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Background@#Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with increased prevalence in the elderly. Telomeres are repetitive DNA sequences found at the end of the chromosome, which progressively shorten as cells divide. Telomere length is known to be a molecular marker of aging. This study aimed to assess the relationship between telomere length and the risk of COPD, lung function, respiratory symptoms, and emphysema index in Chronic Obstructive Pulmonary Disease in Dusty Areas (CODA) cohort. @*Methods@#We extracted DNA from the peripheral blood samples of 446 participants, including 285 COPD patients and 161 control participants. We measured absolute telomere length using quantitative real-time polymerase chain reaction. All participants underwent spirometry and quantitative computed tomography scan. Questionnaires assessing respiratory symptoms and the COPD Assessment Test was filled by all the participants. @*Results@#The mean age of participants at the baseline visit was 72.5±7.1 years. Males accounted for 72% (321 participants) of the all participants. The mean telomere length was lower in the COPD group compared to the non-COPD group (COPD, 16.81±13.90 kb; non-COPD, 21.97±14.43 kb). In COPD patients, 112 (75.7%) were distributed as tertile 1 (shortest), 91 (61.1%) as tertile 2 and 82 (55%) as tertile 3 (longest). We did not find significant associations between telomere length and lung function, exacerbation, airway wall thickness, and emphysema index after adjusting for sex, age, and smoking status. @*Conclusion@#In this study, the relationship between various COPD phenotypes and telomere length was analyzed, but no significant statistical associations were shown.
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Background@#Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD.Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. @*Methods@#To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. @*Results@#Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219,P = 0.015). @*Conclusion@#Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.
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Objective@#To identify the normal range, distribution, and age-dependent differences in the cephalic index (CI) of Korean children with normal brain development and develop a classification of the current CI for Korean children up to 7 years of age. @*Methods@#We retrospectively analyzed 1,389 children who visited our hospital in the emergency room between October 2015 and September 2020 because of suspected head injuries. Finally, 1,248 children (741 male and 507 female) were enrolled after excluding abnormal medical or familial history and divided into 10 groups by age. The CI was measured using brain computed tomography and calculated according to the following equation: cephalic width/cephalic length×100. @*Results@#The averages of CI by age groups were as follows: 89.29 (0–3 months group, n=44); 91.41 (4–6 months group, n=63); 89.68 (7–9 months group, n=62); 87.52 (10–12 months group, n=41); 87.64 (≥2 years group, n=243); 86.63 (≥3 years group, n=178); 85.62 (≥4 years group, n=232); 85.77 (≥5 years group, n=201); 85.15 (≥6 years group, n=75); and 85.34 (≥7 years group, n=109). The CI of Korean children in normal brain development was confirmed to be large, showing a notable difference compared to that of Caucasians. @*Conclusion@#The current CI of Korean children will provide a valuable reference for diagnosing and treating cranial deformities, especially dolichocephaly and brachycephaly as well as to monitor the morphology of the cranium in clinics.
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Background@#Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with increased prevalence in the elderly. Telomeres are repetitive DNA sequences found at the end of the chromosome, which progressively shorten as cells divide. Telomere length is known to be a molecular marker of aging. This study aimed to assess the relationship between telomere length and the risk of COPD, lung function, respiratory symptoms, and emphysema index in Chronic Obstructive Pulmonary Disease in Dusty Areas (CODA) cohort. @*Methods@#We extracted DNA from the peripheral blood samples of 446 participants, including 285 COPD patients and 161 control participants. We measured absolute telomere length using quantitative real-time polymerase chain reaction. All participants underwent spirometry and quantitative computed tomography scan. Questionnaires assessing respiratory symptoms and the COPD Assessment Test was filled by all the participants. @*Results@#The mean age of participants at the baseline visit was 72.5±7.1 years. Males accounted for 72% (321 participants) of the all participants. The mean telomere length was lower in the COPD group compared to the non-COPD group (COPD, 16.81±13.90 kb; non-COPD, 21.97±14.43 kb). In COPD patients, 112 (75.7%) were distributed as tertile 1 (shortest), 91 (61.1%) as tertile 2 and 82 (55%) as tertile 3 (longest). We did not find significant associations between telomere length and lung function, exacerbation, airway wall thickness, and emphysema index after adjusting for sex, age, and smoking status. @*Conclusion@#In this study, the relationship between various COPD phenotypes and telomere length was analyzed, but no significant statistical associations were shown.
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Background@#Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD.Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. @*Methods@#To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. @*Results@#Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219,P = 0.015). @*Conclusion@#Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.
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Objective@#To identify the normal range, distribution, and age-dependent differences in the cephalic index (CI) of Korean children with normal brain development and develop a classification of the current CI for Korean children up to 7 years of age. @*Methods@#We retrospectively analyzed 1,389 children who visited our hospital in the emergency room between October 2015 and September 2020 because of suspected head injuries. Finally, 1,248 children (741 male and 507 female) were enrolled after excluding abnormal medical or familial history and divided into 10 groups by age. The CI was measured using brain computed tomography and calculated according to the following equation: cephalic width/cephalic length×100. @*Results@#The averages of CI by age groups were as follows: 89.29 (0–3 months group, n=44); 91.41 (4–6 months group, n=63); 89.68 (7–9 months group, n=62); 87.52 (10–12 months group, n=41); 87.64 (≥2 years group, n=243); 86.63 (≥3 years group, n=178); 85.62 (≥4 years group, n=232); 85.77 (≥5 years group, n=201); 85.15 (≥6 years group, n=75); and 85.34 (≥7 years group, n=109). The CI of Korean children in normal brain development was confirmed to be large, showing a notable difference compared to that of Caucasians. @*Conclusion@#The current CI of Korean children will provide a valuable reference for diagnosing and treating cranial deformities, especially dolichocephaly and brachycephaly as well as to monitor the morphology of the cranium in clinics.
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Objective@#Alzheimer’s disease (AD) is the most common type of dementia and the prevalence rapidly increased as the elderly population increased worldwide. In the contemporary model of AD, it is regarded as a disease continuum involving preclinical stage to severe dementia. For accurate diagnosis and disease monitoring, objective index reflecting structural change of brain is needed to correctly assess a patient’s severity of neurodegeneration independent from the patient’s clinical symptoms. The main aim of this paper is to develop a random forest (RF) algorithm-based prediction model of AD using structural magnetic resonance imaging (MRI). @*Methods@#We evaluated diagnostic accuracy and performance of our RF based prediction model using newly developed brain segmentation method compared with the Freesurfer’s which is a commonly used segmentation software. @*Results@#Our RF model showed high diagnostic accuracy for differentiating healthy controls from AD and mild cognitive impairment (MCI) using structural MRI, patient characteristics, and cognitive function (HC vs. AD 93.5%, AUC 0.99; HC vs. MCI 80.8%, AUC 0.88). Moreover, segmentation processing time of our algorithm (<5 minutes) was much shorter than of Freesurfer’s (6–8 hours). @*Conclusion@#Our RF model might be an effective automatic brain segmentation tool which can be easily applied in real clinical practice.
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Purpose@#: The purposes of this study were to examine the relationships between knowledge, awareness, safe environment, and performance of standard precautions and identify factors associated with performance of standard precautions. @*Methods@#: This study was a descriptive research. A structured questionnaire on knowledge, awareness, safe environment, and performance of standard precautions was used for the survey with a convenience sample of 150 caregivers. Data were collected from July to August 2019 and were analyzed using descriptive statistics, independent t-test, one way ANOVA, Pearson’s correlation coefficient, and multiple regression with SPSS/WIN 25.0 program. @*Results@#: The mean scores on knowledge, awareness, safe environment, and performance of standard precautions were 15.77±3.34, 7.35±1.91, 4.55±2.05, and 55.20±10.11 respectively. Performance of standard precautions showed a statistically significant positive correlation with knowledge (r=.54, p @*Conclusion@#: The results of the study indicate that factors influencing the performance of standard precautions of caregivers were awareness and safe environment. Therefore, to improve implementation of the standard precautions among caregivers, a safe environment within the hospital must be supported, and appropriate infection management education needs to be provided to caregivers to improve their knowledge and awareness of the standard precautions.
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Objective@#To examine the correlation between ultrasonographic trunk muscle parameters and balance scales in mild acute stroke patients. @*Methods@#A total of 55 stroke patients with hemiparesis and motor power grade ≥4 in the manual motor test were included. The Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), Timed Up and Go Test (TUG), and Trunk Control Test (TCT) were used to evaluate patient balance function. Ultrasonographic parameters were measured on both non-paretic and paretic sides of the rectus abdominis, external oblique, internal oblique, transversus abdominis, and erector spinae muscles. Resting thickness and contraction thickness were measured in all muscles, and contractility and contractility ratio were calculated based on measured thicknesses. The differences between paretic and non-paretic muscle parameters, and the correlation between ultrasonographic parameters and balance scales were analyzed. Stroke patients were divided into two groups according to their fall risk. Ultrasonographic measurements between the two groups were compared. @*Results@#All muscles’ contraction thickness and contractility were significantly different between paretic and non-paretic sides (p<0.001). Contractility ratios of all trunk muscles showed a significant correlation with SARA, BBS, TUG, and TCT (p<0.05). Contractility ratios of all muscles were significantly different between high- and low-risk fall groups (p<0.05). @*Conclusion@#The contractility ratio in stroke patients reflects their balance disturbance and fall risk and it may serve as a new parameter for ultrasound imaging of trunk muscles.
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BACKGROUND AND OBJECTIVES: Perivascular stem cells (PVCs) have been identified as precursors of mesenchymal stem cells (MSCs) that offer promising prospects for application in the development of cellular therapies. Although PVCs have been demonstrated to have greater therapeutic potential compared to bone marrow and adipose tissue-derived MSCs in various diseases, the regulatory role of PVCs on inflammasome activation during macrophage-mediated inflammatory responses has not been investigated.METHODS AND RESULTS: In this study, we found that the PVC secretome effectively alleviates secretion of both caspase-1 and interleukin-1β in lipopolysaccharide-primed and activated human and murine macrophages by blocking inflammasome activation and attenuating the production of mitochondrial reactive oxygen species (ROS). We further showed that the PVC secretome significantly reduces inflammatory responses and endoplasmic reticulum stress in peritoneal macrophages in a mouse model of monosodium urate-induced peritonitis. A cytokine antibody array analysis revealed that the PVC secretome contains high levels of serpin E1 and angiogenin, which may be responsible for the inhibitory effects on mitochondrial ROS generation as well as on inflammasome activation.CONCLUSIONS: Our results suggest that PVCs may be therapeutically useful for the treatment of macrophage- and inflammation-mediated diseases by paracrine action via the secretion of various biological factors.
Subject(s)
Animals , Humans , Mice , Biological Factors , Bone Marrow , Endoplasmic Reticulum Stress , Inflammasomes , Inflammation , Macrophages , Macrophages, Peritoneal , Mesenchymal Stem Cells , Peritonitis , Plasminogen Activator Inhibitor 1 , Reactive Oxygen Species , Stem CellsABSTRACT
Cadmium (Cd), a major component of cigarette smoke, disrupts the normal functions of airway cells and can lead to the development of various pulmonary diseases such as chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms involved in Cd-induced pulmonary diseases are poorly understood. Here, we identified a cluster of genes that are altered in response to Cd exposure in human bronchial epithelial cells (BEAS-2B) and demonstrated that Cd-induced ER stress and inflammation are mediated via CCAAT-enhancer-binding proteins (C/EBP)-DNA-damaged-inducible transcript 3 (DDIT3) signaling in BEAS-2B cells. Cd treatment led to marked upregulation and downregulation of genes associated with the cell cycle, apoptosis, oxidative stress and inflammation as well as various signal transduction pathways. Gene set enrichment analysis revealed that Cd treatment stimulated the C/EBP signaling pathway and induced transcriptional activation of its downstream target genes, including DDIT3. Suppression of DDIT3 expression using specific small interfering RNA effectively alleviated Cd-induced ER stress and inflammatory responses in both BEAS-2B and normal primary normal human bronchial epithelial cells. Taken together, these data suggest that C/EBP signaling may have a pivotal role in the early induction of ER stress and inflammatory responses by Cd exposure and could be a molecular target for Cd-induced pulmonary disease.
Subject(s)
Humans , Apoptosis , Cadmium , CCAAT-Enhancer-Binding Proteins , Cell Cycle , Down-Regulation , Epithelial Cells , Inflammation , Lung Diseases , Oxidative Stress , Pulmonary Disease, Chronic Obstructive , RNA, Small Interfering , Signal Transduction , Smoke , Tobacco Products , Transcriptional Activation , Up-RegulationABSTRACT
BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.