Non-monotonic changes in clonogenic cell survival induced by disulphonated aluminum phthalocyanine photodynamic treatment in a human glioma cell line

<p>Abstract</p> <p>Background</p> <p>Photodynamic therapy (PDT) involves excitation of sensitizer molecules by visible light in the presence of molecular oxygen, thereby generating reactive oxygen species (ROS) through electron/energy transfer processes. The ROS, thus produced can cause damage to both the structure and the function of the cellular constituents resulting in cell death. Our preliminary investigations of dose-response relationships in a human glioma cell line (BMG-1) showed that disulphonated aluminum phthalocyanine (AlPcS₂) photodynamically induced loss of cell survival in a concentration dependent manner up to 1 μM, further increases in AlPcS₂concentration (>1 μM) were, however, observed to decrease the photodynamic toxicity. Considering the fact that for most photosensitizers only monotonic dose-response (survival) relationships have been reported, this result was unexpected. The present studies were, therefore, undertaken to further investigate the concentration dependent photodynamic effects of AlPcS₂.</p> <p>Methods</p> <p>Concentration-dependent cellular uptake, sub-cellular localization, proliferation and photodynamic effects of AlPcS₂were investigated in BMG-1 cells by absorbance and fluorescence measurements, image analysis, cell counting and colony forming assays, flow cytometry and micronuclei formation respectively.</p> <p>Results</p> <p>The cellular uptake as a function of extra-cellular AlPcS₂concentrations was observed to be biphasic. AlPcS₂was distributed throughout the cytoplasm with intense fluorescence in the perinuclear regions at a concentration of 1 μM, while a weak diffuse fluorescence was observed at higher concentrations. A concentration-dependent decrease in cell proliferation with accumulation of cells in G₂+M phase was observed after PDT. The response of clonogenic survival after AlPcS₂-PDT was non-monotonic with respect to AlPcS₂concentration.</p> <p>Conclusions</p> <p>Based on the results we conclude that concentration-dependent changes in physico-chemical properties of sensitizer such as aggregation may influence intracellular transport and localization of photosensitizer. Consequent modifications in the photodynamic induction of lesions and their repair leading to different modes of cell death may contribute to the observed non-linear effects.</p

A hierarchy of effective teaching and learning to acquire competence in evidenced-based medicine

BACKGROUND: A variety of methods exists for teaching and learning evidence-based medicine (EBM). However, there is much debate about the effectiveness of various EBM teaching and learning activities, resulting in a lack of consensus as to what methods constitute the best educational practice. There is a need for a clear hierarchy of educational activities to effectively impart and acquire competence in EBM skills. This paper develops such a hierarchy based on current empirical and theoretical evidence. DISCUSSION: EBM requires that health care decisions be based on the best available valid and relevant evidence. To achieve this, teachers delivering EBM curricula need to inculcate amongst learners the skills to gain, assess, apply, integrate and communicate new knowledge in clinical decision-making. Empirical and theoretical evidence suggests that there is a hierarchy of teaching and learning activities in terms of their educational effectiveness: Level 1, interactive and clinically integrated activities; Level 2(a), interactive but classroom based activities; Level 2(b), didactic but clinically integrated activities; and Level 3, didactic, classroom or standalone teaching. SUMMARY: All health care professionals need to understand and implement the principles of EBM to improve care of their patients. Interactive and clinically integrated teaching and learning activities provide the basis for the best educational practice in this field

Murchison Widefield Array and XMM-Newton observations of the Galactic supernova remnant G5.9+3.1

Aims. In this paper we discuss the radio continuum and X-ray properties of the so-far poorly studied Galactic supernova remnant (SNR) G5.9 + 3.1. Methods. We present the radio spectral energy distribution (SED) of the Galactic SNR G5.9 + 3.1 obtained with the Murchison Widefield Array (MWA). Combining these new observations with the surveys at other radio continuum frequencies, we discuss the integrated radio continuum spectrum of this particular remnant. We have also analyzed an archival XMM-Newton observation, which represents the first detection of X-ray emission from this remnant. Results. The SNR SED is very well explained by a simple power-law relation. The synchrotron radio spectral index of G5.9 + 3.1 is estimated to be 0.42 ± 0.03 and the integrated flux density at 1 GHz to be around 2.7 Jy. Furthermore, we propose that the identified point radio source, located centrally inside the SNR shell, is most probably a compact remnant of the supernova explosion. The shell-like X-ray morphology of G5.9 + 3.1 as revealed by XMM-Newton broadly matches the spatial distribution of the radio emission, where the radio-bright eastern and western rims are also readily detected in the X-ray while the radio-weak northern and southern rims are weak or absent in the X-ray. Extracted MOS1+MOS2+PN spectra from the whole SNR as well as the north, east, and west rims of the SNR are fit successfully with an optically thin thermal plasma model in collisional ionization equilibrium with a column density NH ~ 0.80 × 1022 cm−2 and fitted temperatures spanning the range kT ~ 0.14–0.23 keV for all of the regions. The derived electron number densities ne for the whole SNR and the rims are also roughly comparable (ranging from ~0.20f−1∕2 to ~0.40f−1∕2 cm−3, where f is the volume filling factor). We also estimate the swept-up mass of the X-ray emitting plasma associated with G5.9+3.1 to be ~46f−1∕2 M⊙.</jats:p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Pyrexia of unknown origin: a swollen gland and a glass of milk

Brucellosis is a disease which has rarely been seen in the UK since the pasteurization of milk. It often presents as a pyrexia of unknown origin and should be considered in the differential diagnosis. A case report is presented where the diagnosis was initially thought to be tuberculosis but months later was found to be brucellosis. The article then presents a summary of brucellosis and its management. </jats:p