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1.  Observation of Spontaneous Expressive Language (OSEL): A New Measure for Spontaneous and Expressive Language of Children with Autism Spectrum Disorders and Other Communication Disorders 
A new language measure, the Observation of Spontaneous Expressive Language (OSEL), is intended to document spontaneous use of syntax, pragmatics, and semantics in 2-12-year-old children with ASD and other communication disorders with expressive language levels comparable to typical 2-5 year olds. Because the purpose of the OSEL is to provide developmental norms for use of language, the first step involves assessment of the scale’s feasibility, validity, and reliability using a sample of 180 2-5 year-old typically developing children. Pilot data from the OSEL shows strong internal consistency, high reliabilities and validity. Once replicated with a large population-based sample and in special populations, the scale should be helpful in designing appropriate interventions for children with ASD and other communication disorders.
PMCID: PMC4224614  PMID: 25022249
Autism Spectrum Disorders; Language; Assessment
2.  Multisite Study of New Autism Diagnostic Interview-Revised (ADI-R) Algorithms for Toddlers and Young Preschoolers 
Using two independent datasets provided by National Institute of Health funded consortia, the Collaborative Programs for Excellence in Autism and Studies to Advance Autism Research and Treatment (n=642) and the National Institute of Mental Health (n=167), diagnostic validity and factor structure of the new Autism Diagnostic Interview (ADI-R) algorithms for toddlers and young preschoolers were examined as a replication of results with the 2011 Michigan sample (Kim & Lord, 2011). Sensitivities and specificities and a three-factor solution were replicated. Results suggest that the new ADI-R algorithms can be appropriately applied to existing research databases with children from 12 to 47 months and down to nonverbal mental ages of 10 months for diagnostic grouping.
PMCID: PMC3594108  PMID: 23114567
Early Diagnosis; Autism Spectrum Disorders; Autism Diagnostic Interview-Revised
3.  Combining Information from Multiple Sources for the Diagnosis of Autism Spectrum Disorders for Toddlers and Young Preschoolers from 12 to 47 Months of Age 
Purpose of this study was to systematically examine combined use of the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) for children under age 4 using newly developed and revised diagnostic algorithms.
Single and combined use of the ADI-R and ADOS algorithms were compared to clinical best estimate diagnoses for 435 children with Autism Spectrum Disorders (ASD), 113 children with non-spectrum disorders, and 47 children with typical development from 12 to 47 months of age. Sequential strategies to reach a diagnostic decision by prioritizing administrations of instruments were also evaluated.
Well-balanced sensitivities and specificities above 80% were obtained for ASD diagnoses using both instruments. Specificities significantly improved when both instruments were used compared to one. Scores that can be used to systematically prioritize administrations of instruments were identified.
The ADI-R and ADOS make independent, additive contributions to more accurate diagnostic decisions for clinicians evaluating toddlers and young preschoolers with ASD. Sequential assessment strategies using the scores identified may be appropriate for some children.
PMCID: PMC3235227  PMID: 21883205
Autism Spectrum Disorders (ASD); Autism Diagnostic Interview-Revised (ADI-R); Autism Diagnostic Observation Schedule (ADOS); Early Diagnosis
4.  Restricted and Repetitive Behaviors in Toddlers and Preschoolers with Autism Spectrum Disorders Based on the Autism Diagnostic Observation Schedule (ADOS) 
Lay Abstract
Restricted and repetitive behaviors (RRBs) have long been considered one of the core characteristics of autism. RRBs include a very broad category of behaviors such as preoccupation with restricted patterns of interest (e.g. having very specific knowledge about vacuum cleaners), adherence to specific, nonfunctional routines (e.g. insisting on taking a certain route to school), repetitive motor manners (e.g., hand flapping), and preoccupation with parts of objects (e.g. peering at the wheels of toy cars while spinning them). Most research on RRBs has used caregiver reports either through interviews or questionnaires; thus, the purpose of this study was to use clinicians’ observations of RRBs, made during the Autism Diagnostic Observation Schedule (ADOS: Lord, Rutter, DiLavore & Risi, 2000) to discover how RRBs change over time in very young children who may have ASD and what other factors are related to having RRBs. The ADOS is a 45 minute long, semi-structured, standardized assessment of communication, social interaction and play, which was administered to 121 children with autism, 71 with pervasive developmental disorders-not otherwise specified (PDD-NOS), 90 with a nonspectrum disorder, and 173 children who were typically developing. Even during a relatively short-term observation in the context of an office visit, we found that RRBs occurred more frequently and were more severe in young children with autism and PDD-NOS diagnoses than children in other groups. Diagnostic group differences also emerged in the associations between RRB scores and participant characteristics (e.g. age, NVIQ scores, etc). We also examined different subtypes of RRBs and their associations with NVIQ, age, diagnosis, and gender.
Scientific Abstract
Restricted and repetitive behaviors (RRBs) observed during the Autism Diagnostic Observation Schedule (ADOS: Lord, Rutter, DiLavore & Risi, 2000) were examined in a longitudinal dataset of 455 toddlers and preschoolers (age 8–56 months) with clinical diagnosis of Autism Spectrum Disorders (ASD; autism, n = 121 and pervasive developmental disorders-not otherwise specified (PDD-NOS), n = 71), a nonspectrum disorder (NS; n = 90), or typical development (TD; n = 173). Even in the relatively brief semi-structured observations, Generalized Estimating Equations (GEE) analyses of the severity and prevalence of RRBs differentiated children with ASD from those with NS and TD across all ages. RRB total scores on the ADOS were stable over time for children with ASD and NS; however, typically developing preschoolers showed lower RRB scores than typically developing toddlers. Nonverbal IQ (NVIQ) was more strongly related to the prevalence of RRBs in older children with PDD-NOS, NS and TD than younger children under 2 years and those with autism. Item analyses revealed different relationships between individual items and NVIQ, age, diagnosis, and gender. These findings are discussed in terms of their implications for the etiology and treatment of RRBs as well as for the framework of ASD diagnostic criteria in future diagnostic systems.
PMCID: PMC3005305  PMID: 20589716
restricted and repetitive behaviors (RRBs); autism spectrum disorders (ASD); Autism Diagnostic Observation Schedule (ADOS); toddlers; preschoolers
5.  Free Radical Scavenging Activity and Comparative Metabolic Profiling of In Vitro Cultured and Field Grown Withania somnifera Roots 
PLoS ONE  2015;10(4):e0123360.
Free radical scavenging activity (FRSA), total phenolic content (TPC), and total flavonoid content (TFC) of in vitro cultured and field grown Withania somnifera (Ashwagandha) roots were investigated. Withanolides analysis and comprehensive metabolic profiling between 100% methanol extracts of in vitro and field grown root tissues was performed using high performance thin layer chromatography (HPTLC) and gas chromatography-mass spectrometry (GC-MS), respectively. Significantly higher levels of FRSA, TPC, and TFC were observed in in-vitro cultured roots compared with field grown samples. In addition, 30 day-cultured in vitro root samples (1MIR) exhibited a significantly higher FRSA (IC50 81.01 μg/mL), TPC (118.91 mg GAE/g), and TFC (32.68 mg CE/g) compared with those in 45 day-cultured samples (1.5MIR). Total of 29 metabolites were identified in in vitro cultured and field grown roots by GC-MS analysis. The metabolites included alcohols, organic acids, purine, pyrimidine, sugars, and putrescine. Vanillic acid was only observed in the in vitro cultured root samples, and higher level of the vanillic acid was observed in 1MIR when compared to 1.5MIR. Therefore, it is suggested that 1MIR might serve as an alternative to field grown roots for the development of medicinal and functional food products.
PMCID: PMC4397045  PMID: 25874568
6.  Relationship of Liver Stiffness and Controlled Attenuation Parameter Measured by Transient Elastography with Diabetes Mellitus in Patients with Chronic Liver Disease 
Journal of Korean Medical Science  2014;29(8):1113-1119.
