Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines

The study aimed to assess the effects of polyphenols when used in combination with doxorubicin and etoposide, and to determine whether polyphenols sensitised leukaemia cells, causing inhibition of cell proliferation, cell cycle arrest and induction of apoptosis. This study is based on findings in solid cancer tumours, which have shown that polyphenols can sensitize cells to chemotherapy, and induce apoptosis and/or cell-cycle arrest. This could enable a reduction of chemotherapy dose and off-target effects, whilst maintaining treatment efficacy. Quercetin, apigenin, emodin, rhein and cis-stilbene were investigated alone and in combination with etoposide and doxorubicin in two lymphoid and two myeloid leukaemia cells lines. Measurements were made of ATP levels (using CellTiter-Glo assay) as an indication of total cell number, cell cycle progression (using propidium iodide staining and flow cytometry) and apoptosis (NucView caspase 3 assay and Hoechst 33342/propidium iodide staining). Effects of combination treatments on caspases 3, 8 and 9 activity were determined using Glo luminescent assays, glutathione levels were measured using the GSH-Glo Glutathione Assay and DNA damage determined by anti-γH2AX staining. Doxorubicin and etoposide in combination with polyphenols synergistically reduced ATP levels, induced apoptosis and increased S and/or G2/M phase cell cycle arrest in lymphoid leukaemia cell lines. However, in the myeloid cell lines the effects of the combination treatments varied; doxorubicin had a synergistic or additive effect when combined with quercetin, apigenin, emodin, and cis-stilbene, but had an antagonistic effect when combined with rhein. Combination treatment caused a synergistic downregulation of glutathione levels and increased DNA damage, driving apoptosis via caspase 8 and 9 activation. However, in myeloid cells where antagonistic effects were observed, this was associated with increased glutathione levels and a reduction in DNA damage and apoptosis. This study has demonstrated that doxorubicin and etoposide activity were enhanced by polyphenols in lymphoid leukaemia cells, however, differential responses were seen in myeloid cells with antagonistic responses seen in some combination therapies

Three versions of Perceived Stress Scale: validation in a sample of Chinese cardiac patients who smoke

<p>Abstract</p> <p>Background</p> <p>Smoking causes heart disease, the major cause of death in China and Hong Kong. Stress is one major trigger of smoking and relapse, and understanding stress among smoking cardiac patients can therefore help in designing effective interventions to motivate them to quit. The objective of this study was to examine the psychometric properties of the Perceived Stress Scale (PSS), and to compare the appropriateness of the three versions of the scale (PSS-14, PSS-10, and PSS-4) among Chinese cardiac patients who were also smokers.</p> <p>Methods</p> <p>From March 2002 to December 2004, 1860 cardiac patients who smoked were recruited at the cardiac outpatient clinics of ten acute hospitals in Hong Kong, and 1800 questionnaires were analysed. Participants completed a questionnaire including the PSS, nicotine dependence and certain demographic variables. The psychometric properties of the PSS were investigated: construct validity using confirmatory factor analysis, reliability using Cronbach's alpha and concurrent validity by examining the relationship with smoking- and health-related variables.</p> <p>Results</p> <p>For all the three versions of the PSS, confirmatory factor analyses corroborated the 2-factor structure of the scale, with the positive and negative factors correlating significantly and negatively to a moderate extent (<it>r </it>< -0.5), and high Cronbach's alpha values for the two subscales (alpha > 0.5). All the correlations of the two subscales and the smoking- and health-related variables were statistically significant and in the expected directions although of small magnitudes, except daily cigarette consumption.</p> <p>Conclusions</p> <p>The findings confirmed the satisfactory psychometric properties of all three Chinese versions of PSS. We recommend the use of PSS-10 for research which focuses on the two components of perceived stress, as it shows a higher reliability; and the use of PSS-4 if such partition is not essential and space for multiple measures is limited.</p

Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients

<p>Abstract</p> <p>Background</p> <p>Malignant gliomas are lethal cancers, highly dependent on angiogenesis and treatment options and prognosis still remain poor for patients with recurrent glioblastoma multiforme (GBM). Ephs and ephrins have many well-defined functions during embryonic development of central nervous system such as axon mapping, neural crest cell migration, hindbrain segmentation and synapse formation as well as physiological and abnormal angiogenesis. Accumulating evidence indicates that Eph and ephrins are frequently overexpressed in different tumor types including GBM. However, their role in tumorigenesis remains controversial, as both tumor growth promoter and suppressor potential have been ascribed to Eph and ephrins while the function of EphA7 in GBM pathogenesis remains largely unknown.</p> <p>Methods</p> <p>In this study, we investigated the immunohistochemical expression of EphA7 in a series of 32 primary and recurrent GBM and correlated it with clinical pathological parameters and patient outcome. In addition, intratumor microvascular density (MVD) was quantified by immunostaining for endothelial cell marker von Willebrand factor (vWF).</p> <p>Results</p> <p>Overexpression of EphA7 protein was predictive of the adverse outcome in GBM patients, independent of MVD expression (p = 0.02). Moreover, high density of MVD as well as higher EphA7 expression predicted the disease outcome more accurately than EphA7 variable alone (p = 0.01). There was no correlation between MVD and overall survival or recurrence-free survival (p > 0.05). However, a statistically significant correlation between lower MVD and tumor recurrence was observed (p = 0.003).</p> <p>Conclusion</p> <p>The immunohistochemical assessment of tissue EphA7 provides important prognostic information in GBM and would justify its use as surrogate marker to screen patients for tyrosine kinase inhibitor therapy.</p

Diagnostic thinking and information used in clinical decision-making: a qualitative study of expert and student dental clinicians

<p>Abstract</p> <p>Background</p> <p>It is uncertain whether the range and frequency of Diagnostic Thinking Processes (DTP) and pieces of information (concepts) involved in dental restorative treatment planning are different between students and expert clinicians.</p> <p>Methods</p> <p>We video-recorded dental visits with one standardized patient. Clinicians were subsequently interviewed and their cognitive strategies explored using guide questions; interviews were also recorded. Both visit and interview were content-analyzed, following the Gale and Marsden model for clinical decision-making. Limited tests used to contrast data were t, χ², and Fisher's. Scott's π was used to determine inter-coder reliability.</p> <p>Results</p> <p>Fifteen dentists and 17 senior dental students participated in visits lasting 32.0 minutes (± 12.9) among experts, and 29.9 ± 7.1 among students; contact time with patient was 26.4 ± 13.9 minutes (experts), and 22.2 ± 7.5 (students). The time elapsed between the first and the last instances of the clinician looking in the mouth was similar between experts and students. Ninety eight types of pieces of information were used in combinations with 12 DTPs. The main differences found in DTP utilization had dentists conducting diagnostic interpretations of findings with sufficient certainty to be considered definitive twice as often as students. Students resorted more often to more general or clarifying enquiry in their search for information than dentists.</p> <p>Conclusions</p> <p>Differences in diagnostic strategies and concepts existed within clearly delimited types of cognitive processes; such processes were largely compatible with the analytic and (in particular) non-analytic approaches to clinical decision-making identified in the medical field. Because we were focused on a clinical presentation primarily made up of non-emergency treatment needs, use of other DTPs and concepts might occur when clinicians evaluate emergency treatment needs, complex rehabilitative cases, and/or medically compromised patients.</p

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Evaluation of microstructural parameters of human dentin by digital image analysis

Digital image analysis was used to fully characterize the microstructure of human dentin. With the automatic routine implemented, field and region parameters related to human dentin characterization were obtained in significant statistical quantities. The results obtained for the density, area fraction, distance between neighbors, tilt angle, area and average diameter of the dentinary tubules are presented for unerupted third molars. The results, grouped per class of dentin or per tooth, are discussed in the light of the previous data found on the literature