A randomised, controlled trial evaluating a low cost, 3D-printed bronchoscopy simulator.

Low-fidelity, simulation-based psychomotor skills training is a valuable first step in the educational approach to mastering complex procedural skills. We developed a cost-effective bronchial tree simulator based on a human thorax computed tomography scan using rapid-prototyping (3D-print) technology. This randomised, single-blind study evaluated how realistic our 3D-printed simulator would mimic human anatomy compared with commercially available bronchial tree simulators (Laerdal Airway Management Trainer with Bronchial Tree and AirSim Advance Bronchi, Stavanger, Norway).

Abnormal flow adhesion of sickle red blood cells to human placental trophoblast extracellular matrix.

Pregnancy in sickle cell disease (SCD) has been associated with increased complications such as vaso-occlusive crises, severe anemia and foetal loss. It has been proposed that the sickling of red blood cells (RBCs) inside the placenta circulation could participate to these complications. The present study investigated the adhesion of sickle RBCs on human trophoblast-derived cell and its extracellular matrix.

Antibodies to the Plasmodium falciparum rhoptry protein RAP-2/RSP-2 in relation to anaemia in Cameroonian children.

Previous studies have implicated reactive antibodies to the low molecular weight rhoptry-associated proteins (RAP-1, RAP-2/RSP-2 and RAP-3) in erythroid cell destruction during Plasmodium falciparum infection. In this pilot study, the frequency, specificity and functional capacity of naturally acquired anti-RAP-2/RSP-2 antibodies were investigated in the sera of anaemic and nonanaemic malaria-infected Cameroonian children. All sera recognized RAP-2/RSP-2 by FACS, irrespective of the clinical status of the subjects.

Strain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.

Background: Pregnancy-associated malaria (PAM) is a serious consequence of the adhesion to the placental receptor chondroitin sulfate A (CSA) of Plasmodium falciparum-infected erythrocytes (PE) expressing the large cysteine-rich multi-domain protein var2CSA. Women become resistant to PAM, and develop strain-transcending immunity against CSA-binding parasites. The identification of var2CSA regions that could elicit broadly neutralizing and adhesion-blocking antibodies is a key step for the design of prophylactic vaccine strategies.

Mechanisms of malarial anaemia: potential involvement of the Plasmodium falciparum low molecular weight rhoptry-associated proteins.

Plasmodium falciparum malaria is a major cause of morbidity and mortality throughout the tropics. Anaemia is a constant feature of the disease. Pregnant women mostly primigravidae and children below the age of 5 years are the most afflicted.

Var2CSA DBL6-epsilon domain expressed in HEK293 induces limited cross-reactive and blocking antibodies to CSA binding parasites.

Background: Pregnancy-associated malaria (PAM) is a serious consequence of Plasmodium falciparum-infected erythrocytes sequestration in the placenta through the adhesion to the placental receptor chondroitin sulfate A (CSA). Although women become resistant to PAM as they acquire transcending inhibitory immunity against CSA-binding parasites, hundreds of thousands of lives could be saved if a prophylactic vaccine targeting the surface proteins of placental parasites could be designed. Recent works point to the variant protein var2CSA as the key target for the development of a pregnancy-associated malaria vaccine.

CD44, a signal receptor for the inhibition of the cytoadhesion of CD36-binding Plasmodium falciparum-infected erythrocytes by CSA-binding infected erythrocytes.

The cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) in organ microvessels is a key event in the pathogenesis of cerebral malaria and pulmonary edema. Identification of the molecules involved in the interaction between IEs and endothelial cells has been a major goal of research into severe forms of malaria. In contrast, the consequences of cytoadhesion for endothelial cells have been largely ignored.

Disruption of var2csa gene impairs placental malaria associated adhesion phenotype.

Infection with Plasmodium falciparum during pregnancy is one of the major causes of malaria related morbidity and mortality in newborn and mothers. The complications of pregnancy-associated malaria result mainly from massive adhesion of Plasmodium falciparum-infected erythrocytes (IE) to chondroitin sulfate A (CSA) present in the placental intervillous blood spaces. Var2CSA, a member of the P.

