OBJECTIVE: Cyclosporine(CsA) and tacrolimus, albeit different in structure, exert immunosuppressive effect by similar mechanism. Although most of clinical manifestations, including nephrotoxicity, are similar in the patients using these drugs, there are some differences including gum hyperplasia, neurotoxicity, and hepatic fibrosis between two drugs. There are several reports about association between reactive oxygen species(ROS) and CsA. In contrast, tacrolimus is known to decrease ROS in central nervous system. Thus, we investigated the possibility of different effects of tacrolimus and CsA on the generation of ROS, on the synthesis and degradation of collagen. METHODS: Experiments were done in primary cultured mesangial cells between 4th and 8th passages. CsA was added to the culture dishes in different concentration(making final CsA concentration of 0, 2, 4, 8 microgram/milliliter) and N-acetylcysteine(NAC) was also added in another mesangial cell culture at 4 microgram/milliliter of CsA concentration; tacrolimus was added in similar pattern(making final tacrolimus concentration of 0, 0.1, 0.2, 0.4 microgram/milliliter, NAC in 0.2 microgram/milliliter of tacrolimus concentration). RESULTS: No significant decrease in viability was noted in both cell groups, but growth retardation was weak in tacrolimus treated cells comparing with CsA treated cells. By flow cytometry, we could find the generation of ROS in CsA treated cells, but not in tacrolimus treated cells. In RT-PCR, there is no significant difference in m-RNA expression for a number of molecules including collagen III, MMP-2, TIMP-2, MT1-MMP in either CsA treated cells or tacrolimus cells. But in zymogram, MMP-2 activities were decreased at higher CsA concentration, then increased with addition of NAC. In tacrolimus cells, MMP2 activity was not changed at 0.1 and 0.2 microgram/milliliter; but, at the concentration of 0.4 microgram/milliliter, changed and not reversed by NAC. MMP-9 activity was similar in both cells. CONCLUSION: We could find ROS generation in CsA treated human mesangial cells, but not in tacrolimus treated cells. We think this difference resulted in the decrease of post-transcriptional MMP-2 activity in CsA treated cells and we also think tacrolimus cells in our experiments were not influenced by ROS. From these results, tacrolimus and CsA are different in the generation of ROS that have some effects in the matrix accumulation in mesangial cells. These result does not mean that tacrolimus is superior to CsA in nephrotoxicity, because nephrotoxicity is similar between two drugs. In conclusion, the mechanisms of nephrotoxicity are different between CsA and tacrolimus.
Central Nervous System ; Collagen ; Cyclosporine* ; Extracellular Matrix* ; Fibrosis ; Flow Cytometry ; Gingiva ; Humans* ; Hyperplasia ; Matrix Metalloproteinase 14 ; Mesangial Cells* ; Oxygen ; Tacrolimus* ; Tissue Inhibitor of Metalloproteinase-2

OBJECTIVE: This study evaluates the effect of the specific human papillomavirus (HPV) genotype as a prognostic factor in stage I-IIA cervical cancer patients following primary surgical treatment. METHODS: The medical records of 116 cervical cancer patients treated with primary surgical treatment were reviewed. The HPV genotypes were categorized into following groups: negative and unclassified, HPV 16, HPV 18, and other high risk (HPV 31, 33, 35, 45, 51, 52, 56, and 58). RESULTS: Among the HPV genotypes, HPV 16 predominated (40.52%), followed by intermediate risk and unclassified (25%), HPV 18, 45, and 56 (17.24%) and negative (17.24%). In univariate analysis, HPV genotypes (P=0.03), parametrial spread (P=0.02), depth of invasion (DOI) (P<0.01) and lymph-vascular space invasion (P=0.02) were significantly associated with progression free survival (PFS). In multivariate analysis, HPV 18 (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.29 to 20.90; P=0.02) and > or =one half of DOI (HR, 5.4; 95% CI, 1.08 to 27.31; P=0.04) were significantly associated with PFS. HPV genotypes are not significantly associated with overall survival. CONCLUSION: HPV 18 was a poor prognostic factor for the PFS in stage I-IIA cervical cancer patients following primary surgical treatment. Careful long-term observation and regular exams are recommended for cervical cancer patients with HPV 18 compared to those with other HPV genotypes.
Disease-Free Survival ; Genotype ; Human papillomavirus 16 ; Human papillomavirus 18* ; Humans ; Medical Records ; Multivariate Analysis ; Prognosis ; Uterine Cervical Neoplasms*

Hepatitis A can cause serious illness among adolescents and adults with low vaccination coverage. Even though hepatitis A vaccine is one of the strong candidates for Korean national immunization program, adolescents aged older than 12 yr would not benefit. Our purpose was to assess the willingness and analyze the correlates of Korean mothers for hepatitis A (HepA) vaccination to develop strategies for HepA vaccination. A national telephone survey on 800 mothers with children aged 7-18 yr was conducted with random-digit dialing method. Sixty-two percent and 92% of the mothers reported that they were willing to HepA vaccination at current cost and at half of the current cost, respectively. However, at current cost, only 79% wished to vaccinate their child in an epidemic and 32% wished to vaccinate promptly. Having two or more children, not having future plans to send the child overseas, and low family income were significantly associated with not willing to HepA vaccination. Low perception of the susceptibility for hepatitis A and perception of the current cost as barrier increased the odds of unwillingness to vaccination at current cost and to prompt vaccination. The mothers' willingness to HepA vaccination for the children aged 7-18 yr in Korea was not very high at current cost and associated socioeconomic status and health-belief. Targeted intervention or strategies are needed to increase the HepA vaccination rate among children in Korea.
Adolescent ; Adult ; Child ; Demography ; Female ; Health Status ; Health Surveys ; Hepatitis A/economics/*prevention & control ; Hepatitis A Vaccines/economics/*immunology ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Mothers/psychology ; Republic of Korea ; Social Class ; *Vaccination

OBJECTIVE: Treatment with cyclosporine(CsA) for a long-term period may induce renal glomerulosclersosis and interstitial fibrosis. Reactive oxygen species(ROS) seems to be involved in the process of glomerulosclersosis and interstitial fibrosis. We investigated the effect of CsA on the generation of ROS and extracellular matrix accumulation in cultured human mesangial cells. We also studied the relationship between ROS formation and extracellular matrix and the effect of antioxidant on ROS formation and/or extracellular matrix degradation. METHODS: Mesangial cells were treated with varying dose of Cyclosporine(0, 2.5, 5, 7.5 and 10microgram/ mL) and also with cyclosporine(5microgram/mL) plus N- acetylcysteine(1mM). ROS was measured by flow cytometric analysis. mRNA expression of MMP-2, TIMP-2, MT1-MMP and collagen III was assessed by RT-PCR method. MMP-2 activity was measured by gelatin zymography. RESULTS: No significant difference was noted in cell viability with each CsA concentration. CsA inhibited the cell proliferation in a dose dependent manner and induced the expression of ROS. Antioxidant NAC reversed the effect of cyclosporine. CsA had no effect on the mRNA expression of collagen III, MMP-2, TIMP-2, MT1-MMP. However CsA decreased the MMP-2 activity in a dose dependent manner, which was also reversed by NAC. CONCLUSION: Cyclosporine-induced ROS may be associated with the extracellular matrix accumulation, that is glomerulosclersosis and interstitial fibrosis by inhibiting the cell proliferation and by decreasing the degradation of extracellular matrix. Antioxidant, at least in vitro, may prevent some of the adverse effects of CsA on renal function.
Cell Proliferation ; Cell Survival ; Collagen ; Cyclosporine* ; Extracellular Matrix* ; Fibrosis ; Gelatin ; Humans* ; Matrix Metalloproteinase 14 ; Mesangial Cells* ; Oxygen ; RNA, Messenger ; Tissue Inhibitor of Metalloproteinase-2

PURPOSE: The purpose of this study was to investigate the influence of communication competence and burnout on nursing performance in intensive care units (ICU). METHOD: The participants were 209 nurses from four university hospitals. Measurements included a socio-demographic and job related survey, communication competence inventory, the Maslach burnout inventory and a nursing performance scale. Data were collected from February 6 to 24, 2012, with a self-report questionnaire. The statistical analyses were performed with SPSS 18.0 software. RESULTS: The mean scores for communication competence, burnout and nursing performance were 50.49, 84.72, and 62.18, respectively. Communication competence (r=.44, p<.001) and burn out (r=-.32, p<.001) were significantly correlated with nursing performance. In the multiple linear regression, factors influencing nursing performance were communication competence, age and burnout. These variables explained about 46% of the total variance of nursing performance. Communication competence (beta=.34, p%.001) was the most influential factor. CONCLUSION: Nurses' poor communication skills and burnout can influence the occurrences of medical errors in ICU nursing performance. The results suggest that good communication and burnout resolution skills programs should be implemented to improve nursing performance efficiency.
Burns ; Hospitals, University ; Critical Care ; Intensive Care Units ; Linear Models ; Medical Errors ; Mental Competency ; Surveys and Questionnaires

