Although rheumatoid arthritis has been known to be a common autoimmune disease characterized by chronic inflammation mainly evident in diarthrodial joints, its pathogenesis remains to be clarified. In the present study, to investigate the pathogenic signaling system taken place in the rheumatoid joints, we assessed whether synovial fluid obtained from patients with rheumatoid arthritis contains inducers for proinflammatory cytokines such as interleukin (IL)-12 and IL-23. Peritoneal macrophages isolated from IL-12/IL-23 p40-YFP reporter mice were stimulated with synovial fluid, followed by flow cytometry to screen CD11b+ and YFP-expressing cells, reflective of IL-12/IL-23 p40-producing macrophages. The expression levels of Toll-like receptor (TLR)-2 and -4, which have a potential to mediate IL-12/IL- 23 p40 induction, were determined in synovial cells obtained from a patient with rheumatoid arthritis by RT-PCR analyses. One out of 10 synovial fluid from rheumatoid arthritis patients induced IL-12/IL-23 p40 expression, while all of 10 synovial fluid from osteoarthritis patients did not. Synoviocytes constitutively expressed Toll-like receptor (TLR)-2 and -4 which are candidate receptors for IL-12/IL-23 inducers. Upon LPS stimulation, the levels of TLR-2 and -4 were downregulated and upregulated, respectively. Taken together, these results suggest that some patients with rheumatoid arthritis elicit synovitis through TLR-2- and -4-mediated induction of proinflammatory cytokines IL-12 and IL-23.
Animals ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Cytokines ; Flow Cytometry ; Fluorescence* ; Humans ; Inflammation ; Interleukin-12 ; Interleukin-23 ; Interleukins ; Joints ; Macrophages ; Macrophages, Peritoneal ; Mass Screening* ; Mice* ; Osteoarthritis ; Synovial Fluid* ; Synovitis ; Toll-Like Receptors

Fibroblast-like synoviocytes (FLS) colocalize with leukocyte infiltrates in rheumatoid synovia. Proinflammatory leukocytes are known to amplify inflammation by signaling to FLS, but crosstalk between FLS and regulatory T cells (Tregs) remains uncharacterized. To address this possibility, we cocultured FLS lines derived from arthritic mice with Tregs. FLS that expressed the ligand for glucocorticoid-induced TNF receptor family-related gene (GITR) decreased expression of Foxp3 and GITR in Tregs in a contact-dependent manner. This effect was abolished by blocking antibody to GITR. On the other hand, the Tregs caused the FLS to increase IL-6 production. These results demonstrate that inflamed FLS license Tregs to downregulate Foxp3 expression via the GITRL/GITR interaction while the Tregs induce the FLS to increase their production of IL-6. Our findings suggest that the interaction between FLS and Tregs dampens the anti-inflammatory activity of Tregs and amplifies the proinflammatory activity of FLS, thereby exacerbating inflammatory arthritis.
Animals ; Arthritis ; Hand ; Inflammation ; Interleukin-6 ; Leukocytes ; Licensure ; Mice ; Receptors, Tumor Necrosis Factor ; Synovial Fluid ; T-Lymphocytes, Regulatory

BACKGROUND: Firefighters are exposed to many dangerous working conditions. Many studies have identified the risk of disease for firefighters, but only a few studies have addressed the medical expenses of firefighters, which represents a concrete scale of disease. Our purpose in this study was to determine the medical expenditures of firefighters to assess the overall scale of disease in Korea. We focused on cancer, mental disorders, cardio-cerebrovascular disease, and musculoskeletal disease, the prevalence of which was expected to be high in firefighters. METHODS: This study utilized National Health Insurance Service data. We targeted firefighters, police officers, and government officials. We classified disease based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes. We compared prevalence by the age-standardized prevalence rate, considering standard distribution of the population. Medical expenditure of disease was defined as outpatient fees, hospitalization fees, and drug costs. Total medical expenditures were calculated by the sum of those 3 categories. RESULTS: The age-standardized prevalence of cancer, mental disorders, and cardiovascular disease in firefighters was slightly higher than or similar to that of government officials and police officers (no significant difference). However, medical expenditures for stomach cancer, mental disorders, and most cardio-cerebrovascular diseases were higher in firefighters than in others. In particular, firefighters spent 12 times more money for ischemic heart disease than did government officials. Of musculoskeletal diseases, lumbar disc disorder had the highest expenditures among firefighters. CONCLUSIONS The age-standardized prevalence of most of diseases of firefighters was not as high as in the other groups, but the medical expenses of firefighters were much higher than those of government officials and police officers.

BACKGROUND: Firefighters are exposed to many dangerous working conditions. Many studies have identified the risk of disease for firefighters, but only a few studies have addressed the medical expenses of firefighters, which represents a concrete scale of disease. Our purpose in this study was to determine the medical expenditures of firefighters to assess the overall scale of disease in Korea. We focused on cancer, mental disorders, cardio-cerebrovascular disease, and musculoskeletal disease, the prevalence of which was expected to be high in firefighters. METHODS: This study utilized National Health Insurance Service data. We targeted firefighters, police officers, and government officials. We classified disease based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes. We compared prevalence by the age-standardized prevalence rate, considering standard distribution of the population. Medical expenditure of disease was defined as outpatient fees, hospitalization fees, and drug costs. Total medical expenditures were calculated by the sum of those 3 categories. RESULTS: The age-standardized prevalence of cancer, mental disorders, and cardiovascular disease in firefighters was slightly higher than or similar to that of government officials and police officers (no significant difference). However, medical expenditures for stomach cancer, mental disorders, and most cardio-cerebrovascular diseases were higher in firefighters than in others. In particular, firefighters spent 12 times more money for ischemic heart disease than did government officials. Of musculoskeletal diseases, lumbar disc disorder had the highest expenditures among firefighters. CONCLUSIONS The age-standardized prevalence of most of diseases of firefighters was not as high as in the other groups, but the medical expenses of firefighters were much higher than those of government officials and police officers.

Cardiovascular Diseases ; Drug Costs ; Fees and Charges ; Firefighters ; Health Expenditures ; Hospitalization ; Humans ; International Classification of Diseases ; Korea ; Mental Disorders ; Musculoskeletal Diseases ; Myocardial Ischemia ; National Health Programs ; Occupational Groups ; Outpatients ; Police ; Prevalence ; Stomach Neoplasms

PURPOSE: The purpose of this study was to develop an integrated nursing practicum education matrix based on the learning outcomes of each stage. METHODS: In this Delphi technique study, 10 experts, consisting of six professors and four nurses, participated in the development of the matrix. The first step was an in-depth review for the composition of the questionnaire and the second step was the Delphi technique. The Delphi survey was conducted two times in order to complete the components of the matrix. The survey data was analyzed for statistical averages and standard deviations to decide the order of priority. RESULTS: According to each stage (i.e. fundamental stage, competent stage, and proficient stage), the matrix was composed of education contents, methods, evaluation methods, and curriculum outcomes. CONCLUSION: The integrated nursing practicum education matrix of Y University was completed. The developed matrix will result in a reduction in the gap between nursing education and clinical practice and an improvement in nursing competency.
Competency-Based Education ; Curriculum ; Delphi Technique ; Education* ; Education, Nursing ; Humans ; Learning* ; Nursing* ; Professional Competence ; Students, Nursing

Objective: The Montreal Cognitive Assessment (MoCA) is recommended for assessing general cognition in Parkinson’s disease (PD). Several cutoffs of MoCA scores for diagnosing PD with cognitive impairment (PD-CI) have been proposed, with varying sensitivity and specificity. This study investigated the utility of machine learning algorithms using MoCA cognitive domain scores for improving diagnostic performance for PD-CI. Methods: In total, 2,069 MoCA results were obtained from 397 patients with PD enrolled in the Parkinson’s Progression Markers Initiative database with a diagnosis of cognitive status based on comprehensive neuropsychological assessments. Using the same number of MoCA results randomly sampled from patients with PD with normal cognition or PD-CI, discriminant validity was compared between machine learning (logistic regression, support vector machine, or random forest) with domain scores and a cutoff method. Results: Based on cognitive status classification using a dataset that permitted sampling of MoCA results from the same individual (n = 221 per group), no difference was observed in accuracy between the cutoff value method (0.74 ± 0.03) and machine learning (0.78 ± 0.03). Using a more stringent dataset that excluded MoCA results (n = 101 per group) from the same patients, the accuracy of the cutoff method (0.66 ± 0.05), but not that of machine learning (0.74 ± 0.07), was significantly reduced. Inclusion of cognitive complaints as an additional variable improved the accuracy of classification using the machine learning method (0.87–0.89). Conclusion Machine learning analysis using MoCA domain scores is a valid method for screening cognitive impairment in PD.

The “fourth industrial revolution” (FIR) is an age of advanced technology based on information and communication. FIR has a more powerful impact on the economy than in the past. However, the prospects for the labor environment are uncertain. The purpose of this study is to anticipate and prepare for occupational health and safety (OHS) issues.In FIR, nonstandard employment will be common. As a result, it is difficult to receive OHS services and compensation. Excessive trust in new technologies can lead to large-scale or new forms of accidents. Global business networks will cause destruction of workers' biorhythms, some cancers, overwork, and task complexity. The social disconnection because of an independent work will be a risk for worker's mental health. The union bonds will weaken, and it will be difficult to apply standardized OHS regulations to multinational enterprises.To cope with the new OHS issues, we need to establish new concepts of "decent work” and standardize regulations, which apply to enterprises in each country, develop public health as an OHS service, monitor emerging OHS events and networks among independent workers, and nurture experts who are responsible for new OHS issues.
Commerce ; Compensation and Redress ; Employment ; Mental Health ; Occupational Health ; Periodicity ; Public Health ; Social Control, Formal ; Workers' Compensation

Purpose: Hereditary parkinsonism genes consist of causative genes of familial Parkinson’s disease (PD) with a locus symbol prefix (PARK genes) and hereditary atypical parkinsonian disorders that present atypical features and limited responsiveness to levodopa (non-PARK genes). Although studies have shown that hereditary parkinsonism genes are related to idiopathic PD at the phenotypic, gene expression, and genomic levels, no study has systematically investigated connectivity among the proteins encoded by these genes at the protein-protein interaction (PPI) level. Materials and Methods: Topological measurements and physical interaction enrichment were performed to assess PPI networks constructed using some or all the proteins encoded by hereditary parkinsonism genes (n=96), which were curated using the Online Mendelian Inheritance in Man database and literature. Results: Non-PARK and PARK genes were involved in common functional modules related to autophagy, mitochondrial or lysosomal organization, catecholamine metabolic process, chemical synapse transmission, response to oxidative stress, neuronal apoptosis, regulation of cellular protein catabolic process, and vesicle-mediated transport in synapse. The hereditary parkinsonism proteins formed a single large network comprising 51 nodes, 83 edges, and three PPI pairs. The probability of degree distribution followed a power-law scaling behavior, with a degree exponent of 1.24 and a correlation coefficient of 0.92. LRRK2 was identified as a hub gene with the highest degree of betweenness centrality; its physical interaction enrichment score was 1.28, which was highly significant. Conclusion Both PARK and non-PARK genes show high connectivity at the PPI and biological functional levels.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic synovial inflammation which leads to joint destruction. Gene therapy of RA targets the players of inflammation or articular destruction. However, viral vectors have safety problems and side effects, while non-viral vectors suffer from inefficient gene transfer and fast loss of gene expression. To overcome the limits of non-vial vectors, an EBV-based plasmid which is known to exert prolonged high level gene expression can be used. METHODS: pEBVGFP, pEBVIL-10, and pEBVvIL-10 were constructed by cloning GFP, IL-10, and vIL-10 genes into an EBV-based plasmid, respectively. The pGFP was used as a control plasmid. Each constructs were lipofected into HIG-82 rabbit synoviocytes. The expression of GFP was monitored by FACS and confocal microscopy. IL-10 and vIL-10 expressions were measured by ELISA. RESULTS: GFP expression 2 days after transfection was achieved in 33.2% of cells. GFP-expressing cells transfected with pGFP decreased rapidly from 4 days after transfection and disappeared completely by 11 days. Cells transfected with pEBVGFP began to decrease slowly from 4 days. But GFP expression was detected for over 35 days. In addition, HIG-82 cells transfected with pEBVIL-10 (44.6+/-1.5 ng/ml) or pEBVvIL-10 (51.0+/-5.7 ng/ml) secreted these cytokines at high levels. High level cytokine production by hygromycin selection was maintained at least for up to 26 days after transfection. CONCLUSION: These results suggest that the EBV-based plasmid has a potential to improve non-viral gene transfer system and may be applicable to treat RA without the drawbacks of viral vectors.
Arthritis, Rheumatoid ; Clone Cells ; Cloning, Organism ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Gene Expression* ; Genetic Therapy ; Inflammation ; Interleukin-10 ; Joints ; Microscopy, Confocal ; Plasmids* ; Transfection