Association of vancomycin trough concentration on the treatment outcome of patients with bacteremia caused by Enterococcus species.

BACKGROUND: Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia. METHODS: A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality. RESULTS: A total of 37 patients were enrolled-26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia. CONCLUSIONS: In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.

Effects of Automatic Abdominal Massage Device in Treatment of Chronic Constipation Patients: A Prospective Study.

BACKGROUND AND AIM: Manual abdominal massage has been shown to effectively treat slow-transit constipation, but it is labor-intensive. To offer an alternative treatment option for constipation, the Bamk-001 automatic abdominal massage device was developed. The aim of this study was to assess the effect of the Bamk-001 device on symptom profiles and colon transit time (CTT) in patients with chronic constipation. METHODS: Thirty-seven patients with chronic functional constipation diagnosed using the Rome IV criteria were enrolled prospectively from December 2018 to February 2019. All patients received device-assisted automatic abdominal massage for 15 min twice daily, once in the morning before breakfast and once at night, for 14 days. CTT was measured before and at the end of the study period. Slow-transit constipation and very-slow-transit constipation were defined as CTT ≥ 48 h and ≥ 72 h, respectively. Patients' symptom profiles regarding overall defecation satisfaction and device-related adverse events were analyzed. RESULTS: Among the 37 patients, the mean age was 40.1 ± 11.8, and 5.4% (n = 2) were men. The Bamk-001 device significantly improved CTT from 54.0 (33.6-75.6) to 28.8 (18.0-52.8) h (p = 0.001) in patients with chronic constipation. In subgroup analysis, CTT improved significantly from 54.0 (33.6-75.6) to 28.8 (18.0-52.8) h (p = 0.003) and from 88.2 (74.4-124.8) to 45.6 (27.3-74.1) h (p = 0.005) in the slow-transit and very-slow-transit constipation groups, respectively (p = 0.001). Moreover, all patient symptoms were alleviated after treatment. No serious adverse events were reported. CONCLUSION: The Bamk-001 automatic abdominal massage device showed significant care efficacy, including the improvement in CTT and symptom profiles in patients with slow-transit constipation. The use of an automatic abdominal massage device as an adjunct in the management of constipation is a potentially beneficial intervention for patients with slow-transit constipation.

Efficacy of iron supplementation in patients with inflammatory bowel disease treated with anti-tumor necrosis factor-alpha agents.

BACKGROUND: Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD). However, data on the influence of anti-tumor necrosis factor-alpha (anti-TNF-α) agents and iron supplementation on anemia in patients with IBD are sparse. We assessed the effect of iron supplementation in patients with IBD initially treated with an anti-TNF-α agent. METHODS: Data from 79 IBD patients who started anti-TNF-α treatment at a tertiary hospital were analyzed. The patients were divided into the anti-TNF-α (n = 52) and anti-TNF-α with iron supplementation (n = 27) groups. Effects on laboratory parameters, the prevalence of anemia, and disease activity were evaluated at baseline (year 0) and 1 year later. RESULTS: The hemoglobin (Hb) level significantly increased between years 0 and 1 in both groups [12.0 ± 1.8-13.3 ± 2.0 g/dL in the anti-TNF-α group (p < 0.001) and 9.8 ± 2.4-11.7 ± 2.3 g/dL in the anti-TNF-α and iron supplementation group (p = 0.004)]. In a subgroup analysis of severely anemic patients with IBD, iron supplementation increased the magnitude of the improvement in Hb level (8.5 ± 1.5-11.4 ± 2.1 g/dL; p = 0.001) compared with the anti-TNF-α group (9.3 ± 0.8-11.4 ± 2.7 g/dL; p = 0.081). Disease activity was significantly improved in both groups at year 1 compared with year 0. Persistent anemia was significantly correlated with severe anemia at baseline (p = 0.017). CONCLUSION: In anemic patients with IBD, anti-TNF-α agents led to clinically meaningful improvements in anemia independent of iron supplementation. Also, iron supplementation could be helpful in severely anemic patients with IBD.

Changes in the utilization patterns of antifungal agents, medical cost and clinical outcomes of candidemia from the health-care benefit expansion to include newer antifungal agents.

OBJECTIVES: In 2014, South Korea expanded its national health insurance coverage to include newer antifungal agents, such as echinocandins. This study aimed to investigate the effects of policy change on the prescription patterns of antifungals, medical costs and clinical outcomes of candidemia. METHODS: This retrospective cohort enrolled hospitalized patients with candidemia at three tertiary care hospitals in South Korea from January 2012 to December 2015. The utilization of antifungal agents, medical costs, length of hospital stay (LOS), and mortality before and after the health-care benefit expansion were compared, and the factors associated with all-cause 28-day mortality during the study period were analyzed. RESULTS: A total of 769 candidemia cases were identified. The incidence of candidemia did not significantly vary during the study period (P = 0.253). The proportion of echinocandins, as the initial antifungal agent, and medical costs associated with candidemia significantly increased since the change in insurance coverage (P < 0.001). There was no significant difference in LOS and mortality associated with candidemia before and after the health-care benefit expansion (P = 0.696 and 0.931, respectively). Multivariate logistic regression analysis showed that initial treatment with caspofungin was associated with decreased mortality (adjusted odds ratio: 0.784; 95% confidence interval: 0.681-0.902; reference: fluconazole). CONCLUSIONS: Although the utilization of newer antifungal agents and medical cost for candidemia has significantly increased since the health-care benefit expansion, there has been no change in the outcome of candidemia. However, the further increased use of newer antifungals may improve the outcome of candidemia in this country.

p53 expression status is associated with cancer-specific survival in stage III and high-risk stage II colorectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy.

BACKGROUND: We attempted to elucidate whether p53 expression or TP53 mutation status was associated with cancer-specific survival in adjuvant FOLFOX-treated patients with stage III or high-risk stage II colorectal cancer (CRC). METHODS: We analysed CRCs (N = 621) for the presence of TP53 alterations and for p53 expression, using targeted resequencing and immunohistochemistry. CRCs were grouped into four subsets according to the p53 expression status, which included p53-no, mild, moderate and strong expression. RESULTS: The distributions of CRCs were 19.85, 11.05, 17.7% and 51.5% in the p53-no, mild, moderate and strong expression groups, respectively. Cases in the p53-mild to moderate expression group were associated with a more frequent proximal location, undifferentiated histology, lower N category, extraglandular mucin production, microsatellite instability, CIMP-P1, CK7 expression and decreased CDX2 expression compared with those of cases of the p53-no expression and p53-strong expression groups. According to survival analysis, the p53-mild expression group showed a poor 5-year relapse-free survival (hazard ratio (HR): 2.71, 95% confidence interval (CI) = 1.60-4.60, P < 0.001) and poor 5-year cancer-specific survival (HR: 2.90, 95% CI = 1.28-6.57, P = 0.011). CONCLUSIONS: p53-mild expression status was found to be an independent prognostic marker in adjuvant FOLFOX-treated patients with stage III and high-risk stage II CRC.

Production of (3-hydroxybutyrate-co-3-hydroxyhexanoate) copolymer from coffee waste oil using engineered Ralstonia eutropha.

Polyhydroxyalkonate (PHA) is a type of polymer that has the potential to replace petro-based plastics. To make PHA production more economically feasible, there is a need to find a new carbon source and engineer microbes to produce a commercially valuable polymer. Coffee waste is an inexpensive raw material that contains fatty acids. It can act as a sustainable carbon source and seems quite promising with PHA production in Ralstonia eutropha, which is a well-known microbe for PHA accumulation, and has the potential to utilize fatty acids. In this study, to make poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(HB-co-HHx)), which has superior properties in terms of biodegradability, biocompatibility, and mechanical strength, engineered strain Ralstonia eutropha Re2133 overexpressing (R)-specific enoyl coenzyme-A hydratase (phaJ) and PHA synthetase (phaC2) with deletion of acetoacetyl Co-A reductases (phaB1, phaB2, and phaB3) was used to produce PHA from coffee waste oil. At a coffee oil concentration of 1.5%, and C/N ratio of 20, the R. eutropha Re2133 fermentation process results in 69% w/w of DCW PHA accumulation and consists of HB (78 mol%) and HHx (22 mol%). This shows the feasibility of using coffee waste oil for P(HB-co-HHx) production, as it is a low-cost fatty acid enriched waste material.

Quality Assessment of Randomized Controlled Trials of Moxibustion Using STandards for Reporting Interventions in Clinical Trials of Moxibustion (STRICTOM) and Risk of Bias (ROB).

OBJECTIVES: To assess the quality and completeness of published reports of randomized controlled trials (RCTs) of moxibustion. METHOD: We searched six databases to retrieve eligible RCTs of moxibustion published from 2000 to December 2015. We used the STandards for Reporting Interventions in Clinical Trials of Moxibustion (STRICTOM) and Risk of Bias (ROB) tool to assess the completeness of reporting of RCTs of moxibustion and evaluate the reporting quality of included RCTs. RESULTS: Thirty-four studies of moxibustion were analyzed using STRICTOM and ROB. Of the 34 studies, the completeness percentage of STRICTOM varied from 33% to 100% (mean 68%, median 67%). The completeness of STRICTOM items showed a rising tendency along with the publication year. The STRICTOM items of setting and context (14.7%), rationale for the control (17.6%), and response (26.4%) showed incomplete reporting. The number of RCTs that rated a low risk of bias for allocation concealment (n=6), blinding of participants and personnel (n=1), and blinding of outcome assessment (n=4) appeared to be small. CONCLUSION: The quality of reporting of RCTs of moxibustion remains incomplete according to the STRICTOM and ROB tool at present. Researchers should consider the STRICTOM and ROB for improving not only the completeness of reporting but also the study design. General guidelines for RCTs of moxibustion are also required.

DA-9701 improves colonic transit time and symptoms in patients with functional constipation: A prospective study.

BACKGROUND AND AIM: DA-9701, a newly developed prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, has been shown to effectively treat functional dyspepsia. Recently, it has also been suspected to improve gastrointestinal motor function. The aims of this study were to assess the effect of DA-9701 on colonic transit time (CTT) and symptoms of functional constipation. METHODS: Thirty-three patients with functional constipation based on the Rome III criteria were prospectively enrolled. The patients received 30-mg DA-9701 three times a day for 24 days. CTT was estimated initially and at the end of treatment. Symptoms such as spontaneous bowel movements, straining, stool form, feeling of incomplete emptying and anorectal blockage, abdominal discomfort and pain, overall defecation satisfaction, and incidence of adverse events were also analyzed. RESULTS: Twenty-seven patients completed the study. DA-9701 was associated with a significantly reduced CTT from 34.9 ± 17.6 to 23.7 ± 19.1 h (P = 0.001). Segmental CTT also significantly decreased after treatment (right CTT: from 16.8 [0.0-28.8] to 6.0 [0.0-25.2] hours, P < 0.001; rectosigmoid transit time: from 13.2 [0.0-38.4] to 6.0 [0.0-33.6] hours, P = 0.021). In addition, all constipation-related subjective symptoms, including spontaneous bowel movement frequency, significantly improved compared with those before treatment. Serious adverse events did not occur. CONCLUSIONS: DA-9701 accelerates colonic transit and safely improves symptoms in patients with functional constipation. Therefore, we suggest that this novel agent could help to treat patients with this condition.

Synthesis and Cytotoxicity of Dendritic Platinum Nanoparticles with HEK-293 Cells.

Dendritic platinum nanoparticles (DPNs) have been synthesized from l-ascorbic acid and an amphiphilic non-ionic surfactant (Brij-58) via a sonochemical method. The particle size and shape of the DPNs could be tuned by changing the reduction temperature, resulting in a uniform DPN with a size of 23 nm or 60 nm. The facets of DPNs have been studied by high-resolution transmission electron microscopy. The cytotoxicity of DPNs has been investigated using human embryonic kidney cells (HEK-293), and the biological adaptability exhibited by DPNs has opened a pathway to biomedical applications such as drug-delivery systems, photothermal treatment, and biosensors.

Superior Electrocatalytic Activity of a Robust Carbon-Felt Electrode with Oxygen-Rich Phosphate Groups for All-Vanadium Redox Flow Batteries.

A newly prepared type of carbon felt with oxygen-rich phosphate groups is proposed as a promising electrode with good stability for all-vanadium redox flow batteries (VRFBs). Through direct surface modification with ammonium hexafluorophosphate (NH4 PF6 ), phosphorus can be successfully incorporated onto the surface of the carbon felt by forming phosphate functional groups with -OH chemical moieties that exhibit good hydrophilicity. The electrochemical reactivity of the carbon felt toward the redox reactions of VO(2+) /VO2 (+) (in the catholyte) and V(3+) /V(2+) (in the anolyte) can be effectively improved owing to the superior catalytic effects of the oxygen-rich phosphate groups. Furthermore, undesirable hydrogen evolution can be suppressed by minimizing the overpotential for the V(3+) /V(2+) redox reaction in the anolyte of the VRFB. Cell-cycling tests with the catalyzed electrodes show improved energy efficiencies of 88.2 and 87.2 % in the 1(st) and 20(th)  cycles compared with 83.0 and 81.1 %, respectively, for the pristine electrodes at a constant current density of 32 mA cm(-2) . These improvements are mainly attributed to the faster charge transfer allowed by the integration of the oxygen-rich phosphate groups on the carbon-felt electrode.

Rational design of coaxial structured carbon nanotube-manganese oxide (CNT-MnO2) for energy storage application.

Recently, there has been great research interest in the development of composites (core-shell structures) of carbon nanotubes (CNTs) with metal oxides for improved electrochemical energy storage, photonics, electronics, catalysis, etc. Currently, the synthetic strategies for metal oxides/hydroxides are well established, but the development of core-shell structures by robust, cost-effective chemical methods is still a challenge. The main drawbacks for obtaining such electrodes are the very complex synthesis methods which ultimately result in high production costs. Alternatively, the solution based method offers the advantages of simple and cost effective synthesis, as well as being easy to scale up. Here, we report on the development of multi-walled carbon nanotube-manganese oxide (CNT-MnO2) core-shell structures. These samples were directly utilized for asymmetric supercapacitor (ASC) applications, where the CNT-MnO2 composite was used as the positive electrode and ZIF-8 (zeolitic imidazolate framework, ZIF) derived nanoporous carbon was used as the negative electrode. This unconventional ASC shows a high energy density of 20.44 W h kg(-1) and high power density of 16 kW kg(-1). The results demonstrate that these are efficient electrodes for supercapacitor application.

Surface-Tunable Bioluminescence Resonance Energy Transfer via Geometry-Controlled ZnO Nanorod Coordination.

The use of ZnO nanorods (NRs) as an effective coordinator and biosensing platform to create bioluminescence resonance energy transfer (BRET) is reported. Herein, a hydrothermal approach is applied to obtain morphologically controlled ZnO NRs, which are directly bound to luciferase (Luc) and carboxy-modified quantum dot (QD) acting as a donor-acceptor pair for BRET. BRET efficiency varies significantly with the geometry of ZnO NRs, which modulates the coordination between hexahistidine-tagged Luc (Luc-His6 ) and QD, owing to the combined effect of the total surface area consisting of (001) and (100) planes and their surface polarities. Unlike typical QD-BRET reactions with metal ions (e.g., zinc ions), a geometry-controlled ZnO NR platform can facilitate the design of surface-initiated BRET sensors without being supplemented by copious metal ions: the geometry-controlled ZnO NR platform can therefore pave the way for nanostructure-based biosensors with enhanced analytical performance.

A highly resilient mesoporous SiOx lithium storage material engineered by oil-water templating.

Mesoporous silicon-based materials gained considerable attention as high-capacity lithium-storage materials. However, the practical use is still limited by the complexity and limited number of available synthetic routes. Here, we report carbon-coated porous SiOx as high capacity lithium storage material prepared by using a sol-gel reaction of hydrogen silsesquioxane and oil-water templating. A hydrophobic oil is employed as a pore former inside the SiOx matrix and a precursor for carbon coating on the SiOx . The anode exhibits a high capacity of 730 mAh g(-1) and outstanding cycling performance over 100 cycles without significant dimensional changes. Carbon-coated porous SiOx also showed highly stable thermal reliability comparable to that of graphite. These promising properties come from the mesopores in the SiOx matrix, which ensures reliable operation of lithium storage in SiOx . The scalable sol-gel process presented here can open up a new avenue for the versatile preparation of porous SiOx lithium storage materials.

The formation of nano-layered grains and their enhanced superconducting transition temperature in Mg-doped FeSe0.9 bulks.

To search a proper dopant to further improve superconductivity in 11 type Fe-based superconductors makes sense to both their superconductivity mechanism and possible technological applications. In present work, Mg doped FeSe polycrystalline bulks were obtained by a two-step solid-state reaction method. Even though there are many MgSe and iron impurities existing in the Mg heavy doped FeSe bulks, they exhibit obviously increased Tc compared to undoped FeSe sample. It was found that Mg addition has little effect on the crystal lattice parameters of superconducting ß-FeSe, whereas leads to the formation of nano-layered grain structure consisted of MgSe and ß-FeSe with similar X-ray diffraction characteristics. Lots of nano-structural interfaces between FeSe and MgSe formed in this homogenous layered grain structure have significant effect on the superconducting properties and are responsible for the enhancement of Tc, as like the case of FeSe thin film on some specific substrates. Our work not only demonstrates a powerful way for raising Tc in bulk superconductors, but also provides a well-defined platform for systematic studies of the mechanism of unconventional superconductivity by considering interface effect.

Anti-inflammatory activity of compounds isolated from Astragalus sinicus L. in cytokine-induced keratinocytes and skin.

Inflammation is a part of the complex biological responses of a tissue to injury that protect the organ by removing injurious stimuli and initiating the healing process, and is considered as a mechanism of innate immunity. To identify biologically active compounds against pathogenic inflammatory and immune responses, we fractionated water, aqueous methanol and n-hexane layers from nine kinds of leguminosae and examined anti-inflammatory activity of the fractions in human keratinocytes and mouse skin. Among the fractions, rf3 and rf4, isolated from the aqueous methanol layer of Astragalus sinicus L., exhibited the strongest reactive oxygen species (ROS)-scavenging and anti-inflammatory activities as measured by inhibition of the intracellular ROS production, nuclear factor-kappaB (NF-κB), janus kinase (JAK)/signal transducer and activator of transcription (STAT), and phosphatidylinositol 3-kinase/Akt signaling in cytokine-stimulated human keratinocytes, as well as by effects on T-cell differentiation in mouse CD4(+) T cells. In addition, topical application of rf3 and rf4 suppressed the progression of psoriasis-like dermatitis and expression of pro-inflammatory mediators in interleukin (IL)-23-injected mouse ears. Our results suggest that Astragalus sinicus L. may ameliorate chronic inflammatory skin diseases due to its antioxidant and anti-inflammatory activities via regulation of the intracellular ROS production, NF-κB, JAK/STAT and PI3/Akt signaling cascades as well as immune responses, and these results are the first report that Astragalus sinicus L. exhibits pharmacological activity.

Safflower seed extract inhibits osteoclast differentiation by suppression of the p38 mitogen-activated protein kinase and IκB kinase activity.

Safflower seed has been reported to have a protective effect against bone loss diseases. However, the precise molecular mechanisms underlying the inhibitory effect of safflower seed in osteoclast differentiation remain unclear. In this study, we investigated the inhibitory action of safflower seed extract (SSE) on the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in cultured mouse-derived bone marrow macrophages (BMMs). We found that SSE significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in BMMs without cytotoxicity. The gene expressions of nuclear factor of activated T-cells (NFATc1) and TRAP, which are genetic markers of osteoclast differentiation, were substantially decreased by SSE in a dose-dependent manner. Also, SSE diminished RANKL-mediated intracellular reactive oxygen species (ROS) generation on osteoclastogenesis in a dose-dependent manner. The SSE thereafter suppressed RANKL-induced p38 mitogen-activated protein kinase and IκBα kinase signalling activities which were activated by ROS generation for osteoclastogenesis. Additionally, SSE was found to decrease RANKL-induced actin ring formation, which is required for bone resorption activity. Taken together, our results suggest that SSE acts as a RANKL-induced osteoclastogenesis inhibitor by suppression of ROS generation. This induces a remarkable suppression of the p38 and IκBα kinase pathways, thereby suppressing the gene expression of NFATc1 in osteoclast precursors.

Ponseti Brasil: a national program to eradicate neglected clubfoot - preliminary results.

BACKGROUND: After hearing about the reproducible and excellent results of the Ponseti method for clubfoot treatment, a group of Brazilian orthopaedic surgeons organized and participated in a standardized national program to teach the Ponseti technique in 21 different cities across Brazil. METHODS: A total of 21 Ponseti symposiums were organized in a standard fashion from January, 2007 to December, 2008. They consisted of a two-day program with lectures, hands-on cast application, and discussion of local clinical cases presented by orthopaedic surgeons. Thirteen Brazilian orthopaedic surgeons, who had been trained by the University of Iowa or centers recognized by them, taught the method. Financial support for travel was provided by an English charity: La Vida (Vital Investment for Developing Aid in Latin America). The physicians who attended the symposiums answered questionnaires before and after the training. RESULTS: About 7% of the 8000 orthopaedic surgeons in Brazil (556 orthopaedic surgeons) were trained. These orthopaedic surgeons stated that they had treated about 4905 babies in the previous year via other methods, including extensive surgery. Seventeen percent of the surgeons did not know about the Ponseti technique at the start of the symposium. Eighty-eight percent reported they felt able to treat children with the Ponseti technique after the symposium. Ninety-four percent of respondents reported that the symposium changed their way of treating clubfoot CONCLUSIONS: These Ponseti symposiums brought about an exchange of medical information and empowered the participants. This program is a good educational tool which can be used in eradicating neglected clubfoot in Brazil.

Novel CFTR mutations in a Korean infant with cystic fibrosis and pancreatic insufficiency.

Cystic fibrosis (CF) is an autosomal recessive disease that is very rare in Asians: only a few cases have been reported in Korea. We treated a female infant with CF who had steatorrhea and failure to thrive. Her sweat chloride concentration was 102.0 mM/L. Genetic analysis identified two novel mutations including a splice site mutation (c.1766+2T >C) and a frameshift mutation (c.3908dupA; Asn1303LysfsX6). Pancreatic enzyme replacement and fat-soluble vitamin supplementation enabled the patient to get a catch-up growth. This is the first report of a Korean patient with CF demonstrating pancreatic insufficiency. CF should therefore be considered in the differential diagnosis of infants with steatorrhea and failure to thrive.

Pseudomonas taeanensis sp. nov., isolated from a crude oil-contaminated seashore.

A novel Gram-negative, aerobic, motile, short rod-shaped bacterium, designated MS-3(T), was isolated from a crude oil-contaminated seashore in Taean, Korea. Strain MS-3(T) grew at 4-30 °C, at pH 6.0-9.5 and with 0-5 % NaCl and was oxidase- and catalase-positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain MS-3(T) was most similar to Pseudomonas marincola KMM 3042(T) (97.9 % 16S rRNA gene sequence similarity), P. cuatrocienegasensis 1N(T) (97.8 %), P. borbori R-20821(T) (97.3 %) and P. lundensis ATCC 49968(T) (97.1 %). Relatively low levels of DNA-DNA relatedness were found between strain MS-3(T) and P. cuatrocienegasensis LMG 24676(T) (57.2 %), P. borbori LMG 23199(T) (39.7 %), P. marincola KMM 3042(T) (32.2 %) and P. lundensis KACC 10832(T) (32.1 %), which support the classification of strain MS-3(T) within a novel species of the genus Pseudomonas. The G+C content of the genomic DNA of strain MS-3(T) was 57.6 mol% and the major isoprenoid quinone was Q-9. Strain MS-3(T) contained summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)ω7c; 38.0 %), C(16 : 0) (24.4 %), C(18 : 1)ω7c (12.8 %), C(12 : 0) (9.6 %) and C(10 : 0) 3-OH (4.9 %) as the major cellular fatty acids. On the basis of the phenotypic, genotypic and phylogenetic data, strain MS-3(T) represents a novel species of the genus Pseudomonas, for which the name Pseudomonas taeanensis sp. nov. is proposed. The type strain is MS-3(T) (=KCTC 22612(T) =KACC 14032(T) =JCM 16046(T) =NBRL 105641(T)).

Identification and characterization of a dual-acting antinematodal agent against the pinewood nematode, Bursaphelenchus xylophilus.

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of the pine wilt disease, which has become a major threat to pine forests throughout the world. Despite the availability of several preventive trunk-injection agents, no therapeutic trunk-injection agent for eradication of PWN currently exists. In the characterization of basic physiological properties of B. xylophilus YB-1 isolates, we established a high-throughput screening (HTS) method that identifies potential hits within approximately 7 h. Using this HTS method, we screened 206 compounds with known activities, mostly antifungal, for antinematodal activities and identified HWY-4213 (1-n-undecyl-2-[2-fluorphenyl] methyl-3,4-dihydro-6,7-dimethoxy-isoquinolinium chloride), a highly water-soluble protoberberine derivative, as a potent nematicidal and antifungal agent. When tested on 4 year-old pinewood seedlings that were infected with YB-1 isolates, HWY-4213 exhibited a potent therapeutic nematicidal activity. Further tests of screening 39 Caenorhabditis elegans mutants deficient in channel proteins and B. xylophilus sensitivity to Ca(2+) channel blockers suggested that HWY-4213 targets the calcium channel proteins. Our study marks a technical breakthrough by developing a novel HTS method that leads to the discovery HWY-4213 as a dual-acting antinematodal and antifungal compound.