Investigating Urine Biomarkers in Detrusor Underactivity and Detrusor Overactivity with Detrusor Underactivity Patients.

Bladder inflammation and tissue hypoxia were considered important pathognomonic bladder features in detrusor underactivity (DU) and detrusor overactivity (DO) patients. This study investigated urine inflammatory and oxidative stress biomarker levels in DU and DO with DU (DO-DU) patients. Urine samples were collected from 50 DU and 18 DO-DU patients, as well as 20 controls. The targeted analytes included three oxidative stress biomarkers (8-OHdG, 8-isoprostane, and total antioxidant capacity [TAC]) and 33 cytokines. DU and DO-DU patients had different urine biomarker profiles from controls, including 8-OHdG, PGE2, EGF, TNFα, IL-1ß, IL-5, IL-6, IL-8, IL-10, IL-17A, and CXCL10. Controlling for age and sex, multivariate logistic-regression models revealed that 8-OHdG, PGE2, EGF, IL-5, IL-8, IL-10, and TAC were significant biomarkers for diagnosing DU. In DU patients, urine TAC and PGE2 levels were positively correlated with detrusor voiding pressure. In DO-DU patients, urine 8-OHdG, PGE2, IL-6, IL-10, and MIP-1α levels were positively correlated with maximal urinary flow rate, while urine IL-5, IL-10, and MIP-1α were negatively correlated with the first sensation of bladder filling. Urine inflammatory and oxidative stress biomarker analysis provides a non-invasive and convenient approach for important clinical information in DU and DO-DU patients.

A novel EGFR inhibitor suppresses survivin expression and tumor growth in human gefitinib-resistant EGFR-wild type and -T790M non-small cell lung cancer.

Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) are currently used therapy for non-small cell lung cancer (NSCLC) patients; however, drug resistance during cancer treatment is a critical problem. Survivin is an anti-apoptosis protein, which promotes cell proliferation and tumor growth that highly expressed in various human cancers. Here, we show a novel synthetic compound derived from gefitinib, do-decyl-4-(4-(3-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)propyl) piper-azin-1-yl)-4-oxobutanoate, which is named as SP101 that inhibits survivin expression and tumor growth in both the EGFR-wild type and -T790M of NSCLC. SP101 blocked EGFR kinase activity and induced apoptosis in the A549 (EGFR-wild type) and H1975 (EGFR-T790M) lung cancer cells. SP101 reduced survivin proteins and increased active caspase 3 for inducing apoptosis. Ectopic expression of survivin by a survivin-expressed vector attenuated the SP101-induced cell death in lung cancer cells. Moreover, SP101 inhibited the gefitinib-resistant tumor growth in the xenograft human H1975 lung tumors of nude mice. SP101 substantially reduced survivin proteins but conversely elicited active caspase 3 proteins in tumor tissues. Besides, SP101 exerted anticancer abilities in the gefitinib resistant cancer cells separated from pleural effusion of a clinical lung cancer patient. Consistently, SP101 decreased the survivin proteins and the patient-derived xenografted lung tumor growth in nude mice. Anti-tumor ability of SP101 was also confirmed in the murine lung cancer model harboring EGFR T790M-L858R. Together, SP101 is a new EGFR inhibitor with inhibiting survivin that can be developed for treating EGFR wild-type and EGFR-mutational gefitinib-resistance in human lung cancers.

Urine biomarkers in ESSIC type 2 interstitial cystitis/bladder pain syndrome and overactive bladder with developing a novel diagnostic algorithm.

This study aimed to investigate the diagnostic values of urine cytokines in interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB) patients, and to develop a novel diagnostic algorithm. Urine samples were collected from 40 IC/BPS, 40 OAB patients, and 30 controls. Commercially available multiplex immunoassays were used to analyze 31 targeted cytokines. Urine cytokine profiles were significantly different among study groups and controls. MIP-1ß showed the highest sensitivity (92.2%) for identifying diseased study patients from controls. The cytokines with high diagnostic values for distinguishing between IC and OAB included IL-10, RANTES, eotaxin, CXCL10, IL-12p70, NGF, IL-6, IL-17A, MCP-1, and IL-1RA. The diagnostic algorithm was subsequently developed according to the diagnostic values obtained. MIP-1ß was selected for the initial screening test to diagnose diseased patients and controls with diagnostic rates of 81.6% and 68.4%, respectively. As confirmation tests for IC/BPS, the diagnostic rates of eotaxin, CXCL10, and RANTES were 73.3%, 72.7%, and 69.7%, respectively. As the confirmation test for OAB, the diagnostic rate of IL-10 was 60%. Urine cytokine profiles of IC/BPS and OAB patients differed from those of controls and might be useful as biomarkers for diagnosis. A novel pilot diagnostic algorithm was developed based on these profiles.

Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics.

The objective of the present study was to investigate the diagnostic values of urine cytokines in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and to identify their correlations with clinical characteristics. Urine samples were collected from 127 patients with IC/BPS [European Society for the Study of Interstitial Cystitis (ESSIC) types 1 and 2] and 28 controls. Commercially available multiplex immunoassays (MILLIPLEX map kits) were used to analyze 31 targeted cytokines. Cytokine levels between patients with IC/BPS and controls were analyzed using ANOVA. Receiver-operating characteristic curves of each cytokine to distinguish IC/BPS from controls were generated for calculation of the area under the curve. Patients with IC/BPS had urine cytokine profiles that differed from those of controls. Between patients with ESSIC type 1 and 2 IC/BPS, urine cytokine profiles were also different. Among cytokines with high diagnostic values (i.e., area under the curve > 0.7) with respect to distinguish patients with ESSIC type 2 IC/BPS from controls, regulated upon activation, normal T cell expressed and presumably secreted (RANTES), macrophage inflammatory protein (MIP)-1ß, and IL-8 were of higher sensitivity, whereas macrophage chemoattractant protein (MCP)-1, chemokine (C-X-C motif) ligand 10 (CXCL10), and eotaxin-1 were of higher specificity. In multivariate logistic regression models controlling for age, sex, body mass index, and diabetes mellitus, the urine cytokines with high diagnostic values (MCP-1, RANTES, CXCL10, IL-7, and eotaxin-1) remained statistically significant in differentiating IC/BPS and controls. MCP-1, CXCL10, eotaxin-1, and RANTES were positively correlated with glomerulation grade and negatively correlated with maximal bladder capacity. In conclusion, patients with IC/BPS had urine cytokine profiles that clearly differed from those of controls. Urine cytokines might be useful as biomarkers for diagnosing IC/BPS and mapping its clinical characteristics.

Investigation of the Effects of a Nursing Information System by Using the Technology Acceptance Model.

The purposes of this study are to investigate the effectiveness of implementing a nursing information system and to discuss several issues affecting its successful deployment from the perspectives of nurses, the major users of the system. The methodology was based on the theory of the technology acceptance model. This study adopted a cross-sectional study method to survey and collect data. In total, 167 questionnaires were distributed to subjects. Approximately 94.6%, or 158 valid questionnaires, were collected. The data were analyzed using SPSS and PLS software.The data analysis indicated that the factors that most significantly influenced the willingness of nurses to use the nursing information system were their degrees of satisfaction with the system and their perceptions of its usefulness. A nursing information system that can provide functions that are useful and convenient and that facilitate the avoidance of tedious repetitive writing and improve the quality of provided care can encourage nurse satisfaction with the system and thus stimulate their interest in using it for their work. The ease of use of the system can also affect the willingness of nurses to use it.

CR108, a novel vitamin K3 derivative induces apoptosis and breast tumor inhibition by reactive oxygen species and mitochondrial dysfunction.

Vitamin K3 derivatives have been shown to exert anticancer activities. Here we show a novel vitamin K3 derivative (S)-2-(2-hydroxy-3-methylbutylthio)naphthalene-1,4-dione, which is named as CR108 that induces apoptosis and tumor inhibition through reactive oxygen species (ROS) and mitochondrial dysfunction in human breast cancer. CR108 is more effective on the breast cancer cell death than other vitamin K3 derivatives. Moreover, CR108 induced apoptosis in both the non-HER-2-overexpressed MCF-7 and HER-2-overexpressed BT-474 breast cancer cells. CR108 caused the loss of mitochondrial membrane potential, cytochrome c released from mitochondria to cytosol, and cleaved PARP proteins for apoptosis induction. CR108 markedly increased ROS levels in breast cancer cells. N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the CR108-induced ROS levels, mitochondrial dysfunction and apoptosis. Interestingly, CR108 increased the phosphorylation of p38 MAP kinase but conversely inhibited the survivin protein expression. NAC treatment prevented the activation of p38 MAP kinase and rescued the survivin protein levels. SB202190, a specific p38 MAP kinase inhibitor, recovered the survivin protein levels and attenuated the cytotoxicity of CR108-treated cells. Furthermore, CR108 inhibited the xenografted human breast tumor growth in nude mice. Together, we demonstrate that CR108 is a novel vitamin K3 derivative that induces apoptosis and tumor inhibition by ROS production and mitochondrial dysfunction and associates with the phosphorylation of p38 MAP kinase and the inhibition of survivin in the human breast cancer.

Using the 100-g oral glucose tolerance test to predict fetal and maternal outcomes in women with gestational diabetes mellitus.

BACKGROUND: This 5-year cohort study investigated gestational diabetes mellitus (GDM) using new diagnostic criteria and predictive factors for maternal and fetal outcomes. METHODS: From March 2001 to February 2006, 8557 pregnant women underwent a 50-g glucose challenge test (GCT) at 24 to 28 weeks of gestation. A diagnosis of GDM was based on a a one-hour plasma glucose level >/= 140 mg/dl on the 50 g GCT, followed by at lease two abnormal values on a 100-g oral glucose tolerance test (OGTT), according to the Carpenter and Coustan modification of the National Diabetes Data Group (NDDG) criteria. Maternal and fetal outcomes were compared with women with normal glucose tolerance (NGT). RESULTS: The incidence of GDM was 7.4%. After excluding women with twin pregnancies, 617 women with GDM and 1250 women with NGT were enrolled for comparison. Older age (33.7 +/- 4.1 vs. 32.2 +/- 4.1, p < 0.001), lower weight gain during pregnancy (13.2 +/- 4.4 vs. 14.6 +/- 4.0 kg, p < 0.001), and higher rates of caesarean section (43.8% vs. 32.7%, p < 0.001) occurred in women with GDM compared to those in the NGT group. The rates of macrosomia and neonatal death were higher in the GDM group than the NGT group (7.0% vs. 1.9%, p < 0.001 and 0.6% vs. 0.0%, p = 0.005 respectively). The fasting glucose on the 100-g OGTT was positively correlated with birth weight in the GDM group (r = 0.117, 95% CI 0.038-0.194, p = 0.004). A value exceeding 90 mg/dl was 80% sensitive and 50% specific for macrosomia. CONCLUSIONS: The incidence of GDM in Taiwan is increasing more than before based on current diagnostic criteria. The fasting glucose on the 100-g OGTT correlates closely with birth weight and is also an independent risk factor for macrosomia. Focusing on women with fasting blood glucose concentrations > 90 mg/dL is anticipated to improve outcomes effectively.

The postpartum metabolic outcome of women with previous gestational diabetes mellitus.

BACKGROUND: This study investigated postpartum metabolic abnormality in women with previous gestational diabetes mellitus (GDM) and predictive factors for postpartum glucose intolerance. METHODS: From March 2001 to February 2003, 127 prior-GDM women underwent a 75g oral glucose tolerance test (OGTT) and metabolic assessment at least six weeks after delivery. To identify the predictors, clinical variables obtained at the time of GDM were compared. RESULTS: The cumulative incidence rates of diabetes mellitus (DM) and abnormal glucose tolerance (AGT) i.e. impaired fasting glucose or impaired glucose tolerance, in women with previous GDM were 13.4% and 29.1%, respectively. Postpartum body mass index (BMI), total cholesterol, HDL cholesterol, triglycerides, blood pressure, waist-to-hip ratio and fasting C-peptide were not significantly different among DM, AGT and normal glucose tolerance (NGT) women. However, the C-peptide/glucose score was lower in DM than in AGT and NGT women (p < 0.01). DM or AGT women had higher prepregnancy BMI and fasting glucose level for 100g OGTT than NGT women (p < 0.05) at the time of GDM. The fasting glucose value was an independent risk factor. The cutoff point of three abnormal values in 100g OGTT provided 86% sensitivity and 43% specificity for the prediction of postpartum DM or AGT. CONCLUSIONS: High prepregnancy BMI and increased glycemic deterioration at the time of GDM are found in women developing postpartum DM and AGT. The fasting glucose value for 100g OGTT is an independent risk factor and more than three abnormal glucose values offers good diagnostic efficacy in predicting postpartum glucose intolerance.