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Objectives We aimed to assess the longevity of spike-specific antibody responses and neutralizing activity in the plasma of recovered Middle East respiratory syndrome (MERS) patients. Methods We traced the antibody responses and neutralizing activity against MERS coronavirus (MERS-CoV) in peripheral blood samples collected from 70 recovered MERS patients for 5 years after the 2015 MERS outbreak in South Korea. We also measured the half-life of neutralizing antibody titres in the longitudinal specimens. Results The seropositivity rate persisted for up to 4 years (50.7–56.1%), especially in MERS patients who suffered from severe pneumonia, and then decreased (35.9%) in the fifth year. Although the spike-specific antibody responses decreased gradually, the neutralizing antibody titres decreased more rapidly (half-life: 20 months) in 19 participants without showing negative seroconversion during the study period. Only five (26.3%) participants had neutralizing antibody titres greater than 1/1000 of PRNT50, and a high neutralizing antibody titre over 1/5000 was not detected in the participants at five years after infection. Discussion The seropositivity rate of the recovered MERS patients persisted up to 4 years after infection and significantly dropped in the fifth year, whereas the neutralizing antibody titres against MERS-CoV decreased more rapidly and were significantly reduced at 4 years after infection.

PURPOSE: Neutralizing antibodies can reduce SARS-CoV-2 cellular entry, viral titers, and pathologic damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, Phase I studies. METHODS: In study 1.1, healthy adults were sequentially enrolled to receive CT-P59 10, 20, 40, or 80 mg/kg or placebo. In study 1.2, adult patients with mild SARS-CoV-2 infection were enrolled to receive CT-P59 20, 40, or 80 mg/kg or placebo. Primary objectives of both studies were safety and tolerability up to day 14 after infusion. Secondary end points included pharmacokinetic properties. Study 1.2 also measured virology and clinical efficacy. FINDINGS: Thirty-two individuals were randomized to study 1.1 (6 per CT-P59 dose cohort and 8 in the placebo cohort). By day 14 after infusion, adverse events (AEs) were reported in 2 individuals receiving CT-P59 20 mg/kg (headache and elevated C-reactive protein levels) and 1 receiving CT-P59 40 mg/kg (pyrexia) (all Common Terminology Criteria for Adverse Events grade 1). In study 1.2, 18 patients were randomized (5 per dose cohort and 3 in the placebo cohort). Sixteen AEs were reported in 10 patients receiving CT-P59. No AEs in either study led to study discontinuation. Greater reductions in viral titers were reported with CT-P59 than placebo in those with maximum titers >105 copies/mL. Mean time to recovery was 3.39 versus 5.25 days. IMPLICATIONS: CT-P59 exhibited a promising safety profile in healthy individuals and patients with mild SARS-CoV-2 infection, with potential antiviral and clinical efficacy in patients with mild SARS-CoV-2 infection. ClinicalTrials.gov identifier: NCT04525079 (study 1.1) and NCT04593641 (study 1.2).

Objective: Elderly health care needs increase and nurses' role for elderlies is vital. It is significant to identify nursing students' intention to care for elderlies. Thus, this study investigated nursing students’ willingness to care for elderlies in Korea and the United States. Methods: The study was conducted with 437 undergraduate nursing students from Korea and the United States from May 25 to 31, 2018. Participants completed a survey including frequency and quality of contact, anxiety about aging, empathy, attitude toward elderly, and willingness to care. Results: Study findings from the entire group showed that nursing students’ willingness to care for the elderly was positively associated with contact quality (β = 0.22, P

To evaluate the impacts of fluconazole minimum inhibitory concentration (MIC) according to primary antifungal agents on Candida glabrata bloodstream infection (BSI), a multicenter retrospective cohort study was conducted in Korea, concerning the time period from January 2010 to February 2016. A total of 197 adult patients with C. glabrata BSI were included in the study, and neutropenia (P = 0.026), APACHE II score (P = 0.004), and fluconazole resistance (HR 3.960, 95% CI 1.395-11.246, P = 0.010) were associated with 30-day mortality in multivariate analysis. In subgroup analysis, fluconazole MIC = 32 μg/mL in the azole-treated group (HR 6.691, 95% CI 1.569-28.542, P = 0.010) and fluconazole MIC ≥ 64 μg/mL in the non-azole-treated group (HR 3.337, 95% CI 1.183-9.411, P = 0.023) showed the highest hazard ratio (HR) for 30-day mortality. Increased fluconazole MIC was associated with poor outcome both in azole- and non-azole-treated patients with C. glabrata BSI.

Objectives: This study aimed to characterize the risk factors for mortality in adult patients with invasive pneumococcal disease (IPD) stratified by age groups, after implementation of the national immunization program of 23-valent polysaccharide vaccine (PPSV23) for those aged ≥65 years in the Republic of Korea (ROK). Methods: Clinical data and pneumococcal isolates from adult patients with IPD (≥18 years of age) were collected prospectively from 20 hospitals through the nationwide surveillance program from March 2013 to October 2015. Results: A total of 319 patients with IPD were enrolled. Median age was 69 years. Overall in-hospital mortality was 34.2%: 17.1% in those aged 18–49 years, 23.7% in those aged 50–64 years, 33.0% in those aged 65–74 years, and 51.0% in those aged ≥75 years (p

Dipeptidyl peptidase 4 (DPP4) is a receptor for MERS-CoV. The soluble form of DPP4 (sDPP4) circulates systematically and can competitively inhibit MERS-CoV entry into host cells. Here, we measured the concentration of sDPP4 in the plasma and sputa of 14 MERS-CoV-infected patients of various degrees of disease severity. The concentration of sDPP4 in the plasma of MERS patients (474.76 ± 108.06 ng/ml) was significantly lower than those of healthy controls (703.42 ± 169.96 ng/ml), but there were no significant differences among the patient groups. Interestingly, plasma levels of IL-10 and EGF were negatively and positively correlated with sDPP4 concentrations, respectively. The sDPP4 levels in sputa were less than 300 ng/ml. Viral infection was inhibited by 50% in the presence of more than 8000 ng/ml of sDPP4. Therefore, sDPP4 levels in the plasma of MERS patients are significantly reduced below the threshold needed to exert an antiviral effect against MERS-CoV infection., Highlights • sDPP4, a soluble form of MERS-CoV receptor, in plasma is reduced in MERS patients. • IL-10 and EGF in plasma are negatively and positively correlated with sDPP4. • sDPP4 levels of MERS patients are not sufficient to exert an antiviral effect.

Purpose Chronic suppurative osteomyelitis (CSO) of the jaw is one of the most difficult infectious diseases to manage, because it causes progressive bony destruction and is associated with bacterial inhabitation of the sequestra. A combination of antibiotic therapy and surgical debridement is often used to treat CSO. Nevertheless, various systemic conditions can lead to life-threatening complications. Methods The present study aimed to explore the wound healing progress in 16 cases of CSO through protein expression analysis of postoperative exudates (POE) that were collected 6 h, 1 day, and 2 days after saucerization and/or decortication. A bony lesion was removed during surgery and then examined pathologically, and the CSO POE was examined by immunoprecipitation thus high performance chromatography (IP-HPLC). The POE at 6 h was used as a comparative control. Results Histologically the CSO lesion showed a necrotic granulomatous lesion heavily infiltrated with polymorphonuclear leukocytes, macrophages, and plasma cells, admixed with multiple sequestra inhabited by bacterial colonies. The IP-HPLC analysis displayed a slight increase in innate immunity-related proteins, i.e., NFkB, TNFα, IL-1, IL-6, IL-28, and LL-37, but a gradual decrease of bacteria-related inflammatory proteins, i.e., IL-8, IL-12, CD31, CD68, and lysozyme. The angiogenesis-related proteins, i.e., VEGF-A and VEGF-C, were slightly decreased but TGF-β1 and bFGF were markedly increased on day 2. The osteogenesis-related proteins, i.e., OPG and ALP, were slightly increased, while the osteoclastogenesis-related protein, RANKL was slightly decreased compared to the control. Conclusion These findings indicate that the infected CSO undergoes a rapid wound healing process with active osteogenesis and a gradual decrease in bacteria-related inflammation, predicting a favorable prognosis after surgery. Moreover, IP-HPLC can be useful in monitoring the POE and wound healing processes during the postoperative period.

Objective To contrast the pattern of bony reversal linesin bisphosphonate osteonecrosis of the jaw with infected osteomyelitis derived acute osteonecrosis of the jaw. Study Design This study investigated the histochemical characteristics of reversal lines in 50 cases of BP-related osteonecrosis of the jaw (BRONJ) compared with non–BP-involved bones in 20 cases of chronic osteomyelitis of the jaws. Necrotic bones were stained by using the toluidine blue, Safranin O, Giemsa, van Gieson, and Masson's trichrome staining methods. Results All BP-involved bones in BRONJ were distinguishable from non–BP-involved bones in chronic osteomyelitis of the jaws by multiple thick, irregular, reversal lines, which were strongly stained with toluidine blue, Safranin O, and Giemsa solution. The reversal lines of BP-involved bones (average 31.2 ± 10.85 μm) were thicker than those of osteomyelitic bones (average 11.1 ± 3.76 μm), and they were closely associated with immature bony matrices containing collagenous materials positive for van Gieson and Masson's trichrome staining with statistical significance ( P = .0212 in t test statistics). The immature reversal lines of BP-involved bones continuously appeared as thick non-birefringence lines between lamellate structures as observed under a polarizing microscope, whereas the reversal lines of non–BP-involved bones were gradually thinned as their mineralization advanced. Conclusions BP-involved bones had immature bony matrices outlined by thick reversal lines, which might be crucial to rapid osteonecrosis of BRONJ and also could be hallmarks for the differential diagnosis of BRONJ from chronic osteomyelitis of the jaws.

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.

Background: The purpose of the study was to describe and compare duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and primary foci of infection. We also aimed to redefine persistent SAB considering those results. Methods: We analyzed non-duplicated episodes of SAB in adult patients from three prospective SAB cohorts encompassing 14 hospitals in Korea. The duration of SAB was defined as the number of days from the administration of a susceptible antibiotic after the onset of SAB to the last day of positive blood culture for S. aureus. SAB durations were described and compared based on methicillin resistance and the primary foci of infection. The Cox proportional hazards regression was performed to explore independent risk factors for prolonged bacteremia. Cases in the top quartile for the duration of bacteremia were designated as newly-defined persistent SAB. Findings: A total of 2050 cases were analyzed. The duration of SAB was longer in methicillin-resistant SAB (MRSAB) than in methicillin-susceptible SAB (MSSAB) (median [IQR], 1 [1-3] in MSSAB vs. 1 [0-7] in MRSAB, p < 0.001). While the duration of bacteremia was shortest in the skin and soft tissue infections, they were longer in endocarditis, bone and joint, and endovascular infections, and were independently associated with those foci of infection. Newly-defined persistent SAB showed independent association with in-hospital mortality (aOR, 1.99; 95% CI, 1.54-2.58; p < 0.001). Interpretation: Durations of SAB were dependent on methicillin resistance and the primary foci of infection. The newly-defined persistent SAB is independently associated with in-hospital mortality. Funding: Seoul National University Bundang Hospital Research Fund. Declaration of Interest: None to declare. Ethical Approval: The analyses of cases from April 2015 to February 2018 were approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-1801-442-102).

Objectives Although pyogenic vertebral osteomyelitis (PVO) with no identified microorganism is treated empirically, the clinical outcome is not well understood. Methods We conducted a retrospective review of patients with PVO at a tertiary-care hospital from 2000 through 2012. The study compared clinical features and outcomes of microbiologically confirmed (M-PVO) with clinically diagnosed PVO (C-PVO). Results Of 151 patients with PVO, 75 (49.7%) had M-PVO. Compared to patients with M-PVO, patients with C-PVO had fewer underlying medical conditions. In addition, they presented less frequently with fever, high acute-phase reactants levels, and paraspinal abscess. The rate of treatment failure tended to be lower in the C-PVO group [9.2% (7/76) vs. 17.3% (13/75); p = 0.157]. The overall relapse rate was 6.6% and did not differ significantly between groups; notably this rate was higher in patients who received antibiotics for ≤6 weeks [18.8% (3/16)] and ≤8 weeks [12.1% (4/33)]. The independent risk factors for treatment failure were higher CRP levels [odds ratio (OR) = 1.087; 95% confidence interval (CI): 1.025–1.153; p = 0.005] and fever ≥37.8°C (OR = 8.556; 95% CI: 2.273–32.207; p = 0.002). Conclusions Patients with C-PVO had less systemic inflammatory response and a more favorable outcome compared to M-PVO. Prolonged antibiotic therapy, for at least 8 weeks, might be required for C-PVO, as well as for M-PVO until better outcomes are assured.

We report the first case of catheter-related bacteremia caused by Kocuria salsicia in a patient with short bowel syndrome. The pathogen was initially identified as Kocuria varians by a Vitek 2-based assessment, but its 16S rRNA gene sequence showed 100% similarity to K. salsicia. The patient was successfully treated with vancomycin and removal of the catheter.

We assessed the incidence and clinical characteristics of acute kidney injury (AKI) in critically ill patients infected with pandemic influenza A (H1N1) and its effect on clinical outcomes.We conducted a multicenter, retrospective, observational study of patients with pandemic H1N1-related critical illness admitted to intensive care units (ICUs) of 28 tertiary or referral hospitals in South Korea between September 1, 2009, and February 28, 2010. Outcomes were AKI within 72 hours after ICU admission and 30-day mortality. Acute kidney injury was defined according to the Risk, Injury, Failure, Loss, and End-stage renal failure criteria.Of the 221 patients, 50 (22.6%) developed AKI within 72 hours after ICU admission. Independent risk factors for AKI were age (odds ratio [OR], 1.05; P = .003), chronic kidney disease (OR, 14.82; P = .004), and Sequential Organ Failure Assessment score (OR, 1.45; P.001). Age (OR, 1.04; P = .003), Sequential Organ Failure Assessment score (OR, 1.28; P = .012), state of immune suppression (OR, 4.09; P = .01), mechanical ventilation (OR, 18.24; P = .001), corticosteroid use (OR, 3.09; P = .007), and AKI (OR, 2.86; P = .035) were significantly associated with 30-day mortality.A significant number of patients with H1N1-related critical illness developed AKI within 72 hours of ICU admission, and this early development of AKI was associated with 30-day mortality.

The purpose of this study was to evaluate clinical features and outcomes of bacteremia in patients with liver cirrhosis (LC) and determine whether underlying LC is an independent risk factor for mortality in a population of patients with different underlying diseases.From the database of nationwide surveillance studies for bacteremia, data regarding bacteremia in patients with LC were analyzed and compared with those in patients with other diseases.A total of 195 patients with LC were compared with 1659 patients with other underlying diseases. As for the site of infection, intraabdominal infection was more frequent in the LC group (P 0.001), while pneumonia, urinary tract bacteremia, and primary bacteremia were more prevalent in the other diseases group (all P 0.05). Patients with LC were more likely to have Klebsiella pneumoniae bacteremia (20.1% vs. 14.3%, P = 0.018), but less likely to have coagulase-negative staphylococcal bacteremia (5.1% vs. 10.4%, P = 0.028). The 30-day mortality rate was significantly higher in the LC group compared to the other disease group (27.2% [53/195] vs. 20.3% [336/1659], P = 0.025). Multivariate analysis revealed underlying LC as a significant predictor for mortality (OR, 2.11; 95% CI, 1.43-3.13; P 0.001), along with old age, nosocomial acquisition, pneumonia, severe sepsis, and a higher Pitt bacteremia score.The mortality rate of patients with LC was significantly higher than that of patients with other diseases when they developed bacteremia. Underlying LC was found to be one of the independent risk factors for mortality in patients with bacteremia.

In this paper, a numerical technique for predicting the wear amount of automobile tire is presented. A power function wear model derived based on the laboratory testing of rubber abrasion is adopted to correlate the wear rate of tread rubber blocks with the frictional energy dissipation, and the driving and loading conditions of the tire in the outdoor wear test are extracted from the virtual driving simulation using ADAMS. The tire frictional energy rates produced in each driving mode are computed by the frictional dynamic rolling analysis of 3D patterned tire model. Numerical results are also given to illustrate the theoretical work.

The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB).From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis.Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis.Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB.

