IgY antibodies against cytolysin reduce ethanol-induced liver disease in mice.

BACKGROUND AND AIMS: Patients with severe alcohol-associated hepatitis have high morbidity and mortality. Novel therapeutic approaches are urgently needed. The aims of our study were to confirm the predictive value of cytolysin-positive Enterococcus faecalis ( E. faecalis ) for mortality in patients with alcohol-associated hepatitis and to assess the protective effect of specific chicken immunoglobulin Y (IgY) antibodies against cytolysin in vitro and in a microbiota-humanized mouse model of ethanol-induced liver disease. APPROACH AND RESULTS: We investigated a multicenter cohort of 26 subjects with alcohol-associated hepatitis and confirmed our previous findings that the presence of fecal cytolysin-positive E. faecalis predicted 180-day mortality in those patients. After combining this smaller cohort with our previously published multicenter cohort, the presence of fecal cytolysin has a better diagnostic area under the curve, better other accuracy measures, and a higher odds ratio to predict death in patients with alcohol-associated hepatitis than other commonly used liver disease models. In a precision medicine approach, we generated IgY antibodies against cytolysin from hyperimmunized chickens. Neutralizing IgY antibodies against cytolysin reduced cytolysin-induced cell death in primary mouse hepatocytes. The oral administration of IgY antibodies against cytolysin decreased ethanol-induced liver disease in gnotobiotic mice colonized with stool from cytolysin-positive patients with alcohol-associated hepatitis. CONCLUSIONS: E. faecalis cytolysin is an important mortality predictor in alcohol-associated hepatitis patients, and its targeted neutralization through specific antibodies improves ethanol-induced liver disease in microbiota-humanized mice.

Optimization of immune checkpoint inhibitor treatment planning for relapsed or refractory extranodal NK/T cell lymphoma.

Pembrolizumab (anti-programmed cell death-ligand 1 inhibitor) is a promising salvage therapeutic option for relapsed/refractory extranodal NK/T-cell lymphoma (R/R ENKTL). However, the appropriate duration of pembrolizumab use in R/R ENKTL patients and the optimal timing for administering pembrolizumab remain undetermined. We collected and analyzed clinical information on R/R ENKTL 58 patients who received pembrolizumab to evaluate the optimal treatment durations and clinical information for considering treatment interruption. Treatment outcomes were assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and Epstein Barr virus DNA (EBV DNA) every 3 months. Nineteen (32.8%) patients had been treated with more than three chemotherapies before pembrolizumab administration. The best response rate towards the first try of pembrolizumab was 38.9% (31.5% complete response rate (CR), 7.4% partial response (PR)). During the 41.8-month median follow-up duration, the median progression-free survival (PFS) was 3.1 months, and the median overall survival (OS) was 7.1 months. The failure group, which was characterized by Deaville score (DS) 3-4 and circulating EBV detection, or DS 5 with/without EBV detection, had the worst PFS (p < 0.001) and OS (p < 0.001), followed by the high (DS 1-2 and EBV detection, or DS 3-4 and EBV not detected) and low-risk groups (DS 1-2 and EBV not detected). Among the 21 patients who achieved the best response at the first pembolizumab try, the patients who received planned 24 cycles presented better PFS than those who received incomplete cycles (57.6 months vs 20.9 months, P-value = 0.012). Among 13 patients who received avelumab or pembrolizumab in advance, a few who responded to the second trial of pembrolizumab administration had over one year of chemotherapy vacation. Determining the discontinuation or continuation of pembrolizumab would be considered in selected cases assessed by PET-CT and EBV monitoring. Disruption of pembrolizumab treatment may be advisable for the low-risk group(DS 1-2 and EBV not detected), whereas continuation could be warranted for the high-risk group (DS 1-2 and EBV detection, or DS 3-4 and EBV not detected). Moreover, it might be critical to maintain over 24 cycles to improve the survival outcome of R/R ENKTL.

Characteristics of chronic enteropathy associated with SLCO2A1 gene (CEAS) in children, a unique type of monogenic very early-onset inflammatory bowel disease.

