Down-regulation of Survivin enhances sensitivity to BPR0L075 in human cancer cells via caspase-independent mechanisms

Background: BPR0L075 [6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole] is a novel anti-cancer compound. It inhibits tubulin polymerization and induces mitochondrial-dependent apoptosis in various human cancer cells with different multi-drug resistance (MDR) status. Over-expression of an anti-apoptotic molecule, survivin, causes drug-resistance in various cancers. Survivin inhibits apoptosis by interfering caspase-3 and promotes cell growth by stabilizing microtubule networks. Here, we determined the effects of down-regulation of survivin in BPR0L075 (L075) treatment. Methods: Western blot analysis was used to determine the expression level of survivin in L075-untreated/-treated human oral carcinoma KB and nasopharyngeal carcinoma HONE-1 cancer cells. siRNA was used to down-regulate endogenous survivin. MTT cell viability assay, real-time caspase-3 activity assay and immuno-fluorescence microscopy were used to analyze downstream effects. Results: Survivin expression was up-regulated in both KB and HONE-1 cells in response to L075 treatment. Down-regulation of survivin induced hyper-sensitivity to L075 in KB and re-stored sensitivity to L075 in KB-derived L075-resistant KB-L30 cancer cells. At the molecular level, down-regulation of survivin induced changes in microtubule dynamics in both KB and KB-L30 cells. Surprisingly, down-regulation of survivin did not enhance the activity of caspase-3 in L075 therapy. Instead, down-regulation of survivin induced translocation of the apoptosis-inducing factor (AIF) from cytoplasm to nucleus. Conclusion: Down-regulation of survivin improved drug sensitivity to L075 in both KB and L075-resistant KB-L30 cancer cells, possibly through a tubulin-dependent and caspase-independent mechanism. We suggest that combining BPR0L075 and survivin inhibitor may give better clinical outcome than the use of BPR0L075 monotherapy in future clinical trials

Effects of different ceramic and dentin thicknesses on the temperature rise during photocuring

AbstractBackground/purposeThe aims of this investigation were to describe the effect of different ceramic and remaining dentin thicknesses on substrate temperature during photocuring, and investigate whether the temperature increased by >5.5°C for different dentin/ceramic combinations.Materials and methodsThree groups of dentin thicknesses of 1.0 (D1.0), 1.5 (D1.5), and 2.0 mm (D2.0), and three groups of ceramic thicknesses of 1.5 (C1.5), 2.5 (C2.5), and 3.5 mm (C3.5) were examined. Temperature changes and the maximum temperature were observed under a high-intensity halogen light (QTH-Atralis 10 ECS program at 1200mW/cm2 for 30 seconds, Ivoclar Vivadent AG, Schaan, Liechtenstein). Four groups, D1.0–C1.5 (+11°C), D1.5–C1.5 (+7.2°C), D1.0–C2.5 (+6.7°C), and D2–0C1.5 (+5.8°C), demonstrated temperature changes of >5.5°C.Results and ConclusionsA statistical analysis showed that separate individual thicknesses and combinations of dentin and ceramic had significant effects on temperature changes (P<0.01). It was observed that the ceramic exhibited a smaller temperature shielding effect than dentin. Clinically, it would be optimal to preserve the dentin to avoid damaging pulp tissues. Where there is insufficient overall thickness (≤3.5mm), continuous high-energy output photocuring should be avoided to protect pulp tissues from thermal injury

Constructing Employability Indicators for Enhancing the Effectiveness of Engineering Education for the Solar Industry

The aim of this research is to establish a set of employability indicators that capture the competency requirements and performance expectations that solar energy enterprises have of their employees. In the qualitative component of the study, 12 administrators and 32 engineers in the industry were interviewed, and meetings with focus groups were conducted to formulate a questionnaire for a survey of Taiwanese solar energy companies for the confirmation and prioritisation of the employability indicators. On the basis of the results of the quantitative component, an interpretational model relating competence, job performance, working attitude, and employability for solar corporation recruitment and training purposes as well as for school curricular development was developed. The interpretation model formulated effectively interprets the relationship between solar enterprises’ expectations and students’ employability. The research contributes a framework for the selection and cultivation of talent, as well as providing a basis for fundamental development of the solar engineering curriculum

EFFECT OF DIFFERENT TIBIA ANGLES TO LOADING OF KNEE DURING SPLIT SQUAT

The aim of this study was to investigate the difference of knee joint force and moment during split squats of different front tibia angles. Twelve healthy male college students performed six repetitions of four different split squat types with a standard additional load of 25% BW added using a barbell. Using 10 camera 3D motion capture system and a force plate to collect data. The peak force and moment of knee flexion (sagittal plane) were calculated by using self-designed MATLAB programs. One-way ANOVA test was undertaken using SPSS 20.0 statistical software. The analysis results of the study indicated that all kinetic parameters of the four types split squats were achieved high significant differences (p less than .000). A better understanding of different loading in specific joints and correct exercise execution during training will help protecting practitioners from sport injury

Empiric antibiotic choices for community-acquired biliary tract infections

SummaryBackgroundThe study was conducted to reveal the most appropriate empiric antibiotics for the treatment of community-acquired biliary tract infections (CA-BTI) at a regional hospital in Taiwan.MethodsThe study was performed between October 1, 2010 and October 31, 2012. All positive bile culture results of presumptive community-acquired origins were collected. The associated etiologic microorganisms and their antimicrobial susceptibilities were analyzed. The appropriateness of empiric therapy (defined as the effectiveness of the antibiotics against the etiologic agents) and the subsequent treatment response were examined through the review of medical records.ResultsA total of 115 patients (cholecystitis, 83 cases, 72.2%; cholangitis, 32 cases, 27.8%) and 189 isolates (136 Gram-negative bacilli, 37 Gram-positive cocci, and 16 anaerobes) were analyzed. The most frequent pathogens were Escherichia coli (n = 69, 36.5%), Klebsiella spp. (n = 37, 19.6%), enterococci (n = 29, 15.3%), and Bacteroides spp. (n = 11, 5.8%). Penicillin resistance (5.4%) was low in Gram-positive cocci, whereas higher resistance (>20%) to cefazolin, cefuroxime, and ampicillin–sulbactam was found in Gram-negative bacilli. Anaerobes also demonstrated high resistance to clindamycin (37.5%) but less to metronidazole (12.5%). Appropriate empiric therapy was found in 92 (80%) cases, and among them, 83 (90.2%) were treated successfully. The treatment success rate (69.6%) was significantly lower among the remaining 23 cases with inappropriate empiric therapy (16 of 23 vs. 83 of 92, p < 0.05). A high treatment success rate (97.2%) was observed among cases empirically treated with ceftriaxone plus metronidazole.ConclusionThe combination of ceftriaxone plus metronidazole appears to be the most appropriate empiric antibiotics for the treatment of CA-BTI at this hospital. Because different hospitals may encounter microorganisms of different antimicrobial susceptibilities, similar approaches may be followed by other hospitals where appropriate empiric therapy has not yet been established for the treatment of CA-BTI

Hospital treatment, mortality and healthcare costs in relation to socioeconomic status among people with bipolar affective disorder

BACKGROUND: Evidence regarding the relationships between the socioeconomic status and long-term outcomes of individuals with bipolar affective disorder (BPD) is lacking. AIMS: We aimed to estimate the effects of baseline socioeconomic status on longitudinal outcomes. METHOD: A national cohort of adult participants with newly diagnosed BPD was identified in 2008. The effects of personal and household socioeconomic status were explored on outcomes of hospital treatment, mortality and healthcare costs, over a 3-year follow-up period (2008–2011). RESULTS: A total of 7987 participants were recruited. The relative risks of hospital treatment and mortality were found elevated for the ones from low-income households who also had higher healthcare costs. Low premium levels did not correlate with future healthcare costs. CONCLUSIONS: Socioeconomic deprivation is associated with poorer outcome and higher healthcare costs in BPD patients. Special care should be given to those with lower socioeconomic status to improve outcomes with potential benefits of cost savings in the following years. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © 2016 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence