Epidemiologic Characteristics and Case Fatality Rate of Vibrio vulnificus Infection: Analysis of 761 Cases From 2003 to 2016 in Korea.

BACKGROUND: Vibrio vulnificus infection is a highly fatal disease resulting from the consumption of raw or undercooked seafood and exposure to seawater containing the organism. It has been a nationally notifiable disease since 2000 in Korea. The aims of this study were to assess the trends in the incidence of V. vulnificus infection and its case fatality rate and to determine the epidemiologic characteristics to effectively prevent infection and lower mortality. METHODS: We analyzed the incidence trends of V. vulnificus infection by year, month, and region in 913 cases reported to the Korea Centers for Disease Control and Prevention (KCDC, currently Korea Disease Control and Prevention Agency) by the National Infectious Disease Surveillance System from 2001 to 2016. We analyzed the number of patients with V. vulnificus infection who were under the National Health Insurance Service (NHIS) and whose coastal seawater temperature data were provided by the Korea Oceanographic Data Center of the National Institute of Fisheries Science. Epidemiological investigations were followed up and analyzed for 761 patients from 2003 to 2016. A total of 152 patients who were not followed up were excluded from the analysis. The case fatality rate was analyzed for 325 cases reported to the KCDC from 2011 to 2016. RESULTS: The mean incidence of V. vulnificus infection was 0.12 per 100,000 people, and the highest incidence was reported in September (41.1%) during the study period. The incidence rate per 100,000 people was the highest in Jeonnam (8.23). The number of patients who claimed to the NHIS was the highest in September (105 patients). The average seawater temperature was the highest at 24.1°C in August, and the average seawater temperature from August to October, when many cases occurred, was 22.4°C. The male-to-female ratio was 6:1, and 96.4% of the patients were aged ≥ 40 years. Of the patients, 96.1% had underlying diseases, the most common of which was liver cirrhosis (56.3%). The case fatality rate was 48.9%. CONCLUSION: The occurrence of V. vulnificus infection showed distinct seasonality, with a large number of cases occurring in the months when the seawater temperature was high; there were also distinct geographical characteristics. The incidence of V. vulnificus infection and mortality rates have not decreased for decades, and it is still an important public health problem with a high fatality rate.

Covalent Positioning of Single DNA Molecules for Nanopatterning.

Bottom-up micropatterning or nanopatterning can be viewed as the localization of target molecules to the desired area of a surface. A majority of these processes rely on the physical adsorption of ink-like molecules to the paper-like surface, resulting in unstable immobilization of the target molecules owing to their noncovalent linkage to the surface. Herein, successive single nick-sealing facilitated the covalent immobilization of individual DNA molecules at defined positions on a dendron-coated silicon surface using atomic force microscopy. The covalently-patterned ssDNA was visualized when the streptavidin-coated gold nanoparticles bound to the biotinylated DNA. The successive covalent positioning of the target DNA under ambient conditions may facilitate the bottom-up construction of DNA-based durable nanostructures, nanorobots, or memory system.

Potential roles of aquaporin 9 in the pathogenesis of endometriosis.

Aquaporins (AQPs) are involved in cell migration, proliferation and carcinogenesis in tumor development and physiologic inflammatory processes, but their associations with endometriosis have not been fully evaluated. In this study, tissue samples were obtained from women undergoing laparoscopic surgery for endometriosis and other benign conditions. Analysis of expressions of AQP subtypes in eutopic and ectopic endometrium of patients with endometriosis (Eu-EMS and Ect-EMS, respectively) and eutopic endometrium of control patients without endometriosis (Eu-CTL) were performed using the NanoString nCounter System and western blotting. Human endometrial stromal cells (HESCs) were cultured and transfected with the siRNA of the AQP of interest. Among the AQP1-9 subtypes, endometrial expression of AQP2 and AQP8 was significantly increased, whereas AQP9 expression was significantly decreased in the Eu-EMS group compared to the Eu-CTL group. Comparison of expression of AQP2, AQP8 and AQP9 among Eu-EMS, Ect-EMS and Eu-CTL groups revealed significant differences for only AQP9. Expression of AQP9 in the Eu-EMS group was decreased compared with that in Eu-CTL. After transfection of AQP9 siRNA in HESCs, expressions of MMP2 and MMP9 were significantly elevated. Increased expression of phosphorylated ERK 1/2 and phosphorylated p38 MAPK proteins after transfection was also confirmed using western blot analysis. Increased migration and invasion potentials of HESCs after transfection were determined by migration and wound healing assays. These findings suggest that AQP9 may be involved in the pathogenesis of endometriosis and warrant further investigation as a potential therapeutic target for treating endometriosis.

Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis.

