Background: Recombination activating gene2 (Rag2) knockout (KO) mice are used widely in various research fields, including vaccine development, transplantation studies, and hematopoiesis research, but few studies have compared their phenotypes. This study examined whether there were differences in the immunophenotypes between Rag2 KO mice derived from different sources. In particular, the changes in the organ weight, histological structure, and subpopulation of T and B cells were compared in the spleen and thymus of C57BL/6-Rag2em1hwl/Korl (Rag2/Korl KO) and B6.Cg-Rag2tm1.1Cgn/J (Rag2/J KO) mice. Results: The weight of the spleen and thymus similarly decreased in the Rag2/Korl and Rag2/J KO mice compared to their wild type (WT) mice, even though the other organs were kept at the same weight. A slight difference between the Rag2/Korl and Rag2/J KO group were detected in the number of white blood cells (WBC), lymphocytes (LYM), red cell distribution width (RDW), and platelets (PLT). In addition, the white pulp of the spleen and the cortex region of the thymus decreased in both Rag2 KO mice compared to WT mice. On the other hand, significant differences in the number of CD8+ T and B cell subpopulations between WT and Rag2 KO mice were observed between Rag2/Korl and Rag2/J KO group, while the CD4+ T subpopulation was maintained similarly in both groups. Conclusions These results suggest that Rag2/Korl and Rag2/J KO mice exhibit similar immunophenotypes in the spleen and thymus except for the differences in the number of CD8+ T and B cell subpopulations.

Background: Disruptions of the intestinal epithelial barrier (IEB) are frequently observed in various digestive diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This study assessed the improvement in the IEB during the laxative activity of phlorotannin (Pt) harvested from Ecklonia cava in constipation by examining the changes in the expression of the regulatory proteins for the tight junction (TJ) and adherens junction (AJ), and inflammatory cytokines in Sprague Dawley (SD) rats with loperamide (Lm)-induced constipation after a Pt treatment. Results: The Pt treatment induced laxative activity, including the improvement of feces-related parameters, gastrointestinal transit rate, and histological structure of the mid colon in Lm-treated SD rats. In addition, significant recovery effects were detected in the histology of IEB, including the mucus layer, epithelial cells, and lamina propria in the midcolon of Lm + Pt treated SD rats. The expression levels of E-cadherin and p120-catenin for AJ and the ZO-1, occludin, and Claudin-1 genes for TJ in epithelial cells were improved remarkably after the Pt treatment, but the rate of increase was different. Furthermore, the Pt treatment increased the expression level of several inflammatory cytokines, such asTNF-α, IL-6, IL-1β, IL-13, and IL-4 in Lm + Pt treated SD rats. Conclusions These results provide the first evidence that the laxative activity of Pt in SD rats with Lm-induced constipation phenotypes involve improvements in the IEB.

Background: The gut–brain axis (GBA) in Parkinson’s disease (PD) has only been investigated in limited mice models despite dysbiosis of the gut microbiota being considered one of the major treatment targets for neurodegenerative disease. Therefore, this study examined the compositional changes of fecal microbiota in novel transgenic (Tg) mice overexpressing human α-synuclein (hαSyn) proteins under the neuron-specific enolase (NSE) to analyze the potential as GBA model. Results: The expression level of the αSyn proteins was significantly higher in the substantia nigra and striatum of NSEhαSyn Tg mice than the Non-Tg mice, while those of tyrosine hydroxylase (TH) were decreased in the same group. In addition, a decrease of 72.7% in the fall times and a 3.8-fold increase in the fall number was detected in NSE-hαSyn Tg mice. The villus thickness and crypt length on the histological structure of the gastrointestinal (GI) tract decreased in NSE-hαSyn Tg mice. Furthermore, the NSE-hαSyn Tg mice exhibited a significant increase in 11 genera, including Scatolibacter, Clostridium, Feifania, Lachnoclostridium, and Acetatifactor population, and a decrease in only two genera in Ligilactobacillus and Sangeribacter population during enhancement of microbiota richness and diversity. Conclusions The motor coordination and balance dysfunction of NSE-hαSyn Tg mice may be associated with compositional changes in gut microbiota. In addition, these mice have potential as a GBA model.

Background: To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX. Results: The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 pro-tein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The ­ IC50 level to DOX was lower in both primary cells ­(IC50 = 0.12 μM and 0.20 μM) as compared to the CT26 cells ­(IC50 = 0.32  μM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7–23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8–254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells. Conclusions To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALENmediated Trp53 mutant gene.

Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P<0.001) between mean blood glucose levels in the LMT-1000 (175.8±63.0 mg/dL) and conventional lancet samples (172.5±63.6 mg/dL). LMT-1000 reduced puncture pain by 75.0% and increased satisfaction by 80.0% compared to a lancet. We demonstrated considerable consistency in blood glucose measurements between samples from the LMT-1000 and a lancet, but improved satisfaction and clinically significant pain reduction were observed with the LMT-1000 compared to those with a lancet.

