Decoy receptor 3 protects non-obese diabetic mice from autoimmune diabetes by regulating dendritic cell maturation and function.

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, regulates immune responses through competing with receptors of Fas ligand (FasL), LIGHT and TNF-like molecule 1A (TL1A). We have previously demonstrated that transgenic expression of DcR3 in a ß cell-specific manner significantly protects non-obese diabetic (NOD) mice from autoimmune diabetes. In this study, we further investigated the systemic effect of DcR3 in regulating lymphocytes and dendritic cells in NOD mice. Our results demonstrated that both DcR3 plasmid and protein treatments significantly inhibited insulitis and diabetes. Lymphocytes from DcR3.Fc-treated mice revealed less proliferative potential and transferred ameliorated diabetes. By administration of DcR3.Fc in T1 and T2 double transgenic NOD mice expressing human Thy1 or murine Thy1.1 surface marker under IFN-γ or IL-4 promoter control respectively, we observed a remarkable reduction of Th1 and an increase of Th2 immune responses in vivo. Strikingly, in vitro polarization experiments exhibited that not only Th1 but also Th17 cell differentiation was significantly inhibited in splenocytes treated with DcR3.Fc protein. However, this phenomenon was only observed in splenocytes, not in purified CD4(+) T cells, suggesting that DcR3-mediated inhibition of Th1 and Th17 differentiation is not T cell-autonomous and maybe through other cell types such as dendritic cells. Finally, our results demonstrated that DcR3 directly modulates the differentiation and maturation of dendritic cells and subsequently regulates the differentiation and effector function of T cells.

Operating room cost for coronary artery bypass graft procedures: does experience or severity of illness matter?

OBJECTIVE: Very few studies have addressed the magnitude of the effect of the condition of the patients and the surgical volume on possible cost savings in coronary artery bypass grafting (CABG). The objectives of this study were to analyse and compare the costs of the CABG operating room (OR) between two hospitals, and to examine the effect of surgical volume and severity of illness on the OR costs. METHOD: The charts of patients who were diagnosed with coronary artery disease and who underwent CABG at two acute tertiary care hospitals in 2004 were reviewed retrospectively. Data on patient demographics, length of stay (LOS) and the American Society of Anesthesiologists Physical Status (ASAPS) score were extracted from the patient records. Cost information was obtained from detailed billing charges and from the financial accounting divisions of the hospitals. RESULTS: The high-volume hospital consumed fewer resources than the low-volume hospital (US$5411 vs. US$6407). The age of the patients, surgical volume, operating hours and LOS were associated with the OR cost. Patient age and ASAPS score, hospital, and surgical volume were associated with LOS. Patient age, the number of diseased vessels, doctor volume and pump used or not were positively associated with the operation time. The LOS and the operation time may be the mediators of the relationship between the ASAPS score and cost, and may moderate the association of volume with cost. CONCLUSIONS: This study supports the saying that 'practice makes perfect'. The knowledge and experience of the surgeons and the hospital management team are equally important in the supply of health services to patients with varying severity of illness, and are needed to maintain the competitive position of a hospital.

Uniformed service nurses' experiences with the severe acute respiratory syndrome outbreak and response in Taiwan.

Severe Acute Respiratory Syndrome (SARS) had an enormous effect on Taiwan's public health and the nation's economy. To prevent the spread of the epidemic, the government implemented strategies and measures for the control of the epidemic. The Ministry of National Defense also fully supported epidemic prevention by mobilizing all necessary human and material resources. Under the plan executed by the Ministry of National Defense, the SongShan Armed Forces Hospital became Taiwan's first hospital dedicated exclusively for the treatment of patients with SARS. Uniformed Service Nurses' devoted to caring for patients with SARS during the outbreak made significant contributions to the prevention and control of SARS.

Psychological morbidity, quality of life and their correlations among military health care workers in Taiwan.