The histamine H4 receptor (H4R), a member of the G-protein coupled receptor family, has been considered as a potential therapeutic target for treating atopic dermatitis (AD). A large number of H4R antagonists have been disclosed, but no efficient agents controlling both pruritus and inflammation in AD have been developed yet. Here, we have discovered a novel class of orally available H4R antagonists showing strong anti-itching and anti-inflammation activity as well as excellent selectivity against off-targets. A pharmacophore-based virtual screening system constructed in-house successfully identified initial hit compound 9, and the subsequent homology model-guided optimization efficiently led us to discover pyrido[2,3- e]tetrazolo[1,5- a]pyrazine analogue 48 as a novel chemotype of a potent and highly selective H4R antagonist. Importantly, orally administered compound 48 exhibits remarkable efficacy on antipruritus and anti-inflammation with a favorable pharmacokinetic (PK) profile in several mouse models of AD. Thus, these data strongly suggest that our compound 48 is a promising clinical candidate for treatment of AD.

Glucose metabolism of visceral adipose tissue measured by 18F-FDG PET/CT is related to the presence of colonic adenoma.

This study investigated the relationships between the area and metabolic activity of adipose tissue and the presence of colorectal adenoma (CRA). Our institutional review board approved the study and waived informed consent. A total of 212 subjects who underwent fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and colonoscopy for routine health check-ups were enrolled. The volumetric parameters of areas of visceral (VATav), subcutaneous (SATav), and total adipose tissue (TATav) and calculated visceral-to-subcutaneous adipose tissue ratio (VSR) and visceral-to-total adipose tissue ratio (VAR) were considered. Metabolic parameters of standardized uptake value (SUV) of visceral (vcSUVmax, vcSUVmean), subcutaneous (scSUVmax, scSUVmean), and calculated visceral-to-subcutaneous adipose tissue ratio (VSRmax, VSRmean) were considered. Anthropometric data of height, weight, body mass index (BMI), waist circumference (WC), body fat mass (BFM), skeletal muscle mass (SMM), and diverse laboratory data were also considered as variables. Sixty-six subjects were placed in the CRA group and 146 subjects in the non-CRA group. The presence of CRA was significantly correlated with older age (P  =  .001), male sex (P  =  .041), higher BMI (P  =  .004), higher WC (P  =  .001), higher BFM (P  =  .024), higher VATav (P < .001), higher TATav (P  =  .004), higher VSR (P < .001), higher VAR (P < .001), lower vcSUVmax (P  =  .002), lower vcSUVmean (P < .001), and lower VSRmean (P  =  .002). On multiple regression analysis, vcSUVmax and vcSUVmean were independently associated with the presence of CRA (P  =  .009 and P  =  .045). Lower glucose metabolism of visceral adipose tissue was related to the presence of CRA. Our findings identify the value of visceral metabolic dysfunction as a potential surrogate marker of elevated risk for CRA.

Clinical Dimensions of Bloating in Functional Gastrointestinal Disorders.

BACKGROUND/AIMS: Bloating is common bothersome symptoms and most studies conducted in the Western countries found that bloating was frequently associated with lower gastrointestinal (GI) symptoms but many patients complaint bloating as upper GI symptoms in the clinical setting. This study was conducted to assess the prevalence of bloating, and to identify symptom grouping and finally document the impact of bloating in the diagnosis of functional GI disorders. METHODS: Participants in a comprehensive health-screening cohort were enrolled. They were asked about demographic, medical, and social history and upper and lower GI symptoms by using a validated questionnaire. Factor analysis with principal component analysis method with varimax rotation was used. RESULTS: Among the total of 1050 subjects (mean age, 44.6 ± 10.2 years; females, 46.4%), significant bloating symptoms were found in 282 (26.9%); the prevalence of functional bloating was 6.9%. Factor analysis revealed a 5-component structure with upper GI symptoms, constipation, diarrhea-predominant irritable bowel syndrome (IBS), constipation-predominant IBS, and fecal incontinence. Abdominal bloating loaded on both the upper GI symptoms (0.51 of loadings) and constipation (0.40). On logistic regression analysis, bloating was more predictable for IBS (OR, 7.5; P < 0.001) than functional dyspepsia (FD; OR, 3.7; P = 0.002). Bloating was more frequently combined with IBS according to their severity, but this association was not detected in patients with FD. CONCLUSIONS: Abdominal bloating is common symptom in about a quarter of patients and appears as upper as well as lower GI symptoms. However, abdominal bloating is more predictable for IBS, especially constipation-predominant IBS, than FD.

Following the DNA ligation of a single duplex using atomic force microscopy.

Nick-sealing of a single DNA duplex was studied with the use of atomic force microscopy (AFM). To form a nick between a 47 mer DNA and a 24 mer DNA, the complementary 71 mer template DNA immobilized on an AFM tip was hybridized with the 47 mer DNA and brought into contact with the 24 mer DNA on a substrate surface. The AFM tip and substrate surface were modified with dendron molecules to ensure the formation of a single DNA duplex. When a single nick in the DNA duplex was sealed by DNA ligase during a pause, an increase in the unbinding force was observed after the pause. The change from 24.0 ± 4.4 piconewtons (pN) to 62.8 ± 14.6 pN matched well with the resulting DNA length (71 bp). Additionally, a 30 s pause showed a 3-fold higher nick-sealing probability (60%) than a 10 s pause, while the probability did not increase with a 120 s pause. In the presence of free 47 mer DNAs in solution, the single nick-sealing event could be repeated at other positions.

[Effects on changes in femoral vein blood flow velocity with the use of lower extremity compression for critical patients with brain injury].

PURPOSE: This study was done to evaluate the mean venous velocity (MVV) response with knee and thigh length compression stockings (CS) versus intermittent pneumatic compression (IPC) devices in immobile patients with brain injuries. METHODS: We carried out a randomized controlled study. We analyzed both legs of a randomly chosen sample of 43 patients assigned to one of 4 groups (86 legs). The patients were sequentially hospitalized in the intensive care unit (ICU) in "S hospital" from November 2005 to December 2006. The base line and augmented venous velocity was measured at the level of the common femoral vein. We applied leg compression 42 times over 7 days (for 2 hours at a time at 2 hour intervals). RESULTS: There was a statistical difference among the 4 groups. The difference for the "IPC" group was more significant than the "CS" group. CONCLUSION: These results indicate that the application of IPC can be considered as an effective method to prevent deep vein thrombosis for immobile patients with brain injury.

New insight for fluoroquinophenoxazine derivatives as possibly new potent topoisomerase I inhibitor.

Fluoroquinolones, represented by ciproxacin and norfloxacin, are well-known clinical antimicrobial agents, and their phenyl ring expanded quinophenoxazines are reported as possible antitumor active compounds. These quinophenoxazines are known to inhibit DNA topoisomerase II essential for cell replication cycle. But there were no reports for topoisomerase I inhibition study for these compounds. In this report, we have prepared a few quinophenoxazine analogues and tested their topoisomerases I and II inhibitory activities and cytotoxicity. From the result, we found that quinophenoxazine analogues possessed strong topoisomerase I inhibitory capacity as well as topoisomerase II inhibition. Among the compounds prepared, A-62176 analogues showed strong topoisomerases I and II inhibitory activities. Interestingly, compound 8 missing the 3-aminopyrrolidine moiety at C2 position has similar potent inhibitory capacity against topoisomerases I and II at higher concentrations (20 and 10 microM, respectively). But compound 8 inhibited topoisomerase I function more selectively at lower concentration, 2 microM. Our observation might strongly implicate that fluoroquinophenoxazines can be developed as efficient topoisomerase I inhibitor with the elaborate modification.

Development of immunochromatography strip-test using nanocolloidal gold-antibody probe for the rapid detection of aflatoxin B1 in grain and feed samples.

An immunochromatography (ICG) strip test using a nanocolloidal gold-antibody probe was developed and optimized for the rapid detection of aflatoxin B1 (AFB1). A monoclonal antibody specific to AFB1 was produced from the cloned hybridoma cell (AF78), coupled with nanocolloidal gold, and distributed on the conjugate pad of the ICG strip test. The visual detection limit of the ICG strip test was 0.5 ng/ml, and this method showed a cross-reaction to aflatoxin B2, G1, and G2. In total, 172 grain and feed samples were collected and analyzed by both the ICG strip test and HPLC. The results of the ICG strip test showed a good agreement with those obtained by HPLC. These results indicated that the ICG strip test has a potential use as a rapid and cost-effective screening tool for the determination of AFB1 in real samples and could be applied to the preliminary screening of mycotoxin in food and agricultural products, generating results within 15 min without complicated steps.

Self-assembly of a diblock copolymer on a patterned surface with low-energy electron beam.

A pattern was generated by 500 eV electron beam irradiation on benzaldimine monolayer through a grid and subsequent hydrolysis of nonirradiated regions. While we tried to assemble a block copolymer, polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP), on the pattern, we observed that the polarity difference between the two different regions was not right for discriminating the wetting behavior of two blocks of the polymer. Among various modifications of the retrieved amine, it was found that tribromoacetaldehyde was suitable for this end. Surprisingly, treatment of the aldehyde gave a surface preferring the polystyrene block to poly(4-vinylpyridine) block, while the irradiated section favored the latter block. As a result, island morphology was observed on the tribromoacetaldimine region and hole morphology on the irradiated region when the film thickness was 1.3Lo. Contact angle data were consistent with the observed symmetric wetting on the former region and the asymmetric one on the latter.