High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate analysis showed that the independent predictive risk factors for diabetes were hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR, 1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease.
Graphical Abstract
PMCID: PMC4129204  PMID: 25120322
Chronic Liver Disease; Diabetes Mellitus; Transient Elastography; Fibrosis; Steatosis
7.  Which Emphasizing Factors Are Most Predictive of Hematoma Expansion in Spot Sign Positive Intracerebral Hemorrhage? 
The spot sign is related with the risk of hematoma expansion in spontaneous intracerebral hemorrhage (ICH). However, not all spot sign positive patients undergo hematoma expansion. Thus, the present study investigates the specific factors enhancing the spot sign positivity in predicting hematoma expansion.
We retrospectively studied 316 consecutive patients who presented between March 2009 to March 2011 with primary ICH and whose initial computed tomography brain angiography (CTA) was performed at our Emergency Department. Of these patients, 47 primary ICH patients presented spot signs in their CTA. We classified these 47 patients into two groups based on the presence of hematoma expansion then analyzed them with the following factors : gender, age, initial systolic blood pressure, history of anti-platelet therapy, volume and location of hematoma, time interval from symptom onset to initial CTA, spot sign number, axial dimension, and Hounsfield Unit (HU) of spot signs.
Of the 47 spot sign positive patients, hematoma expansion occurred in 26 patients (55.3%) while the remaining 21 (44.7%) showed no expansion. The time intervals from symptom onset to initial CTA were 2.42±1.24 hours and 3.69±2.57 hours for expansion and no expansion, respectively (p=0.031). The HU of spot signs were 192.12±45.97 and 151.10±25.14 for expansion and no expansion, respectively (p=0.001).
The conditions of shorter time from symptom onset to initial CTA and higher HU of spot signs are the emphasizing factors for predicting hematoma expansion in spot sign positive patients.
PMCID: PMC4200371  PMID: 25328643
Spot sign; Hematoma expansion; Intracerebral hemorrhage
8.  Spread of Carbapenem-Resistant Acinetobacter baumannii Global Clone 2 in Asia and AbaR-Type Resistance Islands 
Antimicrobial Agents and Chemotherapy  2013;57(11):5239-5246.
In this surveillance study, we identified the genotypes, carbapenem resistance determinants, and structural variations of AbaR-type resistance islands among carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from nine Asian locales. Clonal complex 92 (CC92), corresponding to global clone 2 (GC2), was the most prevalent in most Asian locales (83/108 isolates; 76.9%). CC108, or GC1, was a predominant clone in India. OXA-23 oxacillinase was detected in CRAB isolates from most Asian locales except Taiwan. blaOXA-24 was found in CRAB isolates from Taiwan. AbaR4-type resistance islands, which were divided into six subtypes, were identified in most CRAB isolates investigated. Five isolates from India, Malaysia, Singapore, and Hong Kong contained AbaR3-type resistance islands. Of these, three isolates harbored both AbaR3- and AbaR4-type resistance islands simultaneously. In this study, GC2 was revealed as a prevalent clone in most Asian locales, with the AbaR4-type resistance island predominant, with diverse variants. The significance of this study lies in identifying the spread of global clones of carbapenem-resistant A. baumannii in Asia.
PMCID: PMC3811275  PMID: 23939892
9.  Extensively Drug-Resistant Streptococcus pneumoniae, South Korea, 2011–2012 
Emerging Infectious Diseases  2014;20(5):869-871.
To better understand extensively drug resistant Streptococcus pneumoniae, we assessed clinical and microbiological characteristics of 5 extensively drug-resistant pneumococcal isolates. We concluded that long-term care facility residents who had undergone tracheostomy might be reservoirs of these pneumococci; 13- and 23-valent pneumococcal vaccines should be considered for high-risk persons; and antimicrobial drugs should be used judiciously.