Members of the low-molecular-mass rhoptry protein complex of Plasmodium falciparum bind to the surface of normal erythrocytes.

The destruction of erythrocytes is one of the most frequently observed causes of severe malarial anemia. Recently, we showed that tagging normal erythrocytes and cells of erythroid precursors with rhoptry-derived proteins can trigger their destruction. In the present study, we used rhoptry-associated protein (RAP)-1 and RAP-3 gene-disruption mutant Plasmodium falciparum parasites and showed that 2 members of a rhoptry protein complex, RAP-1 and RAP-2, bind to the surface of normal erythrocytes.

Neural cell adhesion molecule, a new cytoadhesion receptor for Plasmodium falciparum-infected erythrocytes capable of aggregation.

The cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) to the endothelial cells lining the microvasculature, clogging the microvessels of various organs, is a key event in the pathogenesis of certain severe forms of malaria, such as cerebral malaria and pulmonary edema. Studies aiming to identify possible correlations between the severity of clinical cases and the presence of particular cytoadhesion phenotypes have been largely unsuccessful. One of the possible reasons for this failure is that some of the key receptors and/or mechanisms involved have yet to be identified.

Dissection of the role of PfEMP1 and ICAM-1 in the sensing of Plasmodium-falciparum-infected erythrocytes by natural killer cells.

Background: Host innate immunity contributes to malaria clinical outcome by providing protective inflammatory cytokines such as interferon-gamma, and by shaping the adaptive immune response. Plasmodium falciparum (Pf) is the etiologic agent of the most severe forms of human malaria. Natural Killer (NK) cells are lymphocytes of the innate immune system that are the first effectors to produce interferon-gamma in response to Pf.

Pregnancy-associated malaria: parasite binding, natural immunity and vaccine development.

Humans living in areas of high malaria transmission gradually acquire, during the early years of life, protective clinical immunity to Plasmodium falciparum, limiting serious complications of malaria to young children. However, pregnant women become more susceptible to severe P. falciparum infections during their first pregnancy.

Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway.

Malaria is undoubtedly the world's most devastating parasitic disease, affecting 300 to 500 million people every year. Some cases of Plasmodium falciparum infection progress to the deadly forms of the disease responsible for 1 to 3 million deaths annually. P.

Characterization of anti-var2CSA-PfEMP1 cytoadhesion inhibitory mouse monoclonal antibodies.

Pregnancy-associated malaria (PAM) is associated with the massive sequestration of erythrocytes infected with CSA-binding parasites in the placenta. Natural protective immunity against PAM is acquired during the course of pregnancies, with the development of anti-PfEMP1 antibodies recognizing placental infected erythrocytes (IEs) from different geographical regions. Mouse monoclonal antibodies (mabs) were raised against Plasmodium falciparum variant surface proteins expressed by CSA-binding parasites.

Immunogenicity of Duffy binding-like domains that bind chondroitin sulfate A and protection against pregnancy-associated malaria.

Sequestration of Plasmodium falciparum-infected erythrocytes in the placenta is implicated in pathological outcomes of pregnancy-associated malaria (PAM). P. falciparum isolates that sequester in the placenta primarily bind chondroitin sulfate A (CSA).

Natural killer cell and macrophage cooperation in MyD88-dependent innate responses to Plasmodium falciparum.

IFN-gamma secretion by natural killer (NK) cells is pivotal to several tumor and viral immune responses, during which NK and dendritic cells cooperation is required. We show here that macrophages are mandatory for NK cell IFN-gamma secretion in response to erythrocytes infected with Plasmodium falciparum (Pf), a causative agent of human malaria. In addition, direct sensing of Pf infection by NK cells induces their production of the proinflammatory chemokine CXCL8, without triggering their granule-mediated cytolytic programs.

Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage.

The destruction of erythrocytes and defects in erythropoiesis are among the most frequently observed causes of morbidity in severe Plasmodium falciparum malaria. The molecular mechanisms involved remain unclear, despite extensive investigation. We show here, for the first time, that tagging with the parasite rhoptry protein ring surface protein 2 (RSP2) is not restricted to the surfaces of normal erythrocytes, as previously reported, but that it extends to erythroid precursor cells in the bone marrow of anemic malaria patients.