To estimate the prevalence of psychological morbidity among health care workers in military hospitals in Taiwan and studies the association between psychological morbidity and quality of life. We sent surveys to 1,269 health care workers working in military hospitals. Participants completed structured questionnaires that included the General Health Questionnaire (GHQ), and the WHO Quality of Life Questionnaire (WHO-QOL). The survey was completed by 65 physicians, 416 nurses, and 304 other specialists. Nurses had the highest GHQ scores (nurses 32.1% vs. physicians 28.3% and other 22.4%). On the WHOQOL, nurses had worse psychological and environment domain scores (12.7 and 13.1, respectively) and physicians scored the worst for the physical and social domain as compared to nurses and other specialists. The younger, hypnotic drug use and life events had higher percentage in psychological morbidity group (Odds Ratio 1.04, 12.5, 2.38; p=0.008, 0.028 and 0.014, respectively). In regression analysis, job category, life event and hypnotic drug use could predict GHQ; age and GHQ could predict QOL (p<0.001). The GHQ might be a mediating factor to QOL. Programs should be developed to educate younger health care workers with psychological morbidity to adjust the stressors associated with their jobs to improve their QOL.

The relationship between varicoceles and obesity in a young adult population.

To determine whether a relationship between obesity and varicocele occurrence exists, the prevalence and severity of varicoceles related to obesity were investigated in a general population of young males. A total of 1050 young males attending the Navy Recruit Training Center were evaluated from their physical screening examinations. All subjects underwent history taking and physical examinations to evaluate for the presence and severity of varicocele. The anthropometric indexes including body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were recorded. All subjects were categorized by quartiles according to each anthropometric index. Means were compared with the Student's t-test. Severity was compared by analysis of variance testing and frequency was analysed using the chi-square method. Statistical significance was considered at p <0.05. A total of 490 (46.67%) subjects had varicoceles. The means of BMI, WC and WHR of those without varicoceles was 23.99 +/- 3.82 kg/m(2), 83.20 +/- 9.97 cm and 0.85 +/- 0.05, respectively. These judged values were greater than those with varicoceles (22.02 +/- 3.18 kg/m(2), 79.19 +/- 9.01 cm and 0.83 +/- 0.05) (p < 0.001). In the univariate regression analysis, BMI, WC and WHR all had a significantly negative correlation with severity of varicocele (all p < 0.001). Analysis comparing varicocele frequency based on each grade per anthropometric index group was performed. The logistic regression revealed that the prevalence of grade II and III varicoceles showed a statistically inverse association with all three anthropometric indexes. The prevalence and severity of varicoceles inversely correlated with obesity. The present data support the explanation that obesity may result in a decreased nutcracker effect, which accounts for prevention of the renal vein compression by the adipose tissue.

Dual degradation of aurora A and B kinases by the histone deacetylase inhibitor LBH589 induces G2-M arrest and apoptosis of renal cancer cells.

PURPOSE: This study is aimed at investigating antineoplastic efficacy of histone deacetylase inhibitor (HDACI) LBH589 on renal cell carcinoma (RCC) and elucidating the novel molecular mechanisms involved in growth arrest and apoptosis by targeting the important nonhistone molecules. EXPERIMENTAL DESIGN: We analyzed the growth-inhibitory effect of LBH589 on RCC by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in vitro and antitumor efficacy by xenograft experiments in vivo. To verify the associated molecular mechanisms involved in LBH589-mediated cell death and cell cycle progression by Western blotting and fluorescence-activated cell sorting analysis. RESULTS: HDACI LBH589 induced degradation of both Aurora A and B kinases through a proteasome-mediated pathway by targeting HDAC3 and HDAC6. The dual degradation of Aurora A and B kinases mediated by LBH589 resulted in inducing G2-M arrest and apoptosis of renal cancer cell lines and our results also showed that LBH589 potently inhibited renal cancer cell growth in vitro and suppressed tumor formation in vivo. The Aurora A and B kinases and HDAC3 are overexpressed in the human RCC tumor tissues examined, which make them perfect targets for HDACI LBH589 treatment. CONCLUSIONS: Our in vitro and in vivo data showed that LBH589 has potent anticancer effect of renal cancer cells. LBH589 and other HDACI treatment resulted in inducing G2-M arrest and apoptosis of renal cancer cells through degradation of Aurora A and B kinases by inhibition of HDAC3 and HDAC6. The clinical efficacy of LBH589 in the treatment of patients with metastatic RCC, especially those with high Aurora kinase and HDAC expression, is worthy of further investigation.

Is obesity correlated with sexual function in young men?

The study investigated the correlation between obesity and sexual function in young men. It was a cross-sectional study in an unselected consecutive sample of military men aged less than 28 years old attending to the Navy Recruit Training Center. There were 772 subjects included in the study, excluding subjects with comorbidities and subjects who had not engaged in sexual intercourse. All men underwent a detailed health examination, including physical assessment and taking of medical history. Obesity was assessed by anthropometric means, including body mass index, waist circumference (WC), and waist-to-hip ratio. Subjects were categorized into 4 groups by increasing order according to each anthropometric indicator (quartile method). Clinical sexual function was evaluated with the International Index of Erectile Function-5 (IIEF-5) scale score. There was no statistical difference in IIEF-5 score between smoking and nonsmoking groups (t test, P = .422). According to analysis of variance, only the anthropometric indicator WC showed a statistically significant correlation with IIEF-5 severity (P = .032). A possible explanation was that the systemic effects of obesity and smoking would take place while combined with the process of aging.

Operating room costs of laparoscopic cholecystectomy: does surgeon volume matter?

Very few studies have addressed the issue of surgeon volume on cost savings of laparoscopic cholecystectomy (LC) in Asian countries. The objectives of the study were to analyze LC operating-room (OR) costs between two study hospitals and to examine the effect of surgeon volume on OR costs. Patients diagnosed with gallbladder disease who underwent LC in October through December 2002 at two acute tertiary-care hospitals were included. Patient demographics and clinical information were derived from patient charts. Cost information was obtained from purchasing departments or specific cost centers. Three multivariate linear regression models were performed to examine the association between surgeon volume, cost, and utilization. There were no significant differences in patient demographics and disease severity between the two hospitals. Hospital A consumed fewer resources than did hospital B (NTdollars 21,674 vs NTdollars 26,417). Direct materials cost, direct professional costs, and indirect costs varied significantly by study hospital and by surgeon volume. High-volume surgeons incurred lower costs and shorter stay as compared with low-volume surgeons. Patients who scored in the American Society of Anesthesiologists physical status (ASA PS) 3 incurred significantly higher costs and longer hospital stays than did patients with ASA PS 1. The present study supports the proposal that hospital management and experience of surgeons are of equal importance in maintaining the standing of hospitals in competitive positions. In addition to the differences in hospital management and surgeon volume, the patient severity of illness also needs to be taken into consideration in cost containment.

Hypertension--a possible vulnerability marker for depression in patients with end-stage renal disease.

OBJECTIVE: This study explored the association of hypertension and psychiatric morbidity in patients with end-stage renal disease (ESRD) under adjusted personality characteristics and parental attachment. METHODS: The mental health of 121 patients with ESRD in a general teaching hospital was evaluated using the 12-item version of the Chinese Health Questionnaire (CHQ). Only 40 males and 49 females completed all the questionnaires. Ten of the 40 males and 21 of the 49 females had high scores (> or = 4) and were allotted to the case group (n = 31). The remaining 58 patients constituted the control group (CHQ < 4). RESULTS: The logistic regression model showed that hypertension, gender, and neuroticism are statistically significant covariates. Hypertension, especially, was strongly associated with depressive vulnerability (odds ratio of hypertension versus without hypertension = 9.07:1). Structural equation modeling revealed that gender difference and hypertension directly influenced the individuals' mental health status and that the influence of hypertension on mental health was highly variable. CONCLUSION: A parsimonious structural equation model provided considerable evidence that hypertension could have an important effect on depression in ESRD patients, when predisposing factors, such as personality characteristics and parental attachment, gender, duration of hemodialysis and other medical diseases were adjusted. Hence, hypertension might be a mediating factor of depressive vulnerability in ESRD patients underling genetic and environmental problems.