BACKGROUND:  Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a unique type of inflammatory bowel disease. CEAS is monogenic disease and is thought to develop from childhood, but studies on pediatric CEAS are scarce. We analyzed characteristics of pediatric CEAS. METHODS: Eleven patients diagnosed with CEAS at Seoul National University Children's Hospital were identified and analyzed. Clinical data of patients were collected. Sanger sequencing of SLCO2A1 was performed on all patients. RESULTS: Patients were diagnosed at a median age of 16.0 years (IQR 11.0 ~ 20.0), and the median age at symptoms onset was only 4.0 years (IQR 2.5 ~ 6.0). Growth delay was observed at the time of diagnosis. Patients showed multiple ulcers or strictures in the small intestine, while the esophagus and colon were unaffected in any patients. Almost half of the patients underwent small intestine resection. The major laboratory features of pediatric CEAS include iron deficiency anemia (IDA), hypoalbuminemia, and near-normal levels of C-reactive protein (CRP). Two novel mutations of SLCO2A1 were identified. The most prevalent symptoms were abdominal pain and pale face. None of the immunomodulatory drugs showed a significant effect on CEAS. CONCLUSIONS: Pediatric CEAS typically develop from very young age, suggesting it as one type of monogenic very early onset inflammatory bowel disease. CEAS can cause growth delay in children but there is no effective treatment currently. We recommend screening for SLCO2A1 mutations to pediatric patients with chronic IDA from a young age and small intestine ulcers without elevation of CRP levels.

Turnover Rates and Factors Associated With Turnover: A Longitudinal Analysis of the Retention Period of Clinical Nurses in Korea Using National Data.

Many countries, including Korea, are struggling with a nursing workforce shortage. This study aimed to identify the actual turnover rate of Korean clinical nurses and the factors affecting the turnover rate, considering the time required for nurses to gain experience at their current medical institution. This longitudinal study followed up on a cohort consisting of all 107,682 nurses from January 1, 2017 to July 30, 2020. Differences in the distribution of retention and turnover according to the medical institutions' and nurses' characteristics were analyzed using the chi-square test. The hazard ratios (HRs) for turnover in each analysis interval were analyzed using multilevel Cox proportional-hazards analysis. The mean turnover rate was 10.0% within 1 year and 33.4% within 3.5 years. Several organizational characteristics (the type and ownership of the hospital, its location, and the bed-to-nurse ratio) and individual characteristics (gender, age, and clinical experience) were found to be associated with turnover risk. Among these factors, compared to hospitals with a bed-to-nurse ratio in general wards of 6.0 or more, those with a ratio of 3.5-3.9 had an HR for 1-year turnover of 0.81 (95% confidence interval [CI] = 0.67-0.98), and those with a ratio of 2.5-2.9 had an HR for 3.5-year turnover of 0.77 (95% CI = 0.66-0.90). The bed-to-nurse ratio is a condition that can be modified through collaboration between government policy-makers and medical institutions. To reduce nurse turnover and retain experienced nurses, appropriate staffing should be implemented.

Hair Growth Effect of DN106212 in C57BL/6 Mouse and Its Network Pharmacological Mechanism of Action.

Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of action of CMX in animals has not been elucidated fully. This study examined the effect of induced hair loss and its side-effects on the skin, and observed the mechanism of action of an alcoholic extract of CMX (DN106212) on C57BL/6 mice. Our results showed that DN106212 was more effective in promoting hair growth than dimethyl sulfoxide in the negative control and tofacitinib (TF) in the positive control when mice were treated with DN106212 for 16 days. We confirmed that DN106212 promotes the formation of mature hair follicles through hematoxylin and eosin staining. We also found that the expression of vascular endothelial growth factor (Vegfa), insulin-like growth factor 1 (Igf1), and transforming growth factor beta 1 (Tgfb1) is related to hair growth using PCR. DN106212-treated mice had significantly higher expression of Vegfa and Igf1 than TF-treated ones, and inhibiting the expression of Tgfb1 had similar effects as TF treatment. In conclusion, we propose that DN106212 increases the expression of hair growth factors, promotes the development of hair follicles, and promotes hair growth. Although additional experiments are needed, DN106212 may serve as an experimental basis for research on natural hair growth-promoting agents.

Long Sleep Duration and Dissatisfaction with Sleep Quality Are Associated with Ischemic Stroke in Young Patients.