A single member of the Plasmodium falciparum var multigene family determines cytoadhesion to the placental receptor chondroitin sulphate A.

In high-transmission regions, protective clinical immunity to Plasmodium falciparum develops during the early years of life, limiting serious complications of malaria in young children. Pregnant women are an exception and are especially susceptible to severe P. falciparum infections resulting from the massive adhesion of parasitized erythrocytes to chondroitin sulphate A (CSA) present on placental syncytiotrophoblasts.

Presence of the parasitophorous duct in Plasmodium falciparum and P. vivax parasitized Saimiri monkey red blood cells.

Although the exchange of metabolites between the intraerythrocytic malaria parasite and the external medium has been studied extensively, the transport of molecules across the erythrocyte cytoplasmic membrane and cytoplasm and the parasitophorous vacuolar membrane needs to be investigated more fully to be completely understood. Recently, the concept of the parasitophorous duct, establishing a continuity between the environment and the vacuolar space surrounding the intraerythrocytic parasite, has been suggested to provide an explanation of how macromolecules can cross two membranes in a cell devoid of an endocytic system. This concept is highly controversial and has been suspected to be an in vitro artefact.

Identification of a 67-amino-acid region of the Plasmodium falciparum variant surface antigen that binds chondroitin sulphate A and elicits antibodies reactive with the surface of placental isolates.

The complications of malaria in pregnancy are caused by the massive sequestration of parasitized erythrocytes (PE) in the placenta. Placental isolates of Plasmodium falciparum are unusual in that they do not bind the primary microvasculature receptor CD36 but instead bind chondroitin sulphate A (CSA). Pregnant mothers develop antibodies that recognize placental variants worldwide, suggesting that a vaccine against malaria in pregnancy is possible.

Placenta cryosections for study of the adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A in flow conditions.

The adhesion of Plasmodium falciparum-infected erythrocytes (IEs) to chondroitin-4-sulfate (CSA) via the PfEMP1-CSA parasite ligand domain is correlated with placental malaria in primigravidae. The recent identification of parasite genes encoding CSA adhesion molecules and the development of pan-reactive monoclonal antibodies against the Pf(CSA) ligand have opened up new avenues for the development of anti-IE sequestration therapies for the prevention of placental malaria. A model closely mimicking placental sequestration of IEs during pregnancy is needed for the preclinical and clinical evaluation of candidate molecules for the induction of antibodies that could protect pregnant women from placental malaria.

Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells.

Severe malaria is characterized by the sequestration of Plasmodium falciparum-infected erythrocytes (IEs). Because platelets can affect tumor necrosis factor (TNF)-activated endothelial cells (ECs), we investigated their role in the sequestration of IEs, using IEs that were selected because they can adhere to endothelial CD36 (IE(CD36)), a P. falciparum receptor that is expressed on platelets.

Recovery of adhesion to chondroitin-4-sulphate in Plasmodium falciparum varCSA disruption mutants by antigenically similar PfEMP1 variants.

Protection against maternal malaria has been associated with the acquisition of a specific antibody response that prevents adhesion of Plasmodium falciparum-infected erythrocytes to the glycosaminoglycan chondroitin-4-sulphate (CSA), which is present in the placental intervillous space. These antibodies are directed against variant forms of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) that mediate binding to CSA.

Immunization with recombinant duffy binding-like-gamma3 induces pan-reactive and adhesion-blocking antibodies against placental chondroitin sulfate A-binding Plasmodium falciparum parasites.

Maternal malaria is associated with the sequestration, in the placenta, of Plasmodium falciparum-infected erythrocytes onto chondroitin sulfate A (CSA), via the duffy binding-like (DBL)-gamma3 domain of the P. falciparum erythrocyte membrane protein 1 (PfEMP1(CSA)) (DBL-gamma3(CSA)). The production of antibodies against CSA-binding infected erythrocytes (IEs(CSA)) is correlated with resistance to maternal malaria in multiparous women.