Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease

Background Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effects, we hypothesized that DEL-1 could be a blood biomarker for COPD. Objective To elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation. Methods Cigarette smoke extract (CSE) or saline was intratracheally administered to wild-type (WT) and DEL-1 knockout (KO) C57BL/6 mice. Subsequently, lung sections were obtained to quantify the degree of emphysema using the mean linear intercept (MLI). Additionally, plasma DEL-1 levels were compared between COPD and non-COPD participants recruited in ongoing prospective cohorts. Using negative binomial regression analysis, the association between the plasma DEL-1 level and subsequent acute exacerbation risk was evaluated in patients with COPD. Results In the in vivo study, DEL-1 KO induced emphysema (KO saline vs. WT saline; P = 0.003) and augmented CSE-induced emphysema (KO CSE vs. WT CSE; P < 0.001) in 29 mice. Among 537 participants, patients with COPD presented plasma log (DEL-1) levels lower than non-COPD participants (P = 0.04), especially non-COPD never smokers (P = 0.019). During 1.2 ± 0.3 years, patients with COPD in the lowest quartile of Log(DEL-1) demonstrated an increased risk of subsequent acute exacerbation, compared with those in the highest quartile of Log(DEL-1) (adjusted incidence rate ratio, 3.64; 95% confidence interval, 1.03–12.9). Conclusion Low DEL-1 levels are associated with COPD development and increased risk of subsequent COPD acute exacerbation. DEL-1 can be a useful biomarker in patients with COPD.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1C1C1007918). This research was also supported by funds (2016ER670100, 2016ER670101, 2016ER670102 and 2018ER670100, 2018ER670101, 2018ER670102) from Research of Korea Centers for Disease Control and Prevention

Clinical and Radiographic Features of Adult-onset Ankylosing Spondylitis in Korean Patients: Comparisons between Males and Females

The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4±8.9 yr and average disease duration was 9.6±6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment

Occurrence and characterization of oseltamivir-resistant influenza virus in children between 2007-2008 and 2008-2009 seasons

PurposeThere was a global increase in the prevalence of oseltamivir-resistant influenza viruses during the 2007-2008 influenza season. This study was conducted to investigate the occurrence and characteristics of oseltamivir-resistant influenza viruses during the 2007-2008 and 2008-2009 influenza seasons among patients who were treated with oseltamivir (group A) and those that did not receive oseltamivir (group B).MethodsA prospective study was conducted on 321 pediatric patients who were hospitalized because of influenza during the 2007-2008 and 2008-2009 influenza seasons. Drug resistance tests were conducted on influenza viruses isolated from 91 patients.ResultsThere was no significant difference between the clinical characteristics of groups A and B during both seasons. Influenza A/H1N1, isolated from both groups A and B during the 2007-2008 and 2008-2009 periods, was not resistant to zanamivir. However, phenotypic analysis of the virus revealed a high oseltamivir IC50 range and that H275Y substitution of the neuraminidase (NA) gene and partial variation of the hemagglutinin (HA) gene did not affect its antigenicity to the HA vaccine even though group A had a shorter hospitalization duration and fewer lower respiratory tract complications than group B. In addition, there was no significant difference in the clinical manifestations between oseltamivir-susceptible and oseltamivir-resistant strains of influenza A/H1N1.ConclusionEstablishment of guidelines to efficiently treat influenza with oseltamivir, a commonly used drug for treating influenza in Korean pediatric patients, and a treatment strategy with a new therapeutic agent is required

A case of biopsy-proven chronic kidney disease on progression from acute phosphate nephropathy

Acute phosphate nephropathy (APhN) following oral sodium phosphate solution (OSP) ingestion as a bowel purgative has been frequently reported. It was recently suggested that APhN could progress to chronic kidney disease (CKD) and a history of APhN might be considered as one of the causes of CKD. However, there are few reports proving APhN as a cause of CKD. Here, we report a case of APhN that progressed to CKD, as proven by renal biopsy

Differentiation of mycobacteria in sputa by duplex polymerase chain reaction for mycobacterial hsp65 gene

Early differentiation of mycobacteria in sputa is crucial. This study was set to evaluate the usefulness of a newly developed duplex polymerase chain reaction (PCR) for hsp65 gene-based method in differentiating mycobacteria in sputum with a positive acid-fast bacilli (AFB) smear before culturing. One hundred forty-seven sputa with positive AFB smear were included for the analysis. Mycobacterial species were identified using a newly developed duplex PCR for hsp65 gene followed by a nested PCR-direct sequencing and the conventional colony-based method. Final decision of mycobacterial species were made based on 1) results of species identification based on mycobacterial colonies or 2) results of species identification of other sputa from the same patients and clinical findings. The duplex PCR-based method correctly identified 83.2% sputa from tuberculosis patients and 82.2% sputa from nontuberculous mycobacteria patients, whereas the colony-based method correctly identified 86.1% and 77.8%, respectively. Sensitivity and specificity of the colony-based method for Mycobacterium tuberculosis were 86.1% and 100%, respectively, whereas those of the duplex PCR-based method were 83.2% and 95.6%, respectively. The duplex PCR-based method, to differentiate mycobacterial species in sputa, produced comparable results as those of the colony-based identification method

The association between mortality and abdominal aortic calcification and relation between its progression and serum calcium concentration in chronic hemodialysis patients

