Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Canine distemper virus induces apoptosis in cervical tumor derived cell lines

Apoptosis can be induced or inhibited by viral proteins, it can form part of the host defense against virus infection, or it can be a mechanism for viral spread to neighboring cells. Canine distemper virus (CDV) induces apoptotic cells in lymphoid tissues and in the cerebellum of dogs naturally infected. CDV also produces a cytopathologic effect, leading to apoptosis in Vero cells in tissue culture. We tested canine distemper virus, a member of the Paramyxoviridae family, for the ability to trigger apoptosis in HeLa cells, derived from cervical cancer cells resistant to apoptosis. To study the effect of CDV infection in HeLa cells, we examined apoptotic markers 24 h post infection (pi), by flow cytometry assay for DNA fragmentation, real-time PCR assay for caspase-3 and caspase-8 mRNA expression, and by caspase-3 and -8 immunocytochemistry. Flow cytometry showed that DNA fragmentation was induced in HeLa cells infected by CDV, and immunocytochemistry revealed a significant increase in the levels of the cleaved active form of caspase-3 protein, but did not show any difference in expression of caspase-8, indicating an intrinsic apoptotic pathway. Confirming this observation, expression of caspase-3 mRNA was higher in CDV infected HeLa cells than control cells; however, there was no statistically significant change in caspase-8 mRNA expression profile. Our data suggest that canine distemper virus induced apoptosis in HeLa cells, triggering apoptosis by the intrinsic pathway, with no participation of the initiator caspase -8 from the extrinsic pathway. In conclusion, the cellular stress caused by CDV infection of HeLa cells, leading to apoptosis, can be used as a tool in future research for cervical cancer treatment and control

Comparing angular and curved shapes in terms of implicit associations and approach/avoidance responses.

Most people prefer smoothly curved shapes over more angular shapes. We investigated the origin of this effect using abstract shapes and implicit measures of semantic association and preference. In Experiment 1 we used a multidimensional Implicit Association Test (IAT) to verify the strength of the association of curved and angular polygons with danger (safe vs. danger words), valence (positive vs. negative words) and gender (female vs. male names). Results showed that curved polygons were associated with safe and positive concepts and with female names, whereas angular polygons were associated with danger and negative concepts and with male names. Experiment 2 used a different implicit measure, which avoided any need to categorise the stimuli. Using a revised version of the Stimulus Response Compatibility (SRC) task we tested with a stick figure (i.e., the manikin) approach and avoidance reactions to curved and angular polygons. We found that RTs for approaching vs. avoiding angular polygons did not differ, even in the condition where the angles were more pronounced. By contrast participants were faster and more accurate when moving the manikin towards curved shapes. Experiment 2 suggests that preference for curvature cannot derive entirely from an association of angles with threat. We conclude that smoothly curved contours make these abstract shapes more pleasant. Further studies are needed to clarify the nature of such a preference

Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial

BACKGROUND: Complete resection of metastases can result in cure for selected patients with metastatic colorectal cancer. METHODS: First BEAT evaluated the safety of bevacizumab with first-line chemotherapy in 1914 patients. Prospectively collected data from 225 patients who underwent curative-intent surgery were analysed, including an exploratory comparison of resection rate in patients treated with different regimens. NO16966 compared efficacy of oxaliplatin-based chemotherapy plus bevacizumab or placebo in 1400 patients. A retrospective analysis of resection rate was undertaken. RESULTS: In First BEAT, 225 out of 1914 patients (11.8%) underwent curative-intent surgery at median 64 days ( range 42-100) after the last dose of bevacizumab. R0 resection was achieved in 173 out of 225 patients (76.9%). There were no surgery-related deaths and serious post-operative complications were uncommon, with grade 3/4 bleeding and wound-healing events reported in 0.4% and 1.8%, respectively. Resection rates were highest in patients receiving oxaliplatin-based combination chemotherapy (P=0.002), possibly confounded by patient selection. In NO16966, 44 out of 699 patients treated with bevacizumab (6.3%) and 34 out of 701 patients treated with placebo (4.9%) underwent R0 metastasectomy (P=0.24). CONCLUSIONS: The rate of serious post-operative complications in First BEAT was comparable to historical controls without bevacizumab. In NO16966, there were no statistically significant differences in resection rates or overall survival in patients treated with bevacizumab vs placebo

Membrane Cholesterol Regulates Lysosome-Plasma Membrane Fusion Events and Modulates Trypanosoma cruzi Invasion of Host Cells

Trypanosoma cruzi, is the etiological agent of a neglected tropical malady known as Chagas' disease, which affects about 8 million people in Latin America. 30–40% of affected individuals develop a symptomatic chronic infection, with cardiomyopathy being the most prevalent condition. T. cruzi utilizes an interesting strategy for entering cells: T. cruzi enhances intracellular calcium levels, which in turn trigger the exocytosis of lysosomal contents. Lysosomes then donate their membrane for the formation of the parasitophorous vacuole. Membrane rafts, cholesterol-enriched microdomains in the host cell plasma membrane, have also been implicated in T. cruzi invasion process. Since both plasma membrane and lysosomes collaborate in parasite invasion, we decided to study the importance of these membrane domains for lysosomal recruitment and fusion during T. cruzi invasion into host cells. Our results show that drug dependent depletion of plasma membrane cholesterol changes raft organization and induces excessive lysosome exocytosis in the earlier stages of treatment, leading to a depletion of lysosomes near the cell cortex, which in turn compromises T. cruzi invasion. Based on these results, we propose that cholesterol depletion leads to unregulated exocytic events of pre-docked lysosomes, reducing lysosome availability at the cell cortex and consequently compromising T. cruzi infection

Variability of the blazar 4C 38.41 (B3 1633+382) from GHz frequencies to GeV energies

The quasar-type blazar 4C 38.41 (B3 1633+382) experienced a large outburst in 2011, which was detected throughout the entire electromagnetic spectrum. We present the results of low-energy multifrequency monitoring by the GASP project of the WEBT consortium and collaborators, as well as those of spectropolarimetric/spectrophotometric monitoring at the Steward Observatory. We also analyse high-energy observations of the Swift and Fermi satellites. In the optical-UV band, several results indicate that there is a contribution from a QSO-like emission component, in addition to both variable and polarised jet emission. The unpolarised emission component is likely thermal radiation from the accretion disc that dilutes the jet polarisation. We estimate its brightness to be R(QSO) ~ 17.85 - 18 and derive the intrinsic jet polarisation degree. We find no clear correlation between the optical and radio light curves, while the correlation between the optical and \gamma-ray flux apparently fades in time, likely because of an increasing optical to \gamma-ray flux ratio. As suggested for other blazars, the long-term variability of 4C 38.41 can be interpreted in terms of an inhomogeneous bent jet, where different emitting regions can change their alignment with respect to the line of sight, leading to variations in the Doppler factor \delta. Under the hypothesis that in the period 2008-2011 all the \gamma-ray and optical variability on a one-week timescale were due to changes in \delta, this would range between ~ 7 and ~ 21. If the variability were caused by changes in the viewing angle \theta\ only, then \theta\ would go from ~ 2.6 degr to ~ 5 degr. Variations in the viewing angle would also account for the dependence of the polarisation degree on the source brightness in the framework of a shock-in-jet model.Comment: 19 pages, 23 figures, in press for Astronomy and Astrophysic

Lineage Analysis of Circulating Trypanosoma cruzi Parasites and Their Association with Clinical Forms of Chagas Disease in Bolivia

Around 30–50% of Trypanosoma cruzi infections in Latin America cause chronic Chagas disease 10–30 years after the primary infection due to lack of effective treatment. The major clinical complications associated with chronic Chagas disease are cardiac myositis (leading to cardiac failure), and autonomous neuroplexus degeneration of the digestive tract that can cause megacolon or megaesophagus. Therefore, there are three major clinical forms of Chagas disease; cardiac, digestive and indeterminate (asymptomatic). The parasites, which can infect humans as well as other mammals, are transmitted by species of triatomines commonly found in the Americas. The parasite is divided in at least six discrete typing units: TcI, TcIIa–e. In humans, the TcI is mainly observed in Central America and northern parts of South America while the TcIIb/d/e is confined mainly to the southern cone of Latin America. We determined which DTU were prevalent in chronic patients in Bolivia, where the three clinical forms and several DTUs of the parasites are present, in order to determine whether there was a link between a particular parasite DTU and a particular clinical outcome. We found a vast majority of TcIId but its kDNA polymorphism showed no association with any of the clinical manifestations of chronic Chagas