Isolates from Hong Kong showed the highest rate of ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the spread of the Taiwan 19F clone and the Spain 23F clone could be one of the major reasons for the rapid increases in antimicrobial resistance among S. pneumoniae isolates in Asia. Data from the multinational surveillance study clearly documented distinctive increases in the prevalence rates and the levels of antimicrobial resistance among S. pneumoniae isolates in many Asian countries, which are among the highest in the world published to date.The global emergence of in vitro antimicrobial resistance in Streptococcus pneumoniae has become a serious clinical concern since the 1980s (1). During the past two decades, the rates of resistance to penicillin, other beta-lactams, and non-betalactam agents have been increasing rapidly in many parts of the world. In particular, data on rates of pneumococcal resistance from Asian countries at the end of the 1990s were alarming.

Blood vessel networks are typically formed by angiogenesis, a process in which new vessels form by sprouting of endothelial cells from pre-existing vessels. This process is initiated by vascular endothelial growth factor (VEGF)-mediated tip cell selection and subsequent angiogenic sprouting. Surprisingly, we found that VEGF directly controls the expression of Plexin-D1, the receptor for the traditional repulsive axon guidance cue, semaphorin 3E (Sema3E). Sema3E–Plexin-D1 signaling then negatively regulates the activity of the VEGF-induced Delta-like 4 (Dll4)–Notch signaling pathway, which controls the cell fate decision between tip and stalk cells. Using the mouse retina as a model system, we show that Plexin-D1 is selectively expressed in endothelial cells at the front of actively sprouting blood vessels and its expression is tightly controlled by VEGF secreted by surrounding tissues. Therefore, although the Sema3E secreted by retinal neurons is evenly distributed throughout the retina, Sema3E–Plexin-D1 signaling is spatially controlled by VEGF through its regulation of Plexin-D1. Moreover, we show that gain and loss of function of Sema3E and Plexin-D1 disrupts normal Dll4 expression, Notch activity, and tip/stalk cell distribution in the retinal vasculature. Finally, the retinal vasculature of mice lacking sema3E or plexin-D1 has an uneven growing front, a less-branched vascular network, and abnormal distribution of dll4-positive cells. Lowering Notch activity in the mutant mice can reverse this defect, solidifying the observation that Dll4–Notch signaling is regulated by Sema3E–Plexin-D1 and is required for its function in vivo. Together, these data reveal a novel role of Sema3E–Plexin-D1 function in modulating angiogenesis via a VEGF-induced feedback mechanism.

Members of the neuroligin (NL) family of cell-adhesion proteins are found at excitatory and inhibitory synapses and are mutated in some familial forms of autism spectrum disorders. Although they display synaptogenic properties in heterologous systems, a function of NLs in vivo in regulating synapse formation and synapse number has been difficult to establish. Here we show that neuroligin-1 (NL1), which is located at excitatory post-synaptic densities, does regulate activity-dependent synaptogenesis as well as mature synapse number on cortical layer 2/3 pyramidal neurons in vivo. However, synapse number is not sensitive to absolute NL1 levels but rather to transcellular differences in the relative amounts of NL1. These effects are independent of the cell-autonomous regulation of NMDA-type glutamate receptors by absolute levels of NL1. Our data indicate that transcellular competitive processes govern synapse formation and number in developing cortex and that NL1 plays a central function in these processes.

Objectives: To investigate the impact of imipenem resistance on the mortality rate among patients with Acinetobacter bacteraemia.Methods: A retrospective, pairwise-matched (1:1), risk-adjusted (age, Pitt bacteraemia score) cohort study was performed at three tertiary care hospitals in Korea from January 2000 to June 2005.Results: Forty patients with imipenem non-susceptible Acinetobacter bacteraemia (INAB group) and 40 matched subjects (1:1 ratio) with imipenem-susceptible Acinetobacter bacteraemia (ISAB group) were included. Both groups had similar clinical features related to the severity of illness. The 30 day mortality rate was higher in the INAB group (57.5%) than the ISAB group (27.5%) (P 5 0.007). The rate of discordant antimicrobial therapy was higher in the INAB group (65.0%) than the ISAB group (20.0%) (P < 0.001). The 30 day mortality rate was higher in the patients with discordant antimicrobial therapy (67.6%) than concordant antimicrobial therapy (23.9%) (P < 0.001). Multivariate analysis showed that age, the Pitt bacteraemia score, immunosuppressive status, and discordant antimicrobial therapy were independent risk factors for 30 day mortality among patients with Acinetobacter bacteraemia (P < 0.05). When discordant antimicrobial therapy was excluded in the multivariate analysis, the imipenem resistance was associated with 30 day mortality (P 5 0.005).Conclusions: Imipenem resistance has a significant impact on the mortality rate among patients with Acinetobacter bacteraemia, and this is mainly attributable to the higher rate of discordant antimicrobial therapy.

Growing axons are guided to their targets by attractive and repulsive cues. In the developing spinal cord, Netrin-1 and Shh guide commissural axons towards the midline. However, the combined inhibition of their activity in commissural axon turning assays does not completely abrogate turning towards floor plate tissue, suggesting that additional guidance cues are present. Here, we show that the prototypic angiogenic factor VEGF is secreted by the floor plate and is a chemoattractant for commissural axons in vitro and in vivo. Inactivation of Vegf in the floor plate or of its receptor Flk1 in commissural neurons causes axon guidance defects, while Flk1-blockade inhibits turning of axons to VEGF in vitro. Similar to Shh and Netrin-1, VEGF-mediated commissural axon guidance requires the activity of Src family kinases. Our results identify VEGF and Flk1 as a novel ligand / receptor pair controlling commissural axon guidance.

Data confirm that macrolide resistance in pneumococci is a serious problem in many Asian countries.

A total of 98 vancomycin-resistant Enterococcus faecium (VREF) isolates from four tertiary-care hospitals in Korea during the period between 1998 and 2004 were analyzed for genotypic characteristics using the multiplex PCR, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and esp gene analysis. Ninety-two isolates of VREF with VanA phenotype and five of six isolates with VanB phenotype possessed the vanA gene. MLST analysis revealed 9 sequence types (STs), which belonged to a single clonal complex (CC78, clonal lineage C1). Five strains showing incongruence between phenotype and genotype (VanB-vanA) did not belong to the same genotypic clone. The esp gene was detected in all VREF strains, showing 12 different esp repeat profiles. Data suggest that an epidemic clonal group of VREF, CC78 with esp gene, is also present in Asia and has differentiated into multiple diverse genotypic clones during the evolutionary process.Since the first isolation of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium in 1988 (17), vancomycinresistant enterococci (VRE) have become one of the major threats to public health in many parts of the world. Although E. faecalis is more common in human infections, vancomycin resistance is more frequently observed in E. faecium isolates. Most vancomycin-resistant E. faecium (VREF) strains isolated in Korea showed the VanA phenotype, which is defined as having high-level resistance to vancomycin and teicoplanin (2). VREF isolates with the VanB phenotype characterized by variable levels of resistance to vancomycin but by susceptibility to teicoplanin have been reported in Korea since 1997 (12). Generally, the vanA gene cluster confers the VanA phenotype and vanB gene cluster is associated with the VanB phenotype. Recently, however, VRE strains with the vanA gene and VanB phenotype have been found in Japan, Taiwan, and Korea (3,6,8,11).VREF is an important concern not only because VREF infection is difficult to treat in clinical practice but also because VREF clones can spread within hospitals as well as between regions or countries. Molecular epidemiologic studies could clarify the genetic relatedness and molecular evolution of VREF clones. In the current study, we have investigated the phenotypic and genotypic characteristics of VREF isolates from four tertiary-care hospitals in Korea by using the broth microdilution test, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and analysis of the esp repeat profile. MATERIALS AND METHODS VREF isolates.A total of 98 vancomycin-resistant E. faecium (VREF) isolates from four tertiary-care hospitals in Korea (Samsung Medical Center, Severans Hospital, Kyunghee University Hospital, and Kyungbuk National University Hospital) were analyzed in this study. The most common specimen source was urine (25 isolates) followed by rectal swab (14 isolates), blood (13 isolates), pus (9 isolates), wound (5 isolates), fluid (5 isolates), sputum (2 isolates), and tissue (2 isolates). Duplicate strains f...

Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.