Mutation of the p53 tumor suppressor gene in transitional cell carcinoma of the urinary tract in Taiwan.

Early detection of a mutated p53 gene is thought to provide useful information in a wide range of human tumors. The aim of this study was to identify the role of the p53 gene in transitional cell carcinoma of the urinary tract. From March 1992 to July 2003, 75 patients (54 men and 21 women) with a mean age of 66.85 years and pathologically diagnosed transitional cell carcinoma were enrolled in this study. Fifty-eight patients had bladder cancer, eight had ureteral cancer, and nine had renal-pelvic cancer. Rapid screening for mutation of the p53 gene was performed using polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and sequencing analysis. Primer sets were designed to amplify fragments within exons 4, 5, 6, 7, and 8 of the p53 gene. Pathology classified 37 tumors as low grade and 38 as high grade. Tumor stage was pT1 or less in 29 patients and at least pT2 in 46 patients. Of the 75 patients in this study, 47 (62.7%) had a p53 mutation. Of the patients with a p53 mutation, 33 (70.2%) had invasive tumors. Invasive tumors were associated with p53 mutation (p < 0.05). Noted in 20 patients (26.7%), exon 4 was the most common site of the mutation. Of the patients with exon 4 mutations, 15 (75%) had invasive tumors and nine (45%) had high-grade tumors. Additionally, among the 20 patients with a common polymorphism at codon 72, 16 (80%) had invasive tumors and 14 (70%) had high-grade tumors. In this study, 62.7% of patients with transitional cell carcinoma had a p53 mutation, suggesting that the p53 gene mutation may be used as a marker of transitional cell carcinoma. Invasive tumors are more likely to have a p53 gene mutation. A simple analysis of the p53 gene using PCR/SSCP is suitable for screening for p53 abnormalities in transitional cell carcinoma. The relationship between cancer risk and the codon 72 polymorphism of exon 4 needs further investigation.

Telomeric length varies with age and polymorphisms of the MAOA gene promoter in peripheral blood cells obtained from a community in Taiwan.

OBJECTIVE: Telomere shortening and increased MAOA gene activity both occur with aging. We undertook to develop a predictive model of telomere shortening and to investigate the possible association between MAOA gene promoter polymorphisms and telomere length as influenced by age and gender. METHODS: A stratified random household sample was selected from a community in southern Taiwan. Of 1231 subjects attending our health-screening program, 441 agreed to have additional venous blood withdrawn for DNA extraction and genetic study. Exactly 433 subjects completed the questionnaires and genetic analysis. Their telomere lengths were distributed (6.4-11.63 kb). RESULTS: The rate of shortening per year was 69 base pairs, and the gender difference in length was not statistically significant (F = 0.091, P = 0.763). The lognormal distribution of telomere lengths was linear. The polynomial regression analysis showed Ln (telomere length) = -2.57-0.007 x age - 0.34 MAOA (adjusted R-square = 0.60). The gender effect on telomere length was not statistically significant (P = 0.52). No interaction effects were found between age, gender and MAOA gene polymorphisms. The high-activity allele of the MAOA promoter polymorphisms were negatively associated with telomere length (P = 0.013). Structural equation modeling confirmed the null model structure. The present data suggest that high-activity MAOA promoter gene polymorphisms, as in aging, are a risk factor for telomeric shortening. CONCLUSIONS: Central nervous system serotonergic activity correlates with human aggressive behavior and depression in many studies, and the MAOA promoter gene may also serve as a clinical marker in the treatment of cardiovascular disease. The predictive model and table of telomere length presented in this study will provide a quick reference for future studies.