Background: The composite summary score (range, 0–24) of abdominal aortic calcification (AAC) devised by Kauppila et al is a simple method of assessing AAC severity. However, few studies have been conducted to determine an optimal AAC cutoff score for the prediction of mortality or to investigate the relation between mineral metabolism and AAC progression using the scoring system. Methods: The medical records of 112 patients on hemodialysis who had undergone simple lateral lumbar radiography every 6 months from August 2009 were reviewed. Patients were followed until November 2012, and the relationship between the degree of AAC at baseline and mortality was evaluated. In addition, the relationship between the progression of AAC and serum concentrations of calcium and phosphate was evaluated in the 75 patients who were successfully followed until November 2012. Results: The mean AAC score at baseline was 5.5±4.8, and the cutoff calcification score for the prediction of mortality was 7.75 (sensitivity=61%, specificity=81%). Patients were allocated to Group A (baseline total calcification score ≤8.0, n=85) or Group B (baseline total calcification score>8.0, n=27), and multivariate analysis showed that Group B was an independent risk factor of all-cause mortality and cardiovascular events. Of the 75 patients successfully followed, 51 showed AAC progression (Group 1) and 24 showed no change or improvement (Group 2). Group 1 was found to have significantly higher mean serum corrected calcium levels during the 2nd year and 3rd year of follow-up than Group 2. Furthermore, repeated-measures analysis of variance showed higher monthly corrected calcium concentrations (P=0.099) and mean corrected calcium levels during the 1st year, 2nd year, and 3rd year of follow-up (P=0.062) in Group 1, but without statistical significance. The cutoff values of mean corrected calcium of the 2nd year and 3rd year for the prediction of AAC progression during follow-up years were 8.96 mg/dL and 9.45 mg/dL, respectively. Serum phosphate levels and corrected calcium×phosphate values were similar in Groups 1 and 2. Conclusion: Patients with an AAC score of>8 at baseline seem to be at higher risk of mortality during follow-up. Of the serum variables examined, such as corrected calcium, phosphate, and corrected calcium×phosphate, corrected calcium was found to be marginally associated with AAC progression. However, a larger-scale prospective study is required to confirm our findings

Interplay between Crystal Structure and Photoluminescence Properties of β‑Ca₃SiO₄Cl₂:Eu²⁺

The crystal structure of β-Ca₃­SiO₄Cl₂ was determined by the <i>ab initio</i> structure determination method based on the synchrotron powder XRD data for the first time, and the luminescence properties of a Eu²⁺-doped β-Ca₃­SiO₄Cl₂ phosphor were characterized. β-Ca₃­SiO₄Cl₂ was found to be monoclinic (space group <i>P</i>2₁/<i>c</i>) with the lattice parameters, <i>a</i> = 5.91234(1) Å, <i>b</i> = 10.20128(1) Å, <i>c</i> = 10.98866(1) Å, β = 90.3423(1)°. This structure can be considered as an intergrowth structure built up from alternating stacks of two layered sublattices, _∞²[Ca₂SiO₄] and _∞²[CaCl₂], along the [100] direction. In this structure, the Ca atoms occupy three crystallographically distinct sites: Ca1­O₄Cl₃, Ca2­O₅Cl₂, and Ca3­O₃Cl₄. The photoluminescence of the Eu²⁺-doped Ca₃­SiO₄Cl₂ phosphor excited at 450 nm blue light shows the 150 nm wide-band emission peaked at 635 nm with about 70% quantum efficiency. The photoluminescence properties, such as centroid shifts, crystal-field splitting, and Stokes shifts, were correlated with the crystal structure through the calculation of shared-electron populations reflecting the bond covalency between Ca and O/Cl. Effects of doping concentrations on the luminescence spectra and temperature stability were also discussed based on the inhomogeneous energy transfer property determined by the structural geometric factor

Interplay between Crystal Structure and Photoluminescence Properties of β‑Ca₃SiO₄Cl₂:Eu²⁺

The crystal structure of β-Ca₃­SiO₄Cl₂ was determined by the <i>ab initio</i> structure determination method based on the synchrotron powder XRD data for the first time, and the luminescence properties of a Eu²⁺-doped β-Ca₃­SiO₄Cl₂ phosphor were characterized. β-Ca₃­SiO₄Cl₂ was found to be monoclinic (space group <i>P</i>2₁/<i>c</i>) with the lattice parameters, <i>a</i> = 5.91234(1) Å, <i>b</i> = 10.20128(1) Å, <i>c</i> = 10.98866(1) Å, β = 90.3423(1)°. This structure can be considered as an intergrowth structure built up from alternating stacks of two layered sublattices, _∞²[Ca₂SiO₄] and _∞²[CaCl₂], along the [100] direction. In this structure, the Ca atoms occupy three crystallographically distinct sites: Ca1­O₄Cl₃, Ca2­O₅Cl₂, and Ca3­O₃Cl₄. The photoluminescence of the Eu²⁺-doped Ca₃­SiO₄Cl₂ phosphor excited at 450 nm blue light shows the 150 nm wide-band emission peaked at 635 nm with about 70% quantum efficiency. The photoluminescence properties, such as centroid shifts, crystal-field splitting, and Stokes shifts, were correlated with the crystal structure through the calculation of shared-electron populations reflecting the bond covalency between Ca and O/Cl. Effects of doping concentrations on the luminescence spectra and temperature stability were also discussed based on the inhomogeneous energy transfer property determined by the structural geometric factor