Summary Objective Ciprofloxacin-resistant Escherichia coli is growing concern in clinical settings. In this study, we investigated the distribution of virulence determinants and phylogenetic groups among community-onset, ciprofloxacin-resistant E. coli isolates causing urinary tract infections (UTIs) in Korea. In addition, the evidence of clonal spread in the community was also examined. Methods From November 2006 to August 2007, 543 community-onset E. coli isolates causing UTIs were collected as part of a multicenter surveillance study. In vitro susceptibility testing was performed using broth microdilution method. Distribution of virulence determinants and phylogenetic groupings were examined. In addition, multilocus sequence typing (MLST) analysis was performed. Results In vitro antimicrobial susceptibility testing revealed that 154 isolates (28.4%) were ciprofloxacin-resistant. Of these, 129 ciprofloxacin-resistant E. coli isolates were further characterized. As a result of phylogenetic subgrouping, we found that phylogenetic subgroup D was the most predominant (46 isolates, 35.7%), followed by B2 (44 isolates, 34.1%), A (21 isolates, 16.3%), and B1 (18 isolates, 14.0%). MLST analysis showed 48 sequence types (STs). The most prevalent ST was ST131 (32 isolates, 24.8%), followed by ST393 (23 isolates, 17.8%). While all ST131 isolates belonged to phylogenetic subgroup B2, which is known to be a highly virulent, all ST393 isolates belonged to subgroup D. ST131 and ST393 showed different profiles of virulence factors; papA, papG allele III, and traT genes were significantly more prevalent in ST131 than in ST393 ( p values, Conclusions Based on genotyping, it is suggested that epidemic and virulent ciprofloxacin-resistant E. coli clones such as ST131 and ST393 have disseminated in Korea. However, the diversity of CTX-M genes in ST131 isolates may indicate that ESBL genes have been acquired independently or several ESBL-producing, ciprofloxacin-resistant E. coli clones may have disseminated in the Korean community.

A patient, a 62-year-old man, received endodontic treatment of the lower left canine complicated by apical overfilling of Calcipex II. At the second day after the root canal filling, the 14th day after placement of Calcipex II intracanal medication, he complained of a gingival swelling in the treated area. The incisional biopsy of the gingival swelling revealed a foreign body granuloma infiltrated with macrophages engulfing the fine Calcipex II granules but with polymorphonuclear leukocytes (PMNs). However, the gingival swelling was healed uneventfully, and the tooth was free of symptoms at 4 months' follow-up. This study first reports the Calcipex II-induced reaction in human periodontium. In the immunohistochemistry using antisera of lysozyme, CD31, CD68, interleukin-8 (IL-8), and poly(ADP-ribose) polymerase 1 (PARP-1), the granule-laden cells are positive for lysozyme, CD31, CD68, and PARP-1, but negative for IL-8. Thus, it is presumed that the granule-laden cells belong to the macrophages/monocytes rather than the PMNs, and that they gradually undergo the apoptotic processes. These data suggest that the canal dressing material, Calcipex II, is able to be widely dispersed into the periodontal tissues, primarily engulfed by macrophages, and resulted in the foreign body granuloma in the absence of acute inflammatory reaction.

FBI-1 (Pokemon/ZBTB7A) is a proto-oncogenic transcription factor of the BTB/POZ (bric-à-brac, tramtrack, and broad complex and pox virus zinc finger) domain family. Recent evidence suggested that FBI-1 might be involved in adipogenic gene expression. Coincidentally, expression of FBI-1 and fatty-acid synthase (FASN) genes are often increased in cancer and immortalized cells. Both FBI-1 and FASN are important in cancer cell proliferation. SREBP-1 is a major regulator of many adipogenic genes, and FBI-1 and SREBP-1 (sterol-responsive element (SRE)-binding protein 1) interact with each other directly via their DNA binding domains. FBI-1 enhanced the transcriptional activation of SREBP-1 on responsive promoters, pGL2-6x(SRE)-Luc and FASN gene. FBI-1 and SREBP-1 synergistically activate transcription of the FASN gene by acting on the proximal GC-box and SRE/E-box. FBI-1, Sp1, and SREBP-1 can bind to all three SRE, GC-box, and SRE/E-box. Binding competition among the three transcription factors on the GC-box and SRE/E-box appears important in the transcription regulation. FBI-1 is apparently changing the binding pattern of Sp1 and SREBP-1 on the two elements in the presence of induced SREBP-1 and drives more Sp1 binding to the proximal promoter with less of an effect on SREBP-1 binding. The changes induced by FBI-1 appear critical in the synergistic transcription activation. The molecular mechanism revealed provides insight into how proto-oncogene FBI-1 may attack the cellular regulatory mechanism of FASN gene expression to provide more phospholipid membrane components needed for rapid cancer cell proliferation.

Background Epoxyeicosatrienoic acids (EETs) are endothelium-derived hyperpolarizing factors that contribute renal protective actions. The aim of this study was to identify the association between genetic variations in soluble epoxide hydrolase (EPHX2, EET-metabolizing enzyme) and kidney allograft dysfunction. Materials and Methods Data from 204 kidney transplant donor-recipient pairs were examined for polymorphisms of exon 8 (R287Q, rs751141 G/A) and 3′ untranslated region (3′ UTR, rs1042032 A/G) of the EPHX2 gene and correlated with clinical data. Results The mean duration of follow-up for recipients was 58 ± 45.3 months who were 39 ± 11.8 years old at the time of operation and displayed estimated glomerular filtration rate (eGFR) of 68 ± 16.5 mL/min/1.73 m 2 at 1 month after transplantation. AA, AG, and GG genotype frequencies in 3′ UTR were 28%, 55%, and 16%, respectively. Twenty-one recipients experienced allograft dysfunction with eGFR 2 ; 10 had AA genotype of rs1042032 polymorphism (chi-square test; A/A vs A/G+G/G; P = .04). Recipients without rs1042032 polymorphism variant allele showed a significant risk for allograft dysfunction (A/A vs A/G+G/G; P = .04; odds ratio, 2.65; 95% confidence interval [CI], 1.03–6.81). Multivariate analysis of the characteristics of patients using a Cox proportional hazard model showed that the AA genotype of rs1042032 polymorphism was predictive of allograft dysfunction (Hazard Ratio = 3.26; P = .04; 95% CI, 1.08–9.59). Conclusion The present study suggested that the presence of the rs1042032 variant allele in EPHX2 was associated with a protective role for allograft function.

Appropriate antimicrobial treatment of community-acquired pneumonia (CAP) should be based on the distribution of aetiological pathogens, antimicrobial resistance of major pathogens, clinical characteristics and outcomes. We performed a prospective observational study of 955 cases of adult CAP in 14 hospitals in eight Asian countries. Microbiological evaluation to determine etiological pathogens as well as clinical evaluation was performed. Bronchopulmonary disease (29.9%) was the most frequent underlying disease, followed by cardiovascular diseases (19.9%), malignancy (11.7%) and neurological disorder (8.2%). Streptococcus pneumoniae (29.2%) was the most common isolate, followed by Klebsiella pneumoniae (15.4%) and Haemophilus influenzae (15.1%). Serological tests were positive for Mycoplasma pneumoniae (11.0%) and Chlamydia pneumoniae (13.4%). Only 1.1% was positive for Legionella pneumophila by urinary antigen test. Of the pneumococcal isolates, 56.1% were resistant to erythromycin and 52.6% were not susceptible to penicillin. Seventeen percent of CAP had mixed infection, especially S. pneumoniae with C. pneumoniae. The overall mortality rate was 7.3%, and nursing home residence, mechanical ventilation, malignancy, cardiovascular diseases, respiratory rate > 30/min and hyponatraemia were significant independent risk factors for mortality by multivariate analysis (P

Summary Objectives The high incidence of invasive liver abscess caused by Klebsiella pneumoniae in Taiwan, contrasted with the rareness of this disease in Western countries, has aroused special interest. There have been few detailed reports from other Asian countries. To investigate a current epidemiology of K. pneumoniae liver abscess in Korea and to determine K serotype distribution in K. pneumoniae strains causing liver abscess, we performed a nationwide prospective study. Methods Community-acquired, culture-proven liver abscess cases were enrolled between 2004 and 2005. Etiologies and clinical features were analyzed. K. pneumoniae isolates were serotyped according to K antigen. Meta-analysis was done to determine the time trend of the etiologies of liver abscess in Korea. Results Out of 371 cases collected prospectively, 290 (78.2%) were caused by K. pneumoniae . Most K. pneumoniae liver abscesses were monomicrobial. Diabetes mellitus was the most common underlying disease (39.9%). Distant metastatic infections were frequently observed (8.7%). magA PCR revealed that 95 (59.4%) out of 160 K. pneumoniae isolates belonged to the K1 serotype. Conclusions Our study indicates that K. pneumoniae has emerged as a major etiologic agent of liver abscess in Korea, and these emerging infections seem to be attributable to invasive K. pneumoniae strains with capsular K1 serotype.

Deoxyhypusine hydroxylase (DOHH) is a novel metalloenzyme that catalyzes the final step of the post-translational synthesis of hypusine (Nepsilon-(4-amino-2-hydroxybutyl)lysine) in the eukaryotic translation initiation factor 5A (eIF5A). Hypusine synthesis is unique in that it occurs in only one protein, denoting the strict specificity of the modification enzymes toward the substrate protein. The specificity of the interaction between eIF5A and DOHH was investigated using human eIF5A (eIF5A-1 isoform) and human recombinant DOHH. DOHH displayed a strong preference for binding the deoxyhypusine-containing form of eIF5A, over the eIF5A precursor or the hypusine-containing eIF5A, indicating a role for the deoxyhypusine residue in binding. In addition to the deoxyhypusine residue, a large portion of the eIF5A polypeptide (>20-90 amino acids) is required for effective modification by DOHH. We have identified the amino acid residues of DOHH that are critical for substrate binding by alanine substitution of 36 conserved amino acid residues. Of these, alanine substitution at Glu57, Glu90, Glu208, Glu241, Gly63, or Gly214 caused a severe impairment in eIF5A(Dhp) binding, with a complete loss of binding and activity in the E57A and E208A mutant enzymes. Only aspartate substitution mutants, E57D or E208D, retained partial activity and substrate binding, whereas alanine, glutamine, or asparagine mutants did not. These findings support a proposed model of DOHH-eIF5A binding in which the amino group(s) of the deoxyhypusine side chain of the substrate is primarily anchored by gamma-carboxyl groups of Glu57 and Glu208 at the DOHH active site.

Deoxyhypusine hydroxylase (DOHH) catalyzes the final step in the post-translational synthesis of hypusine (Nϵ-(4-amino-2-hydroxybutyl)lysine) in eIF5A. DOHH is a HEAT-repeat protein with eight tandem helical hairpins in a symmetrical dyad. It contains two potential iron coordination sites (one on each dyad) composed of two strictly conserved His-Glu motifs. The purified human recombinant DOHH was a mixture of active holoenzyme containing 2 mol of iron/mol of DOHH and inactive metal-free apoenzyme. The two species could be distinguished by their different mobilities upon native gel electrophoresis. The DOHH apoenzyme exhibited markedly reduced levels of iron and activity. DOHH activity could be restored only by the addition of Fe2+ to the apoenzyme but not by other metals including Cd2+,Co2+,Cr2+,Cu2+,Mg2+,Mn2+,Ni2+, and Zn2+. The role of the strictly conserved His-Glu residues was evaluated by site-directed mutagenesis. Substitution of any single amino acid in the four His-Glu motifs with alanine abolished the enzyme activity. Of these eight alanine substitutions, six, including H56A, H89A, E90A, H207A, H240A, and E241A, caused a severe reduction in the iron content. Our results provide strong evidence that Fe(II) is the active-site-bound metal critical for DOHH catalysis and that the strictly conserved His-Glu motifs are essential for iron binding and catalysis. Furthermore, the iron to DOHH stoichiometry and dependence of iron binding on each of the four conserved His-Glu motifs suggest a binuclear iron mediated reaction mechanism, distinct from that of other Fe(II)-dependent protein hydroxylases, such as prolyl 4-hydroxylase or lysyl hydroxylases.

Tissue transglutaminase (TGase 2) has been implicated in numerous cellular functions, i.e., apoptosis, differentiation, extracellular matrix protein cross-linking and organogenesis. Earlier report of the strong transient expression of TGase 2 localized at the anchoring sites of muscle bundles of human embryo and recent findings of a similar transient expression of the TGase 2 in the salivary myoepithelial cells of mouse embryo indicated a definitive role of TGase 2 in the cytodifferentiation of myoepithelial cells. To understand functional role(s) of TGase 2 in the organogenesis of salivary gland, antisense inhibition of TGase 2 expression was performed in the organ culture of mouse embryo submandibular gland. The antisense of TGase 2 transfection tested using oral keratinocyte cell line, KB cells, elicited significant inhibition of cellular transglutaminase expression. The same antisense treatment of submandibular glands in organ culture also resulted in the suppression of cellular TGase 2 expression as indicated by weak immunoreaction against anti-TGase 2 in the myoepithelial cells of submandibular glands in contrast to strong reaction in those of the normal and sense-treated glands. Antisense to TGase 2 treatment induced retarded growth of salivary epithelium in 1 week and severe aberrant growth of salivary ducts and acini in 2 weeks and also expression of apoptotic inducer, Bax specifically localized in the myoepithelial cells, suggesting apoptotic state of myoepithelial cells. These data suggest that the antisense inhibition of TGase 2 expression affects the cytodifferentiation of ductal cells and myoepithelial cells, and resulted in severe retardation of tubuloalveolar structure formation of salivary gland.

A novel member of the Krox family of proteins, designated Krox-25, was identified by screening clones from the cDNA libraries of a rat incisor and mouse embryo craniofacial tissue. Rat and mouse Krox-25 mRNAs are about 2.4 kb long, encoding 225 and 224 amino acids, respectively. Krox-25 consists of five zinc finger motifs homologous to the Drosophila Krüppel segmentation gene and also contains several consensus amino acid sequences for a protein kinase C binding domain. Northern blot analysis revealed an intense expression of Krox-25 mRNA in rat and mouse teeth, although it was expressed weakly in other tissues, including calvaria, brain, lung, thymus, kidney, and submandibular gland of mouse. In situ hybridization showed that Krox-25 mRNA began to be expressed weakly in the early odontogenic mesenchyme and primitive enamel epithelium located at the apical end of the rat incisor, and Krox-25 expression increased in the presecretory ameloblasts and became intense in the secretory ameloblasts. This expression was also similar to the results of immunohistochemistry and Western blot, especially the Krox-25 localization in the nuclei of enamel epithelial cells. These results suggest that Krox-25 plays an important role as a transcription factor for the cytodifferentiation and amelogenesis of enamel epithelium.

Using H+- and He+-ions in the energy range between 100 keV and 10 MeV, the effects of irradiation on polymethylmethacrylate (PMMA) were extensively studied. The surface shrinking phenomenon due to outgassing and the diffusion of the volatile scission products caused by the irradiation process have been investigated as a function of ion energy, ion fluence, dose rate and thermal treatment after the irradiation. Diffusion constants, mean diffusion path lengths and activation energies have been deduced from the shrinking dependency on the temperature. The influence of the ion fluence, the dose rate distinguished in current density and scan density and the particle energy is discussed. With respect to applications in deep ion beam lithography (DIBL) the results lead to the conclusion that one should prefer a rather dispersed instead of a sharply collimated beam in order to prevent an abrupt rupture during the irradiation. On the other hand, long irradiation times should be avoided to prevent inaccuracies with respect to the depth of the microstructures due to shrinking of the surface during irradiation.

Micromachining using a Nd:YAG laser for commercial glass have been developed. The composition of the glass is commercial soda–lime and Borosilicate glasses doped with cobalt oxide. After machining with the second harmonic beams of a pulsed Nd:YAG laser, a raised dome was formed. This report was conducted for researching the relationship absorption coefficient and laser ablation energy, and for finding out the possibility of the fabrication of optical device. The maximum height of the dome in the glass was 6.867 μm and had a radius was about 80 μm. We found that the Co ions acted as sensitizers in the laser machining of the glass and this process can be used for optical device, MLA (micro lens array), 3D lenticular sheet and homogenizer of laser optics, fabrication process.