INTRODUCTION: Suboptimal sleep duration and poor sleep quality have been proposed to increase stroke risk. However, their significance in young ischemic stroke is unclear. We aimed to investigate the importance of sleep duration and quality on young ischemic stroke patients. METHODS: A multicenter matched case-control study was performed to evaluate under-recognized risk factors in young (<45 years) ischemic stroke patients in 8 tertiary hospitals in Korea. A total of 225 patients and 225 age- and sex-matched controls were enrolled in the same period. Detailed information about patients' demographics, socioeconomic state, and traditional and nontraditional risk factors including sleep-related factors were obtained using structured questionnaires. Risk of ischemic stroke was estimated using conditional logistic regression analysis. RESULTS: Although average sleep duration was similar in patients and controls, patients were more likely to have long (≥9 h) or extremely short (<5 h) sleep durations. In addition, the proportion of subjects with dissatisfaction with sleep quality was higher in patients than controls (66.2 vs. 49.3%, p < 0.001). In multivariable conditional logistic regression analysis, long sleep duration (OR: 11.076, 95% CI: 1.819-67.446, p = 0.009) and dissatisfaction with sleep quality (OR: 2.116, 95% CI: 1.168-3.833, p = 0.013) were independently associated with risk of ischemic stroke. CONCLUSIONS: Long sleep duration and dissatisfaction with sleep quality may be associated with increased risk of ischemic stroke in young adults. Improving sleep habit or quality could be important for reducing the risk of ischemic stroke.

Gastrointestinal involvement of passenger lymphocyte syndrome followed by minor ABO-incompatible renal transplantation: A case report.

BACKGROUND: People with group O blood are considered universal organ donors compatible with any other blood group. However, in the case of minor ABO-incompatible transplantation, immune-mediated hemolysis may occur due to concomitant transfer of donor B lymphocytes together with the allograft. These passenger lymphocytes can produce antibodies in the recipients erythrocytes, causing hemolytic anemia known as passenger lymphocyte syndrome (PLS). METHODS: A retrospective chart review was performed. RESULTS: A 6-year-old boy (A+) underwent transplantation of a kidney from his father (O+). On postoperative day (POD) 6, the patient developed fever with no explainable causes. On POD 11, he presented with abdominal pain, hematochezia, and severe diarrhea, with sudden hemolytic anemia. Since then, GI symptoms have continued. On POD 20, direct antiglobulin test (DAT) was positive, and the anti-A IgM/G titer was 2/32. The results of the anti-A antibody elution test were strongly positive (3+). These findings highly suggested PLS. On the same day, the GI symptoms suddenly worsened, and laboratory findings showed hemolysis and thrombocytopenia with disseminated intravascular coagulation (DIC). Abdominal computed tomography (CT) scans suggested ischemic colitis of venous origin, and the patient underwent segmental colectomy with ileostomy formation on POD 23. To remove the anti-A antibodies, the patient underwent therapeutic plasma exchange (TPE) five times until the DAT and anti-A elution test were negative. CONCLUSIONS: We report a case of gastrointestinal involvement of PLS that occurred after minor ABO-incompatible kidney transplantation. This is the first report of ischemic colitis as an atypical manifestation of PLS.

Circulating small extracellular vesicles promote proliferation and migration of vascular smooth muscle cells via AXL and MerTK activation.

The proliferation and migration of vascular smooth muscle cells (VSMCs) after vascular injury lead to neointimal hyperplasia, thus aggravating vascular diseases. However, the molecular mechanisms underlying neointima formation are not fully elucidated. Extracellular vesicles (EVs) are mediators of various intercellular communications. The potential of EVs as regulators in cardiovascular diseases has raised significant interest. In the current study we investigated the role of circulating small extracellular vesicles (csEVs), the most abundant EVs (1010 EVs/mL serum) in VSMC functions. csEVs were prepared from bovine, porcine or rat serum. We showed that incubation with csEVs (0.5 × 1010-2 × 1010) dose-dependently enhanced the proliferation and migration of VSMCs via the membrane phosphatidylserine (PS). In rats with ligation of right carotid artery, we demonstrated that application of csEVs in the ligated vessels aggravated neointima formation via interaction of membrane PS with injury. Furthermore, incubation with csEVs markedly enhanced the phosphorylation of AXL and MerTK in VSMCs. Pretreatment with BSM777607 (pan-TAM inhibitor), bemcentinib (AXL inhibitor) or UNC2250 (MerTK inhibitor) blocked csEV-induced proliferation and migration of VSMCs. We revealed that csEV-activated AXL and MerTK shared the downstream signaling pathways of Akt, extracellular signal-regulated kinase (ERK) and focal adhesion kinase (FAK) that mediated the effects of csEVs. We also found that csEVs increased the expression of AXL through activation of transcription factor YAP, which might constitute an AXL-positive feedback loop to amplify the signals. Finally, we demonstrated that dual inhibition of AXL/MerTK by ONO-7475 (0.1 µM) effectively hindered csEV-mediated proliferation and migration of VSMCs in ex vivo mouse aorta injury model. Based on these results, we propose an essential role for csEVs in proliferation and migration of VSMCs and highlight the feasibility of dual AXL/MerTK inhibitors in the treatment of vascular diseases.