[Association of Internet addiction with health promotion lifestyle profile and perceived health status in adolescents].

OBJECTIVES: To identify the relationship between the internet addiction of adolescents and their Health Promotion Lifestyle Profile and Perceived Health Status, and thereby to detect the impact of internet addiction on the health of adolescents, produce the basic information necessary to develop a prevention program for internet addiction and to plan for a health promotion program. METHODS: This study was designed as a cross-sectional study, and the subjects were the second-grade students of three junior-high and three high schools located in the city of K in Kyung Gi Province. Out of 769 subjects, 764 completed the questionnaires (99.3%); 369 (48.3%) junior-high school students and 395 (51.7%) high school students. The questionnaires were composed of Young's Internet Addiction, Health Promotion Lifestyle Profile, Perceived Health Status, and general characteristics. We used t-test, ANOVA in means comparison between groups, chi2-test in frequency analysis, and multiple regression analysis in multivariate analysis, using the SAS 8.1 program. RESULTS: There was a statistically significant difference in Health Promotion Lifestyle Profile according to internet addiction status (severe addiction vs. other status, P < 0.0001). The Perceived Health Status scores was lowest in the severe addiction group (P < 0.001). There was also a significant negative correlation between internet addiction and Health Promotion Lifestyle Profile (P < 0.0001). The results of multiple regression showed that Young's Addiction Score was significant for the subjects' Health Promotion Lifestyle Profile after controlling for other variables (P < 0.0001). CONCLUSIONS: This study showed that the severe internet addiction group had the lowest score in Health Promotion Lifestyle Profile and Perceived Health Status, which suggests that the addiction could have a negative effect on the health status of adolescents.

Isolation of a new saponin and cytotoxic effect of saponins from the root of Platycodon grandiflorum on human tumor cell lines.

A novel triterpenoid saponin, deapioplatycoside E (1) was isolated from the root extract of Platycodon grandiflorum, together with the seven known saponins 2 - 8, i. e., platycoside E (2), deapioplatycodin D3 (3), platycodin D3 (4), polygalacin D2 (5), platycodin D2 (6), deapioplatycodin D (7) and platycodin D (8). The structure of the new saponin 1 was determined on the basis of spectral analysis and chemical evidence. The crude saponin fraction (ED50: ca. 10 - 15 microg/mL) and compounds 6 - 8 (ED50: ca. 4 - 18 microg/mL) exhibited significant inhibition on the proliferation of five kinds of cultured human tumor cell lines, i. e., A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon), in vitro.

Effect of disodium cromoglycate on mast cell-mediated immediate-type allergic reactions.

We investigated the effect of disodium cromoglycate (DSCG) on mast cell-mediated immediate-type hypersensitivity. DSCG inhibited systemic allergic reaction induced by compound 48/80 dose-dependently. Passive cutaneous anaphylaxis was inhibited by 71.6% by oral administration of DSCG (1 g/kg). When DSCG was pretreated at concentration rang from 0.01-1000 g/kg, the serum histamine levels were reduced in a dose dependent manner. DSCG also significantly inhibited histamine release from rat peritoneal mast cell (RPMC) by compound 48/80. We confirmed that DSCG inhibited compound 48/80-induced degranulation of RPMC by alcian blue/nuclear fast red staining. In addition, DSCG showed a significant inhibitory effect on anti-dinitrophenyl IgE-mediated tumor necrosis factor-alpha production. These results indicate that DSCG inhibits mast cell-mediated immediate-type allergic reaction.

[Effects of a closed endotracheal suction system on oxygen saturation, ventilator-associated pneumonia, and nursing efficacy].

PURPOSE: The purpose of this study was to examine the effects of a closed endotracheal suction system(CES) on oxygen saturation, ventilator associated pneumonia(VAP), and nursing efficacy in mechanically ventilated patients. METHOD: This study was conducted in the intensive care unit of a University Hospital in Gwangju City. Data was collected from July to October, 2003. Seventy mechanically ventilated patients were randomly divided into two groups; 32 for CES and 38 for open endotracheal suction system(OES) protocol. Twenty one nurses were also involved to examine the nurses' attitude of usefulness about CES. RESULT: SaO(2) was significantly different between CES and OES. The incidence of VAP in CES was lower than that of OES. Nursing efficacy was related to time, cost, and usefulness of the suction system. Time of suctioning in CES was shorter than that of OES. CES also contributed significantly to lower the cost of treatment than OES. The usefulness score of CES increased after 6 months of use. CONCLUSION: CES prevented VAP, was cost effective, and a safe suctioning system. CES ncan be used with patients with sensitivity to hypoxygenation and with a high risk of VAP.