Design and implementation of the European-Mediterranean Postgraduate Programme on Organ Donation and Transplantation (EMPODaT) for Middle East/North Africa countries

This prospective study reports the design and results obtained after the EMPODaT project implementation. This project was funded by the Tempus programme of the European Commission with the objective to implement a common postgraduate programme on organ donation and transplantation (ODT) in six selected universities from Middle East/North Africa (MENA) countries (Egypt, Lebanon and Morocco). The consortium, coordinated by the University of Barcelona, included universities from Spain, Germany, Sweden and France. The first phase of the project was to perform an analysis of the current situation in the beneficiary countries, including existing training programmes on ODT, Internet connection, digital facilities and competences, training needs, and ODT activity and accreditation requirements. A total of 90 healthcare postgraduate students participated in the 1-year training programme (30 ECTS academic credits). The methodology was based on e-learning modules and face-to-face courses in English and French. Training activities were evaluated through pre- and post-tests, self-assessment activities and evaluation charts. Quality was assessed through questionnaires and semi-structured interviews. The project results on a reproducible and innovative international postgraduate programme, improvement of knowledge, satisfaction of the participants and confirms the need on professionalizing the activity as the cornerstone to ensure organ transplantation self-sufficiency in MENA countries

Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria

Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection

Modélisation de la sensibilité des sols à l'érosion hydrique.

National audienceDeux modèles de sensibilité des sols agricoles à l’aléa érosion ont été adaptés pour qu’ils puissent être utilisés dans le cadre de projection liés au changement climatique : SCALES et MESALES. Leur adaptation a porté sur la prise en compte d’échelle spatiale et temporelle plus fine, prenant notamment mieux en compte la parcelle agricole et sa gestion, la variabilité climatique et agricole intra-annuelle. Cette adaptation permet de mieux estimer les zones et les périodes à risques, ce qui est important sur des territoires comme ceux testés où les risques restent modérés et liés à certaines situations spatiales et temporelles. L’analyse de la variabilité intra-annuelle montre que la période d’automne et d’hiver est particulièrement sensible. La projection climatique sur 2100, faite à partir de SCALES sur un territoire normand, montre une aggravation de la sensibilité des sols à l’érosion, et un décalage temporel de cette sensibilité de l’automne vers l’hiver. Cette projection n’a intégré que des scénarios climatiques. Elle devra donc encore intégrer des scénarios agricoles futurs dont l’interaction avec le climat pourrait modifier ces premières projections

Parasite polymorphism and severe malaria in Dakar (Senegal): a West African urban area.

International audienceBACKGROUND: Transmission of malaria in West African urban areas is low and healthcare facilities are well organized. However, malaria mortality remains high. We conducted a survey in Dakar with the general objective to establish who died from severe malaria (SM) in urban areas (particularly looking at the age-groups) and to compare parasite isolates associated with mild or severe malaria. METHODOLOGY/PRINCIPAL FINDINGS: The current study included mild- (MM) and severe malaria (SM) cases, treated in dispensaries (n = 2977) and hospitals (n = 104), We analysed Pfdhfr/Pfcrt-exon2 and nine microsatellite loci in 102 matched cases of SM and MM. Half of the malaria cases recorded at the dispensaries and 87% of SM cases referred to hospitals, occurred in adults, although adults only accounted for 26% of all dispensary consultations. This suggests that, in urban settings, whatever the reason for this adult over-representation, health-workers are forced to take care of increasing numbers of malaria cases among adults. Inappropriate self treatment and mutations in genes associated with drug resistance were found associated with SM in adults. SM was also associated with a specific pool of isolates highly polymorphic and different from those associated with MM. CONCLUSION: In this urban setting, adults currently represent one of the major groups of patients attending dispensaries for malaria treatment. For these patients, despite the low level of transmission, SM was associated with a specific and highly polymorphic pool of parasites which may have been selected by inappropriate treatment

Characteristics of the patients recruited for the parasite genotyping study.

<p>*Parasitaemia was counted on Giemsa stained thick smears for 1000 leukocytes and expressed as parasites per microliter of blood, according to WHO standards.</p><p>Geometric means were calculated.</p><p>**Haemoglobin less than 10 g/dL.</p

Genetic diversity of the parasite population.

<p>For a given patient group, the average number of alleles was calculated by the sum of distinct PCR fragments amplified from the group, divided by the number of persons in that group. A) Percentage of patients with multiple infections (deduced from 9-microsatellite loci genotypes) and number of alleles/patient by clinical group; CM were predominantly multi-infected (2.3 isolates/person). B) Percentage of patients with multiple alleles for each microsatellite in each clinical group, C) Total number of alleles for each microsatellite locus in each clinical group. ARA2, TAA109, PFG377, 7A11, TAA87 and BM27 presented a different infection complexity in CM, as compared to HM (Mann Whitney p = 0.0058, p = 0.013, p<0.00001, p<0.00001, p = 0.008, p = 0.008, respectively) D) Number of alleles common to 50% of the isolates in each clinical group. E) Number of alleles common to 75% of the isolates in each clinical group.</p

Genetic diversity of the parasite population (Fst).

<p>193 genotypes were scored at 9 loci, 29 genotypes at 7 loci and 13 genotypes at 6 loci. Reconstruction of haplotypes was carried out for 235 genotypes (15, 77 and 143 at Fann, HPD and MM patients respectively) A) Mean number of distinct alleles observed per locus. Unbiased expected heterozygosity (He) per locus was calculated using the unbiased estimator of Nei corrected for small sample sizes, (SM) severe malaria  =  HM+CM. The total number of alleles per locus is similar in SM and MM isolates (FSTAT, A = 13.7±4.3 for HPD and 11.9±4.4 for dispensary, Fann A = 5.44±1.4). Parasite populations were genetically different for different clinical groups: Fst comparison CM (Fann)−MM = 0.160, Fst CM(HPD)-MM = 0.163, Fst Fann-HPD = 0.157 (p<0.017 for all). B) Canonical Correspondence Analysis of genotypes (CANOCO software) obtained from MM (n = 129 genotypes) and SM (HPD, n = 59 genotypes) at 9 microsatellite loci. The significance of the canonical axes was tested with 1000 Monte Carlo permutations with a 95% confidence interval of the centroid of each population (centroids of populations are surrounded by 95% confidence intervals: o and hashed trait ellipse =  MM; x and plain ellipse  =  HPD-recruited SM). CCA shows a larger genotypic diversity in SM isolates than in MM (Monte-Carlo, p-value = 0.002).</p

Allelic distribution of the nine microsatellites studied.

<p>Fragment size was calculated using a Rox-labelled internal molecular weight marker and cubic polynomial regression (Genscan software). For each microsatellite, alleles were defined according to the size of the PCR product and to the structure of the repeats in the genetic sequence. Size increases from code 1 to n. Frequencies were calculated in reference to the total number of samples in each group (CM: cerebral malaria, HM: hospitalized malaria, MM: mild malaria). Patient self-treatment was associated with higher frequency of ARA2 alleles 8-14; PFPK2 allele 2; TAA87 allele 7; and 7A11 alleles 1-2-4.</p