Efficacy and safety of mucous fistula refeeding in preterm infants: an exploratory randomized controlled trial.

BACKGROUND: This study aimed to evaluate whether mucous fistula refeeding (MFR) is safe and beneficial for the growth and intestinal adaptation of preterm infants with enterostomies. METHODS: This exploratory randomized controlled trial enrolled infants born before 35 weeks' gestation with enterostomy. If the stomal output was ≥ 40 mL/kg/day, infants were assigned to the high-output MFR group and received MFR. If the stoma output was < 40 mL/kg/day, infants were randomized to the normal-output MFR group or the control group. Growth, serum citrulline levels, and bowel diameter in loopograms were compared. The safety of MFR was evaluated. RESULTS: Twenty infants were included. The growth rate increased considerably, and the colon diameter was significantly larger after MFR. However, the citrulline levels did not significantly differ between the normal-output MFR and the control group. One case of bowel perforation occurred during the manual reduction for stoma prolapse. Although the association with MFR was unclear, two cases of culture-proven sepsis during MFR were noted. CONCLUSIONS: MFR benefits the growth and intestinal adaptation of preterm infants with enterostomy and can be safely implemented with a standardized protocol. However, infectious complications need to be investigated further. TRIAL REGISTRATION: clinicaltrials.gov NCT02812095, retrospectively registered on June 6, 2016.

The discovery of novel SNPs associated with group A soyasaponin biosynthesis from Korea soybean core collection.

Soyasaponin is a type of glycoside such as steroids, steroidal alkaloids or triterpenes, which enhance the body immunity. In order to efficiently identify genes and markers related to the soyasaponin, we used a 180K Axiom® SoyaSNP array and whole genome resequencing data from the Korean soybean core collection. As a result of conducting GWAS for group A soyasaponin (Aa and Ab derivatives), 16 significant common markers associated with Aa and Ab derivatives were mapped to chromosome 7, and three candidate genes including Glyma.07g254600 were detected. The functional haplotypes for candidate genes showed that Aa and Ab contents were mainly determined by alleles of AX-90322128, the marker of Glyma.07g254600. In addition, 14 novel SNPs variants closely associated with Aa and Ab derivatives were discovered for Glyma.07g254600. Therefore, the results of this study that identified soyasaponin-associated markers and useful genes utilizing various genomic information could provide insight into functional soybean breeding.

Paeoniflorin Attenuates Lipopolysaccharide-Induced Cognitive Dysfunction by Inhibition of Amyloidogenesis in Mice.

Alzheimer's disease (AD) is a neurodegenerative disease, associated with progressive cognitive impairment and memory loss. In the present study, we examined the protective effects of paeoniflorin against memory loss and cognitive decline in lipopolysaccharide (LPS)-induced mice. Treatment with paeoniflorin alleviated LPS-induced neurobehavioral dysfunction, as confirmed by behavioral tests, including the T-maze test, novel-object recognition test, and Morris water maze test. LPS stimulated the amyloidogenic pathway-related proteins (amyloid precursor protein, APP; ß-site APP cleavage enzyme, BACE; presenilin1, PS1; presenilin2, PS2) expression in the brain. However, paeoniflorin decreased APP, BACE, PS1, and PS2 protein levels. Therefore, paeoniflorin reverses LPS-induced cognitive impairment via inhibition of the amyloidogenic pathway in mice, which suggests that paeoniflorin may be useful in the prevention of neuroinflammation related to AD.

