rapid-Eye-Movement Sleep-Behavior-Disorders Questionnaire. The total K-QUIP-RS score was also correlated with the scores on part II of the UPDRS and the PD Quality of Life-39 questionnaire, and the dopaminergic medication dose. Conclusions The K-QUIP-RS appears to be a reliable assessment tool for impulse-control and related behavioral disturbances in the Korean PD population.

BACKGROUND: AND PURPOSE: This study aimed to determine the clinimetric properties of the Korean version of Parkinson's Disease Sleep Scale-2 (K-PDSS-2) and whether distinct subtypes of sleep disturbance can be empirically identified in patients with Parkinson's disease (PD) using the cross-culturally validated K-PDSS-2. METHODS: The internal consistency, test–retest reliability, scale precision, and convergent validity of K-PDSS-2 were assessed in a nationwide, multicenter study of 122 patients with PD. Latent class analysis (LCA) was used to derive subgroups of patients who experienced similar patterns of sleep-related problems and nocturnal disabilities. RESULTS: The total K-PDSS-2 score was 11.67±9.87 (mean±standard deviation) at baseline and 12.61±11.17 at the retest. Cronbach's α coefficients of the total K-PDSS-2 scores at baseline and follow-up were 0.851 and 0.880, respectively. The intraclass correlation coefficients over the 2-week study period ranged from 0.672 to 0.848. The total K-PDSS-2 score was strongly correlated with health-related quality of life measures and other corresponding nonmotor scales. LCA revealed three distinct subtypes of sleep disturbance in the study patients: “less-troubled sleepers,”“PD-related nocturnal difficulties,” and “disturbed sleepers.” CONCLUSIONS K-PDSS-2 showed good clinimetric attributes in accordance with previous studies that employed the original version of the PDSS-2, therefore confirming the cross-cultural usefulness of the scale. This study has further documented the first application of an LCA approach for identifying subtypes of sleep disturbance in patients with PD.

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have been found to show markedly increased rates of end-stage renal disease, major adverse cardiovascular and cerebrovascular events (MACCEs), and mortality. Therefore, new biomarkers are required for the early detection of such clinical outcomes in patients with CKD. We aimed to determine whether the level of circulating renalase was associated with CKD progression, MACCEs, and all-cause mortality, using data from a prospective randomized controlled study, Kremezin STudy Against Renal disease progression in Korea (K-STAR; NCT 00860431). METHODS: A retrospective analysis of the K-STAR data was performed including 383 patients with CKD (mean age, 56.4 years; male/female, 252/131). We measured circulating renalase levels and examined the effects of these levels on clinical outcomes. RESULTS: The mean level of serum renalase was 75.8 ± 34.8 μg/mL. In the multivariable analysis, lower hemoglobin levels, higher serum creatinine levels, and diabetes mellitus were significantly associated with a higher renalase levels. Over the course of a mean follow-up period of 56 months, 25 deaths and 61 MACCEs occurred. Among 322 patients in whom these outcomes were assessed, 137 adverse renal outcomes occurred after a mean follow-up period of 27.8 months. Each 10-μg/mL increase in serum renalase was associated with significantly greater hazards of all-cause mortality and adverse renal outcomes (hazard ratio [HR] = 1.112, p = 0.049; HR = 1.052, p = 0.045). However, serum renalase level was not associated with the rate of MACCEs in patients with CKD. CONCLUSIONS Our results indicated that circulating renalase might be a predictor of mortality and adverse renal outcomes in patients with CKD.

The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current (I(Gly)). Firstly, we examined with a 5-HT₁ receptor agonist (8-OH-DPAT, 5-HT(1/7) agonist, co-applied with SB-269970, 5-HT₇ antagonist) and antagonist (WAY-100635), but 5-HT₁ receptor agonist did not increase IGly and in the presence of 5-HT₁ antagonist, the potentiation of 5-HT on I(Gly) still happened. However, an agonist (α-methyl-5-HT) and antagonist (ketanserin) of the 5-HT₂ receptor mimicked and inhibited the enhancing effect of 5-HT on I(Gly) in the SG neurons, respectively. We also verified the role of the 5-HT₇ receptor by using a 5-HT₇ antagonist (SB-269970) but it also did not block the enhancement of 5-HT on I(Gly). Our study demonstrated that 5-HT facilitated I(Gly) in the SG neurons of the Vc through the 5-HT₂ receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.
Animals ; Glycine ; Mice ; Neurons ; Neurotransmitter Agents ; Nociception ; Patch-Clamp Techniques ; Receptors, Glycine ; Serotonin ; Signal Transduction ; Substantia Gelatinosa