Background/Aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Objective: To determine the effects of an integrated training device for strength and balance on extremity muscle strength, postural balance, and cognition in older adults using a combination with various rehabilitation training games, in which balance, strength, and cognitive training were configured in a single device. Methods: This prospective study included 20 healthy participants aged 65–85 years. Participants trained for 30 minutes daily, 3 days weekly, for 6 weeks with an integrated training device for strength and balance (SBT-120; Man&Tel Inc., Gumi, Korea). Main outcomes were measured using the Korean Mini-Mental State Examination (K-MMSE), Korean version of the Montreal Cognitive Assessment (K-MoCA), Timed Up and Go Test (TUG), Functional Reach Test (FRT), Berg Balance Scale (BBS), and Manual Muscle Test. Measurements were taken at three time points: T0 (pretreatment), T1 (immediately after treatment), and T2 (4 weeks after treatment). Results: All 20 patients completed the training, and TUG, FRT, and BBS scores significantly improved at T1 and T2 compared to T0. Mean TUG scores decreased by 0.99±2.00 at T1 and 1.05±1.55 at T2 compared to T0. Mean FRT scores increased by 6.13±4.26 at T1 and 6.75±4.79 at T2 compared to T0. BBS scores increased by 0.60±0.94 at T1 and 0.45±1.15 at T2 compared to T0. Moreover, muscle strength and cognition (K-MMSE and K-MoCA scores) increased after training. Conclusion Our findings suggest that an integrated training device for strength and balance can be a safe and useful tool for older adults.

Purpose: To report a rare case of optic perineuritis as the presenting sign of sarcoidosis. Case summary: A 57-year-old man presented with decreased visual acuity and pain with extraocular movement in his left eye starting 2 weeks earlier. He had a history of asymptomatic optic perineuritis in that eye 18 months previously, which had improved after 1 month on oral prednisolone. His best corrected visual acuity had decreased to 20/50 and he also had relative afferent pupillary defect and color vision defects in the left eye. Slit lamp examination results were normal. There were no inflammatory reactions in the anterior chamber or vitreous. Fundoscopy showed optic disc edema. Orbital magnetic resonance imaging showed diffuse enhancement surrounding the left optic nerve. The serum levels of eosinophil cationic protein and angiotensin- converting enzyme were markedly increased. A chest radiograph showed bilateral hilar lymph node enlargement. A biopsy via endobronchial ultrasound-guided transbronchial needle aspiration revealed multifocal non-caseating granulomas. Acid fast bacilli stain showed no evidence of tuberculosis. Based on these findings, he was diagnosed with sarcoidosis. After treatment with high-dose intravenous methylprednisolone and subsequent tapering with oral prednisolone for 6 months, the visual acuity improved. Conclusions Optic perineuritis can be the initial sign of sarcoidosis. Therefore, sarcoidosis should be considered in the differential diagnosis of optic perineuritis.

Purpose: The balloon-stent technique (BST) has certain strengths as an assisted technique for the treatment of complex aneurysms. After Atlas release, the BST can be executed without an exchange maneuver of the balloon to the stent-delivery catheter. The purpose of this article is to share our experience with the BST using the Scepter-Atlas combination. Materials and Methods: Device inspection led us to a simple method to avoid failure in loading Atlas to the Scepter. From March 2018 to December 2019, 57 unruptured distal internal carotid artery (dICA) aneurysms were treated with coil embolization; among which, 25 aneurysms in 23 patients were treated with BST. Clinical and angiographic data were retrospectively collected and reviewed. Results: The technical success rate of the Scepter-Atlas combination increased from 50% to 100% after careful inspection. BST angiographic results were comparable to the stent-assisted coil (SAC) group treated during the immediately post-embolization same period (modified Raymond-Roy classification [MRRC] 1 & 2 84% in BST, 96.3% in SAC) and during short-term follow-up (MRRC 1 & 2 95.8% in BST, 88.4% in SAC). A small number of patients showed periprocedural complications, but none had clinical consequences. Conclusion BST using the Scepter-Atlas combination can provide an effective and safe method for the treatment of dICA aneurysms. Scepters can be used as delivery catheters for Atlas.

Purpose: To report a rare case of optic perineuritis as the presenting sign of sarcoidosis. Case summary: A 57-year-old man presented with decreased visual acuity and pain with extraocular movement in his left eye starting 2 weeks earlier. He had a history of asymptomatic optic perineuritis in that eye 18 months previously, which had improved after 1 month on oral prednisolone. His best corrected visual acuity had decreased to 20/50 and he also had relative afferent pupillary defect and color vision defects in the left eye. Slit lamp examination results were normal. There were no inflammatory reactions in the anterior chamber or vitreous. Fundoscopy showed optic disc edema. Orbital magnetic resonance imaging showed diffuse enhancement surrounding the left optic nerve. The serum levels of eosinophil cationic protein and angiotensin- converting enzyme were markedly increased. A chest radiograph showed bilateral hilar lymph node enlargement. A biopsy via endobronchial ultrasound-guided transbronchial needle aspiration revealed multifocal non-caseating granulomas. Acid fast bacilli stain showed no evidence of tuberculosis. Based on these findings, he was diagnosed with sarcoidosis. After treatment with high-dose intravenous methylprednisolone and subsequent tapering with oral prednisolone for 6 months, the visual acuity improved. Conclusions Optic perineuritis can be the initial sign of sarcoidosis. Therefore, sarcoidosis should be considered in the differential diagnosis of optic perineuritis.