Protective Effects and Mechanisms of Pectolinarin against H2O2-Induced Oxidative Stress in SH-SY5Y Neuronal Cells.

This study aims to investigate the protective effects and mechanisms of pectolinarin against oxidative stress-induced cell damage in SH-SY5Y cells. Neurodegenerative diseases-such as Alzheimer's disease-are potentially associated with oxidative stress, which causes excessive production of reactive oxygen species (ROS) that damage DNA and proteins in neuronal cells. The results of this study demonstrate that pectolinarin can scavenge hydroxyl and nitric oxide radicals in a concentration-dependent manner. Moreover, pectolinarin significantly increased cell viability while reducing ROS production and LDH release in the hydrogen peroxide (H2O2)-induced control group. Additionally, Pectolinarin recovered protein expression from H2O2-altered levels back to close-to-normal SH-SY5Y cell levels for components of the oxidative stress, inflammation, and apoptosis pathways-such as nuclear factor erythroid 2-related factor 2 (Nrf2), kelch-like ECH-associated protein (Keap1), anti-heme oxygenase 1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), B-cell lympho-ma-2 (Bcl-2) protein, and Bcl-2-associated X protein (Bax). These findings suggest that pectolinarin has the potential to be used as a plant material for functional foods to be applied in the treatment of neurodegenerative diseases, such as Alzheimer's disease, by mitigating oxidative stress-induced damage to neuronal cells.

Cold Plasma Treatment Increases Bioactive Metabolites in Oat (Avena sativa L.) Sprouts and Enhances In Vitro Osteogenic Activity of their Extracts.

Cold plasma treatment has been studied to enhance the germination, growth, and bioactive phytochemical production in crops. Here, we aimed to investigate the effects of cold plasma treatment on the growth, bioactive metabolite production, and protein expression related to the physiological and osteogenic activities of oat sprouts. Oat seeds were soaked for 12 h, and then exposed to plasma for 6 min/day for 3 days after sowing. Plasma exposure did not significantly change the growth of oat sprouts; however, increased the content of bioactive metabolites. A single exposure for 6 min on the first day (T-1) increased the content of free amino acids (39.4%), γ-aminobutyric acid (53%), and avenacoside B (23%) compared to the control. Hexacosanol content was the highest in T-3 (6 min exposure on each day for 3 days), 28% higher than that in the control. Oat sprout extracts induced the phosphorylation of adenosine 5'-monophosphate-activated protein kinase and osteoblast differentiation was enhanced by increasing the alkaline phosphatase (ALP) activity; all these effects were induced by plasma treatment. Avenacoside B content was positively correlated with ALP activity (r = 0.911, p < 0.1). These results suggest that plasma treatment has the potential to improve the value of oat sprouts and that it may be used in food fortification to enhance nutritional value for promoting human health.

Effects of Dose Titration on Dipyridamole-Induced Headache: A Randomized, Double-Blind Clinical Trial.

PURPOSE: The aim of this study is to investigate the effect of gradual dipyridamole titration and the incidence of dipyridamole-induced headache in patients with ischemic stroke or transient ischemic attack (TIA). METHODS: A randomized, double-blind, double-placebo, parallel group, phase 4 clinical trial (KCT0005457) was conducted between July 1, 2019, and February 25, 2020, at 15 medical centers in South Korea. The study included patients aged >19 years diagnosed with a noncardioembolic ischemic stroke or TIA within the previous 3 weeks. The participants were randomized 1:1:1 to receive Adinox® (aspirin 25 mg/dipyridamole 200 mg) and aspirin (100 mg) once daily for the first 2 weeks followed by Adinox® twice daily for 2 weeks (titration group), Adinox® twice daily for 4 weeks (standard group), and aspirin 100 mg once daily for 4 weeks (control group). The primary endpoint was incidence of headache over 4 weeks. The key secondary endpoint was mean cumulative headache. RESULTS: Ninety-six patients were randomized into the titration (n = 31), standard (n = 32), and control (n = 33) groups. The titration and standard groups (74.1% vs. 74.2%, respectively) showed no difference in the primary endpoint. However, the mean cumulated headache was significantly lower in the titration group than in the standard group (0.31 ± 0.46 vs. 0.58 ± 0.51, p = 0.023). Further, adverse drug reactions were more common in the standard group than in the titration group (28.1% vs. 9.7%, respectively, p = 0.054), although not significantly different. CONCLUSION: The titration strategy was effective in lowering the incidence of cumulative dipyridamole-induced headache.

