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BACKGROUND: This study investigated characteristics according to demographic, occupational factors of Maslach Burnout Inventory-General Survey (MBI-GS) and related scales to MBI-GS. METHODS: The subjects of the study were 3,331 workers in 3 different workplaces of one electronics company. They filled in demographic factors surveys, occupational factors surveys, MBI-GS, Korean Occupational Stress Scale-Short Form (KOSS-SF), Patient Health Questionnaire-9 (PHQ-9), and World Health Organization Quality Of Life-Abbreviated version (WHOQOL-BREF). The correlations between sub-scales of MBI-GS and KOSS-SF, PHQ-9, WHOQOL-BREF were analyzed respectively. And KOSS-SF, PHQ-9, and WHOQOL-BREF were categorized; mean scores of sub-scales of MBI-GS were compared; and the quartiles of sub-scales of MBI-GS were presented. RESULTS: A comparison of mean scores of MBI-GS according to demographic and occupational factors showed a significant difference according to age, problem drinking behavior, working time, and working duration in exhaustion regardless of sex. In professional efficacy, a significant difference was observed in age, marital status, working type, and working duration. And as a result of correlation analysis, the correlation coefficient between exhaustion and PHQ-9 was the highest regardless of sex. In addition, regardless of sex, exhaustion and cynicism scores tended to increase and professional efficacy score tended to decrease as the work stress level rose. Same tendency is shown in case of the more severe the symptom of depression and the lower quality of life. When the quartile for sub-scales' score of MBI-GS were investigated, the burnout was more pronounced in female than in male. CONCLUSIONS: Many demographic and occupational factors affect burnout were identified in one electronics company, and we investigated which sub-scales of MBI-GS were affected. Through this study, burnout characteristics were identified in a few population group of Korea, and the results are expected to be useful for burnout risk group identification, counseling, etc.
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OBJECTIVE: Kidneys are organs having a biological clock, and it is well known that the disruption of the circadian rhythm increases the risk of chronic kidney disease (CKD), including the decline of renal and proteinuria. Because shift work causes circadian disruption, it can directly or indirectly affect the incidence of chronic kidney disease. Therefore, the purpose of this study was to investigate the association between shift work and chronic kidney disease using a Korean representative survey dataset. METHODS: This study was comprised of 3504 manual labor workers over 20 years of age from data from the fifth and sixth Korea National Health and Nutrition Examination Survey (2011-2014). The work schedules were classified into two types: day work and shift work. The estimated glomerular filtration rate, which is the ideal marker of renal function, was estimated according to the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and chronic kidney disease was defined as urinary albumin to a creatinine ratio equal to or high than 30 mg/g and/or estimated glomerular filtration rate lower than 60 mL/min/1.73 m2. The cross-tabulation analysis and multivariate logistic regression analysis were performed to confirm the association between shift work and chronic kidney disease stratified by gender. RESULTS: The risk of CKD showed a significant increase (odds ratio = 2.04, 95% confidence interval = 1.22, 3.41) in the female worker group. The same results were obtained after all confounding variables were adjusted (odds ratio = 2.34, 95% confidence interval = 1.35, 4.07). However, the results of the male worker group were not significant. CONCLUSIONS: In this study using nationally representative surveys, we found that the risk of CKD was higher female workers and shift work. Future prospective cohort studies will be needed to clarify the causal relationship between shift work and CKD.
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BACKGROUND: Lead and cadmium have been identified as risk factors for hearing loss in animal studies, but large-scale studies targeting the general human population are rare. This study was conducted to investigate the link between heavy metal concentrations in blood and hearing impairment, using a national population-based survey. METHODS: The study participants comprised 6409 Koreans aged 20 or older, who were included in the Fifth and Sixth Korea National Health and Nutrition Examination Surveys (KNHANES 2010-2013). Hearing impairment was categorized into two types, low- and high-frequency hearing impairment, using pure tone audiometry. Low-frequency hearing impairment was defined as having a binaural average of hearing thresholds for 0.5, 1, and 2 kHz exceeding 25 dB, and high-frequency hearing impairment was defined as having a binaural average of hearing thresholds for 3, 4, and 6 kHz exceeding 25 dB. The blood levels of heavy metals (lead and cadmium) were classified into quartiles. Cross-sectional association between hearing impairment and the level of heavy metals (lead and cadmium) was examined in both sexes. Multivariate logistic regression was used to obtain adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among men, the prevalence of low- and high- frequency hearing impairment was 13.9% and 46.7%, respectively, which was higher than the prevalence among women (11.8% and 27.0%, respectively). Regarding lead, the adjusted OR of high-frequency hearing impairment for the highest blood level group versus the lowest group was significant in both men (OR = 1.629, 95% CI = 1.161-2.287) and women (OR = 1.502, 95% CI = 1.027-2.196), after adjusting for age, body mass index, education, smoking, alcohol consumption, exercise, diagnosis of diabetes mellitus, hypertension, and noise exposure (occupational, loud, firearm noises). No links were found between blood lead levels and low-frequency hearing impairment, or between blood cadmium levels and low- or high-frequency hearing impairment in either sex. CONCLUSIONS: The present study findings suggest that even exposure to low-level lead is a risk factor for high-frequency hearing loss. A prospective epidemiologic study should be conducted to identify the causal relationship between human health and exposure to heavy metals, and efforts to reduce heavy metal exposure in the general population should continue.
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Exposure to harmful environmental factors is particularly detrimental to younger children. We investigated the relationship between environmental tobacco smoke (ETS) exposure in pre-schoolers at home and the level of high-sensitivity C-reactive protein (hs-CRP), a predictive factor for cardiovascular disease. This study was conducted in 2014 and was based on the data of preschool children from the Korean Environmental Health Survey in Children and Adolescents (2012 to 2014), a nationally representative sample. Of 577 children, aged three to five years, 482 were eventually selected for the analysis after excluding those with missing variables, or whose hs-CRP level exceeded the reference value. The proportion of pre-school children exposed to ETS at home was 14.8%. The odd ratios (OR)s of hs-CRP > 1mg/L were 4.90 (95% Confidence Interval (CI) = 1.04-23.17) and 11.66 (95% CI = 1.90-71.65) in the groups exposed to ETS 3-4 times and ≥5 times daily, respectively, compared to the non-exposed group. The risk of elevated levels of hs-CRP showed an increasing trend proportionally to the increase in ETS exposure frequency (p for trend = 0.03). Anti-smoking educational programs for parents and guardians may be helpful to reduce ETS exposure at home.
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Proteína C-Reativa/análise , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Saúde da Criança , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Habitação , Humanos , Masculino , Razão de Chances , Pais , FumarRESUMO
BACKGROUND: Shift work disturbs workers' biological clocks and this condition can cause various health problems including cardiovascular disease. The elevated albuminuria level has been significantly associated with the risk of the cardiovascular disease even within a normal reference range. Therefore, this study aimed to investigate the association between shift work and microalbuminuria. METHODS: Workers aged over 20 years from the fifth and sixth Korea National Health and Nutrition Examination Survey(KNHANES 2012-2014; n = 3000) were included in this analysis. The multiple logistic regression analysis was performed to determine the association between shift work and microalbuminuria stratified by gender. RESULTS: The prevalence of microalbuminuria in male subjects was higher among day workers, but the difference was not significant. However, the prevalence of microalbuminuria among females was higher in shift workers with statistical significance. For female, the Odds ratio of microalbuminuria in shift workers was significantly higher with 1.86 (95% CI 1.02-3.39) compared with day workers. After dividing into 5 subgroups of the shift work pattern, the odds ratio of microalbuminuria for fixed night shift was significantly higher at 4.68 (95% CI 1.29-17.00) compared with day workers. CONCLUSIONS: This study showed that shift work was associated with microalbuminuria in female workers. Especially we found out the association between fixed night shift and microalbuminuria in female workers.
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BACKGROUND: Cleanroom air is extremely dry, as it is maintained within 1 % of relative humidity. Few studies have assessed the dermatologic life quality of workers in ultralow-humidity environments. Therefore, we aimed to evaluate the dermatologic life quality of cleanroom workers using the Skindex-29, compared to those of non-cleanroom workers. METHODS: Study participants were 501 cleanroom workers and 157 non-cleanroom workers from a secondary battery factory, who underwent an employee health examination at a single university hospital from September 2014 to September 2015. Results of the self-administered Skindex-29, and McMonnies questionnaire were analyzed. Other information and disease history were also collected during physician's medical examination. Descriptive and multivariate logistic regression analysis were performed. RESULTS: The Skindex-29 score was significantly higher in cleanroom workers than in non-cleanroom workers for all domains, Symptom (16.0 ± 15.9 vs. 6.3 ± 10.2, p < 0.001), Emotion (11.3 ± 17.4 vs. 2.5 ± 7.4, p < 0.001), Function (5.2 ± 11.1 vs. 1.6 ± 4.0, p < 0.001), and Overall (10.8 ± 13.4 vs. 3.5 ± 6.2, p < 0.001). The Skindex-29 score of cleanroom workers was similar to that of patients with skin diseases such as psoriasis, other dermatitis, corns, alopecia etc. Among the cleanroom workers, 37 workers had one or more skin diseases. Among the risk factors, 'working at cleanroom', 'possessing skin disease' and 'McMonnies score' had significant strong correlations with Skindex-29 score, meanwhile age, sex, smoking, drinking and exercise had weak correlations with it. 'Working at cleanroom' and 'possessing skin disease' had highest odds ratios with overall 14.0 (C.I.: 5.9-33.1) and 13.4 (C.I.: 4.5-29.2), and the lowest odds ratios with function domain 3.5(C.I.: 1.7-7.1) and 4.5(C.I.: 2.1-9.5), respectively. The McMonnies score had the highest odds ratio with overall, 6.9(C.I.: 4.5-10.8) and lowest odd ratio with emotion domain 4.2 (C.I.: 2.7-6.4). CONCLUSIONS: Dermatologic life quality among cleanroom workers in the secondary battery factory is shown to be lower than that among non-cleanroom workers in this study. The study suggests that the Skindex-29 may provide helpful information on the dermatologic life quality of cleanroom workers. Therefore, regarding evaluation of dermatologic life quality using Skindex-29, preventive care is necessary for cleanroom workers in ultralow humidity environment.
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BACKGROUND: This study examined levels of blood lead and mercury, and urinary cadmium, and associated sociodemographic factors in 3-18 year-old Korean children and adolescents. MATERIALS AND METHODS: We used the nationally representative Korean Environmental Health Survey in Children and Adolescents data for 2012-2014 and identified 2388 children and adolescents aged 3-18 years. The median and 95th percentile exposure biomarker levels with 95% confidence intervals (CIs) were calculated. Multivariate regression analyses were performed on log transformed exposure biomarker levels adjusted for age, sex, area, household income, and father's education level. The median exposure biomarker levels were compared with data from Germany, the US, and Canada, as well as the levels of Korean children measured at different times. RESULTS: The median levels of blood lead and mercury, as well as urinary cadmium were 1.23µg/dL, 1.80µg/L, and 0.40µg/L (95% CIs, 1.21-1.25, 1.77-1.83, and 0.39-0.41, respectively). The blood lead levels were significantly higher in boys and younger children (p<0.0001) and children with less educated fathers (p=0.004) after adjusting for covariates. Urinary cadmium level increased with age (p<0.0001). The median levels of blood mercury and urinary cadmium were much higher in Korean children and adolescents than those in their peers in Germany, the US, and Canada. Blood lead levels tended to decrease with increasing age and divergence between the sexes, particularly in the early teen years. Median levels of blood lead and urinary cadmium decreased since 2010. CONCLUSION: Sociodemographic factors, including age, sex, and father's education level were associated with environmental exposure to heavy metals in Korean children and adolescents. These biomonitoring data are valuable for ongoing surveillance of environmental exposure in this vulnerable population.
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Cádmio/urina , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Chumbo/sangue , Mercúrio/sangue , Adolescente , Criança , Pré-Escolar , Monitoramento Ambiental , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , República da Coreia , Fatores SocioeconômicosRESUMO
PURPOSE: We evaluated three blood glucose self-monitoring for measuring whole blood glucose levels in preterm and low-birth-weight infants. METHODS: Between December 1, 2012 and March 31, 2013, 230 blood samples were collected from 50 newborns, who weighed, ≤2,300 g or were ≤36 weeks old, in the the neonatal intensive care unit of Eulji University Hospital. Three blood glucose self-monitoring (A: Precision Pcx, Abbott; B: One-Touch Verio, Johnson & Johnson; C: LifeScan SureStep Flexx, Johnson & Johnson) were used for the blood glucose measurements. The results were compared to those obtained using laboratory equipment (D: Advia chemical analyzer, Siemens Healthcare Diagnostics Inc.). RESULTS: The correlation coefficients between laboratory equipment and the three blood glucose self-monitoring (A, B, and C) were found to be 0.888, 0.884, and 0.900, respectively. For glucose levels≤60 mg/dL, the correlation coefficients were 0.674, 0.687, and 0.679, respectively. For glucose levels>60 mg/dL, the correlation coefficients were 0.822, 0.819, and 0.839, respectively. All correlation coefficients were statistically significant. And the values from the blood glucose self-monitoring were not significantly different from the value of the laboratory equipment , after correcting for each device's average value (P>0.05). When using laboratory equipment (blood glucose ≤60 mg/dL), each device had a sensitivity of 0.458, 0.604, and 0.688 and a specificity of 0.995, 0.989, and 0.989, respectively. CONCLUSION: Significant difference is not found between three blood glucose self-monitoring and laboratory equipment. But correlation between the measured values from blood glucose self-monitoring and laboratory equipment is lower in preterm or low-birth-weight infants than adults.
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Blood samples have traditionally been used as the main source of DNA for genetic analysis. However, this source can be difficult in terms of collection, transportation, and long-term storage. In this study, we investigated whether human nail clippings could be used as a source of DNA for SNP genotyping, null-allele detection, and whole-genome amplification. From extracted nail DNA, we achieved amplicons up to a length of ~400 bp and >96% concordance for SNP genotyping and 100% concordance for null-allele detection compared to DNA derived from matched blood samples. For whole-genome amplification, OmniPlex performed better than Multiple Displacement Amplification with a success rate of 89.3% and 76.8% for SNP genotyping and null-allele detection, respectively. Concordance was ~98% for both methods. When combined with OmniPlex whole-genome amplification, human nail clippings could potentially be used as an alternative to whole blood as a less invasive and more convenient source of DNA for genotyping studies.
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Tobacco smoking is a well-known cause of various diseases, however, its toxic mechanisms for diseases are not completely understood, yet. Therefore, we performed biological monitoring to find tobacco smoking-responsive mechanisms including oxidative stress in Korean men (N=36). Whole genome microarray analyses were performed with peripheral blood from smokers and age-matched nonsmokers. We also performed qRT-PCR to confirm the microarray results and compared the gene expression of blood to those of buccal cells. To assess the effects of tobacco smoking on oxidative stress, we analyzed urinary levels of malondialdehyde (MDA), a lipid peroxidation marker, and performed PCR-based arrays on reactive oxygen species (ROS)-related genes. As results, 34 genes were differently expressed in blood between smokers and nonsmokers (ps<0.01 and >1.5-fold change). Particularly, the genes involved in immune responsive pathways, e.g., the Fcγ-receptor mediated phagocytosis and the leukocyte transendothelial migration pathways, were differentially expressed between smokers and nonsmokers. Among the above genes, the ACTG1, involved in the maintenance of actin cytoskeleton, cell migration and cancer metastasis, was highly expressed by smoking in both blood and buccal cells. Concerning oxidative stress, smokers showed high levels of urinary MDA and down-regulation of expressions of antioxidant related genes including TPO, MPO, GPX2, PTGR1, and NUDT1 as compared to nonsmokers (ps<0.05). In conclusion, these results suggest that systemically altered immune response and oxidative stress can be tobacco-responsive mechanisms for the related diseases. Based on consistent results in blood and buccal cells, expression of the ACTG1 can be a tobacco smoking-responsive biomarker.
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Células Sanguíneas/efeitos dos fármacos , Mucosa Bucal/citologia , Mucosa Bucal/efeitos dos fármacos , Fumar/efeitos adversos , Fumar/genética , Adulto , Povo Asiático , Cotinina/urina , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Masculino , Malondialdeído/urina , Análise em Microsséries , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: To measure the prevalence of dry eye syndrome (DES) among clean room (relative humidity ≤1%) workers from 2011 to 2013. METHODS: Three annual DES examinations were performed completely in 352 clean room workers aged 20-40 years who were working at a secondary battery factory. Each examination comprised the tear-film break-up test (TFBUT), Schirmer's test I, slit-lamp microscopic examination, and McMonnies questionnaire. DES grades were measured using the Delphi approach. The annual examination results were analyzed using a general linear model and post-hoc analysis with repeated-ANOVA (Tukey). Multiple logistic regression was performed using the examination results from 2013 (dependent variable) to analyze the effect of years spent working in the clean room (independent variable). RESULTS: The prevalence of DES among these workers was 14.8% in 2011, 27.1% in 2012, and 32.8% in 2013. The TFBUT and McMonnies questionnaire showed that DES grades worsened over time. Multiple logistic regression analysis indicated that the odds ratio for having dry eyes was 1.130 (95% CI 1.012-1.262) according to the findings of the McMonnies questionnaire. CONCLUSIONS: This 3-year trend suggests that the increased prevalence of DES was associated with longer working hours. To decrease the prevalence of DES, employees should be assigned reasonable working hours with shift assignments that include appropriate break times. Workers should also wear protective eyewear, subdivide their working process to minimize exposure, and utilize preservative-free eye drops.
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Development of efficient carriers for small interfering RNA (siRNA) delivery and validation tools for assessing in vivo RNA interference (RNAi) efficiency is crucial to advance RNAi-based therapeutics to the clinic. Here, acid-degradable ketalized linear polyethylenimine (KL-PEI) designed for efficient, stimuli-responsive, and biocompatible siRNA delivery was used to complex with GFP-silencing siRNA (GFP siRNA) for in vivo RNAi. The in vivo gene silencing efficiency of GFP siRNA/KL-PEI polyplexes was evaluated at mRNA, protein, and histological levels using a mouse bearing a GFP-expressing tumor. Intravenously injected GFP siRNA/KL-PEI polyplexes significantly reduced GFP expression in tumors and whole blood of mice, depending on the dosage of GFP siRNA and the time course. Average GFP mRNA levels in the tumors of siRNA/KL-PEI polyplex-injected mice were also reduced. The described siRNA carriers and RNAi validation methodologies in this study may provide insightful clues for the development of RNAi-based therapeutics and preclinical trials.
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OBJECTIVES: Nail has been a substitute DNA source for genotyping. To investigate the integrity and consistency of nail DNA amplification for biomarker study, nail clippings from 12 subjects were collected at monthly intervals. The possibility of longer amplification and existence of GAPDH RNA/protein, were also investigated with three nail samples. METHODS: Three primer sets were designed for quantitative amplification of nuclear and mitochondrial genes and analysis of their consistency. The mean threshold cycles in amplification of the target genes were compared to test the consistency of polymerase chain reaction (PCR) performance among individual factors including age groups, sex, family, the nail source, and by the size of the amplification segments. RESULTS: The amplification of the target genes from nail DNA showed similar integrity and consistency between the nail sources, and among the serial collections. However, nail DNA from those in their forties showed earlier threshold cycles in amplification than those in their teens or seventies. Mitochondrial DNA (mtDNA) showed better DNA integrity and consistency in amplification of all three targets than did nuclear DNA (nucDNA). Over 9 kb of mtDNA was successfully amplified, and nested quantitative PCR showed reliable copy numbers (%) between the two loci. Reverse transcription PCR for mRNA and immunoblotting for GAPDH protein successfully reflected their corresponding amounts. Regarding the existence of RNA and protein in nails, more effective extraction and detection methods need to be set up to validate the feasibility in biomarker study. CONCLUSIONS: Nail DNA might be a feasible intra-individual monitoring biomarker. Considering integrity and consistency in target amplification, mtDNA would be a better target for biomarker research than nucDNA.
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DNA/análise , Unhas/química , Adulto , Fatores Etários , Idoso , Biomarcadores/análise , Criança , DNA/isolamento & purificação , Primers do DNA , DNA Mitocondrial/análise , Estudos de Viabilidade , Feminino , Amplificação de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
BACKGROUND: Implant loosening is associated with inflammatory bone loss induced by ultra-high molecular weight polyethylene wear debris. We hypothesized that a hydroxyapatite-bisphosphonate composite improves periprosthetic bone quality and osseous integration of an intramedullary implant even in the presence of ultra-high molecular weight polyethylene particles in an experimental rat femur model. METHODS: A preliminary in vitro study determined the optimal concentration of zoledronate (50 microM) that would maximally decrease osteoclasts without harming osteoblasts. Hydroxyapatite-coated intramedullary nails were implanted bilaterally in the femora of sixteen rats (the control group), and hydroxyapatite-zoledronate-coated nails were implanted bilaterally in the femora of sixteen rats (the experimental group). Ultra-high molecular weight polyethylene particles were introduced into the femoral canal before implantation. Eight rats from each group were killed at six weeks, and the remaining rats were killed at six months. Periprosthetic bone mass was analyzed by dual x-ray absorptiometry and microcomputed tomography. Osseous integration was examined by biomechanical testing of pullout strength. RESULTS: The mean bone area (and standard deviation) in the periprosthetic bone region was significantly greater (p < 0.0001) in the hydroxyapatite-zoledronate group (2.388 +/- 0.960 mm2) than in the control group (0.933 +/- 0.571 mm2). This difference was larger in the six-week group than in the six-month group (p = 0.03). The average peak pullout force for the treated femora (241.0 +/- 95.1 N) was significantly greater (p < 0.0001) than that for the controls (55.6 +/- 49.0 N). This difference was similar in the six-week and six-month groups. The energy required for nail pullout was significantly greater (p < 0.0001) for the treated femora (521.6 +/- 293.8 N-mm) than for the controls (142.2 +/- 152.1 N-mm). This difference in energy to pullout was similar in the six-week and six-month groups. Regression analysis demonstrated a high correlation between periprosthetic bone mass and peak pullout force for both the six-week (r = 0.766, p = 0.0005) and six-month (r = 0.838, p < 0.0001) groups. CONCLUSIONS: Surface modification of implants with hydroxyapatite-zoledronate improves periprosthetic bone quality and osseous integration. CLINICAL RELEVANCE: Hydroxyapatite-based site-specific delivery of bisphosphonates may be one way of reducing ultra-high molecular weight polyethylene wear particle-induced periprosthetic osteolysis and implant loosening.
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Conservadores da Densidade Óssea/uso terapêutico , Pinos Ortopédicos , Materiais Revestidos Biocompatíveis/uso terapêutico , Difosfonatos/uso terapêutico , Durapatita/uso terapêutico , Imidazóis/uso terapêutico , Osseointegração , Animais , Análise de Falha de Equipamento , Fêmur/fisiopatologia , Fêmur/cirurgia , Fixação Intramedular de Fraturas/instrumentação , Masculino , Polietilenos , Ratos , Ratos Sprague-Dawley , Suporte de Carga , Ácido ZoledrônicoRESUMO
The main treatment for chondrosarcoma is surgical resection with a wide margin. However, there are certain chondrosarcomas, such as those found in the pelvis and the spine, which cannot be resected adequately with surgery alone. Unfortunately, most chondrosarcomas are resistant to radiation and chemotherapy. Radiation and chemotherapy are thought to kill chondrosarcoma cells by inducing apoptosis, or programmed cell death. In this article, we hypothesize that antiapoptotic gene silencing enhances radiosensitivity in chondrosarcoma cells by facilitating apoptotic pathways. We knocked down antiapoptotic genes in chondrosarcoma cells using small interfering RNAs (siRNAs). Two well-established Grade II human chondrosarcoma cell lines were pretreated with siRNAs that specifically target mRNAs for Bcl-2, Bcl-xL, or XIAP. The cells were then treated with radiation. Cell death was assessed by flow cytometry. Cell survival and proliferation were measured by clonogenic survival assays. Chondrosarcoma cells exhibited radioresistance and increased the expression of Bcl-2, Bcl-xL, and XIAP in response to radiation. When one of the Bcl-2, Bcl-xL, or XIAP genes was silenced with the corresponding siRNA, radiosensitivity increased up to 9.2-fold (p < 0.05). When two out of the three antiapoptotic mRNAs were knocked down simultaneously, there was an 11.3-fold increase in cell death after radiation (p < 0.05). Our findings support a novel therapeutic concept that gene silencing may be used as a molecular adjuvant therapy for radioresistant sarcomas.
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Proteínas Reguladoras de Apoptose/genética , Apoptose/genética , Apoptose/efeitos da radiação , Neoplasias Ósseas/patologia , Condrossarcoma/patologia , RNA Interferente Pequeno/farmacologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/radioterapia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Condrócitos/citologia , Condrócitos/efeitos da radiação , Condrossarcoma/genética , Condrossarcoma/radioterapia , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/metabolismo , Tolerância a Radiação/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteína bcl-X/genéticaRESUMO
To understand the biochemical response of RANKL in response to mechanical loading, MC3T3-E1 cells were biequiaxially stretched. A murine RANKL cDNA with double epitopes, pEF6 HA-RANKL-V5His, was transfected into MC3T3-E1 cells, which were then stretched. Endogenous RANKL protein expression increased in response to mechanical loading. Membrane-bound RANKL (HA-RANKL-V5His) increased in cell lysates while soluble RANKL (RANKL-V5His) decreased in the conditioned media after mechanical loading. This may have resulted from the decreased activity of TACE after mechanical loading. Increased membrane-bound RANKL may be one of the mechanisms through which osteoblasts adapt to mechanical loading by regulating osteoclastogenic activity in a region-specific manner.
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Proteínas de Transporte/fisiologia , Glicoproteínas de Membrana/fisiologia , Osteoblastos/fisiologia , Células 3T3 , Animais , Fenômenos Biomecânicos , Proteínas de Transporte/genética , DNA Complementar/genética , Glicoproteínas de Membrana/genética , Camundongos , Condicionamento Físico Animal , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Suporte de CargaRESUMO
Several studies have demonstrated that inflammation in the subacromial bursa is an important component in the pathogenesis of impingement syndrome. We have demonstrated in a previous study that many inflammatory cytokines, including stromal cell-derived factor 1 (SDF-1, CXCL12), are increased in the subacromial bursa [Blaine et al. 2005. J Shoulder Elbow Surg 14(Suppl 1):84S-89S]. SDF-1 is a potent chemotactic and angiogenic factor that stimulates recruitment of inflammatory cells. In the current study, we proposed that the resident cells in subacromial bursal tissue produce SDF-1, which can play a role in the inflammatory reponse of bursal tissue, and that this chemokine can be regulated by steroid (dexamethasone) and nonsteroidal anti-inflammatory medications (NSAIDs). Twenty-two subacromial bursa tissues (18 bursitis and 4 normal bursa) were obtained intraoperatively from patients during shoulder surgery and analyzed using the cDNA Array technique in accordance with an IRB approved protocol. cDNA array results were confirmed with real-time reverse transcription-polymerase chain reaction (RT-PCR). Bursal cells (from 4 normal bursa, 3 bursitis) and two normal bone marrow with whole tissue explants were cultured for one passage. Cell culture supernatants were collected and SDF-1 protein was detected with enzyme-linked immunosorbent assay (ELISA). Cultured bursal cells were treated with a COX-2 inhibitor and dexamethasone, and cells was harvested at 1-day and 4-day intervals. SDF-1 expression was evaluated by real-time RT-PCR and ELISA. cDNA Array analysis demonstrated that the gene expression of SDF-1 was increased in patients with subacromial bursitis compared to controls (p < 0.05). Real-time RT-PCR also revealed that the mRNA expression of SDF-1 in bursitis tissue is increased 10-fold over control tissue. While the normal bursal cells produced negligible amounts of SDF-1 protein, cultured cells derived from bursitis lesion released as much SDF-1 protein (235 pg/100,000 cells) as normal bone marrow stromal cells (283 pg/100,000 cells) as measured by ELISA. The addition of a COX-2 inhibitor and dexamethasone to bursitis cell lines led to decreased SDF-1 expression levels compared to untreated bursitis cell lines. These studies demonstrate that there is a significant elevation of SDF-1 expression in the subacromial bursa of patients with rotator cuff disease. Furthermore, this chemokine can be downregulated by COX-2 inhibitors and steroids. These results provide biologic evidence for the use of steroid and NSAIDs in the treatment of subacromial bursitis. In the future, targeted inhibition of molecules such as SDF-1 in the subacromial bursa may present a therapeutic strategy that may avoid the side effects of these other (steroid and NSAID) medications.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios/farmacologia , Bursite/tratamento farmacológico , Bursite/metabolismo , Quimiocinas CXC/metabolismo , Dexametasona/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bolsa Sinovial/citologia , Bolsa Sinovial/imunologia , Bolsa Sinovial/metabolismo , Bursite/imunologia , Células Cultivadas , Quimiocina CXCL12 , Quimiocinas CXC/genética , Inibidores de Ciclo-Oxigenase 2/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Manguito Rotador/citologia , Manguito Rotador/imunologia , Manguito Rotador/metabolismo , Tendinopatia/tratamento farmacológico , Tendinopatia/imunologia , Tendinopatia/metabolismoRESUMO
The impact of endocrine-disrupting chemicals (EDCs) on human health is not yet clear because of difficulties in ascertaining their biological effects. In the present study, we evaluated exposure to the EDC, bisphenol A (BPA), in 172 Koreans in relation to biomarkers of susceptibility and effect. The subjects completed questionnaires, which documented occupation, education, lifestyle factors, potential sources of BPA-exposure, and the occurrence of self-diagnosed endocrine disorders. None of the subjects were occupationally exposed to BPA; however, urinary levels of conjugated BPA, determined by HPLC/FD, ranged from 0.03-62.4 microg/l (median, 7.86). The frequencies of potential susceptibility biomarkers, the UGT1A6-Arg184Ser and the SULT1A1-Arg213His polymorphisms, were not associated with urinary BPA levels, either as single genes or in combination. Indirect effects of BPA exposure on the susceptibility to mutagens were evaluated by comparing urinary BPA concentrations with MNNG-induced sister-chromatid exchange (SCE) in lymphocytes cultured from the subjects. BPA exposure showed marginal or significant associations with theSCEs induced by the low doses of MNNG (0-0.4 mM). However, there was no overall association between urinary BPA levels and MNNG-induced frequency at doses ranging from 0.2-0.6 mM. Finally, we did not detect an association between urinary BPA concentration and endocrine-related disorders. Even though we were unable to find a strong association between BPA exposure and a biological response, possibly because of the limited number of subjects, we observed that most of the subjects were exposed to BPA. Therefore, continuous biological monitoring of BPA is a prudent measure to prevent possible BPA-related health risks.
Assuntos
Disruptores Endócrinos/urina , Predisposição Genética para Doença , Glucuronosiltransferase/genética , Fenóis/urina , Sulfotransferases/genética , Adulto , Arilsulfotransferase/genética , Compostos Benzidrílicos , Biomarcadores/urina , Células Sanguíneas/efeitos dos fármacos , Células Cultivadas , Doenças do Sistema Endócrino/induzido quimicamente , Doenças do Sistema Endócrino/genética , Exposição Ambiental , Feminino , Humanos , Masculino , Metilnitronitrosoguanidina/efeitos adversos , Pessoa de Meia-Idade , Fenóis/efeitos adversos , Polimorfismo Genético , Troca de Cromátide IrmãRESUMO
OBJECTIVE: To estimate the magnitude of psychosocial distress and examine eligible factors associated with the development of psychosocial distress in Korean employees, using a nationwide sample. METHODS: A total of 6977 workers were recruited from 245 companies. A structured questionnaire was used to assess sociodemographics, health-related behaviors, job characteristics, social support at work, personality traits (locus of control, type A behavior pattern), self-esteem, and psychosocial distress. RESULTS: The results showed that 23% of workers were categorized as high stress, 73% as moderate, and 5% as normal. Hierarchical multiple regression analysis showed that psychosocial distress was more common in younger workers, both male and female. Regular exercise was negatively associated with increase of psychosocial distress. In job characteristics, as expected, low decision latitude, high job insecurity, and low social support at work were related to high psychosocial distress. Personality traits such as locus of control and type A behavior pattern, and self-esteem were more powerful predictors of psychosocial distress than general characteristics, health-related behavior, and job characteristics. There were some gender differences. While men who are less educated and single (unmarried, divorced, and separated) experienced higher levels of psychosocial distress than those who are educated and married, women who feel high job demand experienced higher levels of psychosocial distress than those who feel low job demand. CONCLUSIONS: The proportion of the high stress group was higher than expected, and psychosocial factors like social support and personality characteristics (e.g. locus of control, type A behavior pattern and self-esteem) were more significant factors for psychosocial distress than other variables. This finding suggests that some psychosocial factors, especially inadequate social support, low self-esteem and lack of internal locus of control for the development of psychosocial distress, will also operate as an intervention strategy in the worksite stress reduction program. It is strongly required that worksite stress reduction programs should be established in at both occupational and level as well as in individual levels.
Assuntos
Emprego/psicologia , Psicologia , Estresse Psicológico/epidemiologia , Adulto , Feminino , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To elucidate the correlates of self-rated fatigue in Korean employees. METHODS: The data for 10,176 (men, 7984; women, 2192; mean age, 34.2; SD: 8.8) employees recruited from a nation-wide sample were examined. A structured questionnaire was used to measure the participants' fatigue, sociodemographics (sex, age, education, and marital status), job-related characteristics (work duration, grade at work, work hours, shiftwork, employment type, and magnitude of workplace), and health-related habits (smoking, drinking, coffee intake, and exercise). Two types of measurement for fatigue were used to evaluate the magnitude of fatigue: self-rated question and a standardized measurement tool (Multidimensional Fatigue Scale: MFS). RESULTS: According to the self-rated fatigue, 32% of employees reported that they felt fatigue for the past two weeks, and 9.6% of males and 8.7% of females had experienced excessive fatigue (6 months or more). Hierarchical multiple regression analysis showed that fatigue measured by MFS was more common in women, younger, college or more graduated, single, and employees who do not regularly exercise. Fatigue was also associated with long work hours, and the size of the workplace (< 1000 employees). CONCLUSIONS: These results suggest that fatigue has been considered as a common complaint, and that it is affected by job-related factors like work hours and the workplace size as well as sociodemographics or health-related behaviors. Further research is needed to clarify the effects of fatigue on adverse health,outcomes, work performance, work disability, sick absence and medical utilization, and to examine the relationship of job characteristics (e.g.: work demand, decision latitude) to fatigue.