Designing a Massive Open Online Course (MOOC) in face-to-face sessions. A blended design to teach practical histology.

Teaching histology, through virtual microscopy in educational strategies, undeniably moved towards the digitization and distancing of teaching. The setting up of the Massive Open Online Course (MOOC) entitled "Introduction to Histology: exploring the tissues of the human body" made it possible to exploit the potential to share digital resources with a wider audience while being integrated into the teaching on-campus students. This article described the pedagogical choices prevailing during the design of the MOOC and its combination with face-to-face sessions to achieve specific learning outcomes. The pedagogical alignment of learning outcomes described according to their cognitive levels, with online and face-to-face learning activities and evaluation methods has been demonstrated. The impact of such a blended design into an academic program has been ascertained using perception and performance data. Student satisfaction and engagement as well as motivational cues were identified. The level of performance was maintained in the educational strategy implemented and made it possible to achieve the objectives expected by the teachers. The benefits of integrating a MOOC with classroom-based teaching were highlighted, as well as barriers that could hinder the successful implementation.

[Multiple myeloma : an overview of advances in biology and treatment]. / Le myélome multiple : un tour d'horizon des nouveautés dans sa biologie et son traitement.

Multiple myeloma is the second most common hematological malignancy, characterized by an uncontrollable proliferation of clonal plasma cells. Although progresses in understanding its pathobiology and its treatment are made every day, it remains incurable. Since myeloma is more and more common, especially in the elderly, we would like to propose an overview of its pathobiology, diagnostic criteria and treatment «guidelines¼.

Deuxième pathologie hématologique la plus fréquente, le myélome multiple est une maladie plasmocytaire qui reste actuellement incurable. Pourtant, tous les jours, des progrès sont effectués au niveau de la compréhension de sa physiopathologie et de l'élaboration de stratégies de traitement. Vu son caractère de plus en plus répandu, surtout chez la personne âgée, nous proposons un tour d'horizon de sa physiopathologie, de ses critères diagnostiques et des grandes lignes de sa prise en charge.

[Anemia in patients with severe chronic obstructive pulmonary disease, a comorbity more common than previously thought]. / L'anémie dans la bronchopneumopathie chronique obstructive sévère : une comorbidité plus fréquente qu'on ne le croit.

Chronic Obstructive Pulmonary Disease (COPD) is traditionally associated with polycythemia which results from chronic hypoxemia. Nevertheless, recent studies have shown that anemia may be more frequent than expected in patients with COPD. In this retrospective study, we investigated the prevalence of hemoglobin disorders in a cohort of 100 patients with stable, moderate to severe COPD (II to IV GOLD classification). We identified 31 % patients with anemia while only 15 % had polycythemia. Anemia was more frequent in male patients. We also demonstrated a negative correlation between hemoglobin and CRP levels (R=-0.56, p inferior to 0.0001). COPD patients with anemia had experienced a higher rate of hospitalizations for exacerbation in the previous year than those with polycythemia (p inferior to 0.05). Anemia is a frequent comorbidity in COPD; it is associated with systemic inflammation and a propensity to hospitalization for exacerbation.

Il est classiquement rapporté qu'une polycythémie survient en réponse à une hypoxémie chez les patients souffrant de BronchoPneumopathie Chronique Obstructive (BPCO) sévère. Néanmoins, certaines données récentes ont souligné la présence d'une anémie dans une proportion non négligeable de cas. Nous avons évalué, dans une étude rétrospective, la prévalence des troubles de l'érythropoïèse au sein d'une cohorte de 100 patients BPCO stables (de stades II à IV selon la classification de GOLD). Une anémie était présente chez 31 % de ces sujets tandis qu'une polycythémie était retrouvée dans 15 % des cas. L'anémie était plus souvent observée dans le sexe masculin. Une corrélation inverse existait entre le taux d'hémoglobine et la CRP (r = - 0,56, p inférieur à 0,0001). Les patients BPCO avec anémie avaient été plus souvent hospitalisés pour exacerbation au cours de l'année précédente (p inférieur à 0,05). L'anémie est plus fréquente que la polycythémie chez le patient BPCO sévère; elle est associée à une inflammation systémique et à une tendance accrue aux hospitalisations pour exacerbation.

Uptake by rat liver and intracellular fate of plasmid DNA complexed with poly-L-lysine or poly-D-lysine.

Efficiency of transfection is probably dependent on the rate of intracellular degradation of plasmid DNA. When a non-viral vector is used, it is not known to what extent the plasmid DNA catabolism is subordinated to the catabolism of the vector. In the work reported here, the problem was approached by following the intracellular fate in rat liver, of plasmid [35S]DNA complexed with a cationic peptide poly-L-lysine that can be hydrolyzed by cellular peptidases or with its stereoisomer, poly-D-lysine, that cannot be split by these enzymes. Complexes of DNA with poly-L-lysine and poly-D-lysine are taken up to the same extent by the liver, mainly by Kupffer cells, but the intracellular degradation of nucleic acid molecules is markedly quicker when poly-L-lysine is injected. The association of DNA with the polycations inhibits DNA hydrolysis in vitro by purified lysosomes but similarly for poly-L-lysine and poly-D-lysine. The intracellular journey followed by [35S]DNA complexed with poly-L- or poly-D-lysine was investigated using differential and isopycnic centrifugation. Results indicate that [35S]DNA is transferred more slowly to lysosomes, the main site of intracellular degradation of endocytosed macromolecules, when it is given as a complex with poly-D-lysine than with poly-L-lysine. They suggest that the digestion of the vector in a prelysosomal compartment is required to allow endocytosed plasmid DNA to rapidly reach lysosomes. Such a phenomenon could explain why injected plasmid DNA is more stable in vivo when it is associated with poly-D-lysine.

Cationic lipids destabilize lysosomal membrane in vitro.

Addition of cationic lipids to plasmid DNA considerably increases the efficiency of transfection. The mechanism has not yet been elucidated. A possibility is that these compounds destabilize biological membranes (plasma, endosomal, lysosomal), facilitating the transfer of nucleic molecules through these membranes. We have investigated the problem by determining if a cationic lipid N-(1-(2,3-dioleoxy)propyl)-N,N,N,-trimethylammonium methyl-sulfate (DOTAP, Boehringer, Mannheim, Germany) affects the integrity of rat liver lysosomal membrane. We have measured the latency of beta-galactosidase, a lysosomal enzyme, and found that incubation of lysosomes with low concentrations of DOTAP causes a striking increase in free activity of the hydrolase and even a release of the enzyme into the medium. This indicates that lysosomal membrane is deeply destabilized by the lipid. The phenomenon depends on pH, it is less pronounced at pH 5 than at pH 7.4. Anionic compounds, particularly anionic amphipathic lipids, can to some extent prevent this phenomenon. It can be observed with various cationic lipids. A possible explanation is that cationic liposomes interact with anionic lipids of lysosomal membrane, allowing a fusion between the lipid bilayers which results in a destabilization of the organelle membrane.