7-day versus 14-day tegoprazan-based triple therapy to treat Helicobacter pylori infection: Real-world evidence.

BACKGROUND AND AIM: Potassium-competitive acid blockers (P-CABs) can be used to eradicate Helicobacter pylori infection. We aimed to evaluate the impact of treatment duration (7 vs 14 days) on successful H. pylori eradication with P-CAB-based triple therapy in Korea, where clarithromycin resistance rate is high. METHODS: We retrospectively reviewed the data of patients who received first-line treatment for H. pylori infection with tegoprazan-based triple therapy (50 mg tegoprazan + 1000 mg amoxicillin + 500 mg clarithromycin twice daily for 1 or 2 weeks). The primary endpoint was the eradication rate in intention-to-treat (ITT) analysis. RESULTS: Of the 948 patients included in the study, 435 and 513 received 7-day and 14-day tegoprazan-based triple therapy, respectively. The eradication rate was higher in the 14-day therapy group than in the 7-day therapy group (ITT, 63.9%; 95% confidence interval [CI], 59.3-68.3%] vs 78.6% [95% CI, 74.9-81.9%], respectively, P < 0.001; per-protocol, 70.5% [95% CI, 65.8-74.8%] vs 85.1% [81.7-88.1%], respectively, P < 0.001). Overall adverse event rates did not differ between the two groups. Although six patients in the 14-day treatment group discontinued the prescribed medications due to adverse events, four of them (67%) discontinued the medication within 4 days. CONCLUSIONS: The 14-day tegoprazan-based triple therapy showed a superior eradication rate and acceptable adverse events compared with the 7-day tegoprazan-based triple therapy. A 14-day treatment regimen may be required when H. pylori infection is treated with tegoprazan-based triple therapy in regions with high clarithromycin resistance.

Augmented Reality-Based Visual Cue for Guiding Central Catheter Insertion in Pediatric Oncologic Patients.

BACKGROUND: Pediatric hemato-oncologic patients require central catheters for chemotherapy, and the junction of the superior vena cava and right atrium is considered the ideal location for catheter tips. Skin landmarks or fluoroscopic supports have been applied to identify the cavoatrial junction; however, none has been recognized as the gold standard. Therefore, we aim to develop a safe and accurate technique using augmented reality technology for the location of the cavoatrial junction in pediatric hemato-oncologic patients. METHODS: Fifteen oncology patients who underwent chest computed tomography were enrolled for Hickman catheter or chemoport insertion. With the aid of augmented reality technology, three-dimensional models of the internal jugular veins, external jugular veins, subclavian veins, superior vena cava, and right atrium were constructed. On inserting the central vein catheters, the cavoatrial junction identified using the three-dimensional models were marked on the body surface, the tip was positioned at the corresponding location, and the actual insertion location was confirmed using a portable x-ray machine. The proposed method was evaluated by comparing the distance from the cavoatrial junction to the augmented reality location with that to the conventional location on x-ray. RESULTS: The mean distance between the cavoatrial junction and augmented reality location on x-ray was 1.2 cm, which was significantly shorter than that between the cavoatrial junction and conventional location (1.9 cm; P = 0.027). CONCLUSIONS: Central catheter insertion using augmented reality technology is more safe and accurate than that using conventional methods and can be performed at no additional cost in oncology patients.

Variation in Knowledge of Stroke Warning Signs by Age and Presence of Conventional Risk Factors: A Community Health Survey in Korea.