Purpose: A critical indicator of the overall survival of patients with high-grade glioma is the successful isolation of tumor mesenchymal stem-like cells (tMSLCs), which play important roles in glioma progression. However, attempts to isolate tMSLCs from surgical specimens have not always been successful, and the reasons for this remain unclear. Considering that the amount of surgical high-grade glioma specimens varies, we hypothesized that larger surgical specimens would be better for tMSLC isolation. Materials and Methods: We assessed 51 fresh, high-grade glioma specimens and divided them into two groups according to the success or failure of tMSLC isolation. The success of tMSLC isolation was confirmed by plastic adherence, presenting antigens, tri-lineage differentiation, and non-tumorigenicity. Differences in characteristics between the two groups were tested using independent two sample t-tests, chi-square tests, or Kaplan-Meier survival analysis. Results: The mean specimen weights of the groups differed from each other (tMSLC-negative group: 469.9±341.9 mg, tMSLC positive group: 546.7±618.9 mg), but the difference was not statistically significant. The optimal cut-off value of specimen weight was 180 mg, and the area under the curve value was 0.599. Conclusion Our results suggested a minimum criterion for specimen collection, and found that the specimen amount was not deeply related to tMSLC detection. Collectively, our findings imply that the ability to isolate tMSLCs is determined by factors other than the specimen amount.

Purpose: A critical indicator of the overall survival of patients with high-grade glioma is the successful isolation of tumor mesenchymal stem-like cells (tMSLCs), which play important roles in glioma progression. However, attempts to isolate tMSLCs from surgical specimens have not always been successful, and the reasons for this remain unclear. Considering that the amount of surgical high-grade glioma specimens varies, we hypothesized that larger surgical specimens would be better for tMSLC isolation. Materials and Methods: We assessed 51 fresh, high-grade glioma specimens and divided them into two groups according to the success or failure of tMSLC isolation. The success of tMSLC isolation was confirmed by plastic adherence, presenting antigens, tri-lineage differentiation, and non-tumorigenicity. Differences in characteristics between the two groups were tested using independent two sample t-tests, chi-square tests, or Kaplan-Meier survival analysis. Results: The mean specimen weights of the groups differed from each other (tMSLC-negative group: 469.9±341.9 mg, tMSLC positive group: 546.7±618.9 mg), but the difference was not statistically significant. The optimal cut-off value of specimen weight was 180 mg, and the area under the curve value was 0.599. Conclusion Our results suggested a minimum criterion for specimen collection, and found that the specimen amount was not deeply related to tMSLC detection. Collectively, our findings imply that the ability to isolate tMSLCs is determined by factors other than the specimen amount.

Radon is likely the second most common cause of lung cancer after smoking. We estimated the lung cancer risk due to radon using common risk models. Based on national radon survey data, we estimated the population-attributable fraction (PAF) and the number of lung cancer deaths attributable to radon. The exposure-age duration (EAD) and exposure-age concentration (EAC) models were used. The regional average indoor radon concentration was 37.5 95 Bq/m3. The PAF for lung cancer was 8.3% (European Pooling Study model), 13.5% in males and 20.4% in females by EAD model, and 19.5% in males and 28.2% in females by EAC model. Due to differences in smoking by gender, the PAF of radon-induced lung cancer deaths was higher in females. In the Republic of Korea, the risk of radon is not widely recognized. Thus, information about radon health risks is important and efforts are needed to decrease the associated health problems.
Adult ; Demography ; *Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology/mortality ; Male ; Models, Theoretical ; Neoplasms, Radiation-Induced/*epidemiology/etiology ; Radon/*toxicity ; Republic of Korea/epidemiology ; Risk Assessment ; Smoking ; Survival Analysis

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.