Wolbachia-induced reproductive parasitism and applications

Οι συμβιωτικές σχέσεις εντόμων-μικροοργανισμών (και ιδιαίτερα βακτηρίων) είναι ένα ευρέως διαδεδομένο φαινόμενο με ποικίλες συνέπειες στη βιολογία του ξενιστή, θετικές ή αρνητικές. Ένα από τα πιο διαδεδομένα και καλά μελετημένα βακτήρια είναι το βακτήριο Wolbachia. Το βακτήριο Wolbachia είναι ένα υποχρεωτικά ενδοκυττάριο και μητρικά κληρονομούμενο βακτήριο που συμβιώνει με ένα μεγάλο εύρος ειδών ασπόνδυλων όπως ακάρεα, αράχνες, ισόποδα, νηματώδεις της φιλαρίασης και κυρίως έντομα. Μελέτες έχουν δείξει ότι το βακτήριο Wolbachia πιθανώς συμβιώνει με το 70% όλων των ειδών των εντόμων, καθιστώντας το ως τον πιο διαδεδομένο συμβιωτικό οργανισμό του πλανήτη. Οι αλληλεπιδράσεις του βακτηρίου με τον ξενιστή κυμαίνονται μεταξύ της αμοιβαίας συμβίωσης και της επαγωγής αναπαραγωγικών ανωμαλιών όπως θηλυκοποίηση, παρθενογένεση, θανάτωση των αρσενικών ατόμων ή κυτταροπλασματική ασυμβατότητα. Παρά την ευρεία εξάπλωση και τις επιδράσεις του βακτηρίου στη βιολογία του ξενιστή, στην ειδογένεση και στην οικολογική ποικιλότητα, λίγα είναι γνωστά για τους μοριακούς μηχανισμούς της αλληλεπίδρασης του ξενιστή με το συμβιωτικό αυτό βακτήριο. Πρόσφατες μελέτες εστιάζουν στη δυνατότητα ανάπτυξης μεθόδων βιολογικού ελέγχου εντόμων γεωργικής, περιβαλλοντικής ή ιατρικής σημασίας, οι οποίες βασίζονται στις ιδιότητες του βακτηρίου Wolbachia.Insects have been reported to be associated with a broad variety of microorganisms, affecting the host biology in many different ways. Among them, Wolbachia, an obligatory intracellular and maternally-inherited symbiont, has recently attracted a lot of attention. Beside insects, Wolbachia are found in association with a wide variety of other invertebrate species, including mites, scorpions, spiders, crustaceans, filarial nematodes. Several surveys have indicated that Wolbachia may be symbiont of up to 70% of all insect species, rendering Wolbachia the most ubiquitous intracellular symbiotic organism on Earth. Wolbachia-host interactions range from many forms of reproductive parasitism to mutualistic symbioses. Different Wolbachia strains have been found to induce a number of reproductive alterations such as feminization, parthenogenesis, male-killing or cytoplasmic incompatibility. Despite their common occurrence and major effects on host biology, speciation and ecological diversity, little is known on the molecular mechanisms that mediate Wolbachia-host interactions. Recent studies focus on the potential of Wolbachia-based methods for the biological control of insect pests and disease vectors of agricultural, environmental and medical importance

Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial†

We examined the effect of MSI status in a trial-based cohort of 1254 stage II and III colon cancer (CC) patients treated with 5-FU/LV or FOLFIRI. We confirm that for stage II CC MSI is strongly prognostic for RFS and OS. No significant differences were found between treatment arms. Adding irinotecan to 5-FU did not benefit MSI-H tumors. RFS was better for MSI-H CC both in the right and left colo

Irrational prescribing of over-the-counter (OTC) medicines in general practice: testing the feasibility of an educational intervention among physicians in five European countries

Background: Irrational prescribing of over-the-counter (OTC) medicines in general practice is common in Southern Europe. Recent findings from a research project funded by the European Commission (FP7), the “OTC SOCIOMED”, conducted in seven European countries, indicate that physicians in countries in the Mediterranean Europe region prescribe medicines to a higher degree in comparison to physicians in other participating European countries. In light of these findings, a feasibility study has been designed to explore the acceptance of a pilot educational intervention targeting physicians in general practice in various settings in the Mediterranean Europe region. Methods: This feasibility study utilized an educational intervention was designed using the Theory of Planned Behaviour (TPB). It took place in geographically-defined primary care areas in Cyprus, France, Greece, Malta, and Turkey. General Practitioners (GPs) were recruited in each country and randomly assigned into two study groups in each of the participating countries. The intervention included a one-day intensive training programme, a poster presentation, and regular visits of trained professionals to the workplaces of participants. Reminder messages and email messages were, also, sent to participants over a 4-week period. A pre- and post-test evaluation study design with quantitative and qualitative data was employed. The primary outcome of this feasibility pilot intervention was to reduce GPs’ intention to provide medicines following the educational intervention, and its secondary outcomes included a reduction of prescribed medicines following the intervention, as well as an assessment of its practicality and acceptance by the participating GPs. Results: Median intention scores in the intervention groups were reduced, following the educational intervention, in comparison to the control group. Descriptive analysis of related questions indicated a high overall acceptance and perceived practicality of the intervention programme by GPs, with median scores above 5 on a 7-point Likert scale. Conclusions: Evidence from this intervention will estimate the parameters required to design a larger study aimed at assessing the effectiveness of such educational interventions. In addition, it could also help inform health policy makers and decision makers regarding the management of behavioural changes in the prescribing patterns of physicians in Mediterranean Europe, particularly in Southern European countries

In the eye of the beholder:promoting learner-centric design to develop mobile games for learning

Out of the project EMuRgency a game-based learning environment evolved, which trains school children in providing reanimation and cardiopulmonary resuscitation (CPR). The application gets players to act as if they were in a real case of emergency. This paper reports on a formal usability study conducted with two different groups of learners, regular learners and learners with special educational needs (SEN). With the study we compared the two groups of learners with regard to game usability and effectiveness of the intervention. Our intention was to better understand the different needs and requirements to learning materials that game designer need to take into consideration in order to make the learning experience successful for both groups. A total of 89 children played the game simulation. Results showed differences in perception and effectiveness of individual mechanisms for the two groups with regard to usability or switching between tasks and mobile device.This publication was partly financed by the European Regional Development Fund (ERDF), regions of the Euregio Meuse-Rhine and the participating institutions under the INTERREG IVa program (EMR.INT4-1.2.-2011-04/070, http://www.emurgency.eu)

Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status

INTRODUCTION: To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse. METHODS: The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR. RESULTS: The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007–0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51–101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97–12.84; P = 0.001) were independent predictive factors for CNS relapse. CONCLUSION: CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs

Wolbachia Prophage DNA Adenine Methyltransferase Genes in Different Drosophila-Wolbachia Associations

Wolbachia is an obligatory intracellular bacterium which often manipulates the reproduction of its insect and isopod hosts. In contrast, Wolbachia is an essential symbiont in filarial nematodes. Lately, Wolbachia has been implicated in genomic imprinting of host DNA through cytosine methylation. The importance of DNA methylation in cell fate and biology calls for in depth studing of putative methylation-related genes. We present a molecular and phylogenetic analysis of a putative DNA adenine methyltransferase encoded by a prophage in the Wolbachia genome. Two slightly different copies of the gene, met1 and met2, exhibit a different distribution over various Wolbachia strains. The met2 gene is present in the majority of strains, in wAu, however, it contains a frameshift caused by a 2 bp deletion. Phylogenetic analysis of the met2 DNA sequences suggests a long association of the gene with the Wolbachia host strains. In addition, our analysis provides evidence for previously unnoticed multiple infections, the detection of which is critical for the molecular elucidation of modification and/or rescue mechanism of cytoplasmic incompatibility