BACKGROUND: It is important to recognize stroke in the general public. OBJECTIVES: The purpose of this study was to investigate factors affecting knowledge of stroke warning signs (SWSs) according to age group in the Korean population. METHODS: This study is a cross-sectional study. Using data from the Korean Community Health Survey conducted in Korea in 2017, 198 403 subjects were analyzed. Knowledge about SWSs was assessed by face-to-face interviews using structured close-ended questionnaires with 5 items about stroke symptoms (sudden unilateral weakness of face, arm or leg; sudden difficulty in speaking, or trouble understanding speech; sudden visual impairment in 1 eye, or double vision; sudden dizziness or loss of balance; and sudden severe headache). RESULTS: The overall percentage of subjects with good knowledge of SWSs (>4 correct answers to the SWS questionnaire) was 66.5%. It was highest in the middle-aged subjects (72.6%), followed by the young subjects (63.5%) and the older subjects (61.5%). The youngest of the young subjects and the oldest of the older subjects had the least knowledge. Subjects with conventional risk factors generally had more knowledge about SWSs, except for those with diabetes mellitus. However, in the young subjects, knowledge about SWSs was not increased by the presence of conventional risk factors such as hypertension and dyslipidemia. CONCLUSION: Stoke risk factors are increasing among young people; they still have poor knowledge about SWSs. More education is needed to increase appropriate treatment, especially in young people with stroke-related risk factors.

Inhibitory effect of d-arabinose on oral bacteria biofilm formation on titanium discs.

OBJECTIVES: Biofilm formation on dental implant surfaces can cause peri-implant mucositis and peri-implantitis. Lectins are involved in interactions between bacteria or between bacteria and their hosts. Disrupting these interactions via specific sugars can result in reduced adhesion and biofilm formation. The purpose of this study was to identify sugars that function as antiadhesion or antibiofilm agents on titanium discs. METHODS: Of the sugars tested, the sugars that did not affect the planktonic growth of Streptococcus oralis, Fusobacterium nucleatum, and Porphyromonas gingivalis were selected. The selected sugars were assessed for their ability to inhibit biofilm formation of bacteria in single and consortium species by crystal violet staining, confocal laser scanning microscopy after live/dead staining, and scanning electron microscopy. The sugars were evaluated for their ability to inhibit activity of the quorum sensing molecule autoinducer 2 (AI-2) by bioluminescence assay. RESULTS: Biofilm formation of single bacteria or consortia of S. oralis, F. nucleatum, and P. gingivalis on titanium discs was significantly inhibited in the presence of d-arabinose. Pretreating titanium discs with d-arabinose for 3 min inhibited biofilm formation at a level comparable to that observed when d-arabinose was present over the entire period, suggesting that d-arabinose had initial anti-adhesive activity. In addition, d-arabinose inhibited the activity of AI-2. CONCLUSIONS: d-Arabinose may be a good candidate for application as an antibiofilm agent and AI-2 inhibitor.

Selective Expansion of NKG2C+ Adaptive NK Cells Using K562 Cells Expressing HLA-E.

Adaptive natural killer (NK) cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs) can be expanded in vivo in response to human cytomegalovirus (HCMV) infection. Developing a method to preferentially expand this subset is essential for effective targeting of allogeneic cancer cells. A previous study developed an in vitro method to generate single KIR+ NK cells for enhanced targeting of the primary acute lymphoblastic leukemia cells; however, the expansion rate was quite low. Here, we present an effective expansion method using genetically modified K562-HLA-E feeder cells for long-term proliferation of adaptive NK cells displaying highly differentiated phenotype and comparable cytotoxicity, CD107a, and interferon-γ (IFN-γ) production. More importantly, our expansion method achieved more than a 10,000-fold expansion of adaptive NK cells after 6 weeks of culture, providing a high yield of alloreactive NK cells for cell therapy against cancer.

Discovery of GSK3ß Inhibitors through In Silico Prediction-and-Experiment Cycling Strategy, and Biological Evaluation.

Direct inhibitors of glycogen synthase kinase 3ß (GSK3ß) have been investigated and reported for the past 20 years. In the search for novel scaffold inhibitors, 3000 compounds were selected through structure-based virtual screening (SBVS), and then high-throughput enzyme screening was performed. Among the active hit compounds, pyrazolo [1,5-a]pyrimidin-7-amine derivatives showed strong inhibitory potencies on the GSK3ß enzyme and markedly activated Wnt signaling. The result of the molecular dynamics (MD) simulation, enhanced by the upper-wall restraint, was used as an advanced structural query for the SBVS. In this study, strong inhibitors designed to inhibit the GSK3ß enzyme were discovered through SBVS. Our study provides structural insights into the binding mode of the inhibitors for further lead optimization.