PMCID: PMC4012805  PMID: 24750694
Streptococcus pneumoniae; extensively drug-resistant; bacteria; South Korea; antimicrobial drug resistance
10.  Secondary intestinal amyloidosis presenting intractable hematochezia: a case report and literature review 
Amyloidosis is characterized by an extracellular deposition of insoluble fibrils. Amyloid deposition caused various clinical symptoms associated with affected organs. Secondary amyloidosis without renal involvement and chronic inflammatory conditions is rarely reported. We experienced a case of secondary intestinal amyloidosis presented with recurrent hematochezia and abdominal pain in a 54-year-old male. Sigmoidoscopy and abdominal computed tomography (CT) presented ischemic colitis and necrosis of whole colon. On microscopically, pinkish amorphous materials were infiltrated in the lamina propria and the thickened submucosal vessel walls in colon. The apple-green birefringence with polarized light on Congo red stain was demonstrated in the lamina propria and submucosal vessel walls. The deposits were positive for amyloid A and κ and negative for λ. The echocardiography and cardiac MRI findings showed infiltratives cardiomyopathy involving amyloidosis. Despite of conservative treatment, ischemic colitis and hemorrhage were aggravated and the patient expired.
PMCID: PMC4014268  PMID: 24817984
Amyloidosis; hematochezia; colon
11.  Recent Trends of Antigenic Variation in Bordetella pertussis Isolates in Korea 
Journal of Korean Medical Science  2014;29(3):328-333.
Pertussis is a representative vaccine-preventable disease. However, there have been recent outbreaks in countries where even higher vaccination against the disease. One reason is the emergence of antigenic variants, which are different to vaccine type. In Korea, reported cases have rapidly increased since 2009. Therefore, we analyzed genotype of strains isolated in 2011-2012 by multilocus sequence typing method. As expected, the genotype profiles of tested genes dramatically changed. The major sequence type changed from ST1 to ST2, and new sequence type (ST8) appeared. In the minimum spanning tree, recent isolates belonging to the ACC-I-ST3 subgroup were detected that were composed of ST2, ST3, and ST6. In particular, the ST2 frequency increased to 81%. The novel ST8 was linked to the increased frequency of ST2. In addition, toxic strains carrying the ptxP3 promoter type were confirmed. This ptxP3 type emerged from 2009 and its frequency had increased to 100% in 2012. Based on these results, it can be inferred that the genotypic changes in the currently circulating strains are strongly associated with the recent increasing of pertussis in Korea. Therefore, the surveillance system should be strengthened, and genetic characterization of the isolates should be expanded to the whole genome sequence level.
PMCID: PMC3945125  PMID: 24616579
Pertussis Vaccine; Bordetella pertussis; Antigenic Variation; Multilocus Sequence Typing; Pertussis Toxin; Minimum Spanning Tree
12.  The Reliability and Validity of a Korean Translation of the ASAS Health Index and Environmental Factors in Korean Patients with Axial Spondyloarthritis 
Journal of Korean Medical Science  2014;29(3):334-337.
The objective of this study was to develop a Korean version of the Assessment of Spondyloarthritis International Society-Health Index/Environmental Factor (ASAS HI/EF) and to evaluate its reliability and validity in Korean patients with axial spondyloarthritis (SpA). A total of 43 patients participated. Translation and cross-cultural adaptation of the ASAS HI/EF was performed according to international standardized guidelines. We also evaluated validity by calculating correlation coefficients between the ASAS-HI/EF score and the clinical parameters. Test-retest reliability was excellent. The correlations among the mean ASAS-HI score and all tools of assessment for SpA were significant. When it came to construct validity, the ASAS HI score was correlated with nocturnal back pain, spinal pain, patients's global assessment score, the Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis metrology index (BASMI) and EuroQoL visual analogue scale (EQ VAS) (r = 0.353, 0.585, 0.598, 0.637, 0.690, 0.430, and -0.534). The ASAS EF score was also correlated with the patient's global assessment's score, BASDAI, BASFI, BASMI, and EQ VAS score (r = 0.375, 0.490, 0.684, 0.485, and -0.554). The Korean version of the ASAS HI/EF can be used in the clinical field to assess and evaluate the state of health of Korean axial SpA patients.
Graphical Abstract
PMCID: PMC3945126  PMID: 24616580
Spondylitis, Ankylosing; Spondylarthropathies; Validation Studies
13.  C. elegans sensing of and entrainment along obstacles require different neurons at different body locations 
Scientific Reports  2013;3:3247.
We probe C. elegans mechanosensation using a microfabricated platform where worms encounter a linear array of asymmetric funnel-like barriers. We found that sensing of and moving along barriers require different sets of neurons located at different parts of the animal. Wild-type worms sense and move along the barrier walls, leading to their accumulation in one side of the barriers due to the barriers' asymmetric shape. However, mec-4 and mec-10 mutants deficient in touch sensory neurons in the body exhibited reversal movements at the walls, leading to no accumulation in either side of the barriers. In contrast, osm-9 mutants deficient in touch sensory neurons in the nose, moved along the barrier walls. Thus, touch sensory neurons ALM and AVM in the body are required for C. elegans to sense and move along obstacles, whereas the ASH and FLP neurons in the nose are required only for sensing of but not moving along obstacles.
PMCID: PMC3842086  PMID: 24284409
14.  Effects of Light Intensity and Nitrogen Starvation on Glycerolipid, Glycerophospholipid, and Carotenoid Composition in Dunaliella tertiolecta Culture 
PLoS ONE  2013;8(9):e72415.
Time-course variation of lipid and carotenoid production under high light (300 μE/m2s) and nitrogen starvation conditions was determined in a Dunaliella tertiolecta strain. Nanoelectrospray (nanoESI) chip based direct infusion was used for lipid analysis and ultra-performance liquid chromatography (UPLC) coupled with a photodiode array (PDA) or atmospheric chemical ionization mass spectrometry (APCI-MS) was used for carotenoid analysis. A total of 29 lipids and 7 carotenoids were detected. Alterations to diacylglyceryltrimethylhomoserine (DGTS) and digalactosyldiacylglycerol (DGDG) species were significant observations under stress conditions. Their role in relation to the regulation of photosynthesis under stress condition is discussed in this study. The total carotenoid content was decreased under stress conditions, while ã-carotene was increased under nitrate-deficient cultivation. The highest productivity of carotenoid was attained under high light and nitrate sufficiency (HLNS) condition, which result from the highest level of biomass under HLNS. When stress was induced at stationary phase, the substantial changes to the lipid composition occurred, and the higher carotenoid content and productivity were exhibited. This is the first report to investigate the variation of lipids, including glycerolipid, glycerophospholipid, and carotenoid in D. tertiolecta in response to stress conditions using lipidomics tools.
PMCID: PMC3764108  PMID: 24039760
15.  First Imported Case of Skin Infection Caused by PVL-positive ST30 Community-Associated Methicillin-Resistant Staphylococcus aureus Clone in a Returning Korean Traveler from the Philippines 
Journal of Korean Medical Science  2013;28(7):1100-1102.
Although pandemic community-associated (CA-) methicillin-resistant Staphylococcus aureus (MRSA) ST30 clone has successfully spread into many Asian countries, there has been no case in Korea. We report the first imported case of infection caused by this clone in a Korean traveler returning from the Philippines. A previously healthy 30-yr-old Korean woman developed a buttock carbuncle while traveling in the Philippines. After coming back to Korea, oral cephalosporin was given by a primary physician without any improvement. Abscess was drained and MRSA strain isolated from her carbuncle was molecularly characterized and it was confirmed as ST30-MRSA-IV. She was successfully treated with vancomycin and surgery. Frequent international travel and migration have increased the risk of international spread of CA-MRSA clones. The efforts to understand the changing epidemiology of CA-MRSA should be continued, and we should raise suspicion of CA-MRSA infection in travelers with skin infections returning from CA-MRSA-endemic countries.
PMCID: PMC3708085  PMID: 23853497
Staphylococcus aureus; Methicillin Resistance; Community-Acquired Infections; Carbuncle; Travel
16.  Clinical and Molecular Epidemiology of Community-Onset Bacteremia Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli over a 6-Year Period 
Journal of Korean Medical Science  2013;28(7):998-1004.
Although extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) has emerged as a significant community-acquired pathogen, there is little epidemiological information regarding community-onset bacteremia due to ESBL-EC. A retrospective observational study from 2006 through 2011 was performed to evaluate the epidemiology of community-onset bacteremia caused by ESBL-EC. In a six-year period, the proportion of ESBL-EC responsible for causing community-onset bacteremia had increased significantly, from 3.6% in 2006 to 14.3%, in 2011. Of the 97 clinically evaluable cases with ESBL-EC bacteremia, 32 (33.0%) were further classified as healthcare-associated infections. The most common site of infection was urinary tract infection (n=35, 36.1%), followed by biliary tract infections (n=29, 29.9%). Of the 103 ESBL-EC isolates, 43 (41.7%) produced CTX-M-14 and 36 (35.0%) produced CTX-M-15. In the multilocus sequence typing (MLST) analysis of 76 isolates with CTX-M-14 or -15 type ESBLs, the most prevalent sequence type (ST) was ST131 (n=15, 19.7%), followed by ST405 (n=12, 15.8%) and ST648 (n=8, 10.5%). No significant differences in clinical features were found in the ST131 group versus the other group. These findings suggest that epidemic ESBL-EC clones such as CTX-M-14 or -15 type ESBLs and ST131 have disseminated in community-onset infections, even in bloodstream infections, which are the most serious type of infection.
PMCID: PMC3708098  PMID: 23853481
Escherichia coli; Community-Acquired Infections; Cephalosporin Resistance; Bacteremia; Epidemiology
17.  Bacteremic Pneumonia Caused by Extensively Drug-Resistant Streptococcus pneumoniae 
Journal of Clinical Microbiology  2012;50(12):4175-4177.
The emergence of antimicrobial resistance threatens the successful treatment of pneumococcal infections. Here we report a case of bacteremic pneumonia caused by an extremely drug-resistant strain of Streptococcus pneumoniae, nonsusceptible to at least one agent in all classes but vancomycin and linezolid, posing an important new public health threat in our region.
PMCID: PMC3502956  PMID: 23052301
18.  A third case of USA300 community-associated methicillin-resistant Staphylococcus aureus infection in Korea 
PMCID: PMC3604620  PMID: 23524494
Staphylococcus aureus; Methicillin resistance; Community-acquired infections; Genotype
19.  Atypical florid vascular proliferation in appendix: a diagnostic dilemma 
Diagnostic Pathology  2013;8:12.
Vascular abnormality of the intestine is rare, except angiodysplasia. We report on an unusual case of atypical florid vascular proliferations of the appendix. A 41-year old male presented with melena. Adhesioned blood clots in the appendiceal orifice were observed by colonoscopy. He underwent laparoscopic appendectomy. Microscopically, a tiny exophytic polypoid mass was observed. The mass showed pyogenic granuloma-like features in the superficial portion and infiltrative florid vascular proliferations in the deeper portion. Endothelial cells showed minimal nuclear atypia, and mitotic figures were observed infrequently and showed positivity for CD31 and CD34 and negativity for HHV-8. Differential diagnoses include from benign vascular tumor to angiosarcoma or Kaposi’s sarcoma, but this lesion does not fit the description of any defined vascular entity. We diagnosed atypical florid vascular proliferations and the patient has been well during the five-month postoperative follow-up.
Virtual Slide
The virtual slide(s) for this article can be found here:
PMCID: PMC3567979  PMID: 23347775
Blood vessel; Proliferation; Atypical; Appendix
20.  First Report of Vancomycin-Intermediate Resistance in Sequence Type 72 Community Genotype Methicillin-Resistant Staphylococcus aureus 
Journal of Clinical Microbiology  2012;50(7):2513-2514.
Vancomycin-intermediate resistance has not been previously reported among sequence type 72 (ST72) methicillin-resistant Staphylococcus aureus (MRSA) isolates of SCCmec type IV (ST72-MRSA-IV), which are distinctive community genotype strains in Korea. We report the first case of vancomycin treatment failure due to development of vancomycin-intermediate resistance in infection caused by an ST72-MRSA-IV isolate.
PMCID: PMC3405585  PMID: 22553243
21.  AFM Probing the Mechanism of Synergistic Effects of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate (EGCG) with Cefotaxime against Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli 
PLoS ONE  2012;7(11):e48880.
Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae poses serious challenges to clinicians because of its resistance to many classes of antibiotics.
Methods and Findings
The mechanism of synergistic activity of a combination of (−)-epigallocatechin-3-gallate (EGCG) and β-lactam antibiotics cefotaxime was studied on Extended-spectrum β-lactamase producing Escherichia coli (ESBL-EC), by visualizing the morphological alteration on the cell wall induced by the combination using atomic force microscopy (AFM). Cells at sub-MICs (sub-minimum inhibitory concentrations) of cefotaxime were initially filamentated but recovered to the normal shape later, whereas cells at sub-MICs of EGCG experienced temporal disturbance on the cell wall such as leakage and release of cellular debris and groove formation, but later recovered to the normal shape. In contrast, the combination of cefotaxime and EGCG at their respective sub-MICs induced permanent cellular damages as well as continuous elongation in cells and eventually killed them. Flow cytometry showed that intracellular oxidative stress levels in the cell treated with a combination of EGCG and cefotaxime at sub-MICs were higher than those in the cells treated with either cefotaxime or EGCG at sub-MICs.
These results suggest that the synergistic effect of EGCG between EGCG and cefotaxime against ESBL-EC is related to cooperative activity of exogenous and endogenous reactive oxygen species (ROS) generated by EGCG and cefotaxime, respectively.
PMCID: PMC3496731  PMID: 23152812
22.  Changing Trends in Antimicrobial Resistance and Serotypes of Streptococcus pneumoniae Isolates in Asian Countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study 
Antimicrobial resistance in Streptococcus pneumoniae remains a serious concern worldwide, particularly in Asian countries, despite the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). The Asian Network for Surveillance of Resistant Pathogens (ANSORP) performed a prospective surveillance study of 2,184 S. pneumoniae isolates collected from patients with pneumococcal infections from 60 hospitals in 11 Asian countries from 2008 to 2009. Among nonmeningeal isolates, the prevalence rate of penicillin-nonsusceptible pneumococci (MIC, ≥4 μg/ml) was 4.6% and penicillin resistance (MIC, ≥8 μg/ml) was extremely rare (0.7%). Resistance to erythromycin was very prevalent in the region (72.7%); the highest rates were in China (96.4%), Taiwan (84.9%), and Vietnam (80.7%). Multidrug resistance (MDR) was observed in 59.3% of isolates from Asian countries. Major serotypes were 19F (23.5%), 23F (10.0%), 19A (8.2%), 14 (7.3%), and 6B (7.3%). Overall, 52.5% of isolates showed PCV7 serotypes, ranging from 16.1% in Philippines to 75.1% in Vietnam. Serotypes 19A (8.2%), 3 (6.2%), and 6A (4.2%) were the most prominent non-PCV7 serotypes in the Asian region. Among isolates with serotype 19A, 86.0% and 79.8% showed erythromycin resistance and MDR, respectively. The most remarkable findings about the epidemiology of S. pneumoniae in Asian countries after the introduction of PCV7 were the high prevalence of macrolide resistance and MDR and distinctive increases in serotype 19A.
PMCID: PMC3294909  PMID: 22232285
23.  Post-influenza Pneumonia Caused by the USA300 Community-Associated Methicillin-Resistant Staphylococcus aureus in Korea 
Journal of Korean Medical Science  2012;27(3):313-316.
Panton-Valentine leukocidin (PVL)-positive USA300 clone has been the most successful community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone spreading in North America. In contrast, PVL-negative ST72-CA-MRSA has been predominant in Korea, and there has been no report of infections by the USA300 strain except only one case report of perianal infection. Here, we describe the first case of pneumonia caused by the USA300 strain following pandemic influenza A (H1N1) in Korea. A 50-year-old man was admitted with fever and cough and chest radiograph showed pneumonic consolidation at the right lower lung zone. He received a ventilator support because of respiratory failure. PCR for pandemic influenza A (H1N1) in nasopharyngeal swab was positive, and culture of sputum and endotracheal aspirate grew MRSA. Typing of the isolate revealed that it was PVL-positive, ST 8-MRSA-SCCmec type IV. The analysis of the PFGE patterns showed that this isolate was the same pulsotype as the USA300 strain.
PMCID: PMC3286780  PMID: 22379344
Influenza, Human; Methicillin-Resistant Staphylococcus aureus; Pneumonia
24.  In Vivo Fluorescence Imaging of Bacteriogenic Cyanide in the Lungs of Live Mice Infected with Cystic Fibrosis Pathogens 
PLoS ONE  2011;6(7):e21387.
Pseudomonas aeruginosa (PA) and Burkholderia cepacia complex (Bcc), commonly found in the lungs of cystic fibrosis (CF) patients, often produce cyanide (CN), which inhibits cellular respiration. CN in sputa is a potential biomarker for lung infection by CF pathogens. However, its actual concentration in the infected lungs is unknown.
Methods and Findings
This work reports observation of CN in the lungs of mice infected with cyanogenic PA or Bcc strains using a CN fluorescent chemosensor (4′,5′-fluorescein dicarboxaldehyde) with a whole animal imaging system. When the CN chemosensor was injected into the lungs of mice intratracheally infected with either PA or B. cepacia strains embedded in agar beads, CN was detected in the millimolar range (1.8 to 4 mM) in the infected lungs. CN concentration in PA-infected lungs rapidly increased within 24 hours but gradually decreased over the following days, while CN concentration in B. cepacia-infected lungs slowly increased, reaching a maximum at 5 days. CN concentrations correlated with the bacterial loads in the lungs. In vivo efficacy of antimicrobial treatments was tested in live mice by monitoring bacteriogenic CN in the lungs.
The in vivo imaging method was also found suitable for minimally invasive testing the efficacy of antibiotic compounds as well as for aiding the understanding of bacterial cyanogenesis in CF lungs.
PMCID: PMC3131278  PMID: 21750709
25.  Ameliorating effects of Mango (Mangifera indica L.) fruit on plasma ethanol level in a mouse model assessed with 1H-NMR based metabolic profiling 
The ameliorating effects of Mango (Mangifera indica L.) flesh and peel samples on plasma ethanol level were investigated using a mouse model. Mango fruit samples remarkably decreased mouse plasma ethanol levels and increased the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase. The 1H-NMR-based metabolomic technique was employed to investigate the differences in metabolic profiles of mango fruits, and mouse plasma samples fed with mango fruit samples. The partial least squares-discriminate analysis of 1H-NMR spectral data of mouse plasma demonstrated that there were clear separations among plasma samples from mice fed with buffer, mango flesh and peel. A loading plot demonstrated that metabolites from mango fruit, such as fructose and aspartate, might stimulate alcohol degradation enzymes. This study suggests that mango flesh and peel could be used as resources for functional foods intended to decrease plasma ethanol level after ethanol uptake.
PMCID: PMC3082076  PMID: 21562641
mango; Mangifera indica; plasma ethanol level; metabolomics